Today, I want to thank my team, which has invested a ton of their time. It's not like they're not busy. They've invested a ton of their time in pulling together this story for you guys to experience today. Everyone around us in the company, I wanna say that we're so proud of everything that has happened recently, and we couldn't be more excited about talking to everyone here. We have a number of key opinion leaders, luminaries in their field, who've been enthusiastic about Optical Genome Mapping and Bionano. And they've dedicated days of their lives to come up here and participate and tell their stories. They're gonna be amazing. The other thing that really gets me excited is seeing a lot of people I know and recognize, but even more so seeing people I don't know. We actually brought in some folks who are gonna be new to the story here today. We're a publicly traded company. I don't know if you knew that, but there are a few things that we need to say up front, so we'll be making some statements about preliminary financial results as well as a series of forward-looking statements. I wanna make sure that everybody is aware of our filings, which are available online, and you can review those. With that, let's get started. The status quo is an incredibly difficult competitive force to overcome. Any transformation begins with that courageous step forward. Every cell in your body has DNA, and when those instructions go wrong, disease happens. If we could get into those cells and uncover areas where those instructions have been miswritten, we might be able to understand the nature of disease and intervene in ways that would improve life. With the Human Genome Project, sequencing methods really came to the front, but one of the limitations is they're limited by their ability to pick up structural variations. That part of the genome that has not been addressed, this is where we have the opportunity. Bionano has been pioneering something called Optical Genome Mapping, and it's a way of examining the structure of the genome. If we look at these hematological malignancies, overall, with all the tools and technologies available today, we still only hit 50%. That part of the genome that has not been addressed, those underlying genomic aberrations that have not been detected till now. There is the availability of this technique called Optical Genome Mapping to provide more answers, and that is extremely powerful. Optical Genome Mapping brings a new way of looking at the genome to highlight structural variants in a way that's never been done before. More comprehensive view of variation in the human genome that may impact therapies in the future. All classes of structural variations that are causing any genetic disorder. We can explain diseases much better. Bionano's technology really covers a unique space. It covers a resolution that is not assessed by any other genomic technology. It fills a gap. It fills a huge gap in the understanding of genomes. The answers researchers have been looking for the past three decades. Transform the way the world sees the genome. We are on this journey to transform the way the world sees the genome. We need to work together to bring about the outcomes that we're all very focused on generating. We have a chance to really elevate health and wellness for all pe ople. Great. If you don't know me, I'm Erik Holmlin. I'm the President and CEO of Bionano. This is gonna be a story that we go through with you today to really lay out the Bionano story, it's a story that you haven't heard before. It's really a story about where we're at today and where we're going in the future from where we're at today. This is our agenda. You should have seen it. They can give you a printout of it. What I wanna start with and really cover are the key takeaways that we hope you get from this event today. It's really trying to position for all of you in the financial community, analyst community, where Bionano fits in the Genome Analysis Landscape. There's so much going on, so many solutions, so many technologies. Where does Bionano fit? I think it's a critical question to answer. Who's using our solutions today and why? Where are we pointing those solutions? Where are our target customers? You're gonna get to meet some of them, of course. What our financial growth plan is and what we think about the future financially. Importantly, we're gonna talk about how mapping our proprietary methodology compares to sequencing and, you know, address some of the hurdles that we face going forward to really make Optical Genome Mapping a technique that is very widely adopted. When we think about where we're at today, we're incredibly thrilled about the progress that we've made. I don't know if other management teams acknowledge their own sort of sense of awe at the accomplishments of the company. But I certainly feel that about Bionano, and I feel that about our team, and I'm just so pleased with what we've been able to do to get to 240 of our Saphyr systems installed around the world. Get to revenue levels that are in this range of around $28 million, which is substantial year-over-year growth. The number of clinical research subjects. These are genomes that are being analyzed by some of our KOLs and others as part of clinical trials, all sorts of applications in clinical research. Alex Hastie, who you're going to hear from, he was at a meeting, and he presented the following statistics, and he said that the meeting was in November of 2022, and he said that up until November of 2021, the number of clinical genomes that had been published was equal to the number in the preceding 12 months. The pace of progress is incredible. What we see with Bionano is that we're focused on cytogenetic analysis and what we're really bringing to an area of medicine that's incredibly important. I want you to understand that cytogenetics is the kind of routine clinical practice that we're all experiencing when we get sick, and it's an important area, and we're focused on transforming it. We're very impressed with the work that the pathologists and cytogeneticists do on a daily basis, what they tell us is they want better tools that provide better solutions that can bring better outcomes for their patients. That's what we're focused on. When we look at the digital workflow that we're bringing to the cytogenetic space, 10,000-fold increase in resolution. Alex talked about that in the video, really bringing very, very high resolution to Genomic Aberration Analysis. When we look at the success rate, when you think about being sick and your sample going to a pathologist or a cytogenetics lab, the really good ones deliver a result half the time as the combination of sequencing and other tools, karyotyping and FISH. What we're able to do is really almost double that incremental success rate. Really excited about the progress that we've made, and our focus is to really help you understand where we're headed. This is a image that you'll see a lot over the course of the day, and it represents what we call the Genome Variation Continuum. Others of our team will talk about it, but something you need to know is that anything that goes wrong on this whole spectrum can be a big problem for us, okay? Sequencing, which is an incredibly powerful tool, and we're blown away by the progress that Illumina has made and PacBio has made in advancing it. This is the area of the variant continuum that's addressed reliably with these techniques, and that's where it's being used. Of course, long-read is now emerging. It's not used very much in the clinic yet, but it seems to be a pretty useful tool. Sequencing lives in these areas addressing single nucleotide variants and small structural variants. We're focused on the cytogenetic space. We're focused on this area of the variant continuum that looks at large chromosomal rearrangements and aberrations, and this is the standard of care that has evolved in cytogenetics. Karyotyping, it's been around almost as long as I have. 50 years, I beat karyotyping to the face of the earth, but it's been around a long time now. Certainly, imaging technology has improved, microscopes have improved. The basic methodology is an individual looking through a microscope at chromosomes spread on a slide in order to make decisions about whether you should take chemotherapy or not, whether you should have a bone marrow transplant or not, karyotyping. Arrays have helped, looking at only things that go up and down, gains and losses. FISH has also been a very helpful technique as long as you know what to look for. When we look at these incremental diagnostic yields that are coming out of our analyses, we're often finding that these were areas of the genome that were hit, but we didn't know to look there. FISH can't do it, and this is where Optical Genome Mapping or OGM fits. It covers this whole space between traditional cytogenetics and links up nicely with sequencing. Not only is Optical Genome Mapping a tool that can be thought of as an alternative to traditional cytogenetic methods, but you can see in that, you know, 150 KB range down below, it covers a gap where there's nothing today. Optical Genome Mapping, as we see it, is really an alternative to cytogenetics going forward with a much more powerful and streamlined workflow and a beautiful complement to sequencing. Our vision is that Optical Genome Gapping and sequencing is the future of genome analysis clinically. I have been the CEO of Bionano for a while, you know, Dan, we've been working with Dan and getting ready for this panel, and he remembers that, and he tells people he's known me for a long time. What we talk about is structural variation day in and day out, and something that we find is that it's often a new term. I know that it's becoming more and more popular now, which I think is a great thing, the focus on structural variations. These are incredibly important events that happen in the genome. They're so important that cytogenetic analysis, karyotyping, FISH, microarray, are the first line tests that are recommended by medical societies that set those guidelines, right? When we get sick and there's a sample that goes to the lab, they're going to run traditional cytogenetics as the first line. This is a really important area of medicine. It's also got a lot of patients. When we start to think about it financially in terms of the market size, it's substantial. This is the area that we're focused on, and structural variation is just a key driver when we think of genetic disease and cancer. Leukemias, lymphomas, solid tumors across the board, incredibly important. Another area where structural variation analysis in cytogenetics comes in is in quality control and QA assessments in the cell therapy process. When we think about the overall workflow of deriving either an allogenic cell type or cells from a patient, delivering a gene editing therapeutic payload to give us edited cells and then growing them up before infusion into the patient, clearly, there's the need to be assessing what's happening during that process. When we look at delivering the therapeutic payload, these gene editing systems are becoming increasingly complex. Multiple events are needing to be transformed in the cells in order to deliver the therapeutic effect. Highly complex. There needs to be target effect analysis. There need to be on-target, off-target effect analysis. What we see is that folks that are working on this are looking for solutions. They're turning to traditional cytogenetics, but it's not sufficient for what they're working on. Once you get the edited cells, it's important to verify that the transformation that you've aimed at is there. When you grow the batch of cells in successive rounds of culture, these genomes can go off. Anybody who's done cell culture knows that you can lose the genomic integrity. There need to be a series of analyses that are conducted in this process. What we see now is that biotech and therapeutic companies are coming to us, and a lot of academic medical centers are using Optical Genome Mapping for these applications, we'll hear about them today. When we think about the economic opportunity for us in transforming cytogenetics, we think of it as being very substantial. We've done work to understand the number of labs that are distributed around the world, and we estimate it's about 10,000 labs, and that actually, you know, excludes some more developing countries. When we look at patient samples, we estimate that there's about 10 million patient samples through the combination of leukemias and lymphomas, not only initial diagnoses, but monitoring of patients through therapy. All of the genetic disorders that are being analyzed. You know, it's an incredibly voluminous opportunity from samples on a regular basis. There's, you know, 1,400 pharmaceutical companies working in cell therapy. It says $1,400. It's just supposed to be $1,400. When we add all this up, we estimate that the total available market that we're focused on, which is a subsegment of the genomics market overall, is about $10 billion. This is for this transformation of cytogenetics. The solutions that we're bringing into these labs are our products. Many of you are probably familiar with the Saphyr system. It was originally released in 2017. We actually launched it at AGBT in 2017. When we did, it had amazing throughput, Mark. It was incredible when you pulled it out. You could do about, you know, 50 or so genomes per year, depending on what your depth of coverage was, and it cost about $1,500 to run one genome. The system, if you wanted to bring it into your lab, was about $350,000. What we focused on over the last several years has really been improving that. The throughput has gone way up. We've been able to bring the per cost genome per cost down to $450. Importantly, the system is a lot less expensive now. It's possible to get these systems into labs. We've introduced economic models such as reagent rentals and so forth that will deliver these solutions. We have a new instrument that's underway, and that's gonna increase throughput another 13-fold. We've been focused on making the workflow of Optical Genome Mapping as simple and as powerful as possible. We've brought in two acquisitions. One is Purigen, and that has given us the Ionic System. That's a very powerful solution for automated nucleic acid extraction that can be used throughout genomics now. We're developing a cartridge within that system for Optical Genome Mapping that's gonna be available in the future. The idea of streamlining the front end of the workflow is important. NxClinical, through the acquisition of BioDiscovery, is a software platform that allows for data analysis. That's gonna become VIA when we add Optical Genome Mapping to it. The beauty of VIA is that you'll be able to look at Optical Genome Mapping data, of course, but right alongside sequencing and microarray data. What we hear from folks who are using these techniques and practicing in this important area of medicine is that they're forced to look at multiple different techniques, all sorts of different reports, and we're gonna consolidate that and bring it together for them. Now importantly, the Ionic Purification System and NxClinical, those are standalone products. We can sell those to molecular pathology labs even if they don't have Bionano yet. And we can make them Bionano customers through that. These are been important acquisitions that we've brought in. We also have Bionano Laboratories, which is an independently operated CLIA facility. It's based in San Diego. We also have a CLIA-certified service in Salt Lake City. We use it for these three areas, really to provide a try before you buy solution to anybody who wants to look at Optical Genome Mapping. Also we have a menu of LDTs. Why that's so critical is that clinical labs that might have an interest in adopting Optical Genome Mapping wanna send samples to us 'cause they wanna get clinical reports. When we get those samples, we're able to bill payers and start that reimbursement conversation, which is so important. We offer an array of testing for genetic diseases as well. You know, within the RUO services, we also offer access to the cell therapy QC solutions. This is a powerful platform that we use to develop new methods and make sure that anybody in the world who wants to use Optical Genome mapping can get access to it. These are some of the results that I felt provided us some evidence for us really being on an upswing. This is the data that I spoke about earlier that Alex shared with me, and it's really this idea that we plugged along for many years. A genome here, a genome there, and it's really started to take off. That for us is the best leading indicator of future utilization and future adoption, and we're so grateful to many of the folks in the room today for being part of those studies, and we know that there are many more that are coming. You're gonna hear about all the progress that we're making from our leaders today. Importantly, you're gonna be able to meet some users, and we're so grateful to Dan Brennan for coming on board and helping us to drive those conversations. A panel really focused on how Optical Genome Mapping is used in the cytogenetics environment, then a panel that will focus on how it's being used in different research. I hope you find this to be a very informative day. There'll be time for Q&A at the end, and I wanna turn it over to Christopher Stewart, who's our Chief Financial Officer. Thanks, Erik. Thanks everybody for being here, Bionano's first ever Strategy Day. We're super excited about it. I'm Christopher Stewart, CFO, been with the company for 2.5 years. What I think the most exciting thing for me about Bionano is one, we're a part of this genomics revolution and riding the wave of innovation in genomics. But we have something that other genomics companies don't have, a large existing market with legacy tools that have been around for decades. And customers asking for a new solution, a new digital solution to the legacy cytogenetic techniques that Erik talked about. That's really unique is this large existing market for us. Erik touched on it, but we wrapped up 2022 with right around $28 million. We pronounced in January that we were at the high end, just above the high end of our previously guided revenue range. We've got 240 systems and 165 software customers around the world. We're in almost every continent. The history of our company, we've sold 48,000 flow cells. You can see 3,000 or so were published research, but 48,000 flow cells sold, but we're just scratching the surface of this overall market. There's 10 million potential samples every year. We have 406 employees across four sites. Now to get into the markets that we're going after, we're squarely in the middle of $47 billion dollar segments of the overall genomics TAM. We're focused on Oncology, Genetic Disease, Drug Discovery. Of course, millions of people can benefit from genomic advances, and access to the technology broadly is enhancing every year. Research continues to drive that forward and make it more accessible. We have our unique spot, as Erik talked about, a unique and critical role in genome analysis by reliably revealing these large structural variants. Going after that market, first by converting over the cytogenetic volume today, day in and day out. Then secondly, to as recognition increases, the OGM + NGS is the most practical and effective way to get a whole view of the genome. That'll even open up more markets. Erik showed this slide. I think, again, when we're talking about the markets we're going after, this just shows squarely where we're positioned. Erik talked about it, the most prolific tool being used today, karyotyping, is looking through microscopes, right? Microscopes. We've heard from customers that they're worried about the future for karyotyping and for this cytogenetic analysis because no one's in school, no one's studying karyotyping. They're not going to school to learn how to look at chromosomes under a microscope, right? They're all, everyone's focused on sequencing. you know, they're really actively looking for the next technology, and I think we've proven that we're the right, we're the right one. Erik talked briefly, 10,000 labs, right? in the worldwide markets, 1,000 or so large academic medical centers and hospitals with cytogenetic labs, 4,000 regional reference labs. There's a relatively small number, but they're very large, ultra large reference labs, Labcorp, and Quest and whatnot of the world. That's outside. That doesn't include China, India, and other developed countries. In China alone, there's 3,300 large hospitals, 500 beds or more hospitals, and 2,000 independent clinical labs. Erik mentioned that 1,400 biotech companies focused on various aspects of cell therapy. All of these are potential customers. We've just scratched the surface. We do have a full commercial presence in China, marketing, sales, customer support, and we're expanding into new regions outside of this as soon as this year. We've been developing the market in India for a while now, and we're gonna ramp that up this year. What's driving those 10 million samples? You know, this is it's kind of a dense slide, but across constitutional genetic testing, prenatal, postnatal, blood cancers, and solid tumors, these are the indications that are driving those 10 million samples a year. NIPT positives or no results, infertility, pregnancy loss, developmental and intellectual disorders, birth defects, rugged diseases which it's, you know, rare is in the name, but it's not rare, right? In heme cancers, it's across the board for heme cancers, lymphomas, myelomas, leukemias. On solid tumor, all of these indications, for the most part, are covered in our clinical trials that are ongoing that Alka Chaubey will talk about later today. The key thing is these aren't rare. Like, structural variants aren't a rare thing. They're prevalent and occur across the genome biomarkers for all of these indications. Huge market. Things you hear about every day that affect our family and friends, they all have structural variant causes that today the standard care around the world for all these today includes some combination of FISH, karyotyping, and microarray just waiting for the next digital solution. Some people aren't waiting, some of the customers here. They're already making the move. Erik talked about the cell bioprocessing lab, cell bioprocessing market. This could be a $3 billion opportunity for us. A few years ago, there was 176 clinical assets in development for cancer alone. By 2025, there's estimates that the FDA will be clearing 10- 20 new assets every year, QC is required. They absolutely have to have a way to verify the target effects in the genome, or they're never gonna get into production. It'll be too risky. These assets, these large-scale assets can drive 50 samples- 120,000 samples a year for Optical Genome Mapping through that QC process, both in development and then in production after development. Companies today, what they're currently doing in the development process is using karyotyping. Karyotyping it's not scalable, and it's not accurate enough. It doesn't have the performance, and it just won't scale with this industry. You know, we're getting calls from these companies that are doing this type of work. And they're desperate for a QC solution that they can use to satisfy the regulators before they introduce these products. I just wanted to give an example for customers across these different segments, current customers today, what they're doing and what they hope to do down the road. We're working with one of those large U.S.-based central reference labs. They're currently in the process of replacing FISH panels for chronic lymphocytic leukemia. And, you know, their goal ultimately is to replace FISH panels for all of their heme samples, 40,000 a year. Memorial Sloan Kettering, again, looking at replacing FISH panels for myeloma today, and they would like to replace FISH panels for all blood cancer as well. Common theme, right? Looking to replace the existing tools that have been around a long, long time. PerkinElmer has a LDT out for FSHD, a form of muscular dystrophy. They use that in conjunction with NGS for neuromuscular disorders, they wanna take it, use OGM for all repeat expansion disorders. Finally, we are working with a global pharmaceutical company who's measuring target effects. Target, you know, did the on-target change happen, and is there any off-target effects that they need to be worried about? They want to replace karyotyping for cell QC. These are current customers today and what they're doing and what they're looking to do going forward. What's driven this interest in Optical Genome Mapping and like Erik said, the huge growth in patients analyzed and published in clinical samples? Well, we've done a lot of work on the product. Erik's been the CEO for 12 years, and they did a lot of work on the product. You know, Mark Oldakowski, you'll hear from these people as the day goes on. They've increased the throughput by 13 x. Erik said we reduced the price of the genome from $1,500 down to $450. We've made multiple upgrades to our analysis and recording tools. We've kicked off clinical studies. We've built a worldwide commercial team. We have teams in, like I said, China, Europe, the U.S., and we're expanding into other genomes, and we've published results on over thousands of samples. One of the things that we look at that is reflective of these improvements to the products that we made and the fact that we now have like a commercial-ready product that's usable today is if you look back to the 240 Saphyr Systems that are installed today, the ones that were installed before 2019 were predominantly in universities, research centers, and non-human research labs. Since then, when we've made these improvements to the product, made it really commercial-ready and robust, you see half of our installs are at AMCs and hospitals with cytogenetic labs. Another quarter regional reference labs and the number of systems going into research centers and non-human is much smaller than it was. We think this is showing Optical Genome Mapping move into the type of customers who have regular routine use for these cytogenetic techniques. Here's, you know, why this is important, particularly to me. Those routine users have higher pull-through. You can see, academic medical centers, reference labs, pharma, biotech companies, they drive anywhere from 3x-5x the amount of consumable pull-through on an annual basis. That's today. We're still early in this game, right? Utilization typically progresses with all of these customers. They first bring the system in, they figure out what they can do with it, very tinkering around a few samples a month, and then they progress, they select a first assay, they validate an assay, they move into routine use, and then they move on to menu expansion, adding more menu items to what they do with Optical Genome Mapping. We're still early in the phase. I mean, you know, you saw a lot of those system installs have just been in the last year or two. You know, this is indicative of where we think we're going, but still reflects early in the customer maturation process. I love this chart. It's the last three years of quarterly revenue and Saphyr System install base, Q4 $8.1 million-$8.4 million. When Erik and I look at this chart, we looked at it when we crossed over $8 million, we said, "Jeez, Q1 2020, just over $1 million." We're up almost 8 x, 7 x from Q1 of 2020 through Q4. Full year revenue expected to be right around $28 million. Clearing out kind of the financial stuff, we ended Q3 with a cash balance of just over $180 million, and we did close the Purigen acquisition in Q4 of last year. Here's a little bit more on our current business. We've got good diversification across our revenue streams, as Erik talked about. We've got a little bit more than half the revenue come from our OGM systems and consumables. We also have a strong software business and a services business comprising about 25% of our business. Optical Genome Mapping is the core of our economic engine, right? That's gonna drive the growth as we go down the road, we do have these strategic revenue streams, software, and now isotachophoresis with the Purigen acquisition allows us to get into many more labs that maybe aren't ready for Optical Genome Mapping yet. They're doing sequencing, they're doing other techniques, it gives us an entree into them 'cause we've got amazing software products and amazing DNA isolation products. We also have great geographic diversity. Half our business is in North America. Virtually all of our lab business is in North America. We've got a strong OGM presence in EMEA and a growing presence in APAC. We're excited about the fact that we're starting to see adoption around the world. In fact, some of the other countries outside of the U.S. have a little bit easier time getting reimbursement because our systems are more supportive of new technologies kind of early on. There's some things going on in Europe and Canada you hear about where there is a fair amount of reimbursement for Optical Genome Mapping today. Moving on. Commercial team. We have over the past two, three years, we've built a really strong commercial team. We have 135 commercial folks in 12 countries, 51 commission sales, 24 field support. In the areas where we don't have a direct field sales force, we have authorized distributors, about 23 authorized distributors covering many other parts of the world. We talked about the things that we've done over the past three years to drive some of the results you've seen. Here's what we're working on for the next three years. Fundamentally, these are the things that we believe will clear the remaining barriers to mass adoption, right? It's things like increasing throughput yet again. These are things our customers are asking for. Need more throughput. We need more sample types. Mark will talk to you about that later today. We're expecting to introduce new sample types with our new technology, ITP. We're launching a world-class great analysis and reporting tool set with VIA. That's exciting and exciting for our customers. They're asking for that. We're working on getting key regulatory approvals, including FDA. We're gonna publish more of our clinical study results over the next couple of years and address the needs for reimbursement through coding and coverage. When I look at this, you know, why, you know, why is now the time to invest in Bionano? Because we're gonna be clearing these barriers over the next couple of years to really drive uptick in the market and penetration into that 10 million samples. These are the things that we really think are critical to get over that hump. Now to talk about our financial targets, right? Great growth we expect for the next 3 years- 5 years, 30%-50% CAGR. We're excited about that. Even that isn't reflective of the full potential after we clear those barriers. Super exciting, more to come down the road. We also show our target P&L at scale, and this is our North Star. When we're doing our strategic planning and looking at our product roadmap and the markets we're going after, we're trying to drive towards this P&L in the future. Like, you know, we have to get to scale to get here, but we're building a business that can support a really healthy, strong P&L. We've got the initiatives in place to drive our cost of goods sold down and allow us to be competitive with a highly competitive ASP, but still get a margin in the 50%-70% range. We're introducing scale into our operations that allow us to get to 40%-60% operating expense. We expect we can get to a 10%-20% operating margin as we hit that scale business down the road. I'm super excited about the next three years. I'm super excited for you guys to hear from the rest of the team and our KOLs today. My hope is that they're gonna be reinforcing some of the things that I said. I talked about how we're gonna penetrate this market for 10,000 samples. You're gonna hear from a lot of the folks today about, you know, why they think that's gonna happen as well. Super excited. Appreciate y'all being here. I'm gonna give it back to Erik to introduce the next speaker. Thank you so much, Christopher. I want to hand it over to Dr. Alex Hastie, who's gonna talk you through what we call the OGM difference. I think it's critically important to understand where Optical Genome Mapping as a technology fits in comparison to things that are on your minds, sequencing, long-read sequencing, and it turns out there's been amazing publications out there that really set that story. Alex, I'm going to turn it over to you. Thank you, Erik. Thank you, everyone, for attending today. It's a real pleasure for me to present to you. I think this is a really exciting story. My name is Alex Hastie. I'm the Vice President of Clinical and Scientific Affairs. I've been with Bionano for 12 years. I started right out of my PhD in postdoctoral training as a scientist. I came to Bionano because of the potential that I saw in ultra-long reads to solve problems in detecting structural variants, especially in cancer. That's what I'm gonna talk about today. I'd like to exemplify that first with a specific gene, TP53. This is known as the guardian of the genome because if we lose a copy of TP53, we get cancer. Elephants actually have 40 copies of TP53, but we only have two. If we lose one, we get cancer, if we lose two, we get a very aggressive cancer. Elephants don't get cancer 'cause if they lose a copy, they still have 39 left. This is a really important gene. All genes can have variants, and those variants can affect your biology. Because biology is controlled by the genes that you have. The variants that can affect these genes can occur in many different ways and many different sizes, and you really have to assess all of those variants. The standard of care for testing, genetic testing has evolved to overcome these limitations to address these challenges. On the right side of this continuum that you've already seen, we can see the cytogenetic methods. The genome has 6 billion base pairs in it, and the variants can occur from whole chromosomes down to one base pair. The cytogenetic methods are meant to address the largest variants. The first technique, karyotyping, can find large variants, large chromosomal abnormalities. Additional cytogenetic techniques that Erik already talked about, chromosome microarray and FISH detect variants at higher resolution, but they have other limitations. On the other end of the spectrum is sequencing, which can detect single nucleotide variants and small variants. What you can see in the middle is a large gap of unmet need. There is no technique that is really assessing that gap. During my presentation, I'm going to show you that OGM has the potential to overcome the limitations of all of these cytogenetic methods and close that gap. To visualize this a little bit differently, I have a picture of a karyotype here. This is chromosome 17 on the left. There's two copies of it. Chromosome 17, the left copy of it is the full chromosome. It's 81 million base pairs long, and the one on the right is missing about a third of that chromosome. This third of the chromosome, this 30 million bases includes TP53. On the other side of the slide, you can see the NGS is assessing small variants, one base pair or a few base pairs. These can also disrupt the gene TP53 or any other gene. We have to use techniques that can assess small variants and large variants, but I think this really highlights the tremendous gap from one base pair or a few base pairs up to millions of base pairs that are, that is in the current standard. There has been a lot of hope and promise for NGS to fill this gap, but that has not materialized. Over the last two decades, with NGS technologies making many improvements, we have seen a drastic reduction in cost and an increase in throughput that has enabled new applications. There remains limitations. First of all, the price is still quite high, especially for clinical applications. The second one is really innate to sequencing, which is that the reads are short. They're 150 base pairs long, and this has limited their applicability to small variants. The status quo remains to use cytogenetic methods that are up to half a century old and sequencing to assess the genome as well as possible. Why is it that these short reads are limited to small variants? I'd like to use an analogy of putting a book in a paper shredder. When you do a sample prep for next-generation sequencing, you shear the 6 billion base pair genome into 150 base pair segments. That's analogous to putting a book in a paper shredder and coming out with just single words. When you have those words, you can see if there's spelling errors. You can, and spelling errors are important, so they can make a word meaningless, or they can change the meaning of the word. For example, the word dessert that's circled over there. That's a sweet treat that you have after a meal, but maybe it's spelled wrong. Maybe there's only supposed to be one S, it would be desert. A desert is a, you know, a hot, dry climate. Wait, D-E-S-E-R-T also spells desert like, "Don't desert your team." To know what that word really means and whether it's spelled wrong, you have to put it into context, and that's the OGM difference. OGM uses ultra-long reads to give you the context. Once you have the context, there's a sand dune in the desert, you know what that word is supposed to say, and you know if it was spelled wrong. You have to have the context. The context tells you the story. Let's look back over the years at some of the science to see the OGM difference more clearly. Scientists have been doing benchmarking studies over the years for detection of large structural variants, and they have found that Optical Genome Mapping is very efficient at detecting these large structural variants. Shown in black is the performance of next-generation sequencing in these studies. In various studies of reference genomes at the top, the sensitivity for detecting structural variants by next-generation sequencing is only 10%-30%. They're missing 70%-90% of the large structural variants that can be detected by Optical Genome Mapping. In cancer genomes on the bottom, next-generation sequencing is missing about 70% of those large variants. How about long-read sequencing? Long-read sequencing at 5x-10x the cost of short-read sequencing does find structural variants with higher sensitivity. In these studies, the detection of large structural variants by long-read sequencing is 50%-70%. Still really not good enough, still missing 30%-50% of the large structural variants. When you apply it to cancer genomes, it performs even worse, probably because of the higher complexity of a cancer genome, only detecting about 25% of those large structural variants. Let's talk a little bit more about complexity. This is a set of three different studies that compare Optical Genome Mapping to Nanopore Sequencing in different genomes. These Circos plots are showing the detection of interchromosomal structural variants that have been called by the different techniques. Optical Genome Mapping has clean single or two interchromosomal structural variants in these genomes, while the Nanopore Sequencing result has many hundreds to thousands of interchromosomal structural variant calls, which the authors have concluded are false positives or noise in the system. This is a result of the high complexity of a genomic analysis. It is very difficult to have a technique that has very high specificity and very high sensitivity. What are the KOLs saying today? There's been two recent papers by influential consortia that talk about the ability of short-read and long-read sequencing for detecting large structural variants. They have concluded that short and long-read sequencing are not sufficient for detecting large structural variants. In fact, in the GREGoR Consortium publication, they remind us that short and long-read sequencing only detect about 50% of the structural variants detected by Optical Genome Mapping. Let's look at the requirements for clinical in a clinical setting. In a clinical setting, we have to have high specificity. We have to find the variants that matter without false positives. We have to have high sensitivity. We have to find the variants we're looking for, even if they're rare in the sample, even if they're hard to find. We have to find all of them. We have to do that in the complexity of a genome that's 6 billion bases, and there may be multiple genomes in your sample, like in a cancer sample. In a cancer biopsy. We have to detect variants that are in just a few of those cells. This has to be cost-effective. It needs to have a simple workflow with a fast turnaround time. Bionano is focused on providing a robust solution for clinical translational research. You can see the OGM advantage in the OGM workflow. We start with ultra-long DNA molecules, we convert those into ultra-long reads. We use those ultra-long reads to directly compare to directly detect and visualize structural variants in the genome. This results in very high sensitivity and very high specificity. The other important thing to take from the OGM workflow is that Bionano provides the whole workflow from sample to answer, which is really unprecedented in our industry and really critical for adoption. The other question is, can OGM really overcome all the limitations of multiple cytogenetic techniques in the clinical environment? This slide shows a table of seven recent studies, among many others, which have assessed OGM for detection of clinically relevant structural variants that were initially called by cytogenetic methods, multiple cytogenetic methods. In all of these studies taken together, the sensitivity for detecting these structural variants is over 99%, over 99% concordance with these standard of care techniques. In addition, we find these studies have found about 25% additional clinically relevant structural variants compared to the standard of care. This is really addressing that gap in coverage of the genomic continuum. If we go back to kind of the standard of care and the genomic continuum that we talked about before and generalize different disorders, we can see that next-generation sequencing can detect variants that explain symptoms, diagnose cases in about 40% of individuals. The standard of care cytogenetic methods can solve approximately 25% of cases. If you substitute Optical Genome Mapping according to the results that I've just shown you. We expect a much higher diagnostic rate, and we will close that gap, and we will leave fewer undiagnosed patients. This is my last slide. I just wanted to conclude going back to TP53, which we need to assess TP53 and all other variants that are important for disease. We need to assess with next-generation sequencing. Sequence variants can be important, but we also need to assess it with a high-resolution technique that can detect structural variants genome-wide, and that's Optical Genome Mapping. This is really the reason that I have, you know, dedicated 12 years of my career, working with Optical Genome Mapping to drive this technology forward. With that, I thank you for your attention. Awesome job. Thank you, Alex. He joined Bionano about one week before I did, and some people who've been following the company may know that it was based in Philadelphia at the time, but I lived in San Diego. When I was introduced, Alex and his family knew that maybe there might be a move afoot. Another fellow I've worked with for a very long time is Mark Oldakowski, and he's really been the architect of all these incredible solutions. I want him to tell you about the amazing progress that we've been making, including a series of really important product launches that have just been announced in the last couple of weeks, but then give you a sense of what's coming in the next two years. Mark, I'm going to turn it over to you now. Erik. It's a real pleasure to be here with you all. Like Erik said, I will share with you our current product portfolio and how we're emerging, evolving that for our customer needs. First, I wanna share with you a different dimension to the slide that you've already seen. As you've heard from Alex, OGM by itself is very capable as a stand-alone technology for many applications, and that's its primary use today. We also feel that there is a strong complementarity between OGM and next-generation sequencing, particularly short-read NGS, to really show the most comprehensive view of structural variation in the genome. In fact, we at Bionano are creating an ecosystem where you can bring your favorite NGS data, and there's plenty of them now, into the OGM workflow. We will support that with in the upfront with our Ionic System for DNA and RNA isolation and purification. I'll talk about that a bit more, but that will feed both your NGS system and soon your OGM system. Then on the back end. If you want great results from all that investment that you put into your NGS data, we have a solution with our NxClinical software that provides deep interpretation support for that data. I'll be talking about that throughout my presentation. First, let's look at some of the key metrics that we evaluate within the OGM workflow itself. As has been mentioned since 2017, since the Saphyr launch, we've increased our throughput by 13-fold. We're gonna do that 13-fold improvement again over the next couple of years, starting this year. Along with the platform improvements, we have made tremendous advancements in our labeling and DNA isolation chemistries. With all those changes put together, we have been able to reduce the per sample price tremendously, from $1,500 to $450, and it's gonna drop again. When you think about high throughput, low price per sample, low platform costs, fast turnaround times, and an unparalleled ability to detect structural variants, these are key drivers to adoption. These are the reasons that our customers love this data type, and these are the things that we are going to be amplifying, as I'll show you in the next few slides, and making them better. First, let's go into the little bit of detail of our current product. Saphyr is in the center of our OGM workflow. By any standard in our industry, it's got impressive metrics. On a single Saphyr chip, you can get a maximum output of data of 15 terabase pairs across 3 samples, 3 independent samples. Okay? You can use that bandwidth for rare disease research, where you require lower levels of coverage, or you can choose to run it a bit longer to get more data for higher coverage applications like in cancer or even more data for cell bio-processing applications. Each of those sample runs is gonna cost you the same amount. The only thing that changes is the amount of time that it takes to run the system. That's quite unique. If you decide to maximize your data output from the system, the price per Gbp is going to be as low as $0.09 / Gbp. Which is orders of magnitude than the cheapest sequencers on market today, which is extraordinary. That's our current product. Let's go back to talking about getting your NGS data from whatever sequencer you wanna use into the OGM workflow to combine with the OGM data type to show you more structural variation. On the front end is the Ionic System. Its technology of isotachophoresis is able to extract, concentrate, and purify DNA and RNA from many sample types, including some of the most difficult, an FFPE used for solid tumors. That DNA is then available to run on your sequencer. We also on the back end, if you really care about the results that you wanna get from your NGS data, we have a solution for you, with NxClinical. It is able to use its powerful auto classification algorithms to help you interpret the results that you're getting and allow you to create a report to summarize the critical findings. This is a software that's been used in cytogenetic and molecular labs for many years. It's been proven. These algorithms have been tested through many publications and tens of thousands of samples. Let's get into a little bit of the weeds, and you'll find out why this is important. How are we able to achieve such amazing throughput at such a low cost and get this phenomenal structural variant data? A big part of it is with our consumable, what we call our Saphyr Chip. This consumable is what I call a passive consumable. There is no active electronics in it. It's a passive consumable. It's manufactured in a semiconductor foundry. By being a passive consumable, it allows us to more easily optimize for cost and performance. With our deep understanding of the design, how to manufacture it, and our understanding of how DNA behaves in these confined structures, we're able to push a massive amount of super long DNA through these nanochannels. In fact, through 120,000 nanochannels in parallel at once. You can see that DNA in this video where the DNA is concentrated in its natural form from cells. It gets moved through by the instrument through various structures. Those structures help to unwind and linearize that DNA and make it available for imaging. That imaging provides the information that our analysis tools require to then assess whether certain events are occurring, mutations are occurring De novo. We don't need to know anything that we're looking for. It's whole genome, always De novo. These are not panels. It's always whole genome. One other aspect that allows us to really think about how we can expand this consumable in the future is, we have work going on, and we filed some patents on imagining what we can do inside these nanochannels. For example, putting an in-channel detector or a Nanonozzle to create a different detection modality. We're investing a of effort into pushing those forward through our advanced research. Our patent portfolio is quite broad. It covers our entire workflow, both for OGM and isotachophoresis, and we believe that it secures our on-market products really well and expands our ability to push the new applications there. We also invest quite a bit in these advanced, research applications as well. We have a very robust pipeline of new innovations that could be coming to market in the future. We, invest in those both internally and through acquiring both IP and entities like we have done recently. We have customers that are sharing with us a dilemma. When they run OGM data, they get results that they have not seen before that really impact their research, and they want to run more OGM data. How do we scale with that need? Some things that we've done recently, Eri k alluded to, we just in January have released major improvements to many parts of our workflow on the front end to our labeling and DNA isolation chemistries, what we are referring to as our generation two reagents, to our chip and to various elements of our software, all in concert to be able to provide faster turnaround times and process more samples to help our customers scale robustly. Now, in fact, we believe that with all these improvements, it is possible to get a sample to answer for a complex high-depth cancer whole genome within two days. The other aspect of what we've done with the G2, Generation 2 reagents is that they are now being manufactured in a GMP FDA-registered facility, which sets us up to future filings for regulatory approval. We have also taken the generation two DLS labeling chemistry and worked with our partner, Hamilton, to automate that with their VANTAGE liquid handling system, making the world's first and only automated extraction platform for ultra-high molecular weight DNA. For our customers that are really looking to scale, this system is capable of doing 24 samples in a regular workday. We're very excited about the partnership there, and we're going to be further amping that up. Now, what's next? Beyond the things that we've released to help our customers scale, we're really focused on elevating all four of these pillars that underpin our workflow. Now, when you think about our current Saphyr, it is able to process up to 1,100 high-depth cancer whole genomes per year. Many of our customers are now ready to do much more, and they're asking for much more. That's where our high-throughput Saphyr comes in. Being developed as a benchtop system, this will be the world's fastest whole genome analyzer. It will be able to process 5,000 high sensitivity, clinical-grade cancer whole genomes per year in a single unit configuration and 20,000 in a four-unit work cell. Now, each of these samples that get run in the system are completely independent. No batching, no multiplexing, one sample per flow cell. Now, why is that important? It's important for a number of aspects. One is it provides application menu flexibility. On this system, you can run one sample for a rare disease, low coverage acquisition. You can have another sample that's running a high coverage cancer sample, and yet another one that's running the highest coverage cell bioprocessing specimen. You can have a mix of all those. Whenever they're done, they come off the instrument. That's hugely important, but the other important aspect is that each of these samples could be run at the same negotiated price. If you negotiated, for example, with Bionano, $400 per sample because of your yearly volume commitments, then it will be $400 per sample whether you run one sample that day or 10 samples that day. Okay? Now, sequencing can't say that because in order to leverage the lowest cost, you need to fill up your flow cell, right, with the full multiplex set. Some labs can do that, but most labs have irregular flow of samples, right? We believe that this matches our target customers much better than most technologies in our space. This also allows us to create features that many folks in the clinical community are used to hearing about, like a stat processing, which means that if you identify a sample as a stat sample, it will be treated with the highest priority throughout our workflow, through this system, through our analysis pipeline. The data will come out as fast as possible because that was the most important thing that you needed to have run for whatever reason. We're excited to be able to provide all that flexibility. Those Generation 2 reagents I talked about, fully supported out of the box. This system is also being designed under FDA design controls, it's going to be manufactured in an FDA-registered facility, and it will be part of a filing with the FDA that I'll talk a bit about. We have entered external beta, late last year and are looking for commercial release this year. To keep pace with the amount of data that's coming out of this new high throughput system, we need to drastically accelerate our analysis time. We're doing that with a collaboration with NVIDIA to create a benchtop system that can keep pace. That system will comprise of novel algorithms that Bionano is developing, tied with NVIDIA's most recently released Ada Generation GPU cards. Just to give you a perspective, this high complexity, deep cancer whole genome will be able to be analyzed fully in less than two hours on that system. In its first incarnation, it will be a benchtop system that sits right next to every high-throughput Saphyr, and there will be other incarnations of a data center and a cloud version for more collaborative analysis. Super excited about this collaboration. To feed this high-throughput system, we are putting onto the Ionic support for OGM. What does that mean? That means that Ionic will be able to extract and purify ultra-long molecules of DNA that are suitable to be used with OGM. Back in January of 2022, we started a proof of concept to show us the path how to get there, and we are on that path, and things are going quite nicely there. The other thing that we discovered during that proof of concept was that the concentrating ability of the Ionic device has certain advantages over current on-market DNA binding technologies, especially in the areas of being able to extract DNA from samples that have a minute amount of DNA, minute samples. For example, needle biopsies, other samples that would be more diluted in liquid, like DNA from buccal swabs or saliva. We believe that we'll be able to address those and use those for OGM, once we do, that will unlock additional application, additional markets for us, which we are super excited about. Finally, our VIA software, as was mentioned, is going to be incorporating our OGM data. We started a preview of that software of showing our customers how that OGM data is incorporated in VIA. That brings the powerful interpretation capabilities that have been proven in labs onto OGM data. It streamlines the creation of a report of findings and provides a workflow for labs to adapt to use this in routine analysis. This finishes out the workflow from sample to an assisted interpreted result. All right. Finally, what do we anticipate our milestones to be coming up here? The high throughput Saphyr and its compute will come out into commercial release. This is the first half of 2023, followed in 2024 by the multi-unit work cell. We are going to be continuing to expand our sample menu, focusing a lot of our work on the Ionic System this year and next year, so there's gonna be quite a bit of product announcements for that coming out. Our VIA full support of OGM data is going to come out this year as well. Finally, we're very excited about the progress that we've been making in the regulatory landscape. Our kits have received Class 1 registration in China with the NMPA for indications with blood cancers. We are going to be taking our kits and the next generation Saphyr in front of the FDA in 2024 with our first assay. We're very excited about that, and we believe that we're ready for that. Thank you for your attention. Wow. He got an applause. He deserves more applause for that, but the customers are excited, so that's a good sign. Now, I don't know who's gonna replace Alka. All of us have been up here talking and, you know, you guys have your faces and you're focused on taking notes and everything, but she has this incredible big smile. It's, like so good. You look across the room, you find her, so I'm gonna have to sit there and smile. It's gonna be easy though, because Alka is our Chief Medical Officer, and she joined the company right around the same time Christopher did, towards the end of 2020. She's been a fan of Optical Genome Mapping and a friend of the company for many years. I really think that we talked about all these innovations and product improvements, and I think all of those mattered. Without Alka, I don't think we would have had the force to drive it forward, and so she's been an incredibly impactful person. You know, what we're trying to describe for you today is the process of bringing a novel methodology into a space that we're focused on. We developed an initial product, and it's starting to perform well. We've identified all sorts of things that we need to do in the future to advance that product, to make it penetrate as deeply as possible. The product alone can't achieve those things. There are things that we need to do to get the medical community as a whole on board here in the United States. Adam doesn't have to deal with this in Canada. Here in the United States, we need payers on board. Alka has really been driving these initiatives. Alka, I'm gonna sit here and smile at you encouragingly, and thank you very much. Thank you, Erik. As all of you heard, I joined two years ago, over two years ago, and one of the things was, Well, what is going to be the role? You've heard from, I think, every speaker today, what has been going on in the clinical genomic space, which I was also a part of. You are going to hear from most of the panelists that are now Optical Genome Mapping adopters and users, and the impact that it has made on the global genomics community. My talk is going to focus on all the efforts that we have put in place as part of our clinical development programs to transform medical practice. You heard some of that, you know, along the way. This slide, I think all of you will walk out of here absolutely captivated in your eyes. The point that I want to make here is, as you heard, and as you'll hear from multiple other people, karyotyping is almost five decades old, is still the global standard of care, and we've all been part of this in one form or the other. Now, the question is as over the decades, every new technique that came in became standard of care, but did they all become standard of care at the same time? No. They all evolved over a process, went through this entire path of getting implemented as standard of care, and this is what I intend to show you all today. You saw this initially when Erik was mentioning in his introduction that you look at any genetic disorder, whether it is constitutional genetic disorders in a prenatal or postnatal setting or in your hematological malignancies. You go from any professional medical society, the World Health Organization, NCCN, American Academy of Pediatrics, American Academy of Neurology, all of them recommend these tests that you see, the conventional cytogenetic test, along with sequencing panels and sequencing tests that came in almost a decade ago as the first-line test. In parentheses, you see the reflex test. I think as you can see is that some of these end up being reflex after the first-line test doesn't provide an answer. If you remember what Alex showed you, all of these tests together only provide an answer in 25% of cases. I think you also saw, I will also show you where Optical Genome Mapping has the potential and the promise to replace one or multiple of these standard of care tests. We are talking about transforming medical practice. There are two key elements. The two key elements are: get the medical community on board, and we have, you know, six clinicians and researchers and pathologists in the audience today, and get the payers on board. To get both of these communities on board is dependent on a number of drivers. What you see in the middle are all the things that any technique or technology has had to follow and evolve through to become the standard of care. What we are trying to do, and what these drivers are, there needs to be abundant data on Optical Genome Mapping. Number one, the clinical validity and utility needs to be established. You heard a little bit about specificity, sensitivity. I think that we are really leaps and bounds ahead of any other technology. We also have to demonstrate what is the health economics of any technology for it to become standard of care. We need numerous publications, peer-reviewed publications citing the advantages of any technique. Of course, the publications are tied with adoption and utilization, which you heard Christopher show you that we have seen a tremendous increase in adoption and utilization. When we put all of this together is when key opinion leaders who are the influencers of these medical societies come together to basically recommend any technique to be included in medical guidelines. That is when it has a global impact as standard of care. Of course, we'll focus a little bit on the coding and reimbursement because that is a critical criteria for any clinical adoption. What have we done, as I mentioned, in terms of the drivers? Let's go to the first one, right? Basically, having abundant Optical Genome Mapping data being generated. What we did was we launched large clinical trial programs that you all are aware of, and I think that you get updates periodically from Erik. These are underway to address multiple key drivers. I'm not going to go into the details of this slide, but the one thing that should come out is not only have publications coming out of these clinical trials shown that there is 100% site-to-site reproducibility. Now, this is really important because we have multiple Saphyr at multiple institutions placed, and they're all performing optimally. Not only that, all of these clinical trials have shown that there is 100% concordance with standard of care data, no matter which technique from the list that you have been seeing, across the day to day. These publications are showing that Optical Genome Mapping not only replaces one, but maybe two, three, or four standard of care tests. This is also demonstrating how fast and accurate you're going to get your results on any specific clinical sample. The magic is that, okay, you know, you're as good a standard of care, so what? The so what is there is that filling that gap is giving relevant answers back to these physicians, oncologists for their clinical and translational research that is really powerful and really important for any therapeutic or clinical management. I think you'll see a lot of these trends today. Now, as part of this program, here are listed all of our clinical trial sites. We have all of these principal investigators, some of whom are sitting in the audience today, that are part of these professional medical societies that influence guidelines and reimbursement. I think you'll have the opportunity to ask some of those questions with them today. Wait, we are also making huge international progress. One of our panelists today, Dr. Adam Smith, he Chairs the International Heme Working Group, which is a global effort that he and others have embarked upon to demonstrate how Optical Genome Mapping should be implemented in a standardized format across the globe for Optical Genome Mapping adoption. I think this is really critical and powerful. We've also seen, as published by this multi-site paper, that we have an AML consortium on Optical Genome Mapping, and two of the co-authors, Dr. Ravindra Kolhe and Dr. Rashmi Kanagal-Shamanna, are also sitting here today. This paper also demonstrated a significant increase in diagnostic yield and the potential that Optical Genome Mapping has for hematological malignancies. One of the other key drivers is actually publications. You've been seeing, you know, across the day-to-day, especially from Alex's talk, is that not only does Optical Genome Mapping, you know, perform as equivocal with standard of care, but also gives this really valuable information by increasing the diagnostic yield. What we have seen across the past several years, whether it is cancer or whether it is genetic diseases, what you can see is that the cohort size over here, which is, I'm gonna point, take you back to one of the slides that Erik showed that hockey stick curve, where the number of human clinical genomes has increased exponentialy using Optical Genome Mapping. Erik mentioned Bionano Labs, and so I'm gonna expand on it a little bit. Adoption of Optical Genome Mapping is another key driver. We already had our services lab at Bionano, but we now have this CLIA-certified, and we have applied for CAP accreditation, and we have launched these LDTs. These LDTs that we have launched are to do two most important things. One, to support the global community. By sharing under this CLIA umbrella, we can accelerate and support different laboratories across the globe if they want to adopt Optical Genome Mapping. The second thing is this allows us to engage with payers for coding, pricing, and reimbursement. This is really critical. What you see in the graph below is the progress that we have made in terms of global LDTs that have really come to the front in the past two years, and I think that this is really incredible in terms of demonstrating Optical Genome Mapping adoption. Now, one of the key questions with adoption comes of, what is the reimbursement? We have parallel paths in p lace that are driving Optical Genome Mapping adoption and reimbursement. You can probably ask a few questions from a few of our panelists today, but there are multiple PLA codes, which are Proprietary Laboratory Analyses codes. As you can see, the first one on the list is Augusta University, driven and led by Dr. Ravindra Kolhe. There are multiple PLA codes that are approved and priced, and there are some that are pending pricing determination. They're going through that process. Also, we are in the process of applying for a Category 1 CPT code for Optical Genome Mapping for both constitutional disorders or genetic diseases and cancer. We have initiatives in place where we will be engaging with payers and different Medicare administrative contractors for local coverage determination for Optical Genome Mapping and also with private payers, as Erik alluded to in his introduction. We have all of these parallel paths going on in order to demonstrate Optical Genome Mapping adoption by the genomic community. What I want to highlight with this slide is really something very simple. Around the same time last year, we had these two key publications with human clinical genomes that were published, and you can see the total number of patients published, roughly 400. Around the same time, as of today, what you see now is over 1,000 human genomes published using Optical Genome Mapping across constitutional genetic disorders and across hematological malignancies. This is really critical. This is really critical for the genomics community to be aware, to adopt, and to be able to hold to that promise that they can provide more answers to the samples that come for testing in their laboratories. These are four important metrics that over the past two years, if we just convert them into percentages, these are really staggering. In terms of the human samples that have been run using Optical Genome Mapping, we've seen a 600% increase. For publications involving human genomes, we've seen a 275% increase. This is really significant in terms of where we are intending to go in the future. With respect to clinical utility and validity, this is really important to demonstrate that any tool or technique has the highest amount of precision and performance in any setting. As I've shown you, whether it is a prenatal setting or a postnatal setting or a hematological malignancy setting, there are efforts that have already demonstrated or are underway to keep basically solidifying the stance with respect to clinical utility. We have global efforts ongoing with respect to investigating the health economics involving Optical Genome Mapping. With respect to adoption and utilization, I think you heard from Christopher, the number of flow cell increase and the number of Saphyr being placed. In terms of LDTs, we've seen a 1,500% increase in LDTs developed using Optical Genome Mapping. Where do we go from here? This is all the incredible amount of work that the team and the community did together to be able to come to this point. I'm gonna take you all back to the drivers that I mentioned initially. If you look at all of the drivers that are really needed and important for transforming any medical practice to include any new tool as standard of care, all of these things need to be done. What all we did in 2022 is all mentioned here. I think the critical thing for all of you to note is: How does anything get included into medical guidelines? What we saw last year, and you'll probably hear from some of our panelists today, is that for any technique to be recommended as first-line test in peer-reviewed publications has already started to come out. By virtue of that, these key opinion leaders are going to play a very important role in writing consensus statements to make that global impact. We anticipate a minimum of doubling the human genomes in the next two years, and we also anticipate over 100 publications coming out demonstrating the utility of Optical Genome Mapping in genetic disorders, be it constitutional or hematological malignancies. We will establish the health economic benefits of Optical Genome Mapping over standard of care, and the reason is very simple. If you compare everything that I have shown you, if you go back and read any of the abstracts of these publications, it's actually a no-brainer because what you will see is 1, 2, 3, 4 first-line tests or reflex tests in combination, this is already gonna demonstrate that. Some of the panelists today have used this model to implement Optical Genome Mapping in their laboratories. We will also focus on meeting the key evidence requirements for payer coverage, we are going to monitor and drive by virtue of Bionano Laboratories to support and expand our LDTs globally. As I mentioned, we will be applying for a Category 1 CPT code for both constitutional and heme disorders. In the next two years, we anticipate and believe that there will be a code for Optical Genome Mapping, and we will continue our conversations with payers for appropriate pricing and coverage. I think there was a theme that we were focused on last year that Erik started, "The future is bright." I hope that I've been able to show you that the future is really bright with Optical Genome Mapping, and there is a promise to not only the cytogenetics community, but the molecular community that is going to really bridge these gaps and bring the community together. With that, thank you. Stay tuned. Awesome. Thank you so much, Alka. Amazing progress. This is for any of my Board members who might be following on the webcast. We're actually ahead of schedule, which rarely happens for us. At this point, we're gonna take a little break, maybe about 10 minutes or so, and you can get some refreshments, and then we'll transition into discussion with some of our KOLs who have come. It's break time. My name is Ravindra Kolhe. I'm a Professor of Pathology and Interim Chair in the Department of Pathology at Medical College of Georgia, Augusta University. I practice molecular pathology and cytogenetics. I've been in this field for the last 15 years. When I was growing up in India, when we were studying in school, science was something which was pretty phenomenal where you can actually ask question and get answers. I came to United States, went to graduate school. I learned how to search for these answers, which led to my path to pathology. I'm asking questions like why? Why does someone get a disease? Why does someone get symptomatic? Why does somebody has to go to 6- 7 miscarriages trying to figure out what would be a good way of conception? These are multiple questions we deal with each and every single day. The whole idea of clinical medicine or clinical pathology medicine is trying to answer the questions which we're not able to answer previously. You always have to remember that either this is done in a screening setting where that we already know that something abnormal is gonna happen, or in a setting where that we already know something abnormal has happened, and we're trying to find the answer. Traditionally, the way we have investigated oncology is karyotype to begin with, and that's one of the major investigative methods for decades. We added FISH technology to that, and now more recently, we added next-generation sequencing. If you collectively look at the data we have generated for the last maybe 30, 40, 50 years of doing this, most, if not all that information, is very limited on a huge category of structural variants. These kinds of changes or abnormal aberration in the genome were traditionally missed by a lot of these technologies purely because of the limitations or resolution of these technologies. Optical Genome Mapping perfectly fits in this group, where we're trying to adapt new technology to answer some of these questions. Especially in the structural variant category, where currently something like this does not exist. As more and more labs starts to adapt Optical Genome Mapping, you will see a lot of new information coming out in all the categories of prenatal, postnatal oncology. These structural variants will definitely play a critical role in diagnosis, prognosis, and therapy selection for all these groups. As a pathologist, the thing what I'm passionate about is how we can use technology to answer some of these questions to make better clinical decisions, better clinical management, and then hopefully better clinical outcomes. If you go back and look at maybe 10, 15, 20 years ago when we started with karyotype, we added a FISH to the investigation for myeloid leukemias because we were missing a lot of the things by just doing karyotype. When we reviewed the literature from the last 20 + years, we realized that we really don't need to do a whole genome sequencing. We came up with our own plan, that's where Bionano Saphyr OGM was introduced to us. Bionano Saphyr will definitely help us look at all the things which we have traditionally missed. The most rewarding thing, I mean, as a work is people. We have a very amazing group of people, both in the lab as well as the clinical side. We are finding answers to some of the questions which were very challenging for us for all these years. Not just us, but as a community of pathologists and oncologists. Getting answers to some of these questions is probably one of the most rewarding thing for me personally. Pathology is one of those branches in medicine which has interfaced with pretty much every subspecialty in medicine. On top of that, molecular pathology is an emerging field which dissects all these abnormalities at the genome level. Then that's one of the reasons which I not only love pathology, but I'm very passionate about molecular pathology and this is what I plan to do for next 40 years. I want to welcome to the stage now, Dan Brennan, who many of you know. Leading these discussions. He's gonna talk with Dr. Ravindra Kolhe, who you saw as the subject of that amazing video, really delving into the detective work that people in this field do. Dr. Gordana Raca and Dr. Adam Smith, who are themselves luminaries in the field. Gordana is at Children's Hospital Los Angeles, and Adam leads one of the biggest, if not the biggest, cancer testing laboratory in Canada. They've been Optical Genome Mapping users, pioneers with us, early adopters certainly, but you're gonna hear about the progress they're making. I'm gonna turn it over to you, Dan. Thank you very much. Great. Thanks, Erik. Thanks for having me up here. Just to give you a sense of the format. We have 25 minutes here for Q&A, and then I believe we have about another 10 or 15 minutes afterwards for audience questions, if you have any. Listen, I'm pleased to be up here. It's been a great experience getting to know the company better. Although I, you know, Erik, I've been doing HVT for years, so I've seen you down there. Certainly it's been a great opportunity to go deeper and, you know, for today and having spent time with the luminaries on stage with me here. Obviously, Ravindra, you just heard from on the video. He's at Augusta University, and he's at the Medical College of Georgia. To his left, we have Dr. Adam Smith, who's Associate Professor at the University of Toronto. He's the Director of the Cancer Cytogenetics Lab at the University Health Network, and he Chairs, as you heard during the presentation, a global heme group regarding OGM. Finally, to Adam's left, is Dr. Gordana Raca. She's an MD PhD. She is Director of the Clinical Cytogenomics Lab, Center for Personalized Medicine at the Children's Hospital of L.A., Los Angeles. More extensive bios are obviously available, I believe, in the deck that the company put out. Maybe with that long introduction, I thought it'd be great, just even though, Ravindra, you had the presentation up there, maybe just starting, each of you spend, you know, a minute or two and just give a little background of, you know, what you're doing in your labs and facilities and maybe how, just as an intro, how OGM is fitting in. Thanks, Dan. It was a little bit awkward watching yourself on the big screen, but it was very well done, and this was my first time seeing that, so that was really good. I'm Ravindra Kolhe. I'm a Pathologist by training. I specialize in Molecular Pathology and Cytogenetics, and also do some surgical pathology when I get time. I've been doing this for the last 10, 15 years. Very early adopter for next-generation sequencing. When OGM was introduced to me, the first thought came is we really need to look at heme malignancies. And that's what my journey have been. I'm a Professor of Pathology. I do a lot of things both on the research as well as the clinical side, and I am in Augusta, Georgia, the home of Masters, if you are in golf. Adam? Thanks, Ravindra. Just as a brief disclaimer, my name is Adam Smith, no relation to the Wealth of Nations Adam Smith. Sorry, that's my only finance joke. I'm the Director of Cancer Cytogenetics at the University Health Network in Toronto. I'm also Assistant Professor at the University of Toronto. Our lab came to clinical Optical Genome Mapping a few years ago. We saw a presentation, I think at AMP, and we're very excited by the technology. Especially because around that time as well, we'd been looking at hematological malignancies with complex karyotypes and using techniques like whole genome sequencing and RNA-seq in order to be able to characterize them more completely. We knew that we were missing a lot of things by using these other genome-based techniques. When we looked at the, you know, the informatics pathway that was required to do that kind of work in a clinical scale, it really just wasn't practical. When I saw the OGM presentation, I immediately went to the Head of our Department and I said, "We need to do this now." Very supportive group at UHN, which helped us to bring it in as a pilot project and take us to the position that we're in right now. Great. I'm Gordana Raca from Children's Hospital Los Angeles. My original training was in medicine, but then I got PhD in Genetics and for the training in clinical cytogenetics and molecular testing. I've worked for 17 years now in different clinical testing laboratories, and last seven years at Children's Hospital Los Angeles. We have Center for Personalized Medicine, where we do integrated genetic testing for constitutional germline genetic disorders and oncology, all pediatric tumor tumors. I'm mostly involved with our cytogenomics section, which incorporates cytogenetics, FISH, and chromosomal microarrays, but I also participate in case review and sign-out for all other tests in the laboratory. My interest is particularly in pediatric hematologic malignancies when it comes to clinical sign-outs and then some translational research that I'm involved in. Great. And then. Oh, please. I can also tell about our path to Optical Genome Mapping and maybe from my own angle. I've just mentioned that I'm interested in hematologic malignancies in pediatric population. Those are mostly leukemias, B-lymphoblastic leukemia and acute myeloid leukemia. Those are the key disorders that you have in children. In pediatric leukemias in particular, it's really all about structural variants, about chromosomal translocations that create fusions and then copy number aberrations. We were really in a need for very robust technologies for structural variation detection. To illustrate that, we were for decades doing karyotype and FISH, and we were able to maybe resolve what is the key genetic driver in about 50%, at the most 70% of the cases. Our laboratory then started adding new assays on top of karyotype and FISH just to address that gap. We were doing then arrays on every case and NGS panels, and that got us maybe in BLL to 80%-85% of the cases, so at least 15% of the cases that you still don't have an answer after all those four techniques. Which was very frustrating because you're already wasting so many resources, adding turnaround time. We were really looking for better solutions for pediatric leukemias in particular. I first decided to do a little test and send some of our unknown cases as well as some of our knowns to a research laboratory at Bionano. Sure enough, all of our known cases, we were getting concordant results and then a subset of our known cases. Unknowns were also resolved. We found that critical driver. The stuff that I was reading about in other people's publications, that you can really get the same results as karyotype, FISH, and array combined and increase your diagnostic yield on top of it. When I saw that in our own cases, it's completely different feeling when you read about something in other people's publications and when you see it in your own cases. When I saw that in our own cases, seeing that we can do it more efficiently with just one assay and get more answers if for more high proportion of cases, that's where I was sold and started advocating within our institution for Optical Genome Mapping. That was our path to using Optical Genome Mapping. Great. Thank you. Maybe just discussing sequencing for a moment. It's been presented throughout today so far in terms of, you know, kind of where sequencing fits and where OGM fits. Maybe just within your own respective labs and kind of locations, if you will. Do you see Optical Genome Mapping today and going forward, both with short-read and long-read sequencing? Like, how will they fit together? Are they mutually exclusive? Are they complementary? Could they be competitive? Maybe not as much today, in the future? Just would love to hear your thoughts on that. Maybe we can just go down the line. We'll start with Ravindra. Sure. I mean, as of the beginning of this year, we are clinically live for combining Optical Genome Mapping with short-read sequencing for heme malignancies. Whatever the short-read sequencing have issues with, we're able to complement with Optical Genome Mapping. I think this question about with or without or on top of it, I think it's very difficult and it goes as group- by- group, disease group- by- disease group. For heme malignancies, I think all those things which we have missed with the sequencing, Optical Genome Mapping is finding it. For us, I think it's the karyotype, FISH and array is the most important aspect which we use Optical Genome Mapping for, rather than the sequencing. Thanks. I think from the Canadian perspective too, we have a little bit of a different flavor 'cause we try to keep things as cost effective as possible. I'm not saying that in any kind of derogatory way. I'm just saying that we have a limited amount of healthcare dollars that we can spend. When we looked at, you know, Optical Genome Mapping in relation to how it compared to the standard of care techniques, we saw that advantage. There's of course, no way. Well, we also need, if you look at the guidelines, we also need the information that we get from the sequencing panels that we use. Ultimately what we need to do is we need to drive the selection of therapy for patients. In some diseases, like Ravindra said, you know, there are a variety of different therapy options, and the correct selection of that therapy is really done by having all the right information. Having the structural variants, having the small nucleotide variations, and that's really important. I think that, you know, I think that for us, we need to put those technologies together in most cases. Even in a, I think in a lot of cases from a, from a logistical perspective, there's a lot of diseases that we really don't handle very well in the lab, the rarer diseases, because we just don't have the capacity to have, you know, all these different FISH probes and different assays set up for all these rare diseases that we don't. OGM gives us the capacity to look at all those diseases in high resolution, irrespective of what they come in for. It's, from our perspective, it's a huge advantage and it's a tool that brings equity into the lab, like we haven't seen before. Yep. We often hear that the whole genome test, sequencing is the ultimate test, that you can just do that one test and get all the answers. I would like to argue that that that's not completely true, and that even when you are running whole genome, and even if you are doing additional, very complex at this time, analysis to get structural variation from whole genome and in, especially in the clinical setting, you still will not get there completely. I mentioned that we. I will now get away from my favorite topic, hematologic malignancies, and look at the constitutional side of our laboratory testing, where we run a lot of exome sequencing, starting into genome sequencing and then a lot of gene panels, in focus with what we call focused exomes and so partial exome analysis for constitutional cases. It really is clear that even for those single- gene Mendelian disorders that we are trying to answer by sequencing, a large subset are caused by deletion, duplication of that gene of interest. It became expected that you will be also looking at those events, deletions and duplications, as part of your exome genome. Sure enough, we are doing bioinformatic, very complex analysis to look for those deletions and duplications from our exome, genome, and it's still very complex and it's just not robust and reliable enough to be directly used in clinical testing without some complementary, orthogonal confirmation. That we think Optical Genome Mapping would fit perfectly. For every case, if we could do Optical Genome Mapping as orthogonal confirmatory test for those structural variants that are still really supremely difficult from just short-read sequencing, that would be such a powerful combination. Not only as confirmatory test that we really feel is needed, you know, for being able to use information clinically, but also for stuff that's being missed. There were some beautiful cases in recent genome symposium, Optical Genome Mapping, Bionano symposium, scientific symposium, which was outstanding, and some interesting constitutional cases, highlighting what is being missed from genome sequencing and exome sequencing, even when you do structural analysis, structural variant analysis from NGS short-read data. They showed examples of deletions that are missed in hard to sequence GC-rich regions, regulatory first exon, and that's where your Optical Genome Mapping, it fill the gap. They showed some beautiful examples of insertions of transposons. Those are foreign sequences to our genome that will not align to your reference, your short-read sequencing will be completely blind to those, and those cause a subset of these single gene disorders. That's where I see that, it's complementation to genome sequencing and exome sequencing, Optical Genome Mapping as confirmatory, method is something that, you know, fills those gaps where those other techniques are having weaknesses, is powerful. I think that then, no, there is no competition. I think there is really this complementary, role between the two. Not to mention my favorite, now going back to hematologic malignancies in pediatrics, lymphoblastic leukemia, where there are maybe only out of 24 subtypes, there are only maybe 2 or 3 that are caused by sequence, mutation as the key driver. All other 22 subtypes, it's either translocations reading, creating fusions and or copy numbers. Clearly structural, strong structural assay like Optical Genome Mapping is clear first line for our pediatric leukemias, where you would then kind of have sequencing as a second line. Yes, it's very disease specific. If I look from my angle, for pediatric leukemias, very strong first line for all our constitutional exomes and genomes. OGM confirmation will be needed for a long time to come. Those blind spots for genome and exome are beautifully filled by Optical Genome Mapping. Great. Thank you. Can I add one? I think when this thing was introduced to us, we did a pretty thorough research on this, also published it. We pretty much came to a conclusion that at this given time, the short-term sequencing is just gonna look at Single Gene Mutations and SNVs, and Optical Genome Mapping is gonna do the structural variants in the clinical lab. The amount of stuff, investment and everything you would need to run a whole genome in the clinical lab to achieve the kind of promise it gets, it's near impossible. I mean, we have put together a beautiful proposal, a pathway where you combine these two technologies in heme malignancies and achieve maybe a 100X kind of 100 x more information you would get from what some of those proposals are being put together for whole genome. Great. maybe just, we have eight minutes left in this presentation, and then we still have another 15 minutes after. Just give us a sense of, if you think about top-down the extent of usage that's occurring for Optical Genome Mapping today across, say, the addressable applications at your centers. You know, the management team laid out this 10 million sample per year opportunity. Where are you today? How early are we in that penetration curve, if you will, and what has to happen for that penetration really to accelerate? In my lab, we are very early adopters of OGM. We have two instruments. We are nearing around 1,000 samples in different categories. We are looking at prenatal products of conception in IVF failures, postnatal settings. We are looking at solid tumors. We are looking at cell lines. The key bulk I'm very personally interested is heme malignancies. I think that is the area where most of the early adaptation will happen, along with postnatal setting. Again, the adaptation is gonna be a little bit different in U.S. and outside the U.S. purely because, especially in the clinical labs, because of the reimbursement and the methodology we have here. At this moment, it's gonna be in parallel to karyotype, FISH and array for some time till we convince the payers that this is a true alternative to those three technologies. I know Adam and then my peers in Europe has already moved on from those technologies to OGM for clinical use. I think, I think in U.S., it's gonna take some time, and I think that's where we are. We do run karyotype, FISH, and then OGM short-read sequencing for the complete path for our heme malignancies, and that's where we are right now. Adam? As Ravindra commented, I think we have sort of a different, a different funding package in Canada, the way we fund testing. We have kind of two basic systems. We have kind of what we call a global budget, so like the Ministry of Health says, you know, get X CAD to operate per year, and we have per-test funding. We've had a couple of really exciting announcements in Ontario in the last couple of months. One of those exciting announcements was a funding package for patients with myelodysplastic syndrome or myeloproliferative neoplasm. This is a fairly significant number of patients, maybe 5,000-7,000 new patients in Ontario alone that are gonna be getting testing. This is now funded testing through the government. The government has said, "You can test using legacy techniques, so karyotyping and FISH at X price point, or you can use an alternative technology such as Optical Genome Mapping and still take that funding that we're offering at that price." For us, that price point is basically the price of an OGM, as opposed to running, say, multiple legacy tests. That's really exciting for us. We're actually at a place now where we've launched our first clinical test this week. We January 30th was our clinical launch for testing for myeloid and lymphoid neoplasms with eosinophilia and tyrosine kinase rearrangements. Sorry, that's a mouthful. Even I don't like the name, and I work with it every day. It's, you know, it's a very exciting one. We replaced a very, very complex FISH panel with one test that has greater resolution, higher sensitivity. That's where we are right now today, and we are working very hard in the next 3 months- 4 months to bring on and transfer probably 85% of our frontline karyotyping to OGM. That's how excited we are about this technology. Not so much to add to what Ravindra and Adam said already. Here in U.S., we're a little envious to our cytogenetics colleagues in Europe and in Canada because they are marching ahead with clinical implementation. What is holding us here is reimbursement and then just recognition also by clinical professional societies or our clinicians that this is just as good, and I want to argue better than our standards, definitely better than our standards, which is FISH, and karyotype, and array. I think that all my professional colleagues, other geneticists, are absolutely convinced. What's holding us back in clinical implementation is, as I mentioned, reimbursement and recognition by oncology community. That's why I think what Alka was talking about, all those clinical trials and publications, that they will prove, they afford to prove to payers, that there are potential savings by using Optical Genome Mapping rather than combine traditional technologies. Those trials will also prove that you get just as robust and better results for clinical management. Those things will get us there in U.S. I think that many laboratories are looking into technology and getting experienced with the technology. To move it into routine clinical testing, we will have to get over those barriers. I'll just add super quickly that I got multiple requests for a week now from our clinical group. They're like, "Oh, we haven't been able to resolve this patient. Can we do OGM? Can we do OGM?" Our clinical group is very excited about it. Maybe we'll go from Gordana back this way with this question, which is like a two-parter, which is the first part is all the technological advancements that, you know, Bionano has made, and they showcase, and you're obviously aware of to date and what they're promising going forward to the future. Just how do you think about what's to come, level of kind of impact, if you will? Is it anything really stand out, whether the throughput or the software or, you know, some of the sample prep or the informatics, things like that? Just kind of give us a sense of how meaningful that is for adoption, and then B, just thoughts on guidelines? Like when do you think, you know, there was a lot of details about all the work that's being done to get in the guidelines and then ultimately get reimbursement really expansion. Is that something you think happens in 2024, early 2025? Like, where are we on that pathway? Maybe Gordana. No, all these updates that we heard about today, advances in technology are very exciting to us. I think that Optical Genome Mapping technology has already gone a long away from being something that only researchers were using to now being a mature solution for clinical testing laboratories. We were able to install it and implement it in our laboratory within weeks of time. It's robust, it's reproducible, and it is reasonable investment in equipment. There is no need for a lot of bioinformatics support. It's a full solution, ready to go. It's already mature for clinical application and but for maybe medium, smaller size laboratories. Of course, for every easy ease in workflow is always welcome regardless of your size of your laboratory. The advances that they were talking about today with higher throughput, it will be very exciting for this to be a great solution for larger laboratories, commercial style size laboratories, easier workflows and it will be just fantastic for everybody. You know, very exciting about informatic solutions for automated and integrated analysis between Optical Genome Mapping, sequencing data, and array data. That's another thing that's very important for clinical laboratories. The fewer software you need, the more integration between different assets or to compare the data, you know, the better, the more efficient. I think that as I said, over time, technology already mature to be ready for clinical implementation, but this will just take it to the next level, the updates that we heard about today. I think for us, one of the really important things is you're looking at a few of us up here, and there really aren't that many of us, right? Scientists' time is really precious. The software, the interpretation software that we've been piloting the beta with Bionano is really fantastic. It's gonna allow us to look at all of the structural variation data that we get off the platform and characterize it very quickly and report it very quickly. This is absolutely unique in the space, because when we look at other kinds of large scale genome analyses, we have multiple levels of analysis. We have frontline technologist analysis, then we have a variant interpretation specialist analysis, then we have scientist review and reporting. A lot of that for a lot of labs is really problematic cause not only is it people, but it's also various levels of software integration. You need to take raw data, you have to move it into a package, you have to interpret it, you have to take that package, you have to move to another package to report it. There's all these steps. Labs are paying a lot of money to actually get that integration across the space. What Bionano is actually offering us as a solution where we run the sample, we get the data, we analyze it, and we click a button and paste that report into our clinical reporting system. From my perspective, like as a clinical scientist with limited amount of time, I really. I, you know, this is a super advantage for us, in terms of being able to report higher resolution data more accurately, giving better results, and not actually doing the, you know. I mean, you know what it's like to have to, "I'm gonna cut and paste this little piece of text. Now I'm gonna put it over here." Like, it drives us crazy, you know. Like we know, you know there's a better way to do it, right? There has to be. I've always been really impressed with the software integration. The visualization, even the software that we have right now with Access, the level of visualization that we have of the genome and the tools that we can use to look at variances is really fantastic. It's. We're super excited about what's coming in terms of the software packages that are gonna be released for this. I think the same thing. I mean, the thing to add is you have a faster DNA isolation, increased throughput, and a better reporting and accurate results. It's very rare in clinical medicine that you get all those things from the same manufacturer. It's near impossible. Bionano is the only company in my lab which has all these things coming from one manufacturer. This is very critical in a CLIA and CAP setting. Just to give you an example, when we do sequencing, we do DNA isolation kit from QIAGEN, the library prep is from Agilent, the sequencer is Illumina, and the analysis is Pierian Dx. In this three, I mean, this is all this complex supply chain issue. Let's say if I don't get a QIAGEN isolation kit, which was the problem during COVID. All the downstream of sequencing will stop for oncology patients. If PierianDx server goes down, then we can't do any analysis and reporting. These are the real issues in the clinical lab, and having everything by the one manufacturer makes a pretty significant difference in implementation and adaptation in the clinical space. And the other side is if something doesn't work, then we can only blame one person or one company. That's a pretty significant advantage in the clinical space is like right now when something goes wrong in the sequencing, we don't know if it was the QIAGEN extraction kits or Agilent's library prep kit or actually the sequencer or the Pierian Dx software which is doing the analysis. You are going to see lot more faster adaptation and implementation of Bionano purely because you're gonna get a fast, quick, automated DNA extraction, increased throughput. I think this is gonna be the most important part of all this. The most other important, especially when it comes to me for analysis, reporting, and resulting, is the software, and especially getting integrated the array data as well as the NGS data in one software, which is a game changer for the guy who's sitting whose signature is at the bottom of those reports. I mean, some of these things I didn't even know, and I'm the one who's doing OGM a lot. This was very exciting for me personally to see the extraction, high throughput, and the software piece that what they're working on. We've got about 10 minutes left, and I guess now is the time that either we could see if anyone has any questions in the audience, by all means, or we can keep going. Maybe we have a spotter here. I guess there's a question in the back over here. Hi. question about long-read sequencing technologies and Bionano did a great job presenting the differences, you know, the comparisons between nanopore-based and the false positive rates, et cetera. I was wondering if you guys have looked at PacBio technology potentially, and are there certain applications where you think they might actually have some utility, or do you think just between OGM and short-read sequencing, you can cover all the bases? The short answer is yes. Between OGM and short-read sequencing, we can cover everything as far as clinical is considered. For research, I think it's a different story. One of the most critical factor in lab medicine especially is turnaround time. We want each and every day delayed is a delayed treatment for the patient. If you have a cancer, you don't want to waste 20 days, 25 days, 30 days to get the results back from these bigger technologies. I think one of the other important considerations when you look at either ONT or PacBio, and we've had a little bit of experience because we ran a project with the Ontario Institute for Cancer Research, which is our neighbor. It's actually the same building, but anyways, we'll d on't worry about that. They had an ONT platform and we had the OGM platform. We thought it'd be great to compare data. They said, "Okay, you know, here's 10 samples, Adam. Can you give us the OGM data on these?" I said, "Yeah, sure. No problem." About a month later, I sent them the files. That was two years ago. I'm still waiting for the data back on that one. It's difficult. Long-read sequencing is difficult. I don't wanna. I don't think we should underplay this from a clinical perspective. The other thing that I was talking to one of my colleagues about, and this is important. We're trying to talk about coverage, okay? Coverage is how many times you repeat the sequence that you're looking at to make sure that you know what's going on. You need coverage for two things. You need coverage 'cause you need to be sure that you're detecting that thing when it's in a low quantity, for example. If you have something that's in 5% or 10%, you need to have 200x, 300x, 400x coverage, which is what OGM gives us for a fixed cost per sample. On ONT or for PacBio, it might cost $1,000 to do a genome, but that genome is 30x. You just have to do the math. You have to start multiplying. It's not clinically feasible. It's not financially feasible. The other problem is with ONT, and the guys were telling me this, and this blew me away, is that to get 30x, I got to have a technologist that stands over the cell, and he's got to pump the DNA in every, like, an 1.5 hour In order to get up to the 30x. You know, there's some technical pieces that they're totally solvable, I think. Currently today, in the clinical space, both cost and logistically, it's not practical. Not much to that. I mean, I think they explained it and covered it beautifully, also. The question is about in the clinical setting about detecting abnormalities that are clinically significant and make difference in clinical care. Many of the things that we haven't covered and haven't discovered by short-read genome sequencing and things like tools like Optical Genome Mapping and other structural tools in the past. They're still in research arena and we don't know how to interpret their clinical significance. A lot of research has to happen with long-read sequencing to understand the significance of those alterations before we will be using them clinically. Completely agree with Ravindra and Adam, not feasible financially, logistically and not clinically necessary and justified at this time. Great. Any other questions right now? Okay. Hi. Just maybe a quick one here. You talk about the importance of the health economics, especially on the reimbursement front in the U.S. and the speed in terms of what you can do. Is this something that might be an issue if you have to use it as a complement to other, you know, methods of doing the work? If you have to use it with FISH or next-gen sequencing or, you know, once you ultimately can use Optical Genome Mapping on its own, maybe those things get better? How do we think about cost and speed if you use it with other stuff? You know, Medicare has one same pot. I mean, they don't, they're not gonna get any more money. Anything we go and ask, it has to replace something. OGM technically replaces FISH and karyotype. If you look at how expensive FISH and karyotype is for Medicare, they will be more than happy to pay us for OGM when we say that, "Not only we're gonna give you faster, better, and more information as compared to karyotype and FISH." I think we have some initial discussion. I think having a CPT code and other things put together, this platform definitely has potential as an alternative for FISH and karyotype. Not only purely based on the technical aspect, which we have proven. We have proven the medical necessity, we have proven the technical assessment. Payers, who understand the health economics a lot better than I do, they would love to jump on something like this, and which they have done in the past. I think this is the approach, collectively we will have to do along with Bionano so that the payer comes on board for that. At this moment, where we are still in initial phases, you will see some complementary testing along with them to show the payers that, "Hey, we ran 200 cases, and these are the true, prospective 200 cases where I'm showing you, look, this was karyotype, this was FISH. We didn't find much. This is OGM. We found this thing." Then get the payers on board for something like this. I can just actually give one quick example for that as well. Not all diseases are time-constrained. Certainly, like Gordana and I know that, and Ravindra as well, sorry. All of us know that diseases like acute myeloid leukemia are really time-constrained. Most of our clinicians wanna begin treatment in five days, which means that's our time window. What happens now is we do a karyotype, and we try to get the result with the karyotype. If we need to do something else, we do it with FISH. That means that we're not giving that full result in five days. 'Cause if we don't know before we do the karyotype what we need to do for FISH, so we have sort of this tiered approach to testing. The difference with OGM is that we do the test, and we get pretty much everything we need right up front, and we don't need to do any, a lot of ancillary testing in most cases for cases that we test frontline. Hi. Thank you. Ravindra, thanks for your presentation. I tuned in to your webcast, I think, last week. One of the things I think you said was that OGM detected additional clinically relevant SVs, CNVs and novel gene fusions that will contribute towards the diagnosis, prognosis, and therapy selection of cancer. I think a lot of us in this room are quite familiar with Foundation Medicine and Guardant Health in the solid tumor space. I feel like therapy selection may not have its standard of care perhaps in hematological cancers. Maybe, can you add a little bit of skin to the bones on this topic? Because I feel like you know, oncology is a very large market. I know constitutional genetic disorders in some cases can be smaller markets. Maybe, I guess, what would your recommendation be to Bionano to develop, you know, therapy selection panels across, hematological malignancies? Sure. You know how we came to this point, where is doing all this therapy selection based on a sequencing. We had the TCGA start to sequence all the tumors, all that is was liquid. We identified driver mutations, and that's how, on the other side of that, all the trials started, especially the NCI-MATCH trial. What was missing in the TCGA? Structural variants. There were no technology. I mean, I would wish we could get back to all those samples and do OGM on them and then create this structural variant database. Even after all this, we will still have a huge number of patients who we don't know what's driving their tumors. I think structural variants might be a group where what we have missed in the TCGA and what we have missed in short-read sequencing will add value, not only for diagnosis. We're gonna make a lot better diagnosis. We're already making a better diagnosis with adding OGM. We'll make better classification. If you look at the 2022 heme classification, there is a huge list of AML which are purely based on fusions. I'm not gonna run a 20 fusion panel just to make that sub-classification. A single OGM will give you all those positives or negative for sub-classification of AML. The third and important thing is prognosis. Having a complex karyotype definitely shifts the prognosis, the risk stratification for these myeloid neoplasms. Then the final, it would be is therapy selection. When I say therapy selection, going back to the MATCH trial, there are very few segments in the MATCH trials which are based on fusions. There are very few are based on structural variants purely because we just don't know them. You can't count what you don't see. I think this is where, at the beginning, where we're gonna create this knowledge base of structural variants. Once you get that critical mass of a few thousand cases of heme malignancy, solid tumors, we're gonna find new structural variants in these categories which will be defining, driving. Once you put those things together, the pharmaceutical company is gonna find a target for those structural variants, especially in the fusions or even CN amplification category. That's where you see the true revolution for target selection will happen. For the target selection, at this point, I think we are in the phase where we are really collecting knowledge on structural variants, which I personally think we missed out in the TCGA database. Great. If you wanna make a final comment. I think with that, we're gonna wrap up this first panel because I think we're gonna move to the second one. If you got a final comment? I was just gonna say that in the few hundred samples we've run on OGM in the past two years, we've detected novel fusions. It doesn't happen a lot, right? It's happening like, you know, 5%, 10% of the time in a few hundred. If you look at my lab's history, like we run 1,200, 1,300 karyotypes a year, and I can count on my hand how many novel fusions we've actually, you know, done in 10,000 or 12,000 karyotypes. I totally agree with Ravindra. This is amazing discovery that's gonna drive medical interventions. Final comment about therapy selection. We are a pediatric institution, and there are even fewer targeted, classical targeted therapies for pediatrics, because something has to be tried and true in adults before they can start running pediatric trials. However, our oncologists constantly breathe down our necks to give them genetic results because prognosis is critical and therapy gets tailored based on prognosis, based on risk. Their prognostic genetic marker will dramatically change their therapy, even if it's not targeted therapy specifically for one particular driver, one particular drug, but the intensity of therapy gets changed all the time based on genetics. It's still therapies driven by genetics. Well, fantastic. What a great panel. Obviously, Ravindra, Adam, and Gordana, thank you. I think we're gonna move to the next one. My name is Darren Finlay. I'm a Research Associate P rofessor and Director of Tumor Analysis at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California. I'm a Cancer Biologist. I did my PhD in Dublin, Ireland. Used to have an Irish accent. Faded away now. I moved to La Jolla in 2003. I started doing my PhD in Pharmacology. We've always been interested in trying to find why drugs work for certain patients and not others. Cancer is obviously a disease of DNA. People have mostly focused on genetic mutations. A lot of the samples we get are considered normal by karyotyping. There's technically nothing wrong with these patients. Of course there is because they have leukemia. Although their karyotypes and their cytobanding look normal, once we run this through the Saphyr system, we can detect structural variants easily and with just a level of granularity that's impossible with standard cytogenetic techniques. What we'd really like to do is track structural variants through the progression of the disease and associate this with drug response or drug relapse. Optical Genome Mapping can detect structural variants that are missed by much more labor-intensive and much more time-consuming methods such as karyotyping and cytogenetics, which require, you know, these very sort of arcane, difficult techniques and highly trained pathologists to do the analysis. With OGM, it's essentially a DNA isolation, a labeling, and then it's just load it into the chip, run the machine, and watch it on your laptop. With the Bionano Access software, you don't really actually need a bioinformatics specialist. You can literally grab the images out, stick them in a PowerPoint, and send them to your clinical partners. Who is at Boston Children's Hospital. Thank you, Catherine. Dr. Rashmi Kanagal-Shamanna, who is at a cancer center in Houston called MD Anderson. Pretty sure you've heard of it. These folks have been working on Optical Genome Mapping for a long time, and they're working across a diverse spectrum of applications. Certainly, Rashmi has been very active within these heme consortia, and she can talk to you about her specialties and so forth. Also in applications of Optical Genome Mapping in the cell therapy, quality control, CAR T, and so forth that we've been talking about. That sort of participate here and talk about those research applications. Catherine, we got to know because of her interest in really explaining complex cases, through a consortium that Ravindra and Alka organized around host genome response in COVID. Darren Finlay, as you heard, is an amazing cancer biologist doing groundbreaking research. I'm excited for Dan to bring some further insights into the research applications of Optical Genome Mapping. Thank you. Yeah. The way I look at it as an Analyst with folks like this to my left, it's like my job isn't to screw this up, right? We have three great speakers, obviously. The goal is to get the most out of this session as we can. Obviously, I'm really pleased to be leading the charge here. I thought, although Erik just gave a nice intro, and certainly, we heard about Darren's background, maybe a little bit more from each of you about, you know, explain what your roles are. And maybe just touch upon a little bit how Optical Genome Mapping maybe is starting to be used by you in your work. Yeah, absolutely. I'm Rashmi Kanagal-Shamanna. I'm a Hematopathologist and a Molecular Pathologist, and at MD Anderson Cancer Center, and I'm also the Director of the Microarray Section within the Molecular Diagnostic Lab, which is the CLIA-certified lab. In addition, I have a portion of my time funded by research, so I'm a translational scientist as well, where I am the lead of the hematopathology core for the AML-MDS Moonshots at MD Anderson. When I first got introduced to Optical Genome Mapping was at a vendor booth in one of the, at the Cancer Genomics Consortium. That's where, a t that time, I was kind of, m y research focus is actually myeloid neoplasms, primarily myelodysplastic syndromes, to identify underlying genomic abnormalities to find, you know, to improve prognosis and then find targets for therapy. Through the AML-MDS Moonshots, we've, like, extensively characterized these disorders, right? Using whole genome sequencing, using transcriptomics, proteomics, et cetera. Majority of these cases, we don't have targets to treat these patients, and we don't understand how the disease progresses. Some patients do very well, and then there are patients that progress really bad. One thing we really didn't investigate were the structural variants. The Optical Genome Mapping turned out to be a great platform. Again, similar to one of the other speakers, we initially investigated just 10 cases with the help of Bionano, and the amount of information we found was just stupendous. That's how my interest started. Since then, in our lab, we've kind of, performed mapping on, close to, over 100 patients now, just, baseline myelodysplastic syndrome patients. We recently published, last year, in a leukemia journal, how the data from Optical Genome Mapping, together with the targeted NGS, kind of not only showed concordance, but it identified so many additional, in fact, twice the number of, clinically significant abnormalities. Again, there are tons more of abnormalities that at this time we don't have enough evidence to show these are clinically significant, right? These are all for, you know, that need to be investigated in a research setting. There are. We've identified several that are recurrent among this cohort that we are now working to see what implications these might have. Great. Go ahead, Catherine. I'm Catherine Brownstein. I am at Boston Children's Hospital and Harvard Medical School. I'm the Assistant Director of the Molecular Genetics Core Facility at Boston Children's. We've had a Saphyr System since 2019 and run projects for academics and researchers at the Longwood area and also for industry. In addition to that, I am the Scientific Director of The Manton Center for Orphan Disease Research. We've been using Saphyr System a lot in our as part of trying to solve and end the diagnostic odyssey for patients with unknown conditions where they come to us wanting answers. We got the Saphyr System in 2019. In 2018 or 2017, my then boss, Louis M. Kunkel, who discovered the muscular dystrophy gene, DMD, before the genome was even published, called me down to his office and said, "You need this." I said, "Okay." He's like, "Write a grant." I did. It got denied. Wrote it again, got it. Sure enough, we knew it was gonna be a game changer. Being 2019 and what it was, early 2020 came, it shut down everything in the lab unless you were working on COVID. Fortunately, Bionano stepped up and formed this consortium. We're looking at the host genome, we were able to continue working at Boston Children's, looking at MIS-C, the multisystem inflammatory syndrome of children, just collaborating on the wider efforts. Great. Darren Finlay, I don't know if you wanna just. Sure. Add a little bit to the movie. A little intro. You saw most of it there, but I'm Darren Finlay, and I'm a Research Associate Professor at Sanford Burnham Prebys in La Jolla. I'm also the Director of the Tumor Analysis Shared Resource. We started doing Optical Genome Mapping in 2019. We gave six samples to Alex Hastie's team, and they came to our lab meeting and showed it to us, and we were blown away. We did it the ops away. I ran to my boss and said, "We need to get one of those machines." They said, "Write a grant." But luckily, as I'm Director of a core facility, we were able to use some institutional funds to get a machine, and we've been running. We're an academic lab. You can tell from my clothes. Every sample we get that we run it, I'm still blown away at the things it finds. It's an amazing technology. Great. This is. The The first question we wrote here is a bit high level. But maybe I can ask them in a certain way. Basically, it was what potential do you see for OGM as a tool in discovering new biomarkers, excuse me, and applications around drug development, solving complex cases? It's very kind of generalized, but maybe a better way to articulate it is if you could speak a little bit to everyone in the audience is familiar with a lot of different instruments and tools and technologies that are being used by scientists and pharma companies to do just that, right? To basically develop drugs and find new biomarkers. Maybe could you articulate a little bit like, if we look at, say, over the next five years, where do you think? Like, how powerful will OGM be in certain indications for doing this? Are we in the first pitch of the first inning, or do you feel like the community is becoming aware of the power of this technology? I can go first. I think the community is certainly paying attention to OGM. At least, that's what I gather from. I sit in several of these guidelines meetings, and that's what I'm gathering, which I'm very happy about. Again, going back to the some of the data that we found, we found like things like MECOM rearrangement and NUP98 rearrangements that were completely cryptic. We missed it by karyotype. I mean, it's supposed to be cryptic. NUP98, you will not be able to pick it up by karyotype, by definition. If you don't know, you don't order the FISH anyway. These were actually, we picked it up by doing OGM in retrospect, and now we are having clinical trials targeting these specific abnormalities. One of the oncologists at our institution is leading the Menin Inhibitor trials. If these abnormalities were actually detected, these patients would have become eligible, you know, opened up an opportunity for therapy for such patients. This is just an example. I can tell you of several more that I've kind of described in the paper as well. I think this certainly. This is kind of, I mean, if you look at individual patient who presents with, say, normal karyotype, no abnormality, and he's considered to have a good prognosis, and then if it is NUP98. He suddenly skips the intermediate and goes to adverse. If you can put him on a trial that targets this, that's like a game changer for that patient. I see a lot of potential and the discovery has just beginning. Once more institutions kind of explore into this, data builds up, it's gonna open up. You know, there's gonna be updates in several of the prognostication, the therapeutic guidelines, all of these are gonna evolve. Mm-hmm. Catherine, anything to add? I think we're just getting started. With the price of NGS coming down so much, we're gonna have a lot more people getting exomes and genomes, which means a heck of a lot more negative exomes and genomes. Then they're gonna be coming and still wanting answers and, I really believe OGM's gonna replace karyotyping, which is expensive and slow, and people don't wanna do it anymore and are we got complacent accepting a lot of this complex structural variation that we just couldn't capture, and now we don't need to be complacent anymore. We can delve right into it. Yeah, I mean, I agree with everything. Yep. I mean, scientifically, academically, it's becoming really well-known, but every time I show some data to an academic, they are again amazed. If I show them data from a sample they gave me, it's like you've changed their world. Optical Genome Mapping is the future of cytogenetics. I'd like to add something. The current diagnostic classification schemes that came out, the WHO and the ICC, I was involved in the development of the WHO side, and we have 32 abnormalities that are AML defining. If the patient has low blasts, but in the presence of any of these 32 abnormalities, the diagnosis is upgraded to acute myeloid leukemia. The whole theme is everything is genomic based, and none of those 32 are mutations. I'm only talking about structural variants. That's how things are moving. I guess the clinical panel alluded to it, that you cannot really test for these 32. You cannot have 32 FISH assays on every patient coming through, and as they also emphasized, this OGM would be a single platform. You can identify all of those, and probably treat accordingly. Mm-hmm. Maybe related to that, in terms of the pathway, Darren, you know, even what you highlighted like on the, you know, on the video, in terms of responders and non-responders, and eventually you could see this becoming like, you know, patient needs to get an OGM in order to get put on a drug. Like what's the timetable? What has to happen? Like, where is pharma, do you think, in, you know, Are they aware of the power of this technology today? Like, if you looked out five years, like what does the landscape look like there in terms of OGM being used, you know, with drug therapy? I think OGM is already being used in this respect, but I think we need. The beauty of being an academic scientist is you get to play with all these different technologies, and we like to think we set the bar for what's gonna happen in a few years' time, but we need to actually prove that first in an academic setting and then in a true clinical trial setting that this can actually give the oncologists an extra leg up. Mm-hmm. Anything to add or no? No. Maybe, I wanted to switch gears for a second. You know, we'll come back, but I did wanna talk a little bit about cell QC because that came up during the presentation and it, you know, Erik and team highlighted it to be a really meaningful opportunity. It It was highlighted several times throughout. You know, the company talked about OGM and utility in cell bioprocessing, cell therapy for genome QC, target effect analysis, excuse me, genome integrity analysis. Maybe, we could start with maybe Rashmi. Just maybe provide some examples in your experience of how OGM is being used today or could be being used in this area and just how do you view the utility of OGM versus sequencing or, you know, other types of QC alternatives? Right. OGM, I think, has an important part to play at multiple levels. First of all, I'm working on the CAR T side of things, so I can speak about that. When we kind of get the T- cells from the patient and then we process these cells, put in the CARs, and then we, you know, put those cells back into the patient, right? Before putting a patient's cells back, the alterations that might have happened could have damaged or compromised the integrity of genome. Right now the only way that we look at it is by karyotype. We already know that CAR T is an amazing type of therapy, very expensive. Unfortunately, about 40% of the patients show these responses. 60% do not show this amazing response. What might be the reason? Is it because we are injecting damaged cells back? Possibly, right? That we are not picking up by karyotype. I think OGM, considering its high resolution and the fact that it can pick up, you know, several different types of structural variants, would play a role in kind of policing that before damaged cells are inserted back into this already susceptible patient. This could also save tons of cost for the patient. You know, these patients are usually advanced stage cancer, so if we put ourselves in their shoe, it, financially, it matters a lot. Secondly, I think a publication came out last year which performed whole genome sequencing on the tumor and the microenvironment and demonstrated that the responses correlate with these abnormalities. Again, they only looked at mutations, and I believe that if we also evaluate the structural variants in these, we might come up with a few more predictive markers, and that way to kind of, you know, identify biomarkers, so to speak, to predict CAR T responses. Mm-hmm. Please, Catherine. For us, we're a tertiary medical center, so patients are already coming to us a lot of times with exome or genome or panels, and it's very hard to want to redo a genome, even a long-range genome. OGM is a very logical next step to capture that dark area of the genome that we're missing through just looking at traditional NGS. Also being in academics, and researchers want the most bang for their buck, and so adding on an OGM on top of an existing genome is a very cost-effective way to do a comprehensive analysis. Okay. Similar to what Rashmi said, we are doing very, very similar stuff except with not CAR T-cells, with their close cousins, CAR natural killer cells. It's exactly the same, you know, rationale. You take these cells, you need to make sure they're genetically fit at the start before you're gonna do these very expensive manipulations. You're inserting a gene into them. You don't really know where it goes, how many copies, what other genes it's perturbed. Anytime you either just grow cells in the lab, there's a potential for loss of genomic integrity, and Optical Genome Mapping is just an extremely cheap, fast, and sensitive way to analyze these cells. For $500, you can get 400x coverage in 5 days. These therapies can cost. Oh, my R. Saxon came back. Therapies. These treatments can cost up the order of hundreds of thousands of dollars. Why would you not just do $500 at the end to make sure the patient is gonna get something that works? Maybe just one more follow-up there. In order for OGM to become more like a de facto standard, today I'm sure labs around the world are using, you know, whether it be karyotyping or sequencing or l ike, what do you think happens? Is it just? Are there guidelines? Is it just publications? Just kind of what is the outlook for OGM in QC for cell therapy? I think there is still no publications out there, definitely publications. I think it's easier to kind of for the QC purpose, just because of the risk that we indicated. Just to do a $500 assay before actually putting something back into the patient. That knowledge and awareness is gonna catch on. I think right now there's no other assay that can identify all the structural variants. Like some people have tried microarray, but you cannot really pick up balanced translocations with it. Mm-hmm. Okay. Maybe in terms of some of the roadmap, which I asked the last panel the question, but obviously the improvement in the technology and the throughput and the price point and the ease of use. The company's highlighting a pretty aggressive roadmap today that they've outlined. Just talk a little bit about your use today, you know, across your labs, university, and how the new technology advances. Is it evolutionary or does anything really stand out to you as maybe even accelerate usage? I'd be interested to get your takes. Maybe we'll go this direction first. Darren? Yeah, sure. We use it on every sample we can get. Obviously, our initial focus is leukemia because it's easy to get samples from patients, but we've done this with every patient sample we can get. We've done sarcomas, lots of glioblastomas, lung, and every time we find sort of 40- 80 structural variants on average that have just never been detected in a healthy human before. Sometimes they're events that have been detected in those cancers. Sometimes they're events that have been detected in other cancers. A lot of the time, these are structural variants that have never been seen before. Catherine? Where I'm not working with cancer or leukemia, but actually the resolution of OGM is actually been a game changer. Looking at the amount of structural variation in the general population and being able to accurately assess it in the ill population, sick population. I think we're just moving the needle forward in terms of accurate diagnostics and really figuring out what's truly a disease-causing variant or structural variant, copy number variant, from other things that are benign and just rare, but in the general population. Anything with the new technology that really struck you today? The software or the throughput or the, some of the informatics capabilities? I am so excited for being able to integrate a BAM. I know I nag a lot of the people in this room because I can't wait to see it, and I think that's gonna be a game changer, just even more. Already Bionano Access is easy and I appreciate it because part of my job is teaching clinicians and researchers how to use these programs, analysis programs. OGM is great because of the dynamic Circos plot where you can open it up and kind of see at a glance, a lot of times if the patient has what you are looking for. You know, being able to integrate it with a BAM and actually capture like, for example, true compound heterozygote, will be incredible. Maybe Rashmi, maybe could you just discuss the work at MD Anderson with the Cancer Moonshot, which I think you talked a little bit about for AML and MDS, and now you're, I think, integrating OGM into this? What's driving the decision to do this now? Kind of what do you expect to come from it? Right. As I mentioned, we've worked extensively on OGM and, based on at least the findings that we found, we have now, we are in the process. We are nearly complete with the validation in our CLIA-certified lab, and that is about to go live anytime soon. I told you already that we found several additional abnormalities that we don't have evidence yet to determine whether these are indeed clinically significant or not. That kind of like really excites us. And with the potential that, you know, higher throughput instruments are coming our way, we were kind of thinking of what other applications might be out there. Something that we are already working on is looking for the follow-up. It's not really MRD, but kind of sequential samples that we are evaluating within the setting of clinical trial. As you know, MD Anderson is the hub of all clinical trials. In by clinical trial, we kind of evaluate all patients at the same time, so we get an a fair assessment. This year, we will be publishing our first clinical trial integrating the OGM at baseline. To talk about the sequential manner, I also presented some preliminary data earlier in the symposium. If you look at all of leukemia, there's only a small subset that really has aberrations that for which there's a companion diagnostic and you can track with time. Majority really don't, I feel that OGM would be a good platform to kind of evaluate the clonal evolution or even to see what clones might respond to therapy. Looking further, the plan is, if we do OGM, are we able to identify some emerging clones earlier than what the patient may manifest himself, right? That way we can give some sort of use preventive strategies to prevent the relapse, so to speak. That's our goal. Just because we've had tons of experience, we want to kind of integrate OGM into our AML-MDS Moonshots platform as one of the technologies to kind of routinely evaluate all the leukemias that come through. We have single cell sequencing analyzers, we have whole genome analyzers, and I think OGM would fit very well in there, and that's our immediate plan. Great. Okay. Maybe one for Catherine and then we'll open it up. Catherine, I believe you were involved with some work understanding host genomic, genome genetic factors in COVID response, right, with OGM. I think OGM proved important in that setting. I guess the question is, could you give a little background on that? Do you think that if there are structural variants that factor in a host response to COVID, that you could extend that role of structural variants to other common diseases? Yeah, exactly. We had a nine academic center consortium that weekly, in contrast to what everyone else was doing, looking at the virus, we were looking at the hosts and who were able to had a very severe response to COVID versus people who were much milder and working with researchers all around the world. Being at Boston Children's, we had the first MIS-C samples or cases that were coming into the hospital, and we were able to stay open. Basically, in my facility, it was, I could keep the machines running, to support any COVID research that was going on, and we were able to run 20 MIS-C samples on the Saphyr and we're currently writing up the results, looking at interesting immune-related genes with structural variation that was completely missed by next-gen sequencing. Just quickly, though, before we diagnosed a 3-generation pedigree family with hypophosphatemic rickets who had been genomed to death, microarrayed to death, couldn't find the variant. Finally, my old PhD advisor sent me the blood so we could run on Bionano and found a duplication in the known gene for hypophosphatemic rickets. It wasn't a gene discovery, but it was a diagnosis for a 3-generation pedigree. It's not every day you get to diagnose a 90-year-old woman with what she's had for her entire life. That was a really fun day. Wow. Well, we have a few minutes before we go to Erik and then the management team. Let's look up and see if there's any questions in the audience. Hey, thanks for the, thanks for the question. Just a brief one on structural variants and the role they play in kind of maybe population sequencing going forward. What is stopping, you know, use of, say, Saphyr or Bionano in much larger sequencing projects today? In my opinion, I don't see any reason, any particular reason why OGM should not be kind of incorporated. I think it's just probably the lack of awareness. As I believe there are tons more publications that are coming out this year, and the community is gonna become more aware. In fact, I've been in touch with the All of Us program at the NIH, and they've asked me to kind of share with them the data from OGM. I see that it is gonna become a part of several of these large population efforts moving forward. I totally agree. I think it's just a matter of showing the data. There's a misconception that you can get accurate structural variant calls from NGS, and you can get some structural variant calls, and sometimes you can see what you're looking for. If you don't see what you're expecting, you're still in the nagging back of your mind wondering if it's just a platform issue and if you ran OGM, you would actually be able to see the call. I think publicizing enough of those cases and actually showing the increased value over time will convince the general community. I agree 100%. Just why wouldn't you do this? This is, I wouldn't say free, it's $500, but the amount of information you get for this $500 in a 5-day timeframe at 400x coverage, I think. I know Alex is gonna disagree with me. I think we can detect structural variants down to about 1%. We can't quantify that it's exactly 1%, but we can find them down at that level. Right. All right. Thank you. Catherine, you had mentioned that the price of sequencing is dropping, of course. It's something that's on everyone's mind. The three of you work for some world-renowned institutions that are, I would think, very well-funded. I also don't want to assume that. Maybe if you could share maybe, how well funded are you to conduct unlimited amount of studies using OGM? Do you have any limitations budgetary-wise? As we think about the cost of sequencing dropping, you know, Bionano went from $1,500 to $750 to $450. They've talked about that dropping again. I'm just curious, if that were to drop to $300 or $200, just making up a number, how much more volume do you think you would do as a result of the price drop? Twice as much. I can go first. Yeah, I mean, there's always budgetary constraints for research, no matter what the institution is. So I can speak with respect to the AML-MDS modules that I'm involved in. That's been happening for close to a decade now. Millions of dollars have gone into it. Now that we know there is one component of the genome that we are completely missing, like, we've never evaluated into this portion of the genome, we just we have data to kind of support our proposal that this is what we're gonna do. I believe we are justified in requesting the you know, funding to do more OGM analysis on these patients in that setting. I agree with what she said. We're all, you know, research dollars, no matter where you are hard to come by. We're writing grants for the work that we're doing. The Children's Hospital pays for a lot of research exome sequencing for cases that are not reimbursed through clinical methods. You almost feel dirty, like, when people shove things that should be reimbursed clinically over to the research side, but that's another topic. I think we just need to keep pushing for clinical reimbursement and then also with grant funding for this. I just wrote one for the American SIDS Institute and got it to run OGM on SIDS cases, where undiagnosed, we think it could be a rare Mendelian form of disorder or a first episode seizure or cardiac effect. Just doing more of those, writing it into your grants, and being extremely clear about the economics behind it, where you know you have an existing exome already. Going to a long-range genome just seems kind of redundant, but throwing on OGM on top of it will be a good way to discover more genes, diagnose more cases, and move the field forward. So I also wanted to add in terms of analysis of, for the whole genome sequencing, for example, we need, like, we need to support bioinformaticians as well. That would include a lot more costs. If you think about it, we are kind of, we have a potential for discovery in a portion of a genome that's never been interrogated, and we will not request. I mean, it doesn't require that much of bioinformatic support. I think it just, and, you know, checks all the boxes to kind of get the funding. Maybe could you compare and contrast a bit just on long-read sequencing? I know it's come up in this panel and the prior one. There was a question earlier. Nonetheless, there is still a lot of excitement that given the throughput increase and price decline that the Revio has introduced, and I think that's more automated than, like, pipetting with ONT, that it will become more of a ubiquitous tool. Like, we did a conference in Boston recently and, you know, one of the, you know, Mass General clinicians said, "Yeah, you know, we'd love to adopt clinical sequencing broadly with long reads." Net-net, maybe just give us some color about head-to-head, how, like, long read does compare today in terms of, you know, the cost, the throughput, the workflow. Anything that you would highlight, and why, I think you're gonna tell us OGM is superior, just what are the key factors why? Sure. It's also kind of a repeat of what was said before, but to add to what I believe Adam said. Mm-hmm. Right now in the workflow is we have the short-read targeted NGS. In our CLIA molecular lab, average coverage, the median coverage in any of the amplicon is 3,000x. We have to go to that level to get the 2% as the lower limit of detection variant allele frequency, right? Why that 2%? This is still baseline profiling. I'm not even touching upon the MRD-NGS assay that we are all working towards, which would require tons more coverage. Why 2%? Because all of the diagnostic criteria is based on 2%. To define clonal cytopenia of undetermined significance, CCUS, you need 2% mutation, VAF mutation in any of the myeloid-related genes. You know, if you do not go down to that level, you cannot diagnose it. You're missing all those patients. So coverage is super important. And I think as Adam said, long-read at this time does not offer that coverage. I also am waiting to see some sort of publication or data showing concordance between the standard technologies and the long-read. Perhaps they will come along, but I haven't seen it yet, so that's another issue. Also to speak, the long-read would take some components of the structural variant detection and some components of sequencing, and you get it all in one platform, but you're losing all of these other important variables like the depth of coverage. For a clinical lab, turnaround time is a key factor, right? That's extremely important. All of those are kind of. I don't see that, at least the way things are, I don't see that happening. Right now, I will have to say that continue using the current short-read targeted NGS, combine it with Optical Genome Mapping, would be more informative for clinical decision-making. Mm-hmm. I don't know if anything to add or no? No? Agree completely. Short-read sequencing and Optical Genome Mapping gives us everything we need to get, excuse me, the level of sensitivity or that you would need from long-read sequencing would just be exorbitantly expensive and time-consuming. Mm-hmm. I think Bionano Access or the software really leapfrogged, usability ahead a ton because you were able to get the sequence so or the map so quickly and then bring it up on your computer and get the results so quickly. It really kind of eliminated the need for going to the bioinformaticist and begging for them to look at your long-read sequence. Great. Well, I think. I also think. Oh, please. Sorry about that. I also think, the short-read targeted NGS, over the last decade, right, it's revolutionized genomics and cancer. You're already at this level, and next level is to kind of go to the MRD detection. The OGM will take all the cytogenetics and the other end of the thing in the famous slide up to that level to match up with it. I think that's what the kind of thing I will see in the next decade, at least that's what I predict. The wave that we saw in the last decade with the sequencing is, will now be seen with the structural variant detection. Hopefully, it will not take a decade for that to kind of translate to clinical. It'll be sooner. Exciting stuff. Well, that was great. A great way to end it. Obviously, thank you for being up here, and I think we're gonna conclude the session now. Thank you. I've been the CEO for about 12 years now, and I really love Bionano because it's an amazing place where my personality really gets to come out. When we began to develop Optical Genome Mapping, we had a dream that these solutions could be put into use in groundbreaking clinical research that would impact people's lives. What we've seen is that Optical Genome Mapping used in a variety of clinical research studies is part of identifying a variant and connecting that variant through a community to a potentially life-saving therapy as part of clinical trials and clinical research. As an individual, it's heartwarming. It makes the hair on the back of my neck stand up. The idea of transforming someone's life, elevating their health and wellness is such an incredible honor. It's something that we take very seriously. We feel very humble to have that responsibility. I'm never not blown away by the impact that we're having on a regular basis around the world. I think we have, Erik, correct me if I'm wrong, we're gonna spend you and I. About 15 minutes. 15 minutes, right? Yeah. The rest of the management team is gonna come up. Yeah. Is that right? Okay, great. Is there room for the audience or no? Yeah. At least until the end? Absolutely. Great. Absolutely. Okay. Awesome. Well. Obviously a great day, a lot of excitement, a lot of great messages. Maybe, I thought just leading in with this question so we don't lose it towards the end, we've heard a lot of exciting stuff from the company side and much more so even than from the clinical and research side about the impact that OGM is having and will have and can have. How do you think about the key messages for investors, right? Because it's a lot to take in. You got the science, the technology, and then we had some numbers, not a lot of numbers, but some numbers. What do you think the key messages are, as people are going to be thinking about, you know, tomorrow when they wake up, and they're like, you know, "What did we learn today? I think it's a great kind of idea to sum up. As we put together this whole program, I think there's been a lot of clarity that's come for us as well. What seems to be very clear is that our position within genome analysis and genomics is very well defined now, and it's really going after this industrialization upgrading of cytogenetics and fitting into that clinical translational area and providing this critical information. What impressed me so much today, but in the lead-up to today, was really understanding that it fits in cancer, genetic disease, and now in therapeutics so well, and this idea of complementing sequencing seems so incredibly powerful. So I feel very comfortable to see now that this is an area where we fit, and we can just really focus on driving very deeply into it. We have things that we have to do. We talked about some of those future things that we have to address, but with a track record of delivering so far, I think we're in a great place. Okay. Sequencing obviously gets a tremendous amount of intention amongst not only the scientists and clinicians, but certainly investors, right? I think in some way, Optical Genome Mapping has been kind of forgotten, right? I mean, really, truly, not in a bad way, just hasn't been on the radar as much. The feedback today is like couldn't be more night and day about the impact that it's having already and is going to have in the future. Very clearly, that's what's going to happen, it feels like. Just maybe give us a sense of, like, why do you think? Is it just a function of where the technology was in development, and you finally got to a point with the science? Or what is it that transpired? We heard a lot of things of why suddenly today it seems like we're at a point where things are really inflecting, and then three years ago, I think we probably wouldn't have been able to have this level of enthusiasm. No, I agree. We call ourselves transformers at Bionano. We're really focused on transforming the way the world sees the genome. When I write an email or somebody writes an email to everybody in the company, we say, "Dear Transformers," which we know is kind of nerdy, but at the same time, we really embrace this idea of driving change. We have known for a long time, those of us who've been at the company a long time, Mark, Alex, me, others who have come more recently, like, we've been very clear that this is where we're headed. You know, we've been focused on that and realizing this opportunity, and we've just been sort of clearing the path and paving the way. I think. We're not surprised that we're here. You know, I couldn't have predicted that it would be now. Right. In 2023, right? The timing has been difficult to nail. The opportunity has been clear. There's always been questions. Well, maybe short-read sequencing would overtake Optical Genome Mapping. Now we understand that fundamentally, that's not gonna happen. Well, maybe long-read sequencing, and this was a great open question, but I think what you've seen is that long-read sequencing is now leveling off in terms of its expansion and utility, and they're also focused on making it faster, making it less expensive to operate. The space for Optical Genome Mapping remains wide open. Mark and the incredible product development team have advanced the solution in such a way that folks like Ravindra and Gordana and Rashmi and Catherine and others, Adam, can adopt it and put it to work. It's been about staying focused on a particular direction, delivering in product development to meet the minimum standards that the market requires. That's why I think we're inflecting. Having been down that path, I feel very comfortable that the inflection will actually accelerate because we know the things to do. You know, we knew the things to do to get us to this point, and we did them, and now we know the things that we need to do going forward. I'm very excited about what lies in the future for Bionano, and I wanna say something about some of the companies that we've brought in over the last couple of years. Actually, when we acquired Purigen in November of last year, that was our third acquisition in three years, and these have been important moves. We first brought in a clinical testing services that was called Lineagen, and that brought us a connection directly to patients. Our feeling was that if we wanna talk about helping patients, we should be helping patients and understand that directly. We actually do that on a regular basis. We brought BioDiscovery in, and that was after a process of working with them on developing software. We recognized this is not only gonna be powerful software for Optical Genome Mapping, but people love it. Gordana said, "Why? What? I'm using this NxClinical, and I wanna use it with OGM." We recognized, well, this is gonna be powerful for us if we bring it in-house 'cause it will accelerate the development path. Now we have a product that we can sell to people. Even if they're not ready for OGM, we can provide this software and simplify their lives. We can make them Bionano subscribers. Of course, Purigen, last November with powerful front-end sample prep. I, you know, I have to say thanks to so many of these speakers, but to Ravindra, I mean, he nailed it in terms of the end-to-end workflow. It's really about, you know, people have not recognized the power and potential of Optical Genome Mapping because we've been, you know, developing and getting it to a critical level, and there's been a historic belief, well, sequencing will take care of it, and we're at that crossroads now. I think there's a recognition that sequencing doesn't deliver, and Optical Genome Mapping is really on the upswing, and I see nothing that holds it back. How do you feel about the commercial team? Like the milestone page was put up several times in terms of all the things on your plate going forward, but it feels like the market's really ripe for OGM right now. Yes, you need these, you know, more studies to come out. Obviously, you need like codes and reimbursement, all that stuff's gonna really propel the growth. Net-net, like the market seems very ripe, and there is competition and a lot of other, you know, sequencing technologies out there. One way of saying, there was a slide on there in the commercial team size, but like walk us through a little bit of like the investments that you've made to get ready for this point in your kind of commercial execution, such that you can deliver on the goals that you set forth and ideally maybe even exceed them. Yeah. I think it's a good topic to focus on because we've done the market development to create the opportunity, product development to sort of satisfy and fulfill it, and so the demand is there. We have been figuring out how to commercialize this new and novel technology, which is non-trivial. We have really been able to draft by our team in Europe, which has really come together and developed an excellent model that is really based on leading with technical salespeople who are specialists that can really get customers on board, do what we call the clinical or the technical close. Our regional business managers or sales reps will come in and drive that deal through the funnel, but that liaison on the technical side stays with the customer, and then when they adopt and bring Optical Genome Mapping on board, they get trained and everything. This individual, who's really a customer success manager, stays with them, plans their projects, gets them up and running, and supports them throughout the process that we're going in. This has been a model that's worked incredibly well, and it's novel technology. It requires a technically adroit team to execute the plan. We're now bringing that model and replicating it around the world. Not exactly, a European system is a little bit different than the American system and so on and so forth, but this idea of balancing hardcore technical sales and downstream support with outstanding experienced business managers and sales reps is a model that clearly works. We're ramping that up now, and we've hired a lot of people, and we hear about that. We've hired a lot of people over the last year, and many of them are focused on the commercial side because, as you say, the time is now. We probably have a team that's bigger than you might need for a $28 million company, and that's because we didn't put that team together for a $28 million company. It's, you know, severalfold that. If we're sitting here a year from now, I don't think you'll have another Investor Day a year from now, but if we happen to be sitting here and we're looking back over 2023, what are the three, four key milestones? You had a lot of things on a couple of pages there, so there are a lot of initiatives to propel that growth. Like what do you put towards the top of the list, in terms of what you wanna deliver? Yeah. I mean, I think, so we've been focusing on this end-to-end solution through these acquisitions and, you know, we brought those technologies in before the products were ready to commercialize. Our software is gonna come out this year. Initially, it's gonna come out for hematologic malignancies, and then there'll be a full genome analysis version that comes on in the back half of the year. These kinds of software solutions will not only be so powerful to users to simplify their workflow, but it will accelerate utilization 'cause it just makes it faster and easier to run, so getting the software released in the market. Same thing with the sample prep. The Ionic System, which relies on isotachophoresis, getting that adapted to the isolation of ultra-high molecular weight DNA for Optical Genome Mapping is key. That's coming out. We think it can come out, you know, towards the end of this year, maybe early into next year. Those are two key bookends to the workflow, and then right in the center is the, you know, high throughput Saphyr System. We've done a great job to get folks on board and excited, and all of a sudden, they're starting to exceed the throughput capabilities of a Saphyr. Now, if anybody's watching, we're happy to sell you more Saphyr. We can make as many as you need and build them out, and this is a very powerful platform that will persist in the market. For really high throughput users, we need that new system. Really it's over the course of this year, maybe into early next year, where you see, I mean, a quantum leap in the overall end-to-end workflow for Optical Genome Mapping with an integration with sequencing. It's a very powerful year for transforming the commercial product. Mm-hmm. And maybe back to the commercial strategy. Do you feel like, are there any more meaningful investments? You know, you had the slide on there showing you actually half your business is OUS. We didn't get to a question on the research panel, but there is a lot of appeal for OGM in some of the emerging markets as well. When you think about the target opportunity that you see unfolding over the next three years, where are your biggest investments going in order to capture that opportunity? I mean, we're continuing to expand commercially in a variety of geographies. Currently today, our team is, you know, in North America, direct sales, Europe, Western Europe, direct sales. We have a team that's kind of a hybrid approach in China, Mainland China. We have some direct sales and support, but we leverage partners. Around the rest of APAC, throughout the rest of Asia and Eastern Europe, we tend to leverage distribution partners, and that works well for us. From an investment standpoint, what we're doing are investing in trials. We have a big program ongoing now that Alka and her team have kicked off in India. I can tell you that it's incredibly impactful. We're processing a lot of those samples in our own CLIA lab here in, well, in San Diego. The idea is that that will allow us to recruit the key opinion leaders like we had here today, but throughout India, so that when our high throughput system with the capacity to get a really low cost consumable is ready, you know, that market is just as ripe as the U.S. and European markets are today. We're not really growing the commercial footprint per se, a little bit, you know, partners, some support staff, but it's really about developing those markets through various trials. Got it. I don't know if we're gonna, we can go to some Q&A from the audience. I don't know, will they address it to you and/or to the management team, or you'll just answer? We can bring the whole, w e can bring the whole team up, and then. Yeah. Yeah. We'll just do the Q&A as a group. That might be more efficient. Sure. All right. Probably makes sense. Yeah. I'll slide down to the end. Yeah. All right. We're gonna need all these. We're gonna need all these. Yeah. I'll stand. I don't have much here. You got it? Yeah, that's fine. All right. Wait. I thought we would just go in a line. There we go. This is really open to the audience now, huh? Yeah. I mean, I'm just gonna kick off one, like the 30%-50% CAGR growth rate that you laid out today. How much is baked into that from all these new products and initiatives that you have ongoing? It's a great growth rate. You're basically growing that rate, I think year-over-year in 2022 versus 2021. Does that assume like a big impact from the new technologies that you're looking to roll out, or is it just kinda give some parameters around that 30%-50%, if you don't mind. Yeah. Obviously, the new, the new products that are coming out layer into that, into that growth rate continuing on for the next three years. You know, this year is, for the most part, about continuing to be about Saphyr. And Saphyr will be in the market for a while. These new products are gonna continue to drive that growth and open up more markets for us. Mm-hmm. I don't know if there's questions in the audience. Thanks very much for the day. Jeffrey Cohen. I just had a question about reimbursement and some of the comments that we had previously as far as some of your channels go. Some of the coding and reimbursements coming forth, how do you expect that to drive your business, in what segment and how swiftly, and how much pull-through do you expect on that front domestically? I mean, I think the way that I'll comment on the business side, and then we'll let Alka tell you the date on which the CPT code will be issued. From an economic standpoint, what reimbursement does is it really opens adoption primarily here in the U.S. because we're seeing reimbursement in Canada. We're seeing it. It's a little spotty in Europe, but it's certainly much more common in Europe. We have just a more complicated system to work through here, coding, coverage, and so on and so forth. That process is ongoing. What it means for us sort of economically in terms of utilization, like our current users, they're running the samples that they would actually run, you know, if they had reimbursement. They're using their research funding, right? Yeah, the volume is gonna go up. It's gonna be more, you know, universally utilized. Really what reimbursement does is it gets us beyond the academic medical center. Not every place is like Augusta, is like CHLA, is like Boston Children's that has a budget that can fund the work. It's really about expanding that installed base. That's where the economic drivers come in. With reimbursement and medical guidelines, I mean, that's what leads to the, I don't wanna say complete, but you really have the shift in running Optical Genome Mapping as the lead platform and the others as an alternative that you might like to look at. The question is, what needs to happen to get there? Alka, we're dying to hear the answer to that question. I already gave the answer. I think that one of the things that probably you've heard from everybody is, and I think I alluded to it, that this path of any technology becoming standard of care and being accepted for routine use has gone through the same process, no matter what it was. The coding and reimbursement is really important, it does not dissuade any of the adopters from moving forward. If you look at Array or NGS or an ITP, for example, the time when the consensus statement came out, adoption really accelerated because all the laboratories wanted it. Because everybody wanted to be able to provide that increase in diagnostic yield for the specimens coming in, and especially if the health economics and the cost-benefit analysis is done, which is really clear, as you heard today. That's not going to stop, but it is certainly going to accelerate it further when we do get it. That's the path that we've seen all along. It's already been done, and we have seen that, and that's exactly what we are doing. I think, Kyle. Hey, it's Kyle Mikson with Canaccord. Just on the competitive landscape, there's a lot of these, like, Optical Genome Mapping companies' technologies. Can you just speak to some of those and how you kind of see this all playing out? Is this gonna take the route of, like, NGS, one major player or like Mass Spectrometry, where you have many or a few players at least? Where does Bionano, of course, factor in? Thanks again for the day. It was great. I may ask Alex, whom we call the OGM god, to amplify or follow up on what I'm saying, but I assume you're talking about technologies like Hi-C or Arima or Phase, and then in addition to that, Nabsys and so forth. There are a lot of different techniques that are out there, for sure. Anything that's sequencing-based for us falls into that sequencing category, which is that if you can run it's not going to hurt. It's only going to help. You may not need it, and the value of it may not be substantial. Those are the sort of Hi-C companies. Nabsys, as a technology, I think, is going in the direction that we are, but with, you know, pretty far behind, and a long road ahead of them. Yeah, I can certainly echo that. I mean, I think there's complementarity between most genomics platforms that are based on different methods. There's some complementarity between more similar methods, like different sequencing techniques. In terms of things that are kind of newer to the scene, like Hi-C-based techniques and Nabsys' electrical mapping, they really haven't proven themselves. We have seen some promise and hope, and I mentioned that about NGS for large structural variants. All we've seen so far is promise and hope from these newer technologies. You know, we have to see how they, you know, how they turn out, how things move forward, but they're really far behind. You know, what we're providing is an end-to-end solution today. You know, a story that I tell is when we started working with Genoptix, which, as you know, was acquired by Neo and is really running their, you know, leukemia and lymphoma samples. We started working with them in 2017, and it was our story, similar to the one that you heard today, and they liked that story. It appealed to them, and it made sense. We started running some samples, and it turned out they were really tough. Like, we failed miserably. We did not perform well in leukemias and lymphomas because that's not just like a cell line, you know? You know, we've gone through now 5.5 years of really honing the technique and dialing it in so that we can actually deal with real-life clinical samples on a routine basis and then deliver quality, unimpeachable results consistently over time. Until you've done that, you can't say that anything's gonna be useful in that environment. You know, we went through an incredible learning curve to get there. You know, anybody who's not done that, they've got to go through that, I think. Thank you. Just a question. It seems like in Canada and the EU, reimbursement's not as difficult. Just to play devil's advocate, if they're not using it in Canada and the EU, what's their excuse for that or reason for not using it? If reimbursement is clearly the big, you know, the big obstacle, the big thing to overcome in the U.S., if it wasn't for reimbursement, is there some excuse people give or? Sure. Well, you know, Adam, it didn't actually come up in his comments today, but you did say that there's a fairly significant percentage of labs in Canada that are considering OGM now based on your pioneering work. What is the percentage? Sorry. Yeah. I think pretty much everybody I talk to in Canada has either told me they have a machine, they're buying a machine, or they want a machine. When we talk about funding, the funding announcement that I discussed is two months old. I think what's happening is that it's been recognized at the regulatory level that this is a sort of the next logical step for, you know, clinical applications. It's new, but it's already recognized at the regulatory level. There's still time required for the labs themselves to actually put funding in place, do the validation studies, and implement the test. I think that there's tremendous progress in Canada based on lining up those two critical structures, right? The, you know, we would say getting the payers on board. Well, the payer's on board. Getting the medical community on board. Well, the medical community is on board. Turning to Europe, I think throughout the academic medical centers, which can typically dictate, you know, through their budget what they wanna use, where that medical community is on board, you're seeing the adoption. What I would say is that if there is a lag in Europe, it's basically getting the same alignment across the medical community and, you know, that is a little bit slower process there. The, you know, innovation and introduction of new technologies goes a little bit slower there. I would say medical community on board is progressing kind of globally at a fairly common pace. You know, reimbursement is much further along, when those two things are aligned, you'll see that further accelerated adoption. Both are in progress here in the United States. Thanks, guys, for a great day. you know, reimbursement did come in at $1,263 per test. I think that was for OGM, for constitutional genetic disease. out of curiosity, I know that was recent, but have you seen any lift from that yet? Or maybe just chatter brewing about reimbursement kind of picking up? You know, the man sitting right in front of you is the person who applied for and drove those codes through. That program is laboratory specific, so another lab can't say, "Well, I wanna use that code." It certainly allows labs to see that if I do this work, I will get that code and get that reimbursement. What we see is a tremendous uptick in the application for those codes, so the process is working. What we wanna do is simplify that by bringing a Category 1 CPT code into the mix so that, you know, there would be a generic code which is OGM specific, not laboratory specific. Yes, you've seen a tremendous uptick in the application for codes, and Ravindra still has the codes for hematologic malignancies which are coming. You know, we have brought on a fabulous leader who was at Genomic Health for many years, acquired by Exact Sciences, and she's come on board to lead market access for us. She's working with Ravindra. She's working with other, you know, labs like Ravindra's distributed around the country to drive programs with the Medicare administrative contractors in those different jurisdictions to get local coverage decisions. Like, we're attacking this at basically every level you can attack it, we're gonna be successful. Gordana? Well, speaking of attacking reimbursement at every different possible level, so you talked about medical community asking for it and pushing for it as one component of it, the other component being showing payers that they're actually going to save money by agreeing to reimburse for Optical Genetic Mapping. You mentioned briefly plans for FDA approval, which is a third component that can be like a third angle how to push, because once something's FDA approved, it usually gets paid for. If you would like to maybe add to your plans or tell a little more about your plans for FDA approval, the process. Mark, one of your best customers wants to know. Yes, certainly. I think in my presentation, I painted how we are going to go in front of the FDA in 2024 with a first assay for approval. There's a lot that happens in order to get there. I've mentioned a lot of the things are already in place, us designing all of our products through FDA design controls, manufacturing them in FDA registered facilities. That's happening. Now it's about finishing our high throughput Saphyr System and then getting the assay on it into clinical trials and getting that submission in front of the FDA in 2024. I feel like we are making really solid progress there. If you wanna know more, Hema Shroff is in the back of the room. She's leads regulatory for us. She's actually local to the New York area, so we had her come in. When Hema interviewed with me, she's interviewed with other, you know, leaders, and they talk a big game about FDA, and she thought maybe. You know, it's CEO speak from Erik. He says he wants it, but when, you know, the budget requests come down, then he's gonna back away. Hema, we're on pretty big air right now, so, you know, we're focused on this. We think it's really important because, you know, we've got you know, these thought leaders on board, academic medical centers who have the research budgets. It's almost your mandate to bring in the most capabilities as you can to address these cases. Reimbursement and guidelines will open the doors, but still, if a lab has to develop a laboratory developed test, they may not have the ability to validate and create the LDT. That's that sort of last key barrier we want them to be able to implement as straightforwardly as they possibly can. FDA clearance is the path. Just one last one for me, I promise. The PLA code price for OGM with NGS was over $6,000. Congrats, it's great to see. I know you hired Donna Polizio previously from Genomic Health, Exact Sciences. How should we think about reimbursement coming in for, say, Heme 1 eventually, right? You know, I think Genomic Health got in the high $3,000s, low $4,000 range. Is that reasonable? I think I saw a slide that you're planning to launch 100 LDTs by 2023, 2024. You've launched two. Maybe clarify that and give me a sense for. Globally. Globally? Okay. Well, I mean, so the reference there, we're not gonna launch them. Yeah. The, you know, the community. There would be 100 validated LDTs, not all based in our lab. In fact, the vast majority not. That's key, right? Because payers don't wanna support a few people's, you know, academic interests. They wanna support a mainstream solution. What's the definition of a mainstream solution? A lot of people are using it. The trouble is, of course, they need reimbursement. I cannot explain that conundrum to anybody, but anyhow, we've got to drive that adoption globally, and that's where the 100 comes from. With respect to the value of Optical Genome Mapping in hematologic malignancies, clearly it's the combination of karyotyping and FISH. It's not just, it's, you know, you can't think of it as one FISH panel and one karyotype. You've got the karyotype, you may not repeat that, but there may be successive FISH panels, right? The cost on average for these leukemia patients is non-trivial. There's a tremendous amount of savings there that can be brought to bear. That's the value-based argument that we are in the process of making, you know, to the folks that will price the PLA code. That's gonna come up later this year. Through MolDX and other agencies that would look at, you know, reimbursement of these applications. I saw a hand up. I guess we could do that. We're a few minutes past, and I think there's some- Yeah. Cocktail or. Yeah, there's something good. Do you wanna finish one more question? You had a question? Okay. Obviously really excited about the high throughput OGM system coming online this year. Just kind of curious in terms of the headroom for further technological improvement on OGM. You know, I know you are making improvements on throughput, cost, et cetera, but is there further headroom in terms of being able to detect more of these undiagnosed, right, cases, being able to provide more insights in those cases? I mean, I think the headroom or expansion on the near-ish term really goes to the sample types, right? Right now we have phenomenal solutions for blood, cell lines, bone marrow, and some tissues, but we really want to expand that menu, buccal swabs, all sorts of different sample types that have been challenging to deal with with more traditional isolation methods. We brought this isotachophoresis in. That's an area where we can really expand utility and leverage the high throughput system. You think about a lab that brings a, you know, one particular assay on with one sample type, and then all of a sudden we grow the menu of sample types by a factor of three or five or more. That's why they're gonna need the higher throughput. There are applications within Optical Genome Mapping that we're looking at, zeroing in on classes of diseases, more integrated panels, again, to simplify analysis. There are all sorts of genetic and genomic factors that we can look at in the genome that are of interest to us and have the potential to be future applications. There isn't a definitive roadmap to go there, but I would think you would see the menu of sample types expanding, followed by a variety of applications that would be layered on top of structural variation analysis. Great. Well, I don't know if you wanna wrap it up, Erik. You have a comment to make? I wanna close with this slide here, which I believe we have covered, and this is like the insurance policy. If we didn't cover it, we can make sure. I wanna thank everybody, obviously, for coming out and spending this day with us. I hope you found it for informative. Clearly, we feel like we have established our place in genome analysis, and we like where we're at. You know, this solution that we've been talking about, Kyle rightly brings up other things that are around the edges. This is the only platform capable of this type of comprehensive structural variation analysis. When we talk about the lead that we have, we're pretty far out there. I think we're gonna be alone in doing this, and our focus is really on complementing these other solutions. Publications have been off to an incredible start, thanks to many people in this room. We expect that to really continue to ramp. I mentioned it at the outset, I believe it's part of Mark's DNA to consistently deliver on the product development projects. He gets a lot of help from people. Based on that, we have a lot of confidence in what we're doing going forward. This is a global solution, as we've talked about. We're very excited to be going into a lot of applications that are pharma and therapeutics related. We do have pharma in our customer base, I think going forward, you're gonna see many more of those industrial users. You know, Alka said it, we talk about the future being bright. These are the reasons why. We're thankful to you for following along, and we hope you continue to do so. Thank you to Dan for such an incredible job leading these panels and all of our panelists, and a great job to the team. Thank you to everybody. We have some refreshments and food for those of us who. Oh, this, I forgot about this. Anybody who's going to AGBT, and I know there are a few people, this is a little bit of a teaser of the AGBT program that's coming up.