Greetings, and thanks for joining us to have a conversation with Helen Sabzevari, Chief Executive Officer, and Phil Tennant, Chief Commercial Officer of Precigen. Precigen is a biopharma company specializing in the advancement of innovative precision medicines to address difficult-to-treat diseases which have a high unmet need. Recently, the company received approval for PAPZIMEOS, which is the first and the only drug approved for treating adults with a rare and debilitating and potentially fatal disease, recurrent respiratory papillomatosis. The drug is a non-replicating adenoviral vector-based immunotherapy against HPV 6 and 11 that are believed to be the cause of the disease. FDA has granted full approval to the drug on August 15, almost two weeks ahead of the put-to-play date of August 27, and management is planning to launch the drug in the early fourth quarter of this year. To know more about the drug, the commercial strategy, and welcome Helen and Phil to this fireside chat. Good morning, Helen and Phil. Glad to see you both and appreciate you accepting our invitation to talk to our audience today. Good morning, Arjun. It's great being with you and the audience. Thank you. Helen, just for starters and for those people who are not yet aware of Precigen, what's the business plan here for the company and also how successful have you been in executing the plan to date? First of all, thank you for the opportunity. The business plan, we are an innovative, as you mentioned, biotech company that has been really focusing on bringing an innovative platform with the right indication and right regulatory strategy from the very beginning. With that as our business plan at the core of it, what we have done in the past few years is advance two platforms forward. One is our AdenoVerse platform, which is a very unique and differentiated platform, which Precigen has a full IP around. The other is our overnight CAR- T cells that are manufactured at the site of the hospitals, and it's really autologous CAR- T overnight. What we had done originally was, first of all, make sure that both platforms come to clinic and show its capability for scaling up and commercialization, which we have been very successful in showing the power of both platforms, and especially for AdenoVerse, which we moved very, very rapidly, as you are aware, even during a pandemic, starting the program, starting the IND in the middle of the pandemic in 2021, and receiving, as you mentioned, a full approval by August of 2025, which is an unprecedented speed for a drug development. It doesn't matter which organization you're part of, as big pharma or biotech, this has been an incredible journey with a lot of effort from the teams involved. Part of our business development is on really understanding the science and the platform and applying it to the right indication with the right regulatory strategy from the very beginning. This has allowed us to move very rapidly, despite all the challenges that globally all of the companies have had to face. We have been very successful, and as you are aware, quarter- after- quarter, we have delivered or exceeded our goals for that quarter, which I'm very proud of the accomplishments of Precigen. Yeah, congratulations on that. I should underscore the four-year effort which went in to bring this drug to the market and potentially should be in the market by the end of this year. Just so that people understand a little bit more, can you describe the platforms at a high level? Obviously, we'll go more into the AdenoVerse platform through PAPZIMEOS, but at least a little bit more on the CAR- T part of the platform. Absolutely. Our CAR- T part of the platform is an autologous CAR- T that basically we have initiated a very unique and differentiated platform. It's a non-viral platform that, because of that, you do not need an extensive manufacturing that is required with the viruses and also the cost that is associated. The way it works is very simply: the patients, they come, they have their apheresis done, and their own T cells are basically, we have a platform, an UltraPorator with our ultra-vectors that generate a specific autologous T cell overnight in the hospital. The next day, the patients are capable of receiving their own autologous CAR- Ts. We have done an extensive Phase I, both in hematological as well as solid tumors, and it's end of Phase IB, especially in AML, which we've reported a very significant 27% to 28% complete responses, as well as partial responses in the patient population that basically had two to three months to live. We have finished our phase IB, and we are in the process of having to go for the end of Phase IB meeting with the FDA and discussions for pivotal studies for Phase II. Fantastic. Going straight to the topic of our fireside chat today, what is RRP and how big of a patient population suffers from this indication? RRP, as you mentioned at the beginning, or recurrent respiratory papillomatosis, is a rare disease, is debilitating and devastating. The root cause of this disease is infection of HPV 6 and HPV 11. This can basically undertake of RRP can happen during childhood as children pass through the birth canal of the mothers and they get infected, so they can start having this benign tumor developed on a vocal cord or trachea as early as the age of one and continue for the rest of their life. You can basically get infected as an adult through sexual interactions, and as a result of that, be infected and develop these tumors. As you mentioned, for the past 100 years, this disease has been known, but unfortunately, did not have any FDA-approved therapy that addresses the root cause of this, which is the chronic infection of HPV 6 and HPV 11. Now, for the first time, with using our AdenoVerse platform, which is differentiated than all the other platforms in the sense of not having the much higher capacity to express a number of epitopes and genes in our gorilla adenoviral vectors that are non-replicating, but also the ability to be repeat dosing it and keep enhancing specific CD8 responses, which is at the core of the mechanism of action of this drug, which directly now targets the infected cells. They can also maintain, and by giving a re-dosing of this, you can enhance the immune responses. This is very, very important for people to understand that some of these patients, they go up to before the approval of PAPZIMEOS, the only thing that was available to them was really repeated surgeries. The studies have shown that by almost the fifth surgery, more than 76%, 80% of these patients have now irreversible damage either to their vocal cords or to their trachea. It's quite debilitating, and in some cases, as you mentioned, it can also metastasize and lead to the fatal disease. We are very excited that now PAPZIMEOS is the first and the only treatment, FDA-approved treatment for this patient population, which has set a very high clinical bar out there in regard to the treatment. Regarding the disease itself, in terms of progression of the disease, for example, you said at some point patients could go through five to seven surgeries in a year. Is this something that progresses over time, or how does that work? I'm just trying to figure out, if I find out that I'm suffering from this, should I first go straight to the medicine, or can I wait? How does that work? Yeah, no, absolutely. It's very, very important to, upon the diagnosis, really to go to the physicians. Now, with PAPZIMEOS being approved and for a broad label, which is for all adult RRP, the patients, upon really diagnosis, they can directly go to receive this drug. This is very, very important. The fact of this broad label, it allows, as you mentioned, some of our patients, actually, even in our clinical trial, they had per year 10 surgeries. Can you imagine every four to six weeks, you have to go under a surgery in order just to be able to speak or breathe at this point? Obviously, with the data that came out of Johns Hopkins, it has shown very clearly, as I mentioned, by fifth surgery, you have done irreversible damage. Clearly, neither the patients nor the physician wants this to happen, because once that damage is done, you cannot reverse it. The risks of every surgery, it keeps adding up. This is one of the reasons that physicians really do not like to do these surgeries. Now, with the approval of PAPZIMEOS for all adult RRP patients, patients can receive it at any stage of the disease that they are, if they are just diagnosed or they have had a number of surgeries, all of them can be receiving the PAPZIMEOS for free. For patients who get infected, unfortunately, through their mother during, you know, as they pass through the birth canal, as you said, though the HPV vaccines, like Cervarix and Gardasil, that have been approved, you know, for almost a decade or more now, can they help these patients out in terms of progression of the disease, or that really, those vaccines don't really, those prophylactic vaccines really don't work for this particular indication? As you mentioned, the Gardasil is a prophylactic vaccine, which means that you, like many other vaccines, you get vaccinated prior to getting infected, and the effect is really, it's effective in that setting. Once you are infected, actually, Gardasil does not have the same effect. I can tell you some of our patients that they have been diagnosed with RRP before entrance to our trials, they had received Gardasil, and it didn't have any effect. For our pediatric population, FDA has been very, very interested in, because of the safety, efficacy, and durability of response that we have shown with PAPZIMEOS, that this really be used in the pediatric population. Currently, as part of our immediate plans, is to move in that direction as well and expand the indication for the pediatric patient population. I'll just add to that. In our discussions with thought leaders, there's a general sense that it's going to take a few generations before any significant vaccination in a preventative sense would have an impact in the adult population, and that, you know, that's in the 2040s and beyond. Okay. Phil, in terms of the patient population, both in the U.S. and Europe, I know you have done some work on that. What's the number that we can think that is real, because that had been changing over the last couple of years? Yes. Yeah, I'll let Helen comment on the literature, but I'll speak to the work that we did. We think it was pretty innovative and pioneering and the most robust look at the patient numbers that's ever been done in the U.S., because there's no ICD-10 code, so you can't go into claims data and electronic health records and just pluck these patients out. What we did is we worked with a company that provided access to tens of millions of electronic health records and hundreds of millions of claims data. We were able to definitively identify patients in their electronic health records because the physician had basically typed in something like, "This patient has RRP." What we did, we built algorithms around those patients based upon the diagnostic codes and the surgical codes that they'd had and used AI algorithms to then lift and shift what those patients looked like, the definitive patients, into the broader database. That estimated 27,000 adults in the U.S. alone. If you extrapolate that, obviously, we don't have access to claims data and such ex-U.S., not in the same way. If you were to extrapolate that to ex-U.S., then you're looking at, you know, 100,000, 120,000 or more thousand patients in the top markets, ex-U.S. as well. It's still a rare disease, but it's still a significant burden on patients in the healthcare system. Okay. No, that's good. In terms of starting up, talk about commercialization. I know you were not expecting, I don't know if you were expecting the full approval, but we were not expecting it. Since you got the full approval, how do you regard the label, and were there any surprises in the label itself that you got? Helen? No, from a full approval, clearly, FDA had granted us an accelerated path, as you know, with the confirmatory trial. Throughout the interactions with the FDA, we have been updating our clinical data, which not only included safety, which was grade 1, grade 2, and nothing more than that, and no DLTs, but also a very robust efficacy, 51% complete responders, which means that they didn't require any surgery for a minimum of one year, and 86% overall responses, which patients that they reduced the number of surgeries. As you know, we had a very, very robust endpoint. We didn't go just for a reduction in the number of surgeries, but really to eliminate the surgeries at least for one year. With the durability of a response, which the minimum has been 24 months, and we have patients that they have passed three years, and we will be reporting on those fairly soon in meetings and publications, that was also updated. As a result of that, this was something that the FDA, based on a very robust prospective, statistically significant data, powered pivotal phase I, phase II, and durability plus the efficacy plus the basically safety, FDA, I think, took into consideration all of that for the patients with this disability disease. Instead of having accelerated with confirmatory trial, they gave a full approval, which now has set the PAPZIMEOS as really a standard of care for RRP adult patients. With that, I hand it back to Phil. I would just say, Arjun, I think the broad label just speaks to the illogical nature of trying to treat a chronic infection with risky surgeries. I think through the great work my colleagues did, we were able to work with the FDA to pull through that logic and secure a broad label, which obviously from a commercial perspective is great news. Yeah. Helen, you just were speaking a little bit earlier regarding the severity of the disease, how severe it can get, and in terms of getting to the fifth surgery and almost getting into a very bad situation by then. In your clinical trial, I'm sure we'll get all these details later in the years. In general, can you talk to the patient population itself and the mix of the patient population that were in the trial? Were there any patients where they had to be debulked a little bit before vaccination, I mean, before giving the PAPZIMEOS? Or is it irrespective of how severe the disease is when they come in, they can be given PAPZIMEOS? The way that our trial, pivotal phase I and phase II, was designed is basically the severe patient population, they will come in, and usually this patient population is very simple. They go to their doctors when they cannot speak or they cannot breathe. The reason for that is that these benign tumors have grown on a vocal cord or trachea, and as a result, there is this stress on the patient. The first thing is what these benign tumors, if they were obstructing a vocal cord or trachea, the physicians, they removed it, and then they started the treatment, which is considered a four in subcutaneous injection. It's very easy to administer for a subcutaneous injection over a three-month period. The patients were followed for a minimum of one year. Of course, all of our patients have been followed for much longer than that, but the endpoint was no requirement of surgery for a minimum of one year. That's the way the trial was designed. Yeah, it doesn't matter at what stage of the disease progression they are in, they can be taken in and be given the treatment without additional surgery. Yes. I think what has become important, as we were talking about the broad label, is that now patients that are just diagnosed with the disease can go in and get treated with PAPZIMEOS, or patients that have had the disease for many years can go in and get it. The severity of the disease is not the issue. It's as soon as the patient is diagnosed or requires, then they can go in and receive the treatment. A follow-up to that question is, let's say a patient goes in, gets a surgery done, can that patient be dosed with PAPZIMEOS immediately after the surgery so that they don't have the next surgery? Absolutely. That is the whole plan, that the moment that they are diagnosed, or if they have had already the disease for many years, but then they have required to go in, they go in, and then they can receive the PAPZIMEOS immediately. Okay. All right. Those are good. Phil, when you were looking into the patient numbers, you and your team, I know that you had looked into the claims as well. Were there any of these patients where they were in a situation, once we start taking into this new adjuvant settings and other patients, will that patient number start to grow, or does it not matter because all of them were taken into account in the numbers that you have? Yeah, the 27,000 that I mentioned was based upon the combination of diagnostic and surgical codes that we looked at around these patients. That patient population is fixed, as it were, but we have seen a phenomenon in other rare disease launches where there have been no treatments available or approved treatments, and then you have one or maybe two come to the market in quick succession. You do see an increase in diagnosed prevalence. We do expect there to be an increase in diagnosed prevalence over and above the numbers that we've quoted. Okay. No, that's good. Helen, as you were going into this pituitary date, you had an ongoing phase III study as well. What's happening with those patients? A part of that trial was also to include re-dosing phase. How will that be taken care of as you launch the drug? As you mentioned, as part of the accelerated path, originally, there is a requirement to start a confirmatory trial, which, by the way, it was a single arm as well by FDA. We had already initiated that prior to submission of our BLA. Now, with the full approval of PAPZIMEOS, obviously, there is no further requirement for the confirmatory trial. That trial has gone on hold. Of course, the number of the patients that they had already sort of applied through that, we will, as we always have said, that we will leave no patient behind, and they will be included in other upcoming trials. In regard to one of them is the. It felt significant that this is extremely significant for this rare disease where basically there are no approved treatment options. We looked at the patient population. We talked about the work we did for those to identify those 27,000 patients. We've seen that they are overwhelmingly concentrated in the hospital systems, these IDNs, academic institutions, community hospitals. That's where they are currently being treated. Initially, of course, a lot of our activity is there educating physicians that now, at long last, there is a treatment that addresses the underlying cause of the disease. As we've gotten closer to launch, we've been able to deploy some of our field teams. Our MSLs have been out in field for a few months, establishing relationships with thought leaders at the national and subnational level. We've had our payer specialists out there talking to payers and starting to get them to think about bringing PAPZIMEOS into their workflows. Similarly, we've had our sales leadership in place, and they've been able to talk to population health decision makers at the IDNs again about bringing PAPZIMEOS into their workflow. Now, with the approval, we're able to activate the full sales team across the 18 territories that we've identified that cover over 90% of the identified patient potential. They're being activated as we speak, primarily supporting the IDNs and the patients to bring them together to make sure that we deliver access as quickly as possible. I would also say something about our distribution route. We've built in full flexibility there. If you are an IDN or an institution, a hospital, you can purchase either through buy and bill or through specialty pharmacy. It really is about whatever their preference and their need is. We continue to work with patient advocacy groups, in particular the foundation, with Kim McLellan, and maybe Helen can talk a little bit more about some of the work that we've done there. As Phil mentioned, we have been in very close interaction with the patient advocacy group from the very beginning. This goes back to really our mentality, and today, in conjunction with the RRP Foundation, which has been bringing all the patients, the voice of the patient, as well as the physicians to the table and making sure that the patient receives the treatment that addresses the underlying cause of this, which is now PAPZIMEOS, and really also physicians that they are very, very dedicated to ensure that surgeries are not used because they know that is not a treatment for this disease. Really now, PAPZIMEOS as a standard of care can be used. Phil, when you said you have identified 18 territories, I have two questions. One, what is the payer, you know, private versus payer mix, you know, whether it's private or through the Medicare and Medicaid services? What's the mix there? Also, among those 18 territories, should we assume this is going to be a full blast across the 18 territories, or is it going to be in waves where you have a high concentration in the areas first and then move down the pike? To your first question, we looked at a payer of last record in the database, the claims database that we looked at, and it shows that we expect 60%- 65% to be commercial, 30%- 35% would be Medicare, and the rest would be Medicaid and others. We're working within that framework. In terms of waves, no waves, the 18 territories and the 18 key account managers that we're activating cover 90% of the potential that we've identified. Usually, when you bring a sales team on, you aim for 80% or more. We're actually north of that, and we've identified more than 90% of the procedures and the patients are covered by that footprint. No, it's not in waves. We are providing full support from the get-go to this pent-up demand that we know is waiting at these institutions. Okay. Talking about pent-up demand, right? I had the fortune of watching Gardasil, and you know, those drugs get launched and when they got launched, there was a big, huge influx of drug initially and adoption, and then slowly kind of weaned out. Of course, there are vaccines, and you expect that to happen. In this situation, how should we think about this? Because again, this can be curative, right? As you said, the clinical data showed 51% of them did not have to go back for surgeries or for additional therapy. How should we think about the initial demand? Yeah, adoption. Yeah. We're very excited about that. As we know, for rare disease launches, there is a bit of a dance that the payers, the providers, and the patients have to go through initially, which takes a few weeks before the patient is ready to secure access. We're providing all the support necessary for that process to accelerate that where we can. In particular, we're providing patient support through our hub services. That includes financial assistance where appropriate. Basically, our goal is to ensure that all eligible patients get access. That's what we're doing, and that's how we're activating the market. It does take a few weeks for that all to come through, but we're ready. We have the drug, we're manufacturing enough to cater for that, and we're ready to go. Arjun, maybe I can also add from a perspective of the patient population, clearly 51% of the patients did not require any surgery for a minimum of one year, and they continue to be in basically response for a minimum of 24 months and now going to three years and beyond as we follow them. At the same token, we have the ability of what we refer to as partial responders, as I mentioned, to add for re-dosing. I think that's going to be very, very important from that perspective of the expansion of the indication as Phil and the team. Coming to the reimbursement, I know Phil, you're working on trying to get a JCOD in. How does reimbursement work as of today, and what's the, what should we expect, the progress in terms of getting appropriate reimbursement? No, as I said, it can take a few weeks for this process to work its way through at the institutional level to bring the patient and the payer together. We're supporting that process. It can take three, four weeks or so at the institutional level. You mentioned JCOD, we're in the next wave of applications, which is October 1, and we expect that to be six to nine months before we get the permanent JCOD. In the meantime, that doesn't stop physicians prescribing the medication because there are miscellaneous JCODs that can be used and should be used and will be used to support individual patient access in the interim period. Very good. Talking about the rest of the pipeline outside of PAPZIMEOS, I know you're really focused on this drug for almost 12months- 18 months now. Now that you kind of crossed that, what do you expect needs to get done so that you can start thinking about the rest of the pipeline and, of the different places that you could go, which drugs would you actually start working on if funding was not a question? Absolutely. No, as you mentioned, we focused for the past year, year and a half on PAPZIMEOS, and now that's across the finish line. Obviously, it has transformed the company to go from an R&D company to a commercial company with the future revenues, which is quite exciting, and it will add tremendously for the portfolio and expansion of our portfolio. Clearly, one of the first things that we are focused on is the expansion of the indications, for instance, to genital warts in the HPV-related, basically, field. That, as you're aware, it's quite a large indication, which is with a similar sort of infection indication. Also, focusing, obviously, expansion of indication in a pediatric setting. We are clearly expanding the global for getting approval in ex-U.S. and also our PRGN-2009, which is built on the exact same platform of our AdenoVerse, the platform that PAPZIMEOS is on, and the same group of viral vectors. It's in HPV 16/18-related cancers, such as all head and neck and anal cancer, which made up 5% of total cancers around the world. You can imagine the number of the patients. In our original ASCO data that we showed in our PRGN-2009 had a significant response with a very, very favorable safety profile in basically checkpoint inhibitor patients that they had relapsed and showed 30% basically objective responses, including complete response and partial responses, going up to two years of complete response based on the activity. That's also in our portfolio. As I have mentioned in regard to our Ultra CAR-T, that is a program that we obviously go through the end of phase IB meeting with the FDA. We are looking for a partnership that basically can provide the resources for the CAR-T. Phil, if I can go back for one more question on PAPZIMEOS. When either hospitals or physicians order for the drug, two questions, actually. One, in terms of ordering, does an order include all of the four subcutaneous injections? Two, once started, is it like antibiotics? Once I start, do I have to complete the course, or can I stop once I get through two of them and I feel good that I don't need to go through it? Good question. The prescription and the coverage for the patient will be for all four doses. That's what our clinical trial clearly showed that had the benefit, the excellent benefit that we've seen. The institutions can order the vials one at a time. We don't expect there to be inventory built up. They can order just in time as necessary for each and every patient. Perfect. Coming to the end of this, what are the catalysts that investors should be looking out for, say, over the next 6months- 12 months, Helen? From what I mentioned, clearly, our commercial sort of launch has been already funded, as well as our manufacturing. Precigen is manufacturing PAPZIMEOS at site. We have our cGMP manufacturing, which is quite, have been producing the commercial material and continue to do so, and providing all the doses that are necessary across the U.S. and ex-U.S. That's quite exciting as we have changed the paradigm with now setting up a standard of care PAPZIMEOS in the site. From the perspective of all of our CapEx that have been paid as well with our manufacturing, currently, as we have communicated, we have a good runway to basically revenue and generation of revenue next year. We are not planning to do any dilutive raises. We have a number of inbound options in front of us in regard to non-dilutive manners, which we will take into consideration what is the best options, and this will be communicated. Currently, I think we are really excited about our commercial launch and, as a result, transforming Precigen from an R&D biotech company to a commercial biopharma that, with a very strong portfolio, can benefit from the platform of AdenoVerse, expand the indications, and basically similarly move for our patients in unmet needs in a very agile format, as we have shown to do with PAPZIMEOS, and expand basically and bring the needs of the patients center and front. As a final question, in terms of your financial position and the strength of the balance sheet, what's your current cash position and what sort of a runway do they expect from it, not considering what the revenues that they'll be making? Yeah, as we have communicated already in the last quarter, we had $59 million at the cash runway. As I mentioned, we clearly have already, and that's funded our commercial launch as well as our manufacturing. This clearly will advance us to the revenues. As I mentioned, there are a number of inbound non-dilutive requests to us, which we will be considering and look at the options that are in front of us. We are not doing any kind of a dilutive equity dilutive prices. Thank you. Thank you very much. Good luck with the launch, and I'm sure we'll be talking soon. Thank you very much. Thank you, Arjun. Thank you.