Morning, and thank you for joining us today for Explorer Series One, the NGM Bio Discovery Engine. My name is Brian Schoelkopf, Head of Investor Relations at NGM. We will be making forward-looking statements during today's presentations, including statements about anticipated timing of events, the potential benefits of our product candidates. We refer you to our most recent Form 10-K, which identifies factors that could cause actual results to differ materially from today's forward-looking statements. I encourage you to read the full language on this slide and all the slides that will be presented today. They will be posted on the Investors and Media section of our website. With that, I'm happy to introduce David Woodhouse, Ph.D. and Chief Executive Officer at NGM Bio. David? Thank you, Brian. I'm pleased to welcome you to the first installment of our Explorer Series today. As many of you know, we have plenty going on at NGM Bio with seven named programs, four of which are in Phase II trials and a highly productive discovery engine. There's a lot to dig into across our product candidates and the scientific rationale that inspired them. In December 2020, we hosted our first comprehensive R&D day, which gave a deeper look at our expanding pipeline and our novel approach to drug discovery. Since then, we've continued to make significant progress advancing our broad portfolio. This year, rather than host another multi-hour R&D event, we decided to host a series of more condensed modules, each focused on specific programs and topics to help you get to know our company, our expansive pipeline, and our discovery engine. There is a unifying theme across them all at NGM Bio. We pride ourselves on being explorers on the frontier of life-changing science. We are driven by a purpose to make lasting scientific contributions that improve human life. As you'll hear today, since our very inception, we have explored multiple frontiers of biology to yield new discoveries that could lead to the development of important new medicines. Let's take a look at the roadmap of where we plan to take you over the next few months. In today's session, we'll focus on the foundation of NGM Bio, our discovery engine. You'll hear from our founder and Chief Scientific Officer, Jin-long Chen, followed by a fireside chat with leaders of our scientific team. We'll wrap up today disclosing an exciting new oncology program. In session two, we'll focus on two of our myeloid reprogramming and stromal checkpoint programs, NGM831 and NGM438. In session three, we'll focus on our third myeloid reprogramming and checkpoint inhibition program called NGM707. Finally, in session four, we'll cover NGM621, our anti-complement C3 antibody we think could be a category leading treatment for geographic atrophy. Now, a bit more about today's session on our drug discovery engine. We often refer to our portfolio as an iceberg. While we have many programs visible in our pipeline today, what you can't really see is the massive substance below the waterline, so to speak. To that end, what we aim to provide today is an opportunity to dive below that waterline and explore the part of the company that we believe gives our competitive edge in developing new medicines. High-quality science executed by an extremely talented team and advance with unrelenting rigor and urgency into and through clinical development. As part of today's deep dive, you'll meet members of our talented drug discovery team to describe firsthand how they work together to turn scientific insights into new product candidates. We will also be sharing with you a brand-new program never disclosed before that showcases our integrated target discovery and protein engineering capabilities and exemplifies our ongoing productivity. Before I turn it over to Jin-Long and the rest of the team, let's take a moment to put our drug discovery expertise in the context of our overall business model. Our world-class drug discovery engine established the core of our business when NGM Bio was founded. It remains central to the company today. We have the benefit of many of the top scientific minds in the world advising the company. If you look at our track record over the last decade, we have been a go-to source of external innovation for big pharma. Our ability to repeatedly produce new types of tailored molecules continues to be our most important competitive and strategic advantage. Our strategy is to leverage the steady stream of innovation generated by our drug discovery engine to build a self-sustaining biologics powerhouse fueled by multiple approved products. We often point to companies like Regeneron and Seagen as blueprints for the type of company we are aiming to build. Now, achieving this ambitious goal requires thoughtful, active management of the drug discovery engine output. In fact, one of our key areas of focus is portfolio management and our commitment to making data-driven decisions at each stage of a program's progress. We view this ability to manage the prolific production of our discovery engine as a cornerstone of our corporate strategy, guided by several core philosophies. First, we set an extremely high bar for our product candidates. If a program reaches candidate nomination, it has distinguished itself as a truly promising molecule. In other words, our freezers are full of very interesting and promising candidates that simply don't survive the internal competition for the next development slot. Second, to allow us to cover more breadth from a therapeutic area point of view, we are calculated about our clinical development strategy and where we build expertise. Our focus is on showing early proof of concept in the clinic and then identifying one of two paths for a program, either further development in-house or further development in a collaboration with a partner that allows us to leverage their late-stage development and commercial expertise. Looking at our current pipeline, we're proceeding on our own with our wholly owned oncology portfolio, for which we have the ability to demonstrate proof of concept early in clinical development and then advance programs relatively rapidly. In contrast, our retinal and NASH portfolio either already have late-stage partners, or we plan to establish a partnership once proof of concept data is established. Establishing these two segments of our strategic intent for our pipeline was the primary motivation for us last year when we renegotiated our collaboration with Merck. It helps define two different paths our newly nominated molecules can take through development. Finally, we intentionally pursue a broader portfolio than we expect to take forward on our own. Drug development, of course, is not an easy business, and we like to increase our chances of bringing molecules to market and strategically using partners to subsidize the cost and mitigate risk. To date, approximately half of our funding has come from business development. That's more than $500 million. When we do partner, we retain meaningful back-end economics so that when one of these programs does reach the market, it's capable of providing cash flow back to NGM Bio to enable our long-term self-sustainability goal. Merck continues to be a great partner for NGM, and after revising our collaboration last year to narrow the focus, we once again are open for business in BD for certain of our clinical and preclinical assets. We are at a very exciting time in the journey along this strategic path with multiple programs approaching clinical data readouts that will serve as proof of concept and we believe will validate the power of our approach to portfolio management. Let's now take a look at our pipeline programs. Our most convincing proof of productivity of our approach is our current pipeline. The quantity and diversity of programs in our pipeline, the breadth of diseases targeted, and our anticipated upcoming milestones speak to the robustness and sheer output of our discovery engine. 2022 will be an inflection year for NGM Bio in demonstrating the effectiveness of this strategy. We anticipate three clinical readouts, including a top-line readout from our Phase II CATALINA trial for NGM621, as well as new data from some of our oncology programs, including the very first set from our myeloid checkpoint portfolio. All three of our myeloid checkpoint inhibitor programs should be in the clinic this year, bringing our total number of clinical-stage programs to seven. As I mentioned, the programs you see here are just the tip of the iceberg. Our research labs are continually generating new product candidates at a pace of about one new IND per year, with multiple programs vying for that next candidate nomination spot. Now, many of us, myself included, were drawn to NGM Bio because of Dr. Jin-Long Chen. It's probably most appropriate to describe him as a quintessential drug hunter, pairing scientific ingenuity with a quiet humility informed by decades of experience. I've had the privilege over the last seven years of watching him in action, and some of my favorite moments have been seeing the spark in his eyes when he sees the dots connecting for a program that shows we have harnessed some powerful human biology that's beginning to look like a drug. Jin-Long is, of course, the founder and architect of our discovery engine. Moreover, he has an incredible ability to identify, recruit, and mentor truly visionary scientists. I'm delighted you'll have the opportunity to hear from Jin-Long, as well as some of these remarkable scientists today. With that, I'll turn the session over to Dr. Jin-Long Chen. Thank you, David. When we started NGM, I wanted to create a place where the drug discovery research could thrive, and we could repeatedly create new medicines to help patients fight serious diseases. That's exactly what we have been doing. Each single drug candidate you hear about is a result of the work we've done right here in our labs at NGM. With that in mind, let's talk about how we make our discovery engine tick. Importantly, we marry two essential elements, drug discovery, biology, and versatile technology. We always start with the biology. Disease biology is pretty complex. Lots of gaps in our understanding. As experimental biologists, we use a systematic unbiased approach to connect the dots. The more ways we can look at the problem, the better chance we can narrow our focus on the important, powerful biology. Over the years, we have used a variety of approaches, the cogs in our engine, so to speak. To name just a few, unbiased in vivo screening, human genetics, ligand-receptor deorphanization, study of specialized cell types, and this versatility does give us a competitive edge. We're familiar with all different modalities in our industry. For example, small molecules or gene therapy. But for now, biologics best suits our purpose. The engineered proteins, antibodies form the cornerstone of NGM's drug discovery. We apply the best technologies to get the stuff done, whatever it takes. We're constantly sharpening our tools and adding the new ones, like multifunctional proteins and conjugated antibodies to our toolbox. Today, instead of just describing the concept, I'm going to use our current pipeline to illustrate how our biologists and engineers work together to apply our drug discovery approach. First example, in the early 2000s, gastric bypass surgery had emerged as a way to cure patients' metabolic disease. The first big scientific questions we ask was: What factors are responsible for this such remarkable response? Using an unbiased in vivo AAV screening, we identify a gut factor, FGF19, and then elegantly engineer a recombinant form, which became aldafermin, by systematically dialing the activity in and out to optimize the suitability profile. Although most of the scientists approach FGF pathway by engineered FGF protein like FGF21, we are convinced that antibodies offer significant benefits and advantages if we could find right one. For MK-3655, we screen thousands to identify a unique modulating antibody. Only activate FGFR1C but not other receptors, showing the desired profile. This is not a typical antibody, and finding such a needle in a haystack took real skill. We have also successfully applied in vivo screening beyond FGF pathway. Among the hundreds of factors we evaluate in this unbiased screening, GDF15 stood out as a powerful regulator of metabolic and immune functions. Since relatively little was known about the biology of the GDF15 pathway, we are not afraid to commit a three-year effort to identify the matching receptor, GFRAL. The discovery of this novel receptor opened up the new insights, including the surprise, at least to me. The receptor could only be found in a tiny cluster of the neurons in the hindbrain. Our engineers generate a potent antagonist antibody, which effectively block the pathway. NGM120 is currently being studied in cancer patients. It turned out that we can use the same approach to connect entirely different sets of dots. On the surface, I understand that cancer and metabolic disease may seem to be very different sciences. About seven years ago, we started wondering about factors that were responsible for preventing antitumor immunities, unfortunately limiting immunotherapies like those blocking PD-1. In contrast to mainstream approach focusing on finding another T-cell checkpoints, our scientists, in contrast, concentrate on the bigger scientific question, the role of the different types of the immune cells in the tumor microenvironment play in regulating the immune response. Our scientists focus our attention on the myeloid cells. From a systematic study of these myeloid cells, we identify a family of the inhibitory receptors, namely ILT2, ILT3, ILT4, and LAIR-1. It seems like promising candidates for a novel class of the myeloid checkpoints that we could target. For NGM707, ILT2 and ILT4 are closely related receptors. They're derived from the same ancestor genes. In fact, monkeys only have one single gene and recognize the same ligands. It makes sense to target both receptors to achieve the optimal therapeutic effect. Our engineers design a unique antibody, NGM707, to do exactly that. Although we are not the only ones who wanted to target both receptors, so far there's only few mono-specific anti-ILT4 antibodies, including ours. NGM is the only company with dual antagonists in the clinics. In the case of NGM831 and NGM438, LAIR1 has been shown to interact with collagen. In the case of ILT3, the matching ligand was less clear. Just like our earlier work with GDF15, we tried to find the functional ILT3 ligand, which, interestingly, turned out to be fibronectin. Just like collagen, another component of the extracellular matrix. This finding, we connect a very important dot. Of course, in the big picture became a lot more clear. Components of the ECM appear to act like stromal checkpoints. That is interactions between these receptors and the ECM inhibit antitumor immunity. Based on these findings, we're in a unique position to select therapeutic antibodies, NGM831 and NGM438. They can block both the signals and help the patient to conquer the immune response. Finally, I'm a huge fan of human genetics, and I want to highlight at least one example of how we use this approach to address another important biological question. The identification of factors play a role in GA. A form of the dry AMD, if you will. The disease, unfortunately for which there's no current treatment. A careful review of the genetic data for the risk factors teaches us two lessons. First, complement C3 plays an important role in AMD. Blocking both the alternative and classic pathways of complement activation could be better than just blocking alternative pathway. Antibodies are arguably an ideal modality for the eye. In NGM621, our scientists have engineered a truly impressive antibody for treating GA. It potently and effectively inhibits both pathways. Good residence times in eye without the need for physicochemical modifications like PEGylation. Also importantly, it can be formulated with a viscosity suitable for dosing in the eye. Although this is the first genetics project we have disclosed, it won't be the last. We are continually hunting for important new drugs for patients using human genetics approach. Since the company's inception, we have been driven by a single mission to translate complex, powerful biology into life-changing medicines. we have tried to do today is using our current pipeline to provide you with evidence that we have built the drug discovery capabilities, which will allow us repeatedly, again and again, to uncover important pathways involving human disease and design important medicines to help patients. As David mentioned, what you see right now just scratches the surface of what we can do. For the next part of today's session, I'm pleased to introduce you to the team of our scientists who actually work with me every day. They will share with you their own insights on how our approach to deliver new medicines to patients. Josh Lichtman, our new Head of Biology. Kathy Miller, Head of Biologics. If you will, our engineer. Alex DePaoli, our Head of Translational, a physician scientist. He is the bridge between research and development. Alex, please take it away. Thanks, Jin-Long. It's always exciting to reflect on the programs we've developed based on our rigorous biology-first approach. What I'd like to do now is provide some insights into our approach to identifying and prioritizing powerful pathways to couple with innovative biologics to create the next transformational medicines for patients by speaking with the talented scientific leaders focused on keeping our pipeline rich. By way of introduction, my name is Alex DePaoli, and I lead our translational group at NGM with a focus on seamlessly bridging our R&D efforts. My group and I strive to bring a true bench-to-bedside translational approach to our patient-focused research. As a practicing clinician with training in molecular and clinical endocrinology, coupled with my tenure in industry, I've developed a deep insight into the complexity and opportunity of therapeutic candidate development journey. Now, I'd like my colleagues to introduce themselves, and then we'll discuss NGM's approach to identifying and creating important medicines. Josh. Thanks, Alex. I'm Josh Lichtman. I've been a scientist at NGM for seven years. I actually started here as an intern after my Ph.D at Stanford. I've had the opportunity to work with a lot of groups in the biology department. Now I get the luxury of working with our biology team to help lead our the next generation of our new discovery. The biology group, we really focus on that kind of wow biology. That is the powerful signals and pathways that can lead to potential therapeutic applications. Along that line, we get to work with Kathy and the protein science team, biologics team to develop those drugs and make some nice clinical candidates that we can take into the clinic. Thanks, Josh. I'm Kathy Miller, and I head the Biologics group. I've worked for many years at both large and small companies, and I have worked in different disease areas and have experience on biologic approaches and technologies. The scientists in the Biologics groups have very technology-focused expertise and experience in making biologics as therapeutics. We do this in part because of a close collaboration with research, and this enables us to engineer our biologic formats to suit the therapeutic approach. I think what resonates with me is what you guys said with respect to the fluidity of working together. I think there's a real connection between these groups and others, which creates part of the efficiency and effectiveness of the organization. I wanna go through a few questions to kind of bring out the unique aspects of NGM, and the first one is, what is unique about conducting research at NGM? Yeah, Alex, you know, I think it starts with the fact that we're really bold. That kind of manifests itself in a few different ways, right? The first is that we're not scared to follow biology that we don't fully understand. If we identify those kind of powerful signals, we're willing to push those forward and do the hands-on research necessary to find the clinical applications. The second one is that we're willing to follow biology that's not all completely clear at the beginning, right? If there is a gap, we're willing to use our intuition and our experience to pursue that biology to try to find a therapeutic hypothesis and potential. I think we also have a strong commitment to collaboration and transparency. I mean, we do not do silos here at NGM. In fact, all of our research programs have co-leaders, one from biology and one from the biologics group. This is key in helping us maximize our efficiency by really merging the fresh biology perspectives with the expertise in therapeutics. We also have a similar type of transparency by engaging the CMC group much earlier in our programs in research at NGM. This enables us to have a smooth transition into development. It really comes back to the talent that we have. We have an amazing group of scientists here, and we give them a lot of freedom to explore both the biology and the potential drug modalities. It's really a bottom-up approach we use to generate ideas and to push our programs forward. That gives our scientists a lot of freedom. I'll give you one example. The ILT3 program, when I was a junior scientist here, just less than two years I'd been here, I had the opportunity of kind of kick-starting that program, and now I've been able to see it all the way through the drug discovery process and now going to the clinic. It's a very kind of empowering opportunity for our scientists. It's extraordinarily exciting program. What about the organization is able to enable the work that is done within NGM? What's unique about the organization of NGM? Well, I think that as an organization, the dedication of NGM towards research is truly unique. I think a lot of companies of our size and with our pipeline would shift away from research and put resources into development, but that's just not who we are. We want to be a company that basically a self-sustaining biotech, similar to companies like Seagen and Regeneron. At NGM, we believe that research is truly a driver in this success. Yeah. I think to add to that, Kathy, we're really rigorous. We have a lot of projects and programs that we're working on at any given time, and we have this ability to constantly prioritize and evaluate those programs to identify the few that really have a great potential to make impact in the clinic. It kind of feels like we're very much a startup. We have that kind of fluid exchange of ideas. We're very innovative, and I think that is a really unique part of an organization like NGM. I can't agree with you more. I think the commitment to research, Kathy, that you alluded to is something that we really initiated at the very start of the company, and it's something that we haven't lost the momentum of, and it's really great to see that. That's what's going to continue to foster our pipeline and our opportunity. How do we define the focus of our scientists, of our efforts? I mean, this is an important aspect of prioritization that inevitably must occur. How do we do that? Absolutely. It always comes back to this kind of idea of powerful biology, right? Not just identifying that powerful biology, but really pursuing that wherever it takes us. I think a great example of this is the NGM831 program, right? ILT3 was identified as an important inhibitory receptor on myeloid cells. We had a team who was kind of fully dedicated to identifying the ligand for this receptor. In parallel, we had a team studying liver fibrosis in NASH, and the only way that we were able to identify fibronectin as the ligand for ILT3 was because of the collaborative environment we have at NGM, these teams working together to make that discovery. We had the insight to connect the dots, and between ILT3 as an inhibitory receptor and fibronectin in the stroma, we really identified this kind of stromal checkpoint as an exciting opportunity for us to look for in the clinic. You know, Josh, we didn't just stop there, although we could have, but we kept an eye open for opportunistic applications for our target. You'll be hearing from Julie and Dan later that ILT3 is being explored as a bispecific T-cell engager in cancer. W e are always ready to pivot to new areas if there's opportunity, and essentially there's no challenge that's too big for us to tackle as long as we believe in the biology and the science. I can say this is. It's always been exciting to find that new biology. One of the things that we are faced with is prioritizing these wow biologies or these powerful biologies to identify a drug candidate. How do we recognize as a company, as a group, when there's a drug? Because ideas are plentiful, but when is there really an opportunity to develop a therapeutic? Yeah. It starts with the kind of evaluation of the idea and the biology. What we're constantly doing is asking, "Is there a therapeutic hypothesis for a particular target and a particular disease?" This does require that kind of constant prioritization, right? NGM621 is a perfect example of this. complement C3 is a very kind of well-known human genetics target in AMD, and we identified that human biology and were able to start a drug discovery program that is now looking like it's gonna be very helpful for patients in that disease area. Another one of our programs that my group in biologics is quite proud of is NGM707, and this is a molecule that's a dual specificity antibody. It literally binds two different targets with bivalent binding to ILT2 and ILT4. Not only is that a very unique quality for an antibody therapeutic, but also it's the fact that what makes it unique is the fact that we chose to go for this molecule. We collectively decided to, you know, let's just be bold and go for it. After a lot of rigorous effort by the antibody discovery and engineering group, we now have NGM707, which by the way, is a very cool molecule. Absolutely, very cool molecule and in the clinic and hopefully going to provide benefit to patients soon. Well, thanks very much. I'd like to add that in parallel with these discovery efforts, the translational process is iteratively working to rigorously address the practical aspects of developing an innovative therapeutic, including the disease application, understanding the competitive landscape our therapeutic candidate will be utilized within, identifying clinical development feasibility, and a regulatory path to approval. This integrated process allows the identification of the best candidates for NGM to focus on. I hope this discussion has provided some insight into how NGM is able to develop and maintain such a broad and deep pipeline. I'd like to thank Kathy and Josh and all our team for their important work as part of the collaborative and highly productive discovery engine. Now I'd like to introduce Dan Kaplan. Thank you, Alex. Hello, I'm Dan Kaplan, Head of Translational Immune Oncology at NGM, and today it's my great privilege to unveil NGM936, a first-in-class bispecific T-cell engager antibody for treatment of hematologic malignancies. NGM936 is NGM's first disclosed preclinical bispecific antibody program. This program brings to life the three core characteristics of the NGM discovery engine, which has generated numerous first-in-class candidates in oncology. Powerful, novel biology underpinning diseases such as cancer, using fit-to-purpose technology, in this case bispecific antibody engineering, and then using these approaches in order to develop medicines that have the potential to address significant unmet need and transform outcomes for patients. NGM936 is shown here in the middle between the T-cell and the AML cell. NGM936 is a potential first-in-class bispecific T-cell engager targeting ILT3 and CD3. NGM936 binds to cancer cells via its ILT3 binding arm, shown here in pink, and recruits T-cells via its anti-CD3 scFv arm, shown in yellow. Through this process, NGM936 directs T-cells to kill cancer cells while sparing healthy immune cells. Seven years ago, while most of the immune oncology field was focused on T-cell biology, NGM instead focused on the more poorly understood field of myeloid cells. We began investigating the role that suppressive myeloid cells play in the tumor microenvironment and how these cells can enable cancers to evade immune detection. We focused our efforts on a family of inhibitory receptors that are enriched in suppressive myeloid cells. These receptors are encoded in the LIR locus on human chromosome 19, which is shown here. Now, if we fast-forward to the present, we've developed humanized therapeutic antibodies targeting these LIR family receptors that we're pursuing for the treatment of solid tumors. NGM707, shown here in gold, is an antibody targeting ILT2 and ILT4. NGM438, shown in red, is an antibody targeting LAIR-1. NGM831, shown in blue, is an antibody targeting ILT3. We'll discuss these programs in depth at upcoming Explorer Series events, but today I wanna instead talk about ILT3 as a target for blood cancers. Among circulating blood cells, ILT3 is highly expressed but restricted to monocytic cells. This expression is enriched in acute myeloid leukemia, or AML cells, as compared to healthy monocytes, which makes ILT3 a potentially promising target for the treatment of blood cancers. Additionally, the expression of ILT3 is stable or even upregulated in patients who've relapsed on or been refractory to prior treatments for AML. Sadly, existing therapies are unable to provide lasting benefit for the majority of AML patients. Those patients whose disease progresses following standard therapies have an expected survival of only three months, meaning that there's a tremendous need to identify new targets for therapy to benefit these patients. The effectiveness of many treatments for AML are limited by associated toxicities that reduce the possibility of achieving therapeutic dose levels. This slide shows why ILT3 may be an ideal target that could enable intensive treatment to effectively kill AML cells while sparing most healthy blood cells, thus reducing toxicity. If we look at the left-hand side of this slide, you can see that ILT3, shown in blue, is expressed on both leukemic stem cells and the AML cells that the stem cells give rise to. CD123 and CD33, which are targets of existing AML therapeutics, are also expressed on leukemic stem cells and AML cells. The key distinction between ILT3 and these existing targets is shown on the right-hand side of the slide, which shows that while CD123 and CD33 are expressed on hematopoietic stem cells, ILT3 is not expressed on these cells. Hematopoietic stem cells give rise to all normal blood cells, and thus targeting molecules expressed on hematopoietic stem cells can lead to depletion of healthy blood cells, thus causing serious toxicities and limiting the ability to treat at therapeutic dose levels. The selective expression of ILT3 on leukemia cells as opposed to hematopoietic stem cells means that ILT3 targeting therapies may have the ability to achieve greater efficacy with less toxicity than current therapies. On the coming slides, I'll share with you data supporting the model shown here. Now let's dig into the real data examining ILT3 expression in AML. On the left side of the slide, we're looking at ILT3 expression in samples from patients with different subtypes of AML. We can see that ILT3 is highly expressed in M4 myelomonocytic leukemia and very highly and uniformly expressed in M5 monocytic leukemia. In the right-hand panel, we see that ILT3 is also expressed in rare CD34 positive leukemia stem cells in the blood and bone marrow. A central pillar of our therapeutic hypothesis for targeting ILT3 is that this strategy has the potential to eliminate ILT3 positive leukemia blasts and stem cells, but spare the elimination of healthy bone marrow cells, unlike benchmark molecules targeting CD33 or CD123. When we take a closer look at AML targets in development, such as CD33 and CD123, we see on the left-hand side of this slide that they're expressed on normal hematopoietic stem cells, as shown in the red ovals. Thus, targeting these receptors would be expected to eliminate healthy bone marrow and bone marrow-derived blood cells. This leads to safety concerns of bone marrow depletion and severe myeloablation, which can be fatal. In contrast, in the right-hand panel, we can see that ILT3 has a very favorable expression profile with no expression on normal hematopoietic stem cells or multipotent progenitor cells, as you can see in the blue ovals. In the coming slides, I'll tell you about how we took advantage of the favorable expression pattern of ILT3 to develop a therapeutic with the potential to kill blood cancers while maintaining a strong safety profile. I'd like to now share with you some of the details of our antibody engineering effort that led to the development of NGM936, an ILT3 CD3 T-cell engager optimized for both efficacy and safety. Bispecific T-cell engagers have been shown to be highly potent antitumor agents, demonstrating impressive efficacy in cancers such as B-cell lymphomas. However, the CD3 arm, which binds the T-cells, has been shown to trigger cytokine release that can lead to dangerous cytokine release syndrome, which has caused numerous T-cell engager candidates to be abandoned due to toxicity while limiting the efficacy of others due to dosing constraints. As Kathy and Jin-Long spoke to earlier, challenges such as this are what NGM's protein sciences team lives for. The team set out to engineer a molecule that would maximize efficacy while minimizing safety concerns. They designed and produced over 30 diverse T-cell engager formats, which were then systematically evaluated by the biology team to assess tumor killing and cytokine release. Of these many molecules, NGM936 caught our attention due to its extremely high efficacy and potency of tumor cell killing paired with low cytokine release, which you can see on the right-hand side of this slide is substantially lower than a competitor anti-CD123/CD3 antibody. I'd now like to share with you for the first time some of our preclinical results evaluating the potential safety and efficacy of NGM936. As I described earlier, our therapeutic hypothesis is to eliminate ILT3-positive leukemia cells but avoid normal bone marrow depletion and CRS to minimize dose-limiting toxicities and widen the therapeutic window. To test this, we put normal healthy bone marrow cells into a T-cell killing assay. We found that a CD123 targeting T-cell engager antibody caused a reduction in the number of normal stem cells, as you can see on the left-hand graph, and increased markers of cell death, as you can see on the right-hand graph. This is what you'd expect based on the expression of CD123 on hematopoietic stem cells, as we saw earlier. What we saw with NGM936 was really extraordinary. The viability of bone marrow was much better maintained with NGM936, and there was dramatically less stimulation of cell death markers. Of course, to generate a better treatment for AML, this therapeutic will need to not only be safe but will also need to effectively kill cancer cells. To test this, we assessed T-cell-dependent killing of the MOLM13 AML cell line. We chose this cell line because it expresses similar levels of ILT3 as compared to primary AML patient samples. We tested AML cell killing in two different assay formats. On the left-hand side, you can see data in which we used expanded T-cells for cytotoxicity assays. On the right-hand side, we confirmed these results using whole PBMCs that were not activated. In both assay formats, we see that NGM936, shown in the green curves, powerfully engages T-cells to kill ILT3 positive AML cells with comparable efficacy and potency to a CD123 CD3 antibody, which is shown in the blue curves. I'm gonna wrap up by sharing with you what may be the most important preclinical data that we've generated. Here, we're evaluating NGM936 in a mouse model of AML. In this in vivo model, mice are implanted with human AML cells and then treated with a control antibody, a CD123 CD3 antibody, or NGM936. AML tumor burden is assessed through using flow cytometry. You can see that NGM936 powerfully reduces AML tumor burden with efficacy and potency equivalent to or better than the CD123 CD3 antibody. Thus, we've demonstrated that in our preclinical studies, NGM936 retains full efficacy against AML, but with a safety profile that's superior to existing therapies. We're really excited by these results, and we hope to see similar results for patients in the clinic. I'd like to wrap up by getting back to the question of why the development of NGM936 is so important. Monocytic AML, where ILT3 expression is enriched, carries a greater risk for bone marrow relapse and systemic or extramedullary disease compared to non-monocytic AML. NGM936 has the potential to treat monocytic AML, which can provide a much-needed treatment option to a patient population that faces a five-year survival rate of less than 15%. What I hope you'll take away from our discussion today is that ILT3 may be an ideal target for treating a number of hematologic malignancies, given its high level of expression on numerous blood cancers and cancer stem cells, and just as importantly, its lack of expression on healthy hematopoietic stem cells. We've developed NGM936 as a potent ILT3 CD3 T-cell engager antibody for the treatment of AML and other ILT3-expressing hematologic malignancies. NGM936 has the potential to recruit T-cells to kill ILT3 positive cancer cells while maintaining safety by preserving healthy hematopoietic stem cells and minimizing cytokine release. We're encouraged by the possibility that NGM936 may serve as a safe and effective therapy for patients who currently lack good treatment options. We hope that this presentation brings to life what the team behind the NGM discovery engine is working on every day. On that note, we're really fortunate to have one of our scientists with us today, Julie Roda, who's played an integral role in the development of NGM936, and who can help to put this exciting candidate into further context. Julie, maybe we could start by you telling us, at what point did you start to believe that you had a potential therapeutic candidate on your hands with NGM936, and why? Yeah. There are a lot of different ways that you can assemble a bispecific antibody, starting with a CD3 antibody and an ILT3 antibody. We have a very talented protein sciences team who generated 30-some different engager formats, and we screened them all in assays to look at tumor cell killing and cytokine release. You wanna see potent tumor cell killing, but you also wanna see very low cytokine release because cytokines secreted by activated T-cells contribute to a condition called cytokine release syndrome. This is a common occurrence in patients receiving T-cell engager therapies, and it can be serious. We screened all our antibodies in these different assays, and NGM936 jumped out at us because it was extremely potent, but it also induced very low cytokine release. Even lower cytokine release than competitor antibodies that are known to be safe in the clinic. Once we saw that data, we really knew we were onto something with this molecule. What is so different and unique about NGM936 versus other programs across the industry that are in development for the treatment of AML? The key is the really highly restricted expression profile of ILT3 compared with targets of other CAR- T or T-cell engager approaches. If you look at circulating blood cells, ILT3 is really highly restricted to monocytic cells, which are monocytes, macrophages, and dendritic cells. It's not expressed on hematopoietic stem cells, and it's not expressed on other myeloid cell types like neutrophils. This is important because therapies that target molecules that are more broadly expressed will wipe out these cell populations as well, and that contributes to secondary toxicity like infections, which can be extremely severe and can limit the ability of the patient to stay on the therapy. We think that NGM936 will have an improved safety profile because it will avoid this myelotoxicity, and patients will be able to stay on the therapy longer, and they'll be able to tolerate a higher dose, which will give it a better chance of working. The development of NGM936 was a collaborative effort. Can you talk about the different groups that came together across NGM to enable this program? Yeah. I think this program is such an incredible example of the confluence between our biology and our protein science expertise. From the biology side, based on our deep experience with ILT3, we knew it would make a great target for a specific population of AML patients. We could not have actually made NGM936 if we didn't have such a talented group of protein scientists working on it. First, the team engineered the CD3 and the ILT3 arms to maximize the ILT3 affinity relative to the CD3 affinity in order to improve the safety profile. Second, there are a lot of different ways that you can assemble an ILT3 antibody and a CD3 antibody into a bispecific. Our team was able to design and generate several dozen different configurations of bispecifics. This enabled us to systematically screen them all, and then we selected the molecule with the best therapeutic index. We can really be confident in NGM936 because we had so many great options to choose from. I really get a sense of your enthusiasm for NGM936, and maybe you could share with us a bit more about what gets you most excited specifically about this program. Yeah. This program is so different from other programs I've worked on because it targets such a specific population of patients with a specific subtype of AML with monocytic differentiation. This is a particularly aggressive form of AML. It has worse survival than other forms of AML. The tumors tend to grow outside the blood and bone marrow. There's actually a lot of recent data suggesting that patients with this form of AML are resistant to standard of care therapies like BCL-2 inhibitors. This drug won't work for most AML patients, and as a scientist, that's not normally something you set out to say, but for those patients who it will work for, we think it represents the best possible therapy. Yeah, that's really interesting. Well, thank you so much, Julie. It's been a pleasure speaking with you today, as it always is. Thank you, Dan. It was great chatting with you. With that, I'll turn the call back over to David for closing remarks. Thank you. As you heard a few times already today, we have a high bar for which discovery candidates are advanced. We're excited about the potential for NGM936 and what it could potentially mean for patients in this area of high unmet need. That brings us to the end of our prepared remarks today. In a moment, we'll open the line for Q&A, but first, I'd just like to say thank you all for your attention and for your interest in NGM. I hope today's program has given you a taste of how NGM's discovery engine is bringing a steady stream of innovation into our pipeline. Our next few Explorer Series events will provide a deeper dive into NGM831, NGM438, NGM707, and the NGM621 programs, where you'll have the opportunity to hear from additional members of the team here at NGM. With that, now we'll open the line for questions. Good morning, and thank you again for joining us today for the first session of our Explorer Series. This is Brian Schoelkopf, Head of Investor Relations at NGM Bio. In the room with me are David Woodhouse, our CEO, Siobhan Nolan Mangini, our CFO, Alex DePaoli, Chief Translational Officer, Kathy Miller, Head of Biologics, Josh Lichtman, Head of Biology, and Dan Kaplan, Head of Translational Immuno-oncology. I invite you to submit your questions through the Q&A box in the webcast platform at this time. We'll start with a question from Paul Choi at Goldman Sachs. Two-part question. The first is, can you elaborate on your criteria for advancing from interesting biology to an actual drug candidate? The second part of the question being, are there any other hematologies or solid tumors beyond AML for which ILT3 is relevant? It's David here. Paul, thanks for the questions. Yeah, the first one is actually, I think one of our key expertise is kind of identifying those criteria. In fact, Alex DePaoli is sort of our secret weapon. We call him our Swiss Army knife internally. He's renowned for developing approaches to early clinical trials to really explore exactly the first part of your question. I'll let Alex go first, and then we'll hand it over to Dan to answer the second part of the question related to additional hematologies that might be available for ILT3. Thanks, David. Hi, Paul. What we really focus on, as we've consistently said, is this wow biology or powerful biology. Many of these powerful biologies are going to have multiple potential applications. Our focus is to identify a clinically meaningful, important therapeutic approach for which we have a translational avenue. This translational avenue allows us to utilize some degree of known biology of biomarkers and so forth to elucidate a clear path to a therapeutic development. I think we've seen this many times in drug development and in particular in our programs. I think the ILT3 program is an example of that, where we have been studying the ILT3 approach in solid tumors and the understanding of the application of this biology and the very concise approach towards developing a molecule for a very specific application, became evident and prioritized. Okay. Dan, do you wanna hit on the second part of the question? Yeah. Yep. Thank you, Paul. First, in terms of addressing the broader utility of ILT3 for treating cancers, I think it's important to note that we have two ILT3 programs with each optimized for a particular type of cancer. First we have NGM831, which is an Fc-silent anti-ILT3 antibody for treatment of a broad array of solid tumors. Critically, NGM831 is focused on reprogramming suppressive myeloid cells into beneficial myeloid cells rather than depleting myeloid cells as an effector-competent ILT3 antibody would be expected to do. Then, of course, as we introduced today, NGM936 is an ILT3 CD3 T- cell engager for the treatment of ILT3-expressing hematologic malignancies such as AML, but not limited to AML. In these cancers, the ILT3-expressing blood cells are the tumor cells, and we do want to deplete them. We believe that an ILT3 CD3 T- cell engager is an excellent strategy to deplete these cancer cells. We do think that NGM936 could potentially be used to treat ILT3-expressing hematologic malignancies beyond AML. Monocytic AML could serve as a really nice proof of concept indication for NGM936 because there's a strong rationale for an ILT3 CD3 bispecific being effective in this indication, and then we could potentially take the molecule to other indications. Please stay tuned for more there. Great. Thanks, Dan. Next question here is from Steve Seedhouse at Raymond James. Could you comment on the potency of the ILT3 bispecific against the intracellular signaling of ILT3 as opposed to just AML cytotoxicity, which should be robust given the bispecific design? Whether potent inhibition of the signaling pathway in addition to cytotoxicity will be important to drive a clinical effect in specific forms of AML that you are looking to address. Yeah. Thanks for the question, Steve. I think this is just another layer down, Dan, to the question you were just answering, but, go ahead and expand on it. Yeah. Our view is that in the context of hematologic malignancies such as AML, that the primary focus should be on depletion of these cells. We really view ILT3 as a really nice specific handle to use to identify, target these cells for killing with the T-cell engager format. That is our primary focus there. Great. Next question here. Are you planning on developing more bispecific T-cell engagers? Is this a modality that you are now interested in? Yeah, this will be a good question for Kathy Miller. I think at a high level, we view as you've heard earlier in the presentation, our bispecific technologies as one of the tools in the toolbox. We like to use all of our tools in different ways, whatever it makes sense. Kathy, please expand. Thank you, David. As you said, at NGM, we do have a whole host of tools that we can use to modulate biology. NGM936, as our first announced bispecific program, is not so much a sign of where we're headed. It's more an example of the flexibility that we can enable through our biologics group. We're fortunate to have a skilled biologics team that gave us the flexibility to develop a bispecific T-cell engager as we began to understand the rationale for that being a powerful modality for monocytic AML, leveraging the ILT3 receptor. That said, we do have other preclinical programs that use a bispecific approach, but we'll continue to evaluate modality on a case-by-case basis by letting the biology guide us, rather than being driven by a type of modality or platform that we wish to use. Great. Thanks, Kathy. Next question here is from Ritu Baral at Cowen. A couple parts to this question. What competition are you looking at in AML with similar or the same mechanism? The second part of the question is, how consistent is the expression of ILT3? How easy is it for tumor cells to drop expression and to reach escape? Great. Thanks for the questions, Ritu. Yeah, we certainly have been monitoring the competitive landscape as we do with all our programs to understand and make sure we have an opportunity with the program. I'll turn it over to Dan to give you some context on that and also address the ILT3 expression question. Yeah. If we're to compare NGM936 to other bispecific targeting molecules, other bispecific T-cell engagers, we do believe that NGM936 can distinguish itself based on safety profile and the ability to dose more intensely to additionally achieve better efficacy. If we compare NGM936 to monospecific ILT3 antibody programs for targeting hematologic malignancies, we believe that 936 should be able to have better efficacy. If we compare NGM936 to CAR- T programs, there's reason to believe a bispecific program could be accessible to a wider range of patients. To the second question there about the stability of ILT3 expression. First of all, nearly all monocytic AML patients express ILT3, and it's expressed uniformly across AML blasts. Importantly, ILT3 remains stably expressed on AML blasts even after extensive pretreatment. Great. Thanks, Dan. The next question here from Mayank Mamtani at B. Riley. Could you talk to more on the NGM936 development plan? How does the favorable safety profile enable you to pursue dose escalation work? What might be the DLTs you'd be looking at for in your initial phase I studies? Is the first part of the question. Okay. Yeah, thanks for the question, Mayank. Those are exactly the type of things we're thinking through right now as we're nominating the program. We do think there's an opportunity potentially here, given the focused aspect of the patient population, to develop this rapidly and get it to patients as quickly as possible. We need to think through those right approaches early in. I would say one of the things we're also overlaying on this program is we just nominated three programs in the last 18 months, and so we need to balance kind of our internal resources in terms of how we move this forward. Part of that, particularly given this is in hepatologic cancers, which is a little bit outside our realm of solid tumors for our other programs, it also gives us the opportunity to consider leveraging some external resources, including partners, to move this forward. Those are all the things we're thinking through as we newly nominate this program. Great. The second part of the question here from Mayank. Are you looking for more collaboration activity now that you've revamped the collaboration with Merck? Yeah. I think it's you know, part of the thing we're always looking at is new technologies, and I think regardless of whether we're working with Merck or not, the ability to leverage biology that we've identified through all different tools is something we're constantly looking at. You know, our labs are really good at identifying those. Great. The next question here from Swapnil Malekar at Piper Sandler. Would NGM936 have applicability in unfit AML patients based on the current set of data that we have? Sure. Maybe I'll hand that over to Dan. Oh, yes, indeed. We do believe that NGM936 would be expected to be applicable to unfit AML patients due to the strong expected safety profile of the molecule. Unfit patients are unable to tolerate more toxic AML therapies, but we predict that these patients could tolerate and benefit from NGM936. Okay, great. Thank you, Dan. Final question here today. Can you tell us more about what to expect at the future events in the Explorer Series? More specifically, will you be disclosing any new data at the upcoming events? Sure. As I mentioned earlier, today was the first of our four sessions that is basically a traditional R&D day broken into chapters or episodes. Today, we started with the foundation of the company as an introduction, which is really at the foundation of this discovery engine. The next session will be on our stromal checkpoint programs in our oncology portfolio, namely NGM831 and NGM438. It is timely as NGM831 will be entering the clinic in the next few weeks, followed shortly thereafter in the second quarter by NGM438. The third session will focus on NGM707, our dual ILT2/ILT4 antagonist, which is currently in phase I testing. We will wrap up the series in our last session with our NGM621 program in development for geographic atrophy and currently in Phase II testing, with top-line data expected in the fourth quarter. At each of these sessions to the question, we will be sharing new information on our programs and with that, more context as to why we think the underlying mechanisms hold promise for impacting disease. In the next three sessions, you can also expect we'll be featuring KOLs that are expert in myeloid checkpoint inhibitors and geographic atrophy to provide an external perspective to the discussion. We hope you all can join these upcoming sessions as well. Great. Thanks, David. With that, we will conclude the Q&A session in the first module of our Explorer Series. Thank you.