Hello everyone. Thank you for joining JP Morgan's Annual Healthcare Conference. I'm Gautam Baliga, Vice President in our investment banking team. It's my pleasure to welcome Dr. Praveen Tipirneni, CEO of Morphic Therapeutic, to talk about the company, their exciting programs, and the platform. Before we pass it over to Praveen, I just want to tell the folks that if you want to ask a question, please click on the icon, Ask a Question. I hand it over to Praveen to go through the presentation. Great. Well, hi all. Welcome to Morphic Live at the JPMorgan healthcare Conference. Thank you to JPMorgan and Phil Ross for inviting us once again to this conference. I'm one of the folks who love this conference, so I'm not happy we're not together in person and hope that will change in future years, but we'll make the best of it here. We're looking forward to a phenomenal year at Morphic, where this year we get clinical proof of concept for MORF-057, as well as a validation of our MInT Platform. One thing that is cool about this video format, however, is the ability for you to ask me questions as we go. Please feel free to text Chris Erdman, our head of IR, with any questions, chris.erdman@morphictx.com, or through the conference portal. He can pass them to me, and we can answer them live. Chris, you got that? Okay, good. Let's go. Next slide. We are a publicly traded company and will be making forward-looking statements. I encourage you to review our SEC filings to understand the risk factors associated with an investment in Morphic. On this next slide, before we dive into the specifics of Morphic and the integrin receptor, I just want to take a step back and say that it's difficult to not acknowledge what's going on, the pandemic, the broader world. Also, this is a time to recognize the amazing industry that we're in and its ability to transform people's lives. In this crisis, the solution began with us, all of us, and I'm proud to recognize and be a part of that healthcare community, the doctors, nurses, scientists, who work tirelessly to bring forth solutions to the pandemic and world. In fact, it was the first time in 15 years in which I was called to see patients, so quite an experience. Next slide. Morphic Therapeutic is the integrin company, a family of receptors in the body. Receptors are key to human biology due to their ability to convert extracellular stimuli into intracellular signals. There are thousands of receptors underscoring the extent to which nature has relied on this molecular system for transmission of information. Operator, click once. These are just some of the thousands of receptors in the human body. The receptor takes stimuli and turns that into intracellular signaling. It's a one-way transmission of information that enables us to react to our environment. It's how we react to our environment. Next slide. As this last year has shown us, we don't just react to our environment. No, no way. We shape it. We shape our world. Crises don't break us, they build us. Numerous research shows that people emerge from trauma with a renewed sense of connection, possibility, and purpose. Bidirectionally, we react and shape our environment. At the cellular level, this is called bidirectional signaling, an ability to both sense and communicate both inwards as well as outwards. We react and shape our world. That very human ability to respond and shape the environment at the cellular level, bidirectional signaling. Guess how many receptors of the thousands in humans exhibit that fundamental bidirectional signaling? Next slide. It's not 10, not five, not three. It's just one, the integrins. In the entire human body, there is just one. The integrins are very fundamental biology. Next slide. Let me talk a little bit about the integrin receptor. You see it here depicted in this pictorial, an alpha and a beta subunit. It's a heterodimer, and it's a family of cell surface receptors, as I said, that have a unique ability to signal bidirectionally. In fact, it was named the integrins because they integrate extracellular and intracellular stimuli. Okay, Chris, any questions from the audience so far? Anybody lost? Semper Fi. We leave no man behind here. Okay, let's keep going then. In this next slide, which we have been showing since 2015 because it explains so much, it's a curve of technology evolution known as the Gartner Hype Cycle curve. What it represents is that expectations often outpace reality in new and transformative technologies. You have a peak of excitement, a trough of disillusionment, then people start figuring it out. You see that on the left. After Tim Springer, our founder discovered the integrin target class, 1984. The euphoria, the peak that was in the large molecules anticoagulants, including Integrilin and ReoPro. Clear mortality benefits. Nearly every large pharma tried to develop an oral integrin inhibitor, and every single program resulted in failure, 100%. The trough of disillusionment. Fortunately, Tim Springer continued research in his lab at Harvard until he discovered the conformational discovery that catalyzed the formation of Morphic. Highly promising technologies go through these predictable cycles, with expectations often outpacing reality. This is the story of every target class. You have some low-hanging fruit. The rest turns out to be harder than we initially thought. Takes a decade or so for new biology, chemistry insights, which results in a new generation of drugs. In this case, Tim figured out the various conformations of the integrin receptor and how to modulate them. We saw this with kinases. We saw this with GPCRs, ion channels, transporters. There's the same playbook here you've seen before. We're just running the same playbook. Now you're seeing it with the integrins and that inevitable next generation of drugs. There is a difference, one big difference. In this next slide, this is the integrin target class, 24 members. In the case of those other target classes, that new generation of drugs came across many companies, from many companies. What if that all happened in one company? If one company were able to exploit such a fundamental target class? That's what you have here with Morphic. Remember, α, β subunit, these are heterodimers. They're 24 closely related proteins. If you want to go after this target class in a structure-based drug discovery manner, we are the only game in town. We are the only company with the crystal structures for the integrins. I just actually had this other realization this week while watching JPMorgan. There's lots of chatter about targeted therapy. It's a strength of a specific inhibitor with a clean mechanism and a specific clinical hypothesis. That's the lesson of ArQule, Array BioPharma, Loxo Oncology, and many others in recent years. That's what we're able to do in the integrin target class, and we believe nobody else can. In certain cases, you have validated targets, such as our lead molecule, MORF-057. In much of this space, nobody's been able to interrogate this biology because they don't have specific probes, specific inhibitors. We can, and we do. I'll talk about this a bit ahead with αvβ1. Next slide. This is a Morphic Integrin Technology platform or MInT Platform. It consists of 3 parts. One is that structural elucidation I talked about. We have generated hundreds of integrin crystal structures. Any crystal structure we have wanted to elucidate, we have been able to. The next section is the chemistry. We're able to tune in and out the profiles of, again, the inhibitors to the integrins that we want. The third part is proprietary integrin assays. Remember that this is a 24 closely related protein. Whenever, by definition, you are investing in an individual program, you are getting the biology and the chemistry library for all the integrins around it. By definition, if you're investing in one program, all the follow-on programs accelerate. Each loop of this platform, of this MInT Platform accelerates the next one. A biology, chemistry, integrin flywheel. That's what we have here, and that's what we've seen. Next slide. In the MInT Platform, this is what the MInT Platform has resulted. A deep pipeline, both wholly owned and with partners. At the top there, you see our MORF-057, which we'll spend a lot of time, our well-validated biology for inflammatory bowel disease patients. The pipeline is accelerating behind it. alpha-V beta-1 in fibrosis, we'll talk about a little bit. Very exciting data in alpha-V beta-8, as well as a number of targets after that. With our partners, a number of programs that I will talk about near the end. Next slide. We designed MORF-057 to be an oral vedolizumab. Next slide. Here is the mechanism for α4β7 inhibition. Vedolizumab, a Takeda drug for inflammatory bowel disease, very effective and safe drug. Takeda just increased the guidance for vedolizumab just a couple of days ago, actually, to between $5.5 billion-$6.5 billion. A very successful drug. What you're seeing here is the mechanism, and it's a very clean and straightforward mechanism. The T cells there you see in the vascular circulation, that's the bloodstream there where the T cells are circulating. You don't want your T cells to be on the wrong side of the tracks. The T cell transmigrates to the endothelial space through that interaction of α4β7 with MAdCAM-1. That's what you're seeing in the picture. If the pathology is the T cell being in that subendothelial space. Let me tell you don't want your T cell to be on the wrong side of the tracks. α4β7 inhibition blocks that transmigration and keeps the T cells moving. Next slide. Here's a cartoon I drew to illustrate the challenges in α4β7 drug discovery. This is the Whac-A-Mole game. You probably played at the carnival. Whack, whack the moles. It's hard to whack them all. When we're talking about MORF-057, why is there so little direct competition? Unlike most situations where once you have a validated target, a gun goes off, boom, and you have a dozen programs. That's not the case here. This is an obvious unmet need. If you had a kid with inflammatory bowel disease, would you want him to have a multi-hour infusion at a center or take a pill? An obvious opportunity, a well-validated biology. In this case, it's not hard to recognize the opportunity many people have. The hard part, if not previously impossible, is to generate the actual molecule with all the right properties. Many have tried. It's like the Whac-A-Mole game. You get potency, whack. You lose selectivity. You get selectivity, whack. You lose bioavailability. It's maddening, just like the game. Getting all the required properties into one molecule has not been previously possible. Next slide. We've whacked that mole. As far as we know, we're the only ones who have whacked that mole while getting all the properties into a single molecule that's required to be an effective oral α4β7 inhibitor. We did it with the MInT Platform, our platform. Remember, we have the crystal structures. We can come at this in a structure-based drug discovery manner. That's the power of the MInT Platform. Next slide. I love this slide. I think it's my favorite slide because it really shows the power of this platform. What you're seeing here in this slide is the selectivity. Remember, heterodimer α4β7, alpha and beta subunit. You want to block α4β7 without inhibiting α4β1. α4β1 is responsible for CNS trafficking of the T lymphocytes. You don't want that to be blocked, or else you have the potential for PML. Doing that is very difficult, and as far as we know, we're the only ones who've done it, because they share that alpha subunit. As you can see here on the right-hand side, our selectivity is comparable to vedolizumab, and you can see the huge strides of our compound in comparison to some of the other compounds in this area. Next slide. Over these next three slides, I'm going to show you a stepwise series of data in increasing and relevant studies that gave us the confidence to enter clinical studies with MORF-057. In this slide here, this is our gut-homing assay. This is a really elegant assay, the gold standard assay for α4β7 inhibition. What you're seeing here are those T lymphocytes moving toward its interaction with MAdCAM. That's considered homing. That's what you're seeing in that left bar, the vehicle, the control, homing up 20% to, in this case, the mesenteric lymph nodes. The next bar there is DATK32. Sorry, previous slide. Is DATK32. It's that second bar there. As you can see, blocking that homing. You see MORF-057, our compound in increasing doses. Each result there, blockage of homing, statistically significant, and in the higher doses, at levels that are comparable or better than vedolizumab. Excellent results in our assay. We use this for screening the compounds. Next slide. Here, you're looking in non-human primates. What's been described is T cells increasing in the systemic circulation with blockage of α4β7 in non-human primates. On the left-hand side, you see in a dose-responsive manner with MR5288, which is a tool compound for us, increases in the T cells as we would expect. On the right-hand side, you see the same thing with MORF-057. You see the vehicle on the bottom and the increase in the T cells on the top there. Exactly what you would expect. Next slide. Here is receptor occupancy. You want to block that receptor. You want to occupy that receptor. Once that receptor dance card's full, T cells must move on. That's what you're seeing here. We had to develop an assay, a proprietary assay, develop the first of its kind, a high-fidelity, physiologically relevant receptor occupancy assay, it's the same one that's been deployed for the ongoing phase I study. As you can see here, within two hours, you have actually full saturation. Again, this series of studies really gave us confidence that we had something with MORF-057 and to bring it into the clinic. Next slide. Here's our development plan. We did announce last year that we are entering the clinic with MORF-057. At the top there, you're seeing the phase I SAD. Fairly straightforward, five cohorts, each one approximately eight patients. Following that, we would have a food effect study and a MAD study before entering phase II. This is a schematic of what's yet to come. We're very comfortable with where we are. No impact on timelines. We'll report out our SAD data in the first quarter, but also that all-important receptor occupancy data. Subsequently in mid-year, we'll submit that full data set for presentation at a major medical meeting. With that, we'll move on to phase II. Next slide. I want to talk about this book. I just read this book actually. Last year at JPMorgan, I presented a slide with a hamster wheel that patients with IBD live on. Their life is a nonstop, never-ending race to keep their lives together between work, childcare, treatment, et cetera. These environmental factors are a major obstacle in their life. This book, I just saw it and read it. It's a more academic treatise of the same exact thing. A huge series of studies, Harvard economist Sendhil and Princeton psychologist Eldar Shafir describe a bandwidth tax. It's especially acute in this type of IBD population. All those illogical mistakes you see people making, those without resources, time, support, sleep, are result of the scarcity of numerous resources. Why do obese people not eat healthy food even when it's free? Pay loans, illogical. Why do these people not take vaccines? The humane message of the book is that there's nothing wrong with them. That, in fact, you would act in a very similar way if you were scarce in these resources. We need to provide these people with bandwidth. That's really what MORF-057 is about. What we have here is a bandwidth tax rebate, a humane way to give bandwidth to IBD patients who really need it. Give them a fighting chance for meaningful lives. Here's a quote describing a frontline healthcare worker in this last year. Quote, Time meant everything to her. She was up for all challenges. She shopped gleefully, played in the sandpit, showed up in aged care facilities. Tirelessly, she gave herself to the community with no regret. We have the bandwidth tax rebate. MORF-057 can transform their lives. Next slide. I'm going to show you select examples from our proprietary pipeline generated by our MInT Platform. Next slide. Here's alpha-V beta-1. Implicated in fibrosis, originally a surprising finding from Dean Sheppard's lab many years ago. What we have been able to do with alpha-V beta-1, because we have a very specific probe, is we believe, and we have an understanding, a proprietary understanding at this point, that the mechanism is very different than what's publicly known. That's really the power of that MInT Platform, right? The ability to get specific probes and interrogate that biology in a way that no one's ever interrogated it before. We are right now working on indications, both the type of indications that the world at large believes αvβ1 is suited for, but also a proprietary understanding of indications, and we're working through that right now. Next slide. I want to talk to you about αvβ8, which we're incredibly excited about. This is my second favorite slide. We all know that there are tumors immune to anti-PD-1. In fact, the vast majority of patients do not respond to PD-1s. Those rising lines there you see, that's a tumor volume there on the left-hand side. Those rising lines are the tumor burden, and anti-PD-1 antibody can't contain those tumors. That line of a combination PD-1 with our αvβ8 in this EMT6 murine breast cancer model, very dramatic results. The results are even more stark on the right-hand Kaplan-Meier there, the survival curve. There's a lot of data underneath this, but this early data suggests we can really improve on treatment options that have been intractable before. Actually, just this morning, alpha-V beta-1 and alpha-V beta-8 reminded me of a patient that I treated. This was actually a moment that's really very memorable and meaningful to me. I was moonlighting as an ER physician at Penn while I was getting an MBA there to pay for tuition. I transferred a patient from a nursing home I thought to be stable. As soon as I put my hand on his abdomen, I knew this was an acute emergency. I could feel the contours of his bowel through the fascial wall. He had an acute bowel obstruction, fibrosis, secondary to colon carcinoma. These are the potential indications for alpha-V beta-1 and alpha-V beta-8. That patient actually ended up dying later that morning in surgery, but hopefully in the future, we will have treatment options for him. Next slide. Next slide. Let me talk about our partnerships here. You see AbbVie and Janssen. AbbVie, very exciting partnership, multi-target deal, where we do this discovery and then AbbVie, upon having an IND-ready package, opts in and then takes forward on development. The first target there that we did with them, alpha-V beta-6, we reported that AbbVie exercised the option with a $20 million payment, and right now, they are moving it forward. Great partnership with AbbVie, and we're very excited about the programs that we're working with them on. Janssen, it's a different type of collaboration here. It's a very early stage, very intertwined collaboration with obviously the very bright folks at Janssen. That partnership in the cardiometabolic area is also going very well. We just announced, last week actually, an expansion of that with now moving into biologics and activators, right? That gives us even more potential of this platform that we developed. Very excited about the Janssen relationship as well, going well. Next slide. In summary, let me just leave you with these three things. Number one, we are the only ones with the crystal structures across the integrin class. Number two, MORF-057 is poised for clinical proof of concept, a bandwidth tax rebate for IBD patients. Finally, number three, everything accelerates from here. Remember, 24 closely related proteins. If you invest in one, it inevitably accelerates the following programs, which we have seen. Next slide. Just for a second, let us go back to where we started the pandemic. If there's one thing we learned over this last year in the world and in Morphic, it's to never underestimate the resilience of the human spirit. We respond to our environment, but we also shape it powerfully, that bi-directional signaling. What Morphic is about is about restoring that resilience. Important bi-directional signaling at the cellular level in integrin dysfunction. That problem can and will be solved only at Morphic Therapeutic. You can see, we're well on our way. Thank you. At this point, thanks for allowing me time to speak about Morphic and integrins. I'm going to pause, have the rest of the Morphic team join us, and we'll be glad to take any questions. Operator? This was excellent presentation. Thank you, Praveen. Thanks, Gautam. Just as a reminder to everyone, if you want to submit a question, please click on the icon, Ask a Question. The first question, Praveen, we have is on MORF-057. Could you please provide a few more details on what we can expect? How should we think about the receptor occupancy levels and related drug and dose levels? What data will be important, which will inform a de-risking event for our trials in the next phase? Why don't I pass that to Marc, and then if need be, Marc, feel free to pass it to whoever you want. Absolutely. Thanks, Praveen, and guys, feel free to add on if I miss anything. I think what we've been saying for a long time is that we really expect at the end of the day to see a 90% receptor occupancy level at a safe dose. As Praveen mentioned in his talk right at the beginning, we anticipate to be an oral ENTYVIO. ENTYVIO, as we know, and all it does as far as we know, is occupy very extensively the α4β7 receptor on the surface of T-cells in the blood. To be able to do that and say that we're an oral ENTYVIO, we need to see a substantial receptor occupancy in the 90+% range at a safe dose. I think I also asked for a timeline, Marc. In terms of timeline, as Praveen mentioned, there's really going to be two steps, Gautam. Our first step will be a top-line data release of the SAD study, the single ascending dose portion of the phase I study. Secondarily, by the middle of next year, we expect to present the entire phase I data set, which includes the SAD and the MAD data at a scientifically peer-reviewed congress. Thank you. Just piggybacking on that question. Would the healthy volunteer data be predictive of efficacy of the drug? How should we think about the PK/PD data as well on the effect on T-cells here? Absolutely. Again, guys, feel free to tack on. Given what we know about ENTYVIO already as a generally safe and very well-tolerated and very efficacious drug, and that as far as we know, its primary, maybe its only mechanism of action is to get into the bloodstream and substantially cover the α4β7 receptor and block that interaction with MAdCAM-1, as Dr. Tipirneni just mentioned. We think that by replicating that, we should have a very similar safety and efficacy profile. From that perspective, even in the SAD study, even though it's a single dose, even though it's healthy volunteers, they still have the same α4β7 receptor on the surface of their T-cells. If we can demonstrate that engagement at a safe dose and then measure the receptor occupancy even at Cmin, so the minimum concentration of the drug about 12 hours after giving it, we think that has fairly large read-through to ultimate clinical effect. Thank you, Marc. Just a follow-up there. When you give timings, are you looking middle of the year, this year for the data set? Yes for full phase I? Exactly. When Praveen said Q1, he means Q1 this year, and mid-year, that means mid-year this year. Excellent. Thank you. Praveen, you discussed a little bit about collaborations with AbbVie and Janssen. Could you please provide your plans for other wholly owned programs? Is the plan to fully develop them internally and look for any regional or other partnerships at the right time? Well, thanks, Gautam. I'll answer that, and of course, others, we've had discussions internally, so feel free to jump in. I think I do look at the world from that question perspective, similar to an investor. I look at it from a return on invested capital perspective. I look and build up from first principles who can do it the most efficiently, who has the infrastructure in place, and that's what I go with. Even in that, when we were negotiating some of those deals we had some leverage because it was competitive, and people asked if I wanted to co-promote, and I said, No, I don't want to co-promote it. Who's ever made money on a co-promote? Said, It looks good on a headline, but what value is it? It's really about building up from the fundamentals. I think we will look to the value that we can receive. I think, just in my statements there, you can see how I think about it, who has an infrastructure, who's most efficient at it, and in certain programs, that would be us, and in certain programs, that would not be us. If anyone else wants to jump in, feel free. Agreed. Thanks, Praveen. Another question, a little bit more bigger picture. Given the role this plays in TGF-β pathway, what do we see as overall opportunity and potential for various cancer types, whether it's mono or combo therapies in IO? I freely admit that I am not the oncology expert, even though I'm trying to get up to speed. We have Marc for that, and we have Bruce here, but I'm not going to answer that question. Maybe I can start and Marc can add. Our clear focus here is on solid tumor types. There's a variety of places where you can look at tumors that are resistant to therapy with PD-1, and we're looking at the best opportunities for those as we go forward now. We'll match the biology that we see emerging from this with what we see come out. Lung cancer is a solid tumor type. Pancreatic cancer is another solid tumor type where we could see some potential, but we want to apply it to the best-case scenarios based on the rest of the studies that we're doing. We'll start to publish some of our data at some scientific meetings this year as well to start to describe our mechanistic understanding of it, as well as what types of tumors we're most interested in. I just briefly add that, obviously the advent of checkpoints have revolutionized cancer care, especially in the solid tumor space. The data that we're seeing, although early, very exciting to me, because checkpoints, while extremely exciting and helpful in many cases, are not a panacea. To have a way to kind of unleash the checkpoints to themselves unleash the immune system against the tumor is very exciting, especially when the data are so dramatic as they appear to be. Again, don't want to get over our skis, but internally anyway, a lot of excitement around this program. Great. Thank you, Marc. Looks like we have no further questions. Again, Praveen, it was great to have you present here at our conference. Really exciting to go through your presentation. Thanks. I wish all the best for rest of the conference. Yeah. Thanks, Gautam, for inviting us. Always a pleasure to be here. On behalf of our whole team, thanks to JPMorgan.