Good day everyone, and welcome to Syndax conference call. Today's call is being recorded. At this time, I would like to turn the call over to Maghan Meyers of Argot Partners. Please begin. Thank you, operator. Welcome, thank you to those of you joining us on the line and the webcast this morning for a review of Syndax's announced collaboration with Incyte for the development of axatilimab. I'm Maghan Meyers with Argot Partners, with me this morning to discuss this collaboration are Dr. Briggs Morrison, Chief Executive Officer, Michael Metzger, President and COO, and Daphne Karydas, Chief Financial Officer. Also joining us on the call today for the question and answer session is Dr. Peter Ordentlich, Chief Scientific Officer. Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements represent our views as of today, September 27th, 2021, only. A replay of this call will be available on the company's website, www.syndax.com, following this call. I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer of Syndax. Thank you very much, Maghan Meyers, and thank you to everyone who's joining us on today's call. We are delighted to be announcing today that Syndax and Incyte have entered into a broad, long-term global collaboration that brings together two companies with a solid track record of innovation to accelerate and maximize the development of axatilimab, our potentially best-in-class monoclonal antibody therapy targeting the CSF1 receptor. As you know, we presented our phase I chronic graft-versus-host disease data at ASH in December of last year. The reaction to our data was extremely positive, given our belief in the broad clinical potential of axatilimab, we initiated a process to look for a global partner to collaborate with us on the further development of this exciting molecule. We are thrilled to announce today that we have entered into a collaborative agreement with Incyte. To briefly summarize, axatilimab is an IgG4 monoclonal antibody that binds to the CSF1 receptor and blocks the interaction with its ligands, CSF1 and IL-34, thereby decreasing the proliferation and function of CSF1R-dependent monocytes and macrophages. Based upon impressive preclinical data demonstrating the effectiveness of CSF1R inhibition in a model of chronic graft-versus-host disease, we ran a phase I clinical trial to ask whether axatilimab would be useful in the treatment of this disease. The phase I data we presented at ASH last year showed a 57% overall response rate in very heavily pretreated patients across the various doses tested and showed that axatilimab was generally safe and well-tolerated. Based upon the data being generated in the phase I dose escalation phase, we chose to open a phase II expansion cohort to further explore the 1 milligram per kilogram dose administered every two weeks. As announced earlier this year, we completed enrollment of 23 patients in that single-arm phase II trial and have guided that we will be presenting a full update of the 40 patients who have been enrolled in our combined phase I and II trials later this year. We've also announced the design and initiation of our global pivotal trial in chronic graft-versus-host disease called AGAVE-201. This trial is enrolling patients with chronic graft-versus-host disease whose disease has progressed after two prior therapies. Patients must be at least six years of age and have met overall entry criteria. This is a pivotal dose-ranging trial in which patients will be randomized to one of three treatment groups, each investigating three distinct doses of axatilimab, two given every two weeks and 1 dose regimen administered every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronic graft-versus-host disease. Secondary endpoints will include duration of response and validated quality-of-life assessments using the Lee Symptom Scale. Enrollment to the study is underway, and we are on track to deliver top-line data in 2023. As we have noted previously, we have also been working extensively with experts in the field of fibrotic diseases and found a strong consensus that the scientific basis for the efficacy of axatilimab in chronic graft-versus-host disease is likely to extend to a wide variety of fibrotic diseases such as IPF and scleroderma. As we have previously communicated, we obtained orphan drug designation from the FDA for the use of axatilimab in IPF, and we are working with experts and regulators to develop a trial to appropriately test axatilimab in that setting. It is against this backdrop that we today are announcing our collaboration with Incyte to accelerate and maximize the development of axatilimab. In addition to the potential for sequencing axatilimab and Incyte's JAK inhibitors as monotherapy in chronic graft-versus-host disease, we also have the ability to evaluate combination therapy with these two complementary mechanisms of action. The two different mechanisms of action could allow for the potential for a combination in both the steroid-refractory and steroid-naive chronic graft-versus-host disease setting, with the potential to arrive at a safe and effective combination that could potentially lead to a steroid-free regimen. Before Michael walks you through the details, I just want to note that this collaboration will allow us both to maximize the value of axatilimab in chronic graft-versus-host disease and will allow us to initiate a phase II POC trial in idiopathic pulmonary fibrosis. We'll have more to say about the details of the IPF POC trial in the future, but for now, I'd like to turn things over to Michael to summarize the details of the collaboration. Michael? Thanks, Briggs. I'm personally very excited to be announcing this important collaboration as it marks a critical value-enhancing milestone for the program and for the company. As Briggs mentioned, based on the emerging data in chronic graft-versus-host disease, we realized several months ago that this mechanism, CSF1R, and in particular our antibody, had significant potential beyond cGVHD and that extensive clinical development in a number of high-value fibrotic indications with high unmet medical need was indeed warranted. To maximize the potential of the drug, we conducted a thorough process in search of the ideal global partner for axatilimab and ultimately concluded that Incyte, with its significant expertise in GVHD with ruxolitinib and a track record of successful co-development and co-commercialization partnerships, they would be the best suited to help Syndax build a broad and valuable anti-fibrotic franchise. Critical to Syndax's long-term strategy is to identify and unlock potential value within our pipeline and then find a way to exploit this value globally while retaining major economic value in the U.S. We are confident that this global partnership will help us fulfill on all of these ambitions. The deal provides $152 million upfront, $117 million in cash, and notably $35 million in equity at a 30% premium, which we believe is a strong endorsement of our company and its overall value proposition. The cash infusion and investment will help to strengthen the company's balance sheet while enabling us to accelerate and expand on the development of axatilimab and our menin program, both of which will be in registration trials this year. The overall collaboration structure we designed is fit for purpose. In the U.S., Syndax and Incyte split profits 50/50. This enables us to retain significant upside while we actively participate both strategically and in the ongoing development of the molecule. There is also cost-sharing for development. Syndax is responsible for 45% of costs, limiting our downside and extending our cash. Finally, we have an opportunity for co-commercialization in the U.S. with the option to provide up to 30% of the sales force. This opt-in right allows us to participate in the launch of an important product alongside a strong commercial partner that has extensive experience across indications including oncology and immunology. Outside the U.S., we'll rely on Incyte to develop and launch the product in all major markets to maximize its full potential as a global brand. The economics to Syndax over the course of the collaboration are enhanced with key regulatory and sales milestones covering multiple indications throughout the world. The payments total an additional $450 million and Syndax receives double-digit royalties on ex-U.S. sales. Also important to highlight is the development plan, which calls for the partners to design novel combinations with axatilimab and Incyte's JAK inhibitors with the goal of establishing axatilimab in earlier settings within chronic graft-versus-host disease and expanding its market opportunity. As we previously mentioned was our intention, Syndax will initiate a phase II proof of concept trial in IPF, the first expansion outside of establishing chronic graft-versus-host disease as a beachhead and into other fibrotic diseases where we believe axatilimab could have a significant impact. Successful development in IPF could lead to an additional approval in a very important indication of considerable value and would provide support for axatilimab in other fibrotic-driven diseases that the parties could explore over the course of the collaboration. Now, let me turn it back over to Briggs. Thanks so much, Michael. Let me close the call by again emphasizing our excitement about the broad franchise opportunity for axatilimab and our excitement about maximizing this opportunity through our collaboration with Incyte. We've been very impressed by the thoroughness and thoughtfulness of our Incyte colleagues and look forward to working with them as this collaboration unfolds. As always, I'd like to thank the wonderfully talented team here at Syndax and our committed long-term investors who are helping us to build this great company. With that, I'd like to open the call for questions. If you would like to ask a question, please press star then one. If your question has been answered and you'd like to remove yourself from the queue, please press the pound key. Our first question comes from Philip Nadeau with Cowen and Company. Your line is open. Good morning. Congratulations on the deal. A few questions from us. First, on the milestones, could you give us some sense of what it will take to trigger those milestones or maybe just a broad breakdown of development versus regulatory versus commercial? Michael, you want to take that one? Yeah, sure. Hi, Philip. Thank you. Yeah, we haven't disclosed the breakdown of the milestones, but I would say that they break down pretty significant approval milestones, late regulatory milestones, as well as commercial. They sort of are evenly split. Significant milestones around development as well as commercial. Got it. Okay. Second, on the combinations with JAK inhibitors, it does seem like that could be differentiating in the marketplace. Can you talk a bit more about when those trials could start and maybe what the development path is? Yeah. This is Briggs. Happy to take that. Obviously, we just announced the deal, so we're working diligently to work through those details with our colleagues at Incyte. Things, of course, could start as early as next year, and as is our practice, once we have a trial design that's agreed to by both parties and agreed to by the regulators, then we'll share it with people, the design, the number of patients, and the timelines. Perfect. Thanks for taking our questions. Congrats again on the deal. Thanks, Phil. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is open. Great. Thanks for taking the questions. Hi, Briggs and team. I just had two, one clinical, one commercial. On the clinical question, just could you remind us of any preclinical data and/or any early clinical data that support the use of axatilimab to treat IPF? Secondly, regarding the development costs where Incyte is responsible for 100% of the costs, could you quickly clarify what you mean by indications that are specific to ex-U.S. countries? As I wasn't aware of any diseases that have no prevalence in the U.S. but for ex-U.S. If you could specify which diseases you're referring to, that would be super helpful. Thank you. Michael, you want to take the second question first, just to clarify that? Yeah, sure. Thanks, Yigal. I think the way to think about it is when we were referring to 100% of the cost ex-U.S., we were talking about trials that are specifically needed to get through regulatory hurdles ex-U.S. They're not specific to any particular indication, but there may be trials for GVHD or IPF or others that are required for ex-U.S. geographies, and those will be covered by Incyte. In terms of overall cost structure, which I think I outlined in my remarks, we'll be covering 45%. They'll be covering 55%. That's generally how you should think about the breakdown between U.S. and ex-U.S. Yigal, let me take your question about the scientific rationale for IPF. As you will recall, we licensed the CSF1R antibody from UCB, and UCB has an extensive preclinical package, not yet published, but an extensive preclinical package supporting scientific rationale for IPF. That's what we've been using as we've been speaking with experts, and some of that data was included as we got our orphan designation from the FDA. I think as you've also commented, some of the responses that we've seen in the chronic GVHD setting, the biology there is very similar to what you see in IPF, and we've seen some very nice pulmonary, not just stabilization of FVC, which is the endpoint people use in IPF trials, but actually improvements in FVC. There's additional clinical information from natural history studies of patients with IPF showing that the non-classical monocytes predict a poor outcome for patients. We think there's quite a bit of both preclinical observations from our GVHD trials and longitudinal data to support the rationale for testing the drug in IPF. Great. Thank you. Our next question comes from Joel Beatty with Baird. Your line is open. Hi. Congrats on the deal. The first question is, could you characterize the level of proof of concept data that you'd want to show in the next IPF trial to prompt Incyte on their decision on whether to opt in or not? The second question is, for the royalties, it looks like the Europe and Japan are mid-teens, while other countries ex-U.S. are low double digits. Can you just clarify if that low double digits means lower than the mid-teens or could it be higher? Thanks. Michael, why don't we have you take the second question again first? Yeah, sure, Joel. Thanks. We didn't break out specifically ex-U.S. milestones where they fell. We said double-digit royalties. I'm not sure where that comes from. Yeah, there are double-digit royalties throughout various geographies, I think that's the specificity we've provided so far. You think about it. Joel, just in terms of the design of the IPF trial, again, as I mentioned earlier, we'll say more about the details of the design, the sample size, and the timing. I guess the one thing I would say, as we've been discussing with experts in the field about how to do what people call proof of concept trials, we've come to the conclusion that you really only can get proof of concept if you're using a clinical endpoint. You can think of the IPF proof of concept trial as sort of a smaller version of what would be considered a pivotal trial using pivotal trial endpoints, where we haven't yet been convinced, or I should say the experts we've been consulting have advised us that some of the biomarker-driven trials or intermediate kind of endpoints that people use can have both false positive and false negative rates. Our current thinking, and again, we'll say more once the trial design is finalized, is that we would use pivotal endpoints like FVC to establish proof of concept. Got it. Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open. Hey, thanks for taking the questions. Just any, I guess, a question for Daphne, just thoughts around how far this could extend your cash runway? Sure. Thanks, Peter. With the addition of the $152 million, again, $117 million upfront and $35 million in equity investment on the balance sheet, this would take our cash runway to early 2024. Perfect. Thank you. Then just as we think about fibrotic diseases, are there other drugs in the space that we should be thinking about that you kind of require access to for combination trials or other things that could change the landscape there? Yeah, I think, Peter, the short answer is, of course. I think in GVHD, with Incyte's recent approval in chronic graft-versus-host disease, and the complementary mechanisms of action, we think that's a very clear and important combination to study. In IPF, as you know, there are only two approved drugs, and so back to the question about the IPF trial, we would, of course, be studying our drug in combination with those two approved drugs. As you go into other diseases, scleroderma, liver fibrotic diseases, et cetera, there would be additional agents that might be of interest to combine. Got you. Thank you. Just a final question, just regards other indications and I guess prior indications, is the door closed for oncology for CSF1R for your molecule? Well, I wouldn't say the door is closed, but I would say that the data that both we and others have generated testing a CSF1R antibody in combination with a PD-1 pathway antagonist have not been particularly promising. We continue to monitor that science, and there are academic scientists who have suggested to us that there may be a specific patient selection approach there, but at this point, that is not a priority for the program. Great. Okay. Thanks so much. Thanks for taking my questions. Our next question comes from Justin Zelin with B. Riley Securities. Your line is open. Hi. Congrats on the deal. My first question is, the press release notes that Syndax retains the option to co-promote. Can you provide some color on what you expect would dictate your decision to go forward with a co-promote or not? Michael, you want to take that one? Sure. Well, I think as you know, we have a portfolio of molecules. We'll be hopefully at a similar stage of development and launch with our menin program when we get our first approval and have the opportunity to sell the drug in chronic graft-versus-host disease. I think there are some portfolio questions about how do we want to build a field force and all that. I think there's that. There's also where are we with regard to resources and so forth. I think there's a number of considerations around how we view our portfolio and what else we may have on tap within our pipeline, but I think it provides us great flexibility to really learn and work with a great partner on the commercial side, especially in Incyte. We have excellent flexibility to leverage that as we move our portfolio forward. Got it. Thanks. My next question is on the development cost share. Do you expect that that will include AGAVE-201, or is it more like the combination trials or new trials that are initiated from here? Yeah, I'll just make a follow-up comment there. All development is shared in the way that we have presented it. 45/ 55 in terms of AGAVE-201, that's included as well. All right, perfect. One more question from me. Are there any specific overlapping toxicities between ruxolitinib and axatilimab that we should be thinking about or keeping an eye on heading into the combination trial? Yeah, Justin, thanks for that question. The short answer is no, which is, in fact, what makes it such an attractive combination. The axatilimab, the data we presented at ASH last year, the drug was quite well tolerated with really just some transient LFT abnormalities, no cytopenias or the kinds of things that occasionally you can run into with a JAK inhibitor. At this stage of the game, it is that non-overlapping toxicity, non-overlapping mechanisms of action that make the combination so attractive. Great. Thanks for taking the questions. Our next question comes from Avatar Jones with Morgan Stanley. Your line is open. Hi. This is Avatar. One for us this morning. Just another question regarding the JAK combination. Could you really provide a little color on that scientific rationale and any commentary that you have in regards to the recent discussions of JAK safety and how this approach plays out in the context of that? Sure. Peter, do you want to make a couple comments about the scientific rationale for the combination, and I can comment on the safety? Yes, sure. Obviously the two mechanisms target sort of different components of particularly GVHD in terms of the T cell component and more of the inflammatory reaction where the JAK inhibitors are more effective. We think the combination overlaps very nicely in targeting both the monocytes and macrophages that contribute to the fibrosis and more of the T cells, which contribute to the inflammatory side? I guess I would say we always think in terms of benefit/risk, and so I think the risks that have been identified with the JAK inhibitor class are potentially of less impact in this patient population where the benefit is sorely needed. These are patients who have life-threatening diseases. Obviously we'll continue to monitor all of the known JAK safety issues. I think in this case, the benefit/risk is really a different calculation than it is in some of the autoimmune diseases. Got it. Understood. Thank you. There are no further questions. I'd like to turn the call back over to Dr. Briggs Morrison for any closing remarks. Great. Thanks very much, operator. Again, thank you everybody for joining us on the call. As you can tell, we're really quite excited. We think this unlocks tremendous value for axatilimab and importantly allows us to maximize the value of that molecule and of our menin program. Thanks so much for your questions, and we look forward to following up with you in the future. This does conclude the program. You may now disconnect. Everyone, have a great day.