Syndax Pharmaceuticals, Inc.

Good day, everyone, and welcome to the CINDEX first quarter 2021 earnings conference call. Today's call is being recorded. At this time, I would like to turn the call over to Megan Myers of Argo Partners. Please begin.

Thank you, Operator. Welcome and thank you to those of you joining us on the line and the webcast this afternoon for a review of CINDEX's fourth quarter 2021 Financial and Operating Results. I'm Megan Myers with Argo Partners, and with me this afternoon to discuss the results and provide an update on the company's progress are Michael Metzger, Chief Executive Officer, Dr. Briggs Morrison, President and Head of R&D, and Alex Nolte, Chief Accounting Officer. Also joining us on the call today for the question and answer session is Dr. Peter Ordunlik, Chief Scientific Officer, and Dr. Anjali Ganguly, Chief Business Officer. This call is being accompanied by a slide deck that has been posted on the company's website, so I would ask you to please turn to our forward-looking statements on slide two. Before we begin, I would like to remind you that any statement 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 business factors, including those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q, as well as those reports filed with SEC. Any forward-looking statements represent our views as of today, March 1st, 2022 only. A replay of this call will be available on the company's website www.syndax.com following this call. With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Thank you, Megan, and thank you to everyone joining us in today's call and webcast. Before we turn to the deck, let me start my comments by first welcoming Kate Madigan to Syndax as our new Chief Medical Officer. Kate completed her formal education and training at Dartmouth and USC and has had a distinguished professional career at some of America's most prestigious pharmaceutical firms. We are truly honored to have her joining our team, and you will hear more from her on future calls. I would also like to take this opportunity to thank Michael Myers for his exceptional contributions to Syndax over the past seven years. Michael has flawlessly led the development of both of our programs into their registration trials. Michael is committed to seeing Syndax successfully transition into its next phase of growth and we are grateful that he will remain an active advisor to the company. Now, turning to slide three, 2021 was a truly transformational year for Syndax. We initiated registration trials for both of our lead programs, SMDX5613 and Axotilimab. We entered into a global partnership and collaboration with a world-class partner, Insight, on Axotilimab to expand the potential for this program. And we ended the year with an exceptionally strong balance sheet following $152 million upfront payment from our collaboration and $81.2 million in net proceeds from our December offering, following strong data disclosures for both of our lead programs at the 2021 American Society of Hematology Medical Conference. Especially given the current challenging market backdrop, we are starting 2022 with an extremely solid balance sheet position. This gives us the resources to expand both of our assets into new indications and the flexibility to aggressively pursue business development opportunities to augment our pipeline with potential best in class molecules. Slide four provides a high level summary of our current corporate priorities as we strive to realize a future in which people with cancer live longer and better than ever before. The momentum is really building its index. Our three pivotal phase two trials for SMDX5613 our highly selective Menden inhibitor, which we call Augment 101 cohorts 2A, 2B, and 2C, is progressing very well and is actively enrolling patients. For axotilamab, our antibody against CSF1R, enrollment is ongoing in our pivotal Agave 201 trial, and we are now underway working closely with our new partner, Insight, to maximize the value of this important program. I want to emphasize that we now have two registrational programs ongoing for two first-in-class and potentially best-in-class medicines for two areas of important unmet medical need. It is an enormously exciting time for the company as we anticipate filing potentially two NDAs in 2023 and are starting to expand the organization to support the commercial launch of both 5613 and Axotilimab in the United States. Let's now turn to slide five and provide further details on where we are with S&D X5613. First, we have opened three single-arm Phase II trials that FDA has agreed may each serve as a pivotal trial. Each of these single-arm Phase II trials represent an independent path to a separate indication. Augment 101 Cohort 2A will enroll patients with relapsed refractory MLR-ALL. Cohort 2B will enroll patients with relapsed refractory MLR-AML. And Cohort 2C will enroll patients with relapsed refractory MPM1-AML. Each trial is open to patients aged one month or older, and each trial will enroll independent of the other two. We may seek additional regulatory approval for S&D X5613 based on the results of any one of these trials should one trial enroll faster than the others, or we may seek initial regulatory approval with any two or all three, just depending on when they complete enrollment. We are happy to report that additional site initiation and patient accrual across the cohorts is going extremely well. We are very optimistic that we will be able to complete enrollment in at least one of these cohorts this year. Given our current trajectory and our view of the landscape, we anticipate being the first company to achieve regulatory approval for a Mennon inhibitor. Needless to say, we believe being first to market is extremely important and accretive to the long-term value of Syndax. We have agreement with FDA Now, for each trial, the primary endpoint will be the percentage of patients achieving CRCRH, with secondary endpoints including durability of CRCRH response, transfusion independence, overall survival, and safety. Importantly, the trial design allows patients to be treated with 5613 after bone marrow transplant, a design feature that allows us to start to understand the role of 5613 in the post-transplant maintenance settings. We also have agreement with FDA on the statistical design of each trial. Each trial enrolls 64 patients and up to 10 pediatric patients. Finally, we have agreement with FDA that 163 milligrams every 12 hours given with a strong CYP3A4 inhibitor is an appropriate phase two dose, and that is the dose we are using in each of these trials. We know that the vast majority of eligible patients are on a strong CYP3A4 inhibitor, and in an effort to enroll the cohorts as quickly as possible, at least one cohort to complete this year, we have now prioritized the enrollment of these patients versus those not on a strong CYP4 inhibitor. Once one cohort closes to enrollment, we plan to increasingly focus on accumulating the data required for labeling, which includes the necessary dose adjustment, often referred to as the ARMA dose. Let me remind you that this CLIMFARM data is not in any way limiting on our ability to enroll and complete the pivotal trial. Beyond the Augment Pivotal Program in relapsed refractory disease, slide six highlights some of the additional opportunities we are exploring with 5613, all of which build on the excellent safety and efficacy profile we have thus far seen with 5613. The panel on the left highlights the trial we are planning in collaboration with the Leukemia and Lymphoma Society, otherwise known as LLS. They have selected 5613 as the first Mennon inhibitor to be tested specific targeted therapy for patients with MLR or MPM-1 AML in their umbrella trial that they call BEAT-AML. The collaboration we have agreed to with them will test 5613 in combination with venetoclax and azacitidine in newly diagnosed AML patients who are unfit for induction chemotherapy and will consist of a Phase I followed by a Phase II-III trial, which could serve as the basis for a regulatory filing. Our scientists have generated preclinical data that supports the benefit of menin inhibition in combination with chemotherapy. And therefore, the middle panel of the slide highlights a trial to explore the use of 5613 in combination with standard salvage chemotherapies used for pediatric patients with ALL or AML that we are calling Augment 102. And the panel on the right illustrates a third trial that explores the activity in 5613 in patients with AML who have MRD-positive disease. This trial is being conducted as part of the Intercept Master Clinical Trial being led by the Australian Leukemia and Lymphoma Group. The Intercept Trial is focused on investigating novel therapies to target early relapse and clonal evolution as preemptive therapy in AML. The trial will enroll patients with measurable residual disease progression following initial treatment. A group of patients at very high risk of relapse that represent an important unmet medical need. A general observation in the treatment of cancer is that the earlier in the patient's disease course that you treat, the better patients do and the longer the patients stay on medicine. The Intercept Trial is a very creative approach to treating patients early in their disease course. I will also note that 5613 is the first MENIN inhibitor to be included in the Intercept AML Master Clinical Trial. We believe the selection of 5613 for inclusion into two Master Clinical Trial protocols highlights the enthusiasm that investigators have shown for treating patients with acute leukemias with 5613. As mentioned on our last quarterly call, we are excited to expand the clinical opportunities for 5613 beyond the initial approval in relapsed refractory acute leukemias. Slide 7 highlights our goal as a company to be first to market in relapsed refractory disease and then be first to garner additional value-enhancing indications by expanding the use of 5613 into newly diagnosed and maintenance settings in patients with MLR and MPM1 mutant acute leukemias. We see the opportunity to treat patients with these forms of mutant acute leukemia, which account for up to 40% of the eligible patient population, as early in their treatment journey as possible, and then drive them into remission and maintain them in that state for months, if not years. That emerging paradigm for men in inhibition is what will enable this to be one of the most important new franchises in heme malignancies and why we are so keen to invest in 5613 at this stage. Let me now turn to axotilamab, our potentially best-in-class monoclonal antibody therapy targeting CSF1 receptor. Slide 8 is our pivotal trial for axotilamab in CGBHD. This trial is the axotilamab for graft-versus-host disease trial called Agave 201. The trial is enrolling patients with CGVHD 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 a distinct dose of axotilamide given either every two weeks or every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for CGBHD. Secondary endpoints will include duration of response and validated quality of life assessments using the Lee symptom scale. Enrollment to the study is going quite well, and we are on track to deliver top line data in the first half of 2023. We were also delighted to announce during the quarter that Syndax and Insight closed our global collaboration that brings together two companies with a solid track record of innovation to accelerate and maximize the development of axotilamab. As you know, we presented our Phase I-II CGBHD data at ASH in December of last year, which received a very positive reaction and further underscored its best-in-class profile. Through our collaboration, Syndax and Insight will pursue an expanded set of indications in CGBHD and other fibrotic diseases. The development plan calls for the partners to design novel combinations with axotilamab in InsightsJAC inhibitors with a goal of establishing axotilamab in earlier settings within CVHD and expanding its market opportunity. As we previously mentioned was our intention, Syndex will initiate a robust Phase II trial in IPF in the fourth quarter of this year. The first expansion outside of establishing CGBHD as a BCHET into other fibrotic diseases where we believe axotilumab could have a significant impact. Successful development in IPF could lead to an additional approval and a very important indication of considerable value and would provide support to axotilumab and other fibrotic-driven diseases that the parties could explore over the course of the collaboration. Slide 9 highlights our view of the broad clinical and commercial opportunity for axotilumab. We believe chronic GVHD represents a high unmet medical need and an important commercial opportunity, with approximately 14,000 patients suffering from CGVHD in the U.S. today. The recent approvals of Jacofe and Cadman's Belimucidil will begin to delineate the commercial opportunity in CGVHD. Despite recent advancements in this area, to our knowledge, axotilamab is the only agent in clinical development that specifically targets the monocyte macrophage lineage. Both Syndax and Insight believe the data generated to date with axotilamab suggests it has the potential to play an important role in the treatment of CGBHD, both as a monotherapy and given its safety profile in combination with complementary medicines such as jacofi and other JAK inhibitors within the Insight portfolio. Through combinations in the frontline setting, as well as the opportunity to expand to ex-U.S. markets, we envision the CGVHD opportunity more than doubling, as shown on this slide. As we move Axotilimab into additional indications, starting with IPF, we really see Axotilimab contributing materially to the value of our company moving forward. Finally, slide 10 summarizes the transactions that led to the acquisition of Menin MLLR and Axotilimab program. We believe these transactions underscore our robust capabilities to identify and evaluate high-value differentiated assets, as well as the clinical development expertise to bring these compounds through key value inflection points. We anticipate in 2022 that we will be able to continue to expand our pipeline through product acquisitions or in licensing of quality differentiated assets. We expect to remain among preferred partners of such transactions. I'll now like to turn the call over to Alex to review our financial results. Alex?