Syndax Pharmaceuticals, Inc.

Good day, everyone, and welcome to the CINDEX fourth quarter and full year 2023 earnings conference call. Today's call is being recorded. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number five on your telephone keypad. If you would like to withdraw your question, press star and the number five once again. At this time, I would like to turn the call over to Sharon Clary, Head of Investor Relations at Syndex Pharmaceuticals.

Great. Thank you, Operator. Welcome, and thank you all for joining us today for a review of Syndex's fourth quarter and full year 2023 financial and operating results. I'm Sharon Clary, and with me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer of Dr. Neil Gallagher, President and Head of R&D, and Keith Goldan, Chief Financial Officer. Also joining us on the call today for the question and answer session are Dr. Peter Ardenlik, Chief Scientific Officer, and Dr. Anjali Ganguly, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the investor page of the company's website. You can now turn to our forward-looking statements on slide two. Before we begin, I'd 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 factors section in the company's most recent annual report on Form 10-K, as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, February 27, 2024 only. A replay of this call will be available on the company's website, www.syndax.com, following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Thanks, Sharon, and thank you to everyone joining us on the webcast. 2023 was a year of tremendous progress in execution for Syndax, marked by the delivery of positive pivotal data and regulatory submissions for both Revimenib and Axotilamab. We look forward to continuing this momentum in 2024 with two potential approvals and commercial launches. Syndex is firmly on the path to distinguishing itself as a commercial stage SMIDCAT biotechnology company. And with opportunities to expand well beyond the initial indications for Revumenib and Axotilimab, we envision creating long-term value with these franchises for years to come. On slide three, let me take a moment to review some recent accomplishments. With Revimenib, our highly selective menin inhibitor, we made significant clinical and regulatory progress in the fourth quarter. At the 2023 American Society of Hematology annual meeting in December, we presented robust data from the Phase I and Phase II portions of the Augment 101 trial that included a late-breaking oral presentation highlighting pivotal results from the KMT2A acute leukemia cohort, as well as multiple phase one combination trials that demonstrated Revumentib's ability to safely and effectively combine with standards of care. In late December, we announced the submission of an NDA filing for Revumentib under the FDA's Real-Time Oncology Review, or RTAR program, for the treatment of adult and pediatric relapsed or refractory KMT2A-rearranged acute leukemia. Submitting the NDA under RTOR ensures early engagement with the FDA throughout the review process, helping to de-risk the submission and provide a potentially expedited timeline to reviewment of approval. We expect to receive a PDUFA action date for reviewment of this quarter, which should align with a third quarter approval date. For axotilamab, our anti-CSF1R antibody, I'm excited to announce today that the FDA granted us priority review and a PDUFA action date of August 28, 2024, for the treatment of chronic graft-versus-host disease, or GVHD, after failure of at least two prior lines of systemic therapy. Positive data from the pivotal Agave 201 trial presented at a plenary scientific session at ASH in December formed the basis of the BLA submission. And last quarter, we also initiated a Phase II double-blind randomized clinical trial for the treatment of idiopathic pulmonary fibrosis, or IPF, that Neil will later detail in this call. Financially, we are in a very good position. We strengthened our balance sheet in the fourth quarter with an additional $258 million in cash, and Keith will go into more detail in our financials later in this call. We continue to prepare for commercialization in 2024. Our first mover advantage is of high strategic importance, and we are busy ensuring that we successfully execute two first and best-in-class drug launches. For Revimenib, we are focused on pre-launch activities, and we are finalizing our go-to-market strategies for both Revimenib and Exotilamab that we look forward to communicating in the coming months. In January, we exercised our option under our agreement with our partner Insight to co-commercialize Axotilamab in the United States and provide 30% of the commercial effort as there is a considerable benefit to promoting two products simultaneously to a highly overlapping and targeted physician-prescriber universe. 2024 is shaping up to be a historical year for Syndax as we prepare to launch two first and best-in-class products, and I am confident that we have the expertise, resources, and determination to achieve our goals. Now let's turn to slide four, and I'll begin a recap of some recent clinical data for Revumenev that investigators presented at the ASH annual meeting in December. There was significant excitement for Revumenev in the reaction to the data that investigators presented, which clearly demonstrated Revumenev's potential to become a cornerstone for the treatment in NPM1 and KMT2A acute leukemia. The data presentations have translated to continued strong enrollment in our clinical trials through additional engagement from the medical community, as well as additional requests for investigator-sponsored trials that could ultimately expand the use of the drug once approved. In the late-breaker presentation for the Augment 101 pivotal trial, we indicated that KMT2A acute leukemia patients achieved clinically significant responses to treatment with a high overall response rate of 63%, and responses were observed across all major subgroups. Revumentum delivered a high rate of deep responses with a CRCRH rate of 23%, 70% of which were MRD negative. At the time of the data cutoff, the median duration of CRCRH response was 6.4 months based on a Kaplan-Meier estimate with 46% or six patients remaining in response. Moving to slide five. In the Augment 101 trial, 39% of the overall responder population proceeded to a stem cell transplant, which is higher than historical benchmarks in this population of less than 5%. Many of these patients proceeded to transplant prior to achievement of a CRCRH. At the time of the data cutoff, 71% of patients who underwent a transplant had either restarted Revimentib or were eligible to restart as maintenance therapy. A few of these patients had been receiving maintenance treatment for as long as eight months, with several continuing on therapy, highlighting the potential for long-term treatment with Revumatic. Physicians with whom we have engaged are impressed by Revumatic's ability to induce rapid tumor clearance in heavily pretreated patients, enabling many of them to undergo a potentially curative bone marrow transplant. Treating physicians have repeatedly told us that they want to use Revumative as early as possible during treatment to bring more patients to transplant and then extend responses by continuing treatment following transplant engraftment. We unanimously heard from KOL's At Our Ash investor event and continue to hear from physicians today their belief that continued use of Revumative post-transplant should lead to the best possible outcomes, and it is an attractive option for these patients. Turning to slide six. The final pivotal cohort of the Augment 101 trial continues to enroll relapsed or refractory MPM1 mutant AML patients. It is designed to enroll 64 patients and up to 20 pediatric patients. With multiple presentations highlighting the consistency of Menin inhibition across MPM1 mutations and KMT2A rearrangements as a monotherapy agent, and in combination with standards of care, we continue to see the excitement building for Revimenib and MPM1. We are quite pleased with the recruitment in the trial and are reaffirming our guidance of expected completion of enrollment in the late first quarter or early second quarter of this year. We expect to report top-line data from the trial in the fourth quarter of 2024, and importantly, we continue to look forward to a potential approval in 2025 based on an SNDA filing for NPM-1 following Revu-Medim's anticipated initial approval in KMT2A acute leukemia. The Phase I MPM-1 data that we've reported for Revimenib supports our conviction that Revimenib could be an important treatment for this AML population. Across monotherapy and in combination, we've generated consistent results between KMT2A and MPM-1 acute leukemias. In the Phase I portion of Augment 101, 50% of MPM-1 patients achieved an overall response and 36% achieved a CR or CRH response. And importantly, all patients with a CR-CRH were MRD negative. Consistent with the KMT2A population, Revimenib also enabled a high percentage of MPM1 responders to proceed to transplant, 43%, and responses have been durable. This is despite many of the patients failing prior venetoclax therapy and receiving prior stem cell transplants. It's worth noting that Revimenib has been well-tolerated in patients with relapsor refractory MPM1 AML, In the Phase 1 results, there were no Grade 4 or 5 QT prolongations, no patients experienced more than Grade 2 differentiation syndrome, and no patients discontinued due to treatment-related adverse events. Now, turning to Slide 7, we believe that RevuMeta will form the backbone of treatment for patients with KMT2A and MPM1 acute leukemias. Our clinical strategy extends beyond the initial relapse or refractory indications and into the frontline and post-transplant maintenance settings through combinations with approved therapies. In the frontline setting, there are basically two broad categories of patients, those who are fit and can tolerate intensive chemotherapy, and those who are deemed unfit for intensive chemotherapy and would traditionally receive venetoclax plus azacitidine. Our frontline strategy is to add Revumenev onto standard of care treatments to show that Revumenev can be used effectively in combination, thereby increasing efficacy without negatively impacting the tolerability or safety profile of those regimens. We started combination development with venetoclax plus azacitidine in frontline unfit AML population in the BEAT AML trial. The trial is expanding to validate the recommended phase two doses, and we expect to have an additional data update for this trial later this year. In parallel, we are planning the venetoclax plus azacitidine pivotal trial that we expect to initiate by year end. To address frontline AML patients fit enough to tolerate intensive chemotherapy, we initiated a Phase I dose escalation trial of Revumetib in combination with standard of care induction therapy known as 7 plus 3. Here, we also anticipate identifying an RP2D for Revumetib and initiating a pivotal trial for this combination soon thereafter. On slide 8 is the data from the BEAT AML trial, a Phase I trial being conducted by the Leukemia and Lymphoma Society. In this trial, frontline AML patients who are unfit for induction chemotherapy are dosed with a triplet of revumentib, venetoclax, and azacitidine in 28-day cycles. In an interim look at data from 13 patients, 100% achieved a complete remission, or CRC, and all patients for whom we had an MRD assessment achieved an MRD negative response. This is significantly higher than what would be expected from venetoclax plus azacitidine alone based on the results of the VIALA-A trial where patients achieved a 66% CRC rate and only 24% achieved an MRD-negative response. Importantly, I'd like to emphasize that there was no impact on the safety or tolerability observed by adding Revimediv to this doublet regimen. Turning to slide nine. Gravimenta was also evaluated in another all-oral venetoclax combination among patients with relapsorefractory AML. Interim data from this trial, known as SAVE-AML, was conducted by investigators from the MD Anderson Cancer Center and presented at ASH. The SAVE trial evaluated the oral combination of revimenev, venetoclax, and a fixed-dose combination of dacitabine and cetaziridine in relapse or refractory AML or mixed phenotype acute leukemias. In the interim presentation, nine patients with either NPM1, KMT2A, or NUP98 mutations were enrolled into the trial. These patients had received a median of three prior lines of therapy, and over half of them had received prior venetoclax and prior hypermethylating agents. At the interim assessment, 100% of patients achieved a response and 78% achieved a complete remission. Importantly, responses were observed across all three patient subsets, NPM1, KMT2A, or NUP98. This triple combination was also well-tolerated at both active doses of Revimed in the trial, including the current monotherapy RP2D, with no new or increased safety signals observed beyond what would be expected with venetoclax and a hypomethylating agent. Now to slide 10. KMT2A and MPM1 acute leukemias represent up to 40% of all AML patients, and there are no FDA-approved targeted therapies for this population. Inclusive of the expansion opportunities, there is the potential to address upwards of 12,000 MPM1 and KMT2A acute leukemia patients across various settings. We believe relapse or refractory KMT2A acute leukemia alone represents a $750 million market opportunity in the U.S. The annual incidence of KMT2A acute leukemia is about 2,600 patients, and the majority are refractory to frontline standard of care treatments. We estimate a median duration of therapy across the treated population of approximately nine months, and we believe the clinical data supports pricing competitively with other targeted therapies in AML, such as the FLT3 or IDH inhibitors. We anticipate that with the only age and disease agnostic label in KMT2A acute leukemia, along with no other treatment options approved in this population and no near-term competition, Revimenib should become the treatment of choice for patients with relapsed or refractory KMT2A acute leukemia. We expect that our first mover advantage and the experienced physicians will gain treating patients with Revimenib could extend meaningfully beyond KMT2A and allow us to build a formidable franchise in the next few years, augmented by a second indication in MPM1 AML. Our market research suggests that if approved, oncologists are likely to prescribe Revumetib as either their second or third-line agent of choice for the treatment of NPM1 AML. We estimate that this population would be slightly larger than the relapsed or refractory KMT2A acute leukemia population, and based on our Phase I results, we also believe overall efficacy and treatment duration will be consistent between the KMT2A and NPM1 relapsed or refractory populations. Having two distinct market segments in acute leukemias available to us, KMT2A and NPM1, would create a total accessible population of somewhere between 5,000 and 6,500 patients in the relapsed or refractory setting and an addressable market opportunity approaching $2 billion in the U.S. Beyond acute leukemia, we are also investigating the opportunity to expand to solid tumors. Our proof-of-concept signal-seeking phase 1 clinical trial in metastatic colorectal cancer is ongoing. This trial is based on preclinical science that supports the role of menin-KMT2A interaction in beta-catenin-driven tumors. We are following these patients and expect to provide an update on the progress of the dose escalation phase of the trial in the second quarter of 2024. we would perceive single-agent activity reflected as responses or prolonged stable disease as encouraging in this third-line patient population. Let me now turn to axotilamab, our monoclonal antibody targeting the CSF1 receptor beginning on slide 11. As noted earlier, we're thrilled that the BLA for axotilamab in adult and pediatric patients with chronic GVHD after failure of at least two prior lines of systemic therapy has been given a PDUFA action date of August 28, 2024 by the FDA. Data from the Global Pivotal Agave 201 trial formed the basis for this application. The Agave 201 trial, which was showcased during the Plenary Scientific Session at ASHE, met its primary endpoint of overall response rate by cycle 7, day 1, using the 2014 NIH consensus criteria for chronic GVHD across all three dose groups. The overall response rate was 74% at a dose of 0.3 milligrams per kilogram administered every two weeks. The responses were durable, with a median duration of response not yet reached at the time of data cutoff, and 60% of responders were still responding at one year. Axotilinab was well-tolerated in the trial with a low 6% rate of discontinuation. The most common adverse events were consistent with the on-target effects observed in prior trials. Axotilinab is differentiated from other approved therapies for chronic GVHD in that it is the first investigational chronic GVHD treatment to target inflammation and fibrosis through the inhibition of disease-associated macrophages. On slide 12, you will note that responses, including CRs, were seen across all organs involved, and notably in fibrosis-dominated organs, including esophagus, joints, fascia, and lung. Over 85% of patients reported a reduction in chronic GVHD-related symptom burden in agave 201, which supports the potentially pronounced impact this mechanism can have on patients suffering from chronic GVHD. These results reinforce its potential as a first and best-in-class CSF1R monoclonal antibody in chronic GVHD. I'll now turn the call over to Neil to speak about the IPF trial that we started in late fourth quarter, as well as the scientific rationale for the use of axotilamab in IPF.