Syndax Pharmaceuticals, Inc.

Thank you for standing by, and welcome to the CINDEX Second Quarter 2021 Financial Results Conference Call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question at that time, please press star then 1 on your touch-tone telephone. As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Melissa Forrest, with Oracle Partners. You may begin.

Thank you, Valerie. Welcome and thank you to those of you joining us on the line and the webcast this afternoon for a view of Syndax's second quarter 2021 financial and operating results. With me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morrison, Chief Executive Officer, and Daphne Kouridis, Chief Financial Officer. Also joining us on the call for the question and answer session is Michael Metzger, President and Chief Operating Officer, Dr. Michael Myers, Chief Medical Officer, and Dr. Peter Ordentlich, Chief Scientific Officer. This call is being accompanied by a slide deck that has been posted on the company's website, so I'd ask that you please turn to the forward-looking statements on slide two. 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 factors 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 the company's views as of today, August 9th, 2021 only. A replay of the call will be available on the company's website at the conclusion of the call. And with that, I'm pleased to turn the call over to you, Dr. Briggs Morrison, Chief Executive Officer of Syndex.

Thanks very much, Melissa, and thank you to everyone joining us on today's call and the webcast. Slide three 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. We've continued to make great progress in both of our clinical programs during the second quarter of this year. Augment 101, our Phase I-II trial of SNDX5613, our selective Mennon inhibitor, is progressing as anticipated with a meaningful FDA meeting coming up this quarter. Today, we are announcing that we are initiating two trials that capitalize on the favorable combinability profile of 5613, and importantly, one of the trials represents our first opportunity to move into the frontline therapy of AML. For axotilamab, our antibody against CSF1R, enrollment is ongoing in our pivotal Agave 201 trial. We therefore remain on track to have two registrational programs ongoing this year for two first-in-class and potentially best-in-class medicines for two areas of important unmet medical need. Thanks to the support of our many committed investors, we are well-financed to vigorously pursue both of our existing programs, and to aggressively look for additional opportunities to bring targeted oncology drugs into our pipeline. Let's now turn to slide four in our recent data disclosure from the phase one portion of the Augment 101 trial of SNDX5613 for the treatment of leukemia. As we noted in our recent data disclosure, in our phase one trial, 5613 has been well tolerated over multiple cycles with no patient discontinuing for a drug-related adverse event. We were, of course, excited to have also observed clear evidence of monotherapy activity in this population of patients with relapse or refractory acute leukemia with either MLLR or NPM1C mutations, with most responders achieving MRD negative status. Our pharmacodynamic data confirmed the mechanism of action, and perhaps most importantly, we had identified a candidate recommended phase two dose that met all of our pre-specified criteria. We also previously communicated that we were exploring intermediate doses that represent an increase in dose over the candidate recommended phase two dose. Since our last call, we have now completed our review of the initial results from the intermediate doses, which are 276 milligrams twice a day in arm A and 163 milligrams twice a day in arm B. These intermediate doses have also met all of our pre-specified criteria for a recommended phase 2 dose, and therefore we have updated our recommended phase 2 dose selection. On slide 5, we include the DLP results in the dose selection portion of the trial. In arm A, you see we have moved from 113 to 226 to 339, and finally to 276. no DLTs observed at the intermediate dose level of 276. In RMB, we moved from 113 to 226, and finally to 163, with, again, no DLTs at the intermediate 163-milligram dose level. Both 276 in RMA and 163 in RMB have been well-tolerated and now represent our nominated recommended Phase II dose. As you may recall, the only DLT we have seen with 5613 is grade three QTC prolongation, and we did not see that in the 276 arm A or the 163 arm B cohorts. We attribute this to efforts we have made with our investigative sites to implement simple clinical measures to minimize the incidence of QT prolongation. I again want to reinforce why we are so excited about what we are seeing in our phase one program. Let me first remind everyone that this is a Phase I trial. Patients had received on average three prior therapies. About 40% of patients had relapsed after a bone marrow transplant, which is a very negative prognostic sign, and almost 60% had previously received venetoclax. These are very difficult to treat patients, and we were delighted to see a 48% overall response rate, a 23% CR-CRH rate, and 67% of the responses achieving an MRD negative status. Every physician currently treating acute leukemia who has reviewed this data with us has been excited by the efficacy we are seeing. We are aware of the regulatory precedence for the approval of novel targeted therapies for patients with relapsed refractory acute leukemia. And while there are no guidelines on a specific rate that is required for approval, We have previously pointed out the rates that were reported for recently approved FLT3 and IDH inhibitors that suggest that a CR-CRH rate above 20% has been acceptable to FDA. The Phase 1 data we have generated from around 50 patients treated in our ongoing Augment 101 trial gives us confidence that 5613 will achieve that level of efficacy or better in our Phase 2 trial. Slide 6 shows our go-forward plans for 5613. We had the option to initiate the Phase 2 portion of Augment 101 as previously communicated. We have our updated recommended Phase 2 dose. However, our clinical and regulatory team decided not to start the Phase 2 portion at risk and instead decided to first garner endorsement from FDA regarding our recommended Phase 2 dose selections. This decision was in keeping with the excellent working relationship we've established with the agency and are being awarded fast-track designation. The end-of-phase one meeting is anticipated to occur this quarter, as we have previously communicated, with the phase two portion to open soon thereafter. While we have not officially started the phase two expansion portion of the trial, we are continuing to enroll additional patients at our proposed recommended phase two dose, and have FDA agreement that these newly enrolled patients may be included in our Phase II expansion cohorts pending, of course, their approval of our recommended Phase II dose. We anticipate presenting a full and substantive update of Augment 101 at a medical conference at the end of this year. We will have treated over 40 patients with either MLLR or NPM mutations and anticipate having a relatively mature data set To date, we've only shown the CR-CRH rate for our phase one population as a whole, but we are excited that at the end of the year, given this larger and more mature data set, that we will be able to break out the CR-CRH rate for MLR versus NPM1. We will also present a promising first look at the durability of the CR-CRH responses, which is an important aspect of the efficacy of 5613. We believe these updates at a medical conference at the end of the year will be important and could meaningfully address key aspects of the 5613 profile. As I've mentioned previously, the Phase II portion of the trial will enroll three distinct expansion cohorts, patients with MLLR-ALL, patients with MLLR-AML, and patients with NPM1 mutant AML. The Phase II portion will enroll both pediatric and adult patients, thereby providing us a potential path to regulatory approval with a broad label, including both adults and pediatrics. I should note that the results are positive. This Phase II portion of Augment 101 could potentially support a regulatory filing given existing regulatory precedents. We look forward to soon finalizing the details of the trial with FDA and believe we could potentially have top-line data for one or more of the cohorts sometime next year. Over the last period, we have also been conducting extensive research into the broad landscape of clinical opportunities for 5613 beyond the initial approval in relapsed refractory acute leukemias, as illustrated on slide seven. Our goal as a company is to be first to market in relapsed refractory disease and then be first to garner additional value-driving indications. Today, we are announcing our first steps towards building out the 5613 franchise. Our scientists, in collaboration with scientists at MD Anderson, have recently published preclinical data supporting the use of our menin inhibitor in combination with venetoclax. The reference is provided on the slide. The Leukemia and Lymphoma Society, otherwise known as LLS, is sponsoring an umbrella trial that they call BeatAML. They have been assessing potential menin inhibitors to include in the trial and based on the strength of our data, have selected 5613 as the first menin inhibitor to be tested as a specific targeted therapy for patients with MLLR or NPM1 AML. The collaboration we agreed to with them will test 5613 in combination with venetoclax and azacitidine in newly diagnosed AML patients that are unfit for induction chemotherapy and will consist of a Phase I and a Phase II-III trial which potentially could serve as the basis for regulatory filing. Our scientists have also generated preclinical data that supports the use of a menin inhibitor in combination with chemotherapy. As a result, we are also initiating a second phase one trial exploring 5613, which we called Augment 102, in combination with standard salvage chemotherapies used for pediatric patients with either ALL or AML. We anticipate announcing additional trials over the remainder of the year that will further build out the 5613 franchise. Let me now turn to slide eight, Anaxitilumab, our potentially best-in-class monoclonal antibody therapy targeting the CSF1 receptor. As you know, we presented our phase one chronic graft-versus-host disease data at ASH in December of last year. You may recall that we had opened a phase two expansion cohort at the one milligram per kilogram dose, and as previously announced, that cohort has now been fully enrolled. Later this year, we anticipate presenting the full updated data from both the 17 patients from the phase one portion of the trial, as well as the 23 patients enrolled in the phase two expansion cohort at the one mg per kg dose. I should emphasize that our base case assumption is that this 1 mg per kg dose will be our label dose, and hence the Phase II expansion cohort data is quite relevant as a de-risking event to the eventual outcome of our pivotal trial. Slide 9 is our pivotal trial for axotilumab in chronic graft-versus-host disease. This trial is the axotilumab for graft-versus-host disease trial called Agave TIL-1. The trial is enrolled in 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 a distinct dose of axotilumab given either every two weeks or 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 least symptom scale. Enrollment to the study is underway, and we are on track to deliver top-line data to 2023. We believe that chronic GVHD represents a high unmet medical need and an important commercial opportunity with approximately 14,000 patients suffering from chronic graft-versus-host disease in the U.S. today. With the most recent pivotal results from both Insights of Jackify and Cadmium's Velumocidil and the recent approval of Velumocidil, we will soon see commercial launches that will begin to delineate the commercial opportunity in chronic graft-versus-host disease. Despite recent advancements in this area, to our knowledge, axotilumab is the only agent in clinical development that specifically targets the monocyte macrophage lineage. We believe the data generated to date with axotilumab suggests it has the potential to play an important role in the treatment of chronic graft-versus-host disease, both as monotherapy and given its safety profile in combination with complementary medicines. We've also been working extensively with experts in the field of fibrotic diseases, and have found a strong consensus that the scientific rationale for the efficacy of axotilamab in chronic graft-versus-host disease supports its potential in a wide variety of fibrotic diseases such as idiopathic pulmonary fibrosis and scleroderma. We're actively evaluating options by which to build out the axotilamab franchise beyond chronic graft-versus-host disease and to take advantage of what we believe are significant set of opportunities that can materially enhance shareholder value. As we have previously communicated, we obtained orphan drug designation from FDA for the use of axitolamab in IPS. And finally, on slide 10, we summarized the transactions that led to the acquisition of the 5613 and axitolamab programs. We believe these transactions underscore our robust capabilities to evaluate and identify high-value differentiated assets as well as the clinical development expertise to bring these compounds through key value inflection points. We anticipate we will be able to continue to expand our pipeline through product acquisitions or in-licensing of quality, differentiated assets, and we expect to remain among the preferred partners for such transactions. I'll now turn the call over to Daphne to review our financial results.