Syndax Pharmaceuticals, Inc. (NASDAQ:SNDX) Q3 2023 Earnings Call Transcript

Syndax Pharmaceuticals, Inc. (NASDAQ:SNDX) Q3 2023 Earnings Call Transcript November 2, 2023

Syndax Pharmaceuticals, Inc. beats earnings expectations. Reported EPS is $-0.73, expectations were $-0.8.

Operator: Good day, everyone, and welcome to the Syndax Third Quarter 2023 Earnings Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

Sharon Klahre: Thank you, Operator. Welcome, and thank you all for joining us today for a review of Syndax's third quarter 2023 financial and operating results. I'm Sharon Klahre, and with me this afternoon to provide an update on the Company's progress and discuss financial results are Michael Metzger, Chief Executive Officer; 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 Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the Investors page of the Company's website. You can now turn to our forward-looking statements on Slide 2.

Lab technicians in safety glasses and lab coats conducting a clinical trial of a new pharmaceutical.

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 may represent our views as of today, November 2, 2023, only. A replay of this call will be available on the Company's website, www.syndax.com following its completion. With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer, of Syndax.

Michael Metzger: Thank you, Sharon, and thank you all for joining the webcast. This continues to be an exciting year for Syndax and I look forward to sharing a number of updates with you on the significant progress we have made. Throughout the third quarter, we delivered on key pipeline milestones that are highlighted on Slide 3, including reporting positive top line AGAVE-201 pivotal data of axatilimab for the treatment of chronic graft-versus-host disease. We also reported positive top line pivotal AUGMENT-101 data for revumenib in adult and pediatric patients with relapsed/refractory KMT2A rearranged acute leukemia. Together these results put us on a clear path to becoming a commercial stage biopharmaceutical company in 2024 with two potentially first and best-in-class products.

We are also happy to provide data today from additional relapse or refractory NPM1 patients that were enrolled in the final stages of the Phase 1 portion of the AUGMENT-101 trial. Neil will walk us through the data a little later in this call, but in summary, we are encouraged by the by the 36% CR/CRh rate and deep responses that we are seeing in the NPM1 population. Responses elicited by revumenib in the NPM1 population are durable with some patients in remission beyond 22-months further supporting the rationale that revumenib can provide a meaningful benefit to NPM1 patients and emphasizing its blockbuster commercial potential across both KMT2A and NPM1 acute leukemia. We continue our positive momentum heading into the end of 2023 with a primary focus on completing two potential regulatory filings by year-end and launching both drugs in 2024.

This will put Syndax in a very unique position to create value as a mid cap biotech company. We will have a significant presence at the American Society of Hematology ASH annual meeting, including at our planned investor event and expect to provide several data updates on both these programs at that time. I am pleased to share that as of a few days ago, we initiated the NDA submission of revumenib for KMT2A of 2 leukemia under the FDA's real time oncology review program or RTOR. We view RTOR as a significant benefit for the revumenib program. It complements our BTD and fast track status for KMT2A and provides a more efficient review process to ensure that revumenib is available to patients as early as possible. Under RTOR, the sponsor has consistent engagement with the FDA throughout the submission process.

Drugs are accepted for review into this program need to meet specific eligibility criteria, the most important of which is the likelihood of demonstrating substantial improvement over available therapy. In accordance with FDA guidance for AML and in line with the approvals of other AML agents in the relapsedrefractory setting, we anticipate revumenib would be granted full approval based on the results of AUGMENT-101. With our partner Incyte, we also remain on track to complete the BLA filing for axatilimab by year-end. As you saw from our press release earlier today, data from both the AGAVE-201 and AUGMENT-101 pivotal trials including post transplant maintenance data along with revumenib combination data from the SAVE trial will be presented at the ASH meeting in December.

Beyond the Congress presentations, we will also have the opportunity to share additional data from ongoing revumenib combination trials at our ASH investor event, which will further reinforce revumenib's compelling clinical profile and meaningfully add to its value proposition. We are well funded with $379 million in cash as of September 30. Our current balance sheet not only supports our planned commercial launches and the trials that we have outlined, but also allows us to expand beyond our core registration indications and pursue select business development opportunities. Now let's dive into revumenib, our highly selective main inhibitor. I will ask Neil to provide a recap of the results from the AUGMENT-101 pivotal trial, speak to the ASH abstracts and review the data from the NPM1 patients in the Phase I portion of the AUGMENT-101 trial.

Neil?

Neil Gallagher: Thank you, Michael. I will now review the AUGMENT-101 pivotal data in relapsed or refractory KMT2A acute leukemia beginning on Slide 4. As previously reported, the independent data monitoring committee reviewed the data and recommended that trials stop early for efficacy in accordance with a predefined interim analysis. We are very pleased with the robustness of the data that we reported. Almost two-third of these heavily pretreated patients achieved clinically significant responses, enabling many to receive potentially curative transplant. Importantly, a high proportion all responders in the trial were started on revumenib in the post transplant maintenance setting. The desire for physicians to restart revumenib as post transplant maintenance speaks to its efficacy and tolerability and their belief that it may offer a better outcome for their KMT2A acute leukemia patients.

Importantly, the ability of these heavily pretreated patients to both respond to and tolerate revumenib therapy also underscores its potential to be adopted into frontline combinations. Turning to Slide 5. The majority of patients in the efficacy evaluable population, which include adult and pediatric AML and ALL patients, achieve clinically significant responses to treatment with a high overall response rate of 63%. The CR/CRH rate in this population was 23%. The response rates observed in KMT2A AML specifically were consistent with those in the overall efficacy of valuable population, with 65% achieving a response and 24.5% achieving CR or CRH. The MRD negative rate among CR/CRH responders also impressive at 70%. At the time of the data cutoff, the median duration of CR/CRH response was 6.4 months across both the efficacy of valuable and AML populations, with 46% or six patients remaining in response.

Of note, this is a Kaplan Meier estimate, and the data will continue to mature over time. Therefore, the median DOR may extend beyond 6.4 months, slip additional follow-up. Turning to Slide 6. Not only did we observe a high overall response rate of 63%, but 39% of responding patients proceeded to bone marrow transplant, which is notably higher than the historical benchmark in this population of less than 5%. Eight patients were transplanted prior to achieving CR/CRH at the discretion of the attending physician. Clearly, if physicians had decided to wait a little longer prior to transplant, then more of these patients could have achieved a best response CR/CRH. For example, if all 8 of these patients had achieved CR/CRH, then the rate would have been 37%.

71% of these patients, 10 of 14, either restarted revumenib or were eligible to restart as maintenance therapy. At the time of data cutoff, some patients were treated in the maintenance portion for as long as eight-months and several are continuing on therapy, which we believe speaks to revumenib compelling overall clinical profile and the potential for long-term maintenance in this setting. The ability of revumenib to rapidly induce BLAST free responses in heavily pretreated patients, thereby enabling them to undergo potentially curative bone marrow transplant followed by post transplant maintenance, represent a potential paradigm shift in the standard of care in this setting. We have a presentation at the ASH meeting that will highlight revumenib for post transplant maintenance, including patients on therapy in remission beyond 18-months.

The data from AUGMENT-101 indicate that revumenib is well tolerated and the safety profile is consistent with what was previously reported. We believe that the emerging benefit risk profile of revumenib support its use not only as a monotherapy in the relapsedrefractory setting before and after transplant but also its potential use in combination with frontline standards of care for which initial data are forthcoming will be forthcoming later this year. Turning to Slide 7. Today, we announced encouraging data from 3 additional patients with NPM1 mutated relapsed or refractory AML included in the Phase 1 portion of the AUGMENT-101 trial for a total of 14 NPM1 patients treated at doses meeting the RP2D criteria. These patients are enrolled in Phase 1 to complete the pharmacokinetic characterization of revumenib.

Among these 14 patients, seven achieved a response to treatment for a 50% overall response rate, five of 14 achieved a CR or CRH rate of 36%, and 100% of the CR/CRH responders were MRD negative. On Slide 8, you may see that these responses are durable with four of five of the patients remaining in response, three already beyond 6 months, one beyond 22-months and one over a 30-month at the time of the analysis. Revumenib also enabled 43% of NPM1 responders to proceed to transplant. One of the patients who proceeded to transplant have been enrolled following the AUGMENT-101 protocol update, which allowed patients to restart revumenib post transplant. This patient remains on revumenib maintenance at the time of the analysis. Similar to the Phase 2 results observed regulation revenue in that was well tolerated in patients with relapsed refractory NPM1 AML.

There were no grade four or five QT prolongations, no patients experienced more than Grade 2 differentiation syndrome, and no patients discontinued due to treatment related adverse events. As Michael said earlier, these data continue to support our conviction. The revumenib will be an important treatment for NPM1 AML as well as from KMT2A acute leukemias, and we expect that NPM1 pivotal trial results will be consistent with the data generated to date and highly supportive of a first to market approval. The pivotal cohort of the AUGMENT-101 trial continues to enroll relapsed refractory NPM1 mutant AML patients. The trial is designed to enroll 64 patients and up to 20 pediatric patients. While the trial continues to recruit well in the U.S. and internationally, we now forecast completion of enrollment in the late first quarter or early second quarter next year due to a few high enrolling sites in Europe coming online later than we expected in the third quarter.

Coupled with the recent events in Israel where we have a high concentration of sites. I would note that Israel accounts for 16% of our enrolling sites, and historically, these have been very high enrolling. We are now looking to make up for any potential shortfall at our sites, but it is difficult for us to predict the impact that the evolving geopolitical situation may have an enrollment. Nonetheless, we expect to be in a position to report data in the fourth quarter of 2024 and importantly, continue to look forward so a potential approval in 2025 based on an sNDA filing following revumenib's anticipated initial approval in KMT2A. Turning to Slide 9. In addition to sharing the AUGMENT-101 pivotal data at ASH, we look forward to Dr. Issa highlighting his saved trial results in an oral presentation on Saturday morning during the meeting.

This is an investigator sponsored Phase 1b trial conducted by Dr. Issa at the MD Anderson Cancer Center, evaluating an all oral combination of revumenib with venetoclax and a fixed dose combination of cecitabine and cetadiridine in children and adults with relapsed refractory AML or mixed phenotype acute leukemias. At the time of the data cutoff, the trial was enrolling at the current monotherapy RP2D of 163 milligrams every 12-hours with a strong CYP3A4 inhibitor. In total, eight patients with either NPM1, KMT2A or NOT98 mutations were enrolled in the trial, having received 2.5 median prior lines of therapy. Approximately two-thirds of patients received prior venetoclax. All patients on a strong CYP3A4 inhibitor and were on a strong CYP3A4 inhibitor and were therefore treated with revumenib in either 113 milligrams Q12 early or 160 milligrams 163 milligrams 63 miligrams early.

Seven of eight patients were evaluable for response. All seven, 100%, achieved a response. Six of seven achieved a CRC, and two of seven, 28% achieved a CR/CRH. Importantly, responses were observed across relapsed or refractory NPM1 KMT2A or NUP98 acute leukemia patients. Three patients transitioned to hemakudic stem cell transplantation following response, and two continue in remission and have started maintenance as of the data cutoff. We are highly encouraged by the combinability of reviveninib with Venetoclax and the hypomethylating agent in this trial. This combination was well tolerated at active doses, including the current monotherapy, RP2D. I will now turn the call back to Michael.

Michael Metzger: Turning to Slide 10, we believe that revumenib could form the backbone of treatment for patients with KMT2A rearranged and NPM1 mutant acute leukemias and as demonstrated by its compelling efficacy and safety profile, we have expanded our clinical strategy beyond the relapsed or refractory setting into earlier settings and post transplant maintenance including combinations with approved therapies. In an attempt to accelerate the generation of evidence of clinical benefits seen with revumenib across various settings of KMT2A and NPM1 acute leukemias, we are collaborating with groups and leading investigators in addition to the clinical trials that Syndax is conducting. In addition to the SAVE trial that Neil described earlier, we plan to present initial data from the Beat AML and AUGMENT-102 trials in the fourth quarter at our planned investor event at ASH.

The Phase I Beat AML trial is part of our collaboration with Leukemia and Lymphoma Society and revumenib is being combined with Venetoclax and azacytidine to treat newly diagnosed AML patients who are unfit for induction chemotherapy. Enrollment is ongoing in the dose finding stage of the trial to confirm the RP2D for this combination and we continue to expect to share data on safety and efficacy from the trial at our ASH investor event. The AUGMENT-102 trial is designed to assess the safety of revumenib in combination with standard salvage chemotherapies for patients with relapse or refractory acute leukemias. We anticipate presenting an update on the initial safety and potential RP2D from the trial at our ASH investor event. We look forward to initiating a trial of revumenib in combination with standard of care intensive chemotherapy known as seven plus three in newly diagnosed patients with acute leukemia in late 2023 or early 2024.

This trial will also include an option for maintenance with revumenib monotherapy. Beyond the acute leukemia trials we have laid out here, we are rolling a proof of concept signal seeking phase one clinical trial in metastatic colorectal cancer based on compelling preclinical science supporting the role of the menin-KMT2A interaction in beta teeny driven tumors. The trial is advancing nicely through the dose escalation phase and we are nearing NRP2D. We would perceive responses or prolong stable disease as encouraging in its difficult to treat patient population with the monotherapy and we expect to follow these patients to gather sufficient efficacy into 2024. We anticipate being able to provide an update on the progress at the dose escalation phase of the trial in the first quarter of 2024.

Now to Slide 11. KMT2A and NPM1 acute leukemias represent up to 40% of AML patients and there are no FDA approved targeted therapies for this population. Including the expansion opportunities, there is the potential to address upwards of 12,000 NPM1 mutant and KMT2A rearranged acute leukemia patients across various settings. We are committed to bringing these encouraging clinical benefits to even more patients as this remains an area with significant unmet need. We believe that relapse or refractory KMT2A acute leukemias alone represent a $650 million to $750 million market opportunity in the U.S. based on the estimated patient population, duration of treatment and current pricing assumptions. KMT2A-rearrangement represent approximately 10% of AML and ALL, which translates into an incidence of approximately 2,600 KMT2A-rearranged acute leukemia patients, a very high percentage of whom are refractory to frontline standard of care treatments.

Based on the enthusiasm we are hearing from physicians and the potential to shift the treatment paradigm in KMT2A to incorporate maintenance treatment post transplant, we believe the median duration of therapy across the treatment population would be approximately nine-months and we believe the data generated in AUGMENT-101 support pricing competitive with or above other targeted therapies in AML such as FLT3 or IDH inhibitors. With no treatment options approved for these patients and no near-term competition, revumenib could easily become the treatment of choice for all patients with KMT2A acute leukemia based on obtaining the only age and disease agnostic label in KMT2A acute leukemia. We expect that our first mover advantage and experienced physicians will gain treating their patients term with revumenib could extend meaningfully beyond KMT2A and allow us to build a formidable franchise in the next few years.

Supported by the compelling NPM1 data we presented today, we believe revumenib will also provide meaningful benefit in relapsed or refractory NPM1 patients. Our market research suggests that if approved, oncologists are likely to reach for revumenib as either their second or third line agent of choice for patients with NPM1 mutant AML. We estimate that this population will be slightly larger than relapsed 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 populations. Having first mover access to two distinct market segments in acute leukemias, KMT2A and NPM1 creates a total accessible population of 5,000 to 6,000 patients in the relapsed refractory setting and an addressable market opportunity of approximately $1 billion to $1.5 billion for revumenib in the U.S. alone.

We anticipate that revumenib will begin to carve out a dominant share of the relapsed and refractory NPM1 market starting in 2025. Now let's dive into axatilimab, our monoclonal antibody targeting the CSF1 receptor beginning on Slide 12. In collaboration with Incyte, we shared positive results from the global pivotal AGAVE-201 trial evaluating the efficacy, safety and tolerability term of axatilimab in 241 patients with active chronic GVHD whose disease had progressed after at least two prior therapies. As a reminder, the trial met its primary endpoint of overall response rate by cycle 7 day 1 using the 2014 NIH consensus criteria term or chronic GVHD across all 3 dose groups. The overall response rate or ORR was 74% at a dose of 0.3 miligrams per kilogram administered every 2 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. Axatilimab was well tolerated in the trial with a low 6% rate of discontinuations and the most common adverse events were consistent with the on target effects that were observed in prior trials. I want to remind you that robust efficacy was observed despite the patients being very advanced and heavily pretreated. As an example, I would highlight that there are meaningful differences in patient populations between the axatilimab AGAVE-201 trial and the Rezurock ROCKstar trial, both of which targeted patients with chronic GVHD who had received two or more prior lines of therapy. Notably, patients in the AGAVE-201 trial had a longer median time since diagnosis or severe chronic GVHD and had received more prior lines of therapy, including a greater number of patients that received Jakafi than patients included in the Rezurock trial.

We believe these points of differentiation underscore how impressive the AGAVE-201 trial results are and point to the significant value axatilimab could bring to patients if approved. These results not only support the promise of axatilimab safety and efficacy profile, but reinforce potential as a first and best in class CSF1R monoclonal antibody term in chronic GVHD. Axotilumab is the first investigational chronic GVHD treatment to target inflammation and fibrosis through the inhibition of disease associated macrophages and the AGAVE-201 data demonstrates the potentially pronounced impact this mechanism alone or in combination with standard of care therapies already available for the management of this disease may have on patients suffering from chronic graft versus host disease.

In collaboration with Incyte, we intend to file a BLA by year-end 2023. Additionally, we look forward to showcasing the full results during the plenary session at ASH. Turning to Slide 13, approximately 14,000 U.S. patients suffer from chronic graft versus host disease, 50% of whom require treatment beyond second line due to disease progression, inadequate response or disease manifestations that aren't wholly addressed with current treatments. Unfortunately, there are no cures for this advanced population of chronic GVHD patients. Patients are initially treated with corticosteroids and then cycled through a variety of additional therapies. While patients may be treated with several of the approved therapies, the order in which they are used may depend on the physician's experience with how a given agent may address specific manifestations of the disease.

Jakafi and Rezurock have had successful commercial launches which speaks to the unmet need in chronic GVHD that translates to a substantial commercial opportunity. It is our conviction that axatilimab could provide an effective differentiated practice changing intervention for this underserved population. Axatilimab suppresses monocyte derived macrophage activation and proliferation, which may provide more comprehensive control of the disease than currently approved therapies. This is a key differentiator and also towards moving axatilimab earlier in the treatment paradigm to potentially prevent organ damage before it occurs. Because axatilimab is an antibody, drug, drug interactions are expected to be minimal and axatilimab's unique mechanism of action may offer the benefit of being an ideal combination partner with standard of care therapy is currently used for the treatment of chronic GVHD.

The opportunity to expand to ex-U.S. markets and additional high value indications as well as combinations in earlier settings in chronic GVHD both in adults and pediatrics could build significant additional value for axatilimab. We are looking forward to the initiation of additional trials of axatilimab, including a 26-week randomized placebo controlled Phase 2 trial in 135 idiopathic pulmonary fibrosis patients expected to begin by year-end as well as a combination trial to be conducted by Incyte in chronic GVHD patients with Jakafi in mid-2024. I will now turn the call over to Keith to review our financial results. Keith?

Keith Goldan: Thank you, Michael. Let me take a few minutes to discuss our financial results for the quarter ended September 30, 2023. Turning to Slide 14, the results of our operations for the third quarter of 2023 and the comparison to the prior year's quarter are included in our press release, so I won't repeat them in these remarks. Additional financial details are available in our third quarter 2023 report, which was filed earlier today on Form 10-Q. I would like to point out that our net loss for the Q3 was $51.1 million or $0.73 per share compared to a net loss of $35.4 million or $0.58 per share for the comparable period last year. The difference in our net loss was driven largely by an increase in employee related expenses and professional fees within both SG&A and R&D, combined with increased clinical and manufacturing expenses.

We ended the third quarter with $379.3 million in cash, equivalents, and short- and long-term investments, and 69.9 million shares in prefunded warrants outstanding. Our balance sheet is expected to provide runway into the second half of 2025, which allows us to appropriately invest to maximize the value of our pipeline and importantly, it also allows us to transition into a commercial stage organization in 2024. Looking ahead, I would like to provide financial guidance for the rest of this year. For the full year of 2023, the company expects research and development expenses to be $160 million to $165 million and total operating expenses to be $225 million to $230 million, both of which are inclusive of approximately $30 million of non-cash stock compensation expense.

Note that this is a reduction from our prior guidance of $160 million to $175 million for R&D expense and $225 million to $240 million for total operating expenses. With that, let me now turn the call back over to Michael.

Michael Metzger: Thank you, Keith. Before we open the call for questions, I would like to provide a summary of what was presented today. In the near-term, we remain laser focused on delivering all the data readouts, including the full AUGMENT-101 and AGAVE-201 data sets as well as data from several other combination trials at the ASH annual meeting and our planned investor event by year-end. We are excited to provide positive final Phase 1 results for revumenib treatment in relapsed refractory NPM1 patients, further demonstrating its best in class profile in another important indication with high unmet medical need. Pivotal data from these trials will serve as the basis for potential U.S. registrational filings, including an NDA submission in relapsed refractory KMT2A acute leukemia for revumenib and an Incyte initiated BLA submission in chronic GVHD for axotilumab by year end 2023.

Both revumenib and axitilumab have significant market opportunities with the potential to gain quickly gain considerable market share and have a meaningful impact on the lives of underserved patients in each setting. In addition, we continue to explore ways to capture the maximum value of our current pipeline by expanding into opportunities beyond the initial registration indications and in doing so aim to bring the encouraging clinical benefits of our lead candidates to even more patients in need. It has been a transformational year for Syndax, and we expect to maintain this momentum in the coming months with a number of upcoming value generating milestones that are laid out on Slide 15. I remain confident that we have the resources and expertise to execute on our goals and the strategic long-term vision that will enable our successful transition into a commercial stage biopharmaceutical organization.

As always, I would like to extend my gratitude to the Syndax team, collaborators, and most importantly, the patients, trial sites and investigators involved with our clinical programs. Through your integral work, we are advancing our mission of realizing a future which people with cancer live longer and better than ever before. I would also like to thank our committed long-term investors who continue to share in our vision and support us in building Syndax. With that, I would like to open the call for questions. Operator.

Operator: [Operator Instructions] Our first question is from Brad Canino at Stifel. Your line is open. Please ask your question.

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