Syndax Pharmaceuticals, Inc. (NASDAQ:SNDX) Q4 2022 Earnings Call Transcript

Syndax Pharmaceuticals, Inc. (NASDAQ:SNDX) Q4 2022 Earnings Call Transcript March 3, 2023

Operator: Good day, everyone, and welcome to the Syndax Fourth Quarter 2022 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 the review of Syndax’s fourth quarter and full year 2022 financial and operating results. I’m Sharon Klahre, and with me this afternoon to provide an update on the Company’s progress and to discuss financial results are: Michael Metzger, Chief Executive Officer; Dr. Briggs Morrison, President and Head of R&D; and Keith Goldan, Chief Financial Officer. Also joining us on the call today for question-and-answer session are Dr. Peter Ordentlich, Chief Scientific Officer; Dr. Anjali Ganguli, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the Investor page of the Company’s website. We can now turn to our forward-looking statements on Slide 2.

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 may represent our views as of today, February 28, 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, Syndax.

Michael Metzger: Thank you, Sharon, and thank you to all of you joining on the webcast today. Now turning to Slide 3. 2022 was a year of growth and strong execution for Syndax. We made great progress working towards our long-term goals, all of which put us firmly on the path of becoming a fully integrated commercial stage biopharmaceutical company delivering two best-in-class products to patients in areas of high unmet medical need. On Revumenib, we made significant progress, enrolling patients in the AUGMENT-101 pivotal trials announced breakthrough therapy designation for patients with relapsed/refractory KMT2A rearranged acute leukemia and presented robust updated Phase I data that further supported Revumenib’s best-in-class clinical profile in two oral sessions at the 2022 American Society of Hematology Annual Meeting.

Further, we initiated additional Phase I trials designed to test Revumenib in a variety of settings, including combinations with standard-of-care regimens. For axatilimab, we completed enrollment in the pivotal AGAVE-201 trial, published the initial Phase I/II chronic graft-versus-host disease data set in the Journal of Clinical Oncology and made progress expanding the axatilimab development program in collaboration with our partner, Incyte. We are fortunate to have Incyte as a strong collaborator to help us successfully advance axatilimab development. Additionally, in December, we bolstered our balance sheet with a $172.5 million follow-on offering, our cash runway is now expected to extend into the second half of 2025, allowing us to appropriately invest to maximize the value of our pipeline, prepare for two potential U.S. commercial launches in 2024 and pursue potential business development opportunities.

Our focus, determination and unending commitment to patients has propelled us forward to this critical year, a year that we expect will be marked by pivotal readouts and registration filings for our 2B drug candidates, both of which are first and potentially best-in-class treatments. 2023 is an incredibly significant year for Syndax, and I’m confident that we have the expertise and resources to execute on our goals, along with the determination to realize the future in which people with cancer live longer and better than ever before. Turning to Slide 4, we provide a high-level summary of our current corporate priorities. Starting with Revumenib, our highly selective Menin inhibitor, our pivotal Phase II AUGMENT-101 trial evaluating Revumenib in patients with relapsed/refractory NPM1 mutant or KMT2A rearranged acute leukemia is progressing well.

We are happy to report that we have completed enrollment of a sufficient number of patients with a KMT2A rearrangement to support a registration filing, and we are on track to report top line data from the trial in the third quarter of 2023. This data would provide the basis for an NDA filing by year-end 2023. I will provide more details on AUGMENT-101 later in the call. In addition to the AUGMENT-101 trial, we have ongoing trials testing Revumenib in earlier lines of therapy and in combination with standard of care medicines to treat these forms of acute leukemia. We are committed to unlocking the full potential of this important therapy. With that goal in mind, we expect to have several additional data readouts in 2023 for Revumenib. These include initial top line data from AUGMENT-102 chemo combination trial in relapsed/refractory acute leukemia patients, safety data from the dose escalation phase of the BAML cooperative trial of Revumenib in combination with venetoclax/azacytidine, in newly diagnosed AML patients and initial top line data from the first solid tumor proof of concept trial in metastatic colorectal cancer.

Moving to axatilimab, our antibody against CSF-1R. We remain on track to report top line data in mid-2023 from the pivotal Phase II AGAVE-201 trial, evaluating axatilumab in patients with chronic graft versus host disease or cGVHD, and plan to submit a BLA filing by the end of 2023. To maximize the value of the axatilimab program, we anticipate initiating additional trials in 2023, including a combination of axatilimab and ruxolitinib in frontline cGVHD that we expect Incyte to be in later this year as well as a Phase II trial of axatilimab in idiopathic pulmonary fibrosis, or IPF, that we anticipate kicking off in the first half of 2023. We continue to evaluate potential opportunities to in-license earlier-stage targeted oncology compounds that we believe could become high-value differentiated assets.

We believe that we have sufficient capital to bring in new early-stage assets but our bar for doing so is quite high as any compound would need to complement our current pipeline and fit in with our long-term corporate strategy. Let’s now turn to Slide 5, and I’ll provide further details on the revumenib program. As you recall, the Phase II portion of AUGMENT-101 is designed as three single-arm pivotal trials with distinct patient populations that enroll independently. These patient populations are KMT2A rearranged ALL, KMT2A rearranged AML and NPM1 mutant AML. The primary endpoint of each pivotal trial is a percentage of patients achieving CR/CRh with secondary endpoints, including durability of CR/CRh response, transfusion independence, overall survival and safety.

In December, we received Breakthrough Therapy designation or BTD for Revumenib for the treatment of all adults and pediatric patients with relapsed/refractory KMT2A rearranged acute leukemia, whether presenting as acute myeloid or acute lymphoid phenotype. The receipt of BTD underscores the potential if approved for Revumenib to be the first drug to address the breadth of unmet medical needs in KMT2A or leukemia, accounting for up to 10% of all acute leukemias. Based on the broad breakthrough therapy designation and our ongoing conversations with regulators, we will pool the data generated from both the AML and ALL-KMT2Ar cohorts into a single NDA filing aimed at an indication to treat all relapsed/refractory acute leukemia patients with a KMT2A rearrangement.

Thanks to the enthusiastic support of our investigators. We have already enrolled a sufficient number of patients with KMT2A rearrangements in the Phase II portion of the AUGMENT-101 trial to enable this filing strategy. We expect to share top line data from this population in the third quarter and file an NDA for the treatment of relapsed/refractory KMT2Ar acute leukemia in adult and pediatric patients by the end of 2023. Separately, we continue to enroll relapsed/refractory NPM1 mutant AML patients and expect to report completion of enrollment for these patients in the second half of 2023. These trials are enrolling well, and there was significant excitement for Revumenib by investigators at the ASH Annual Meeting in December, where we presented updated Phase I data that Briggs will take you through on Slide 6.

Briggs?

Dr. Briggs Morrison: All right. Thank you so much, Michael. So as many of you know at the ASH Annual Meeting in December of last year, Dr. Ghayas Issa from the MD Anderson Cancer Center presented updated results from the Phase I portion of the AUGMENT-101 trial in two oral presentations. Of the 60 patients evaluable for efficacy in the Phase I portion, 30% attained a CR/CRh. And notably, in patients treated at the recommended Phase II dose, CR/CRh was the same in both KMT2AR and NPM1 subsets at 27%. The median duration of CR/CRh response was impressive in this very advanced patient population at 9.1 months. There was a high MRD negativity rate of 78% among patients achieving CR/CRh, which is very meaningful in this patient population as it enables patients to proceed to potentially curative bone marrow transplant.

We also reported compelling data on 12 patients who achieved a response on Revumenib treatment and then went on to receive a stem cell transplant. And additionally, three transplant patients who were treated with Revumenib maintenance therapy in the capacitate use setting following stem cell transplant or non-myeloablative stem cell boost, two of whom remained in remission for over a year as of the data cutoff. As a reminder, in the pivotal trial, patients can be restarted on Revumenib after bone marrow transplant, the design feature that provides data on the potential role of Revumenib in the post-transplant maintenance setting. Revumenib continues to be well tolerated, and there have been no discontinuations due to treatment-related adverse events.

As we look across the development landscape, we believe the data continued to support Revumenib’s compelling clinical profile and position it as not only first-in-class, but a best-in-class treatment. I’ll now turn it back over to Michael.

Michael Metzger: Great. Thanks, Briggs. Turning to Slide 7. Given the compelling clinical and safety profile we have observed with Revumenib, our clinical development plan seeks to expand its use beyond relapsed/refractory setting into earlier settings and in combination with approved therapies. Here we highlight our ongoing trials of Revumenib across the full treatment landscape. Starting with the Phase Ib AML umbrella trial. As part of our collaboration with the Leukemia and Lymphoma Society, Revumenib is being combined with venetoclax/azacytidine to treat newly diagnosed AML patients with an NPM1 mutation or KMT2A rearrangement who are unfit for induction chemotherapy. Revumenib is the first menin inhibitor to be included in the trial, which will assess safety as well as initial efficacy.

Enrollment is ongoing, and we expect initial safety data from this trial to be available in 2023. Longer term, we expect that positive — the AML trial results could lead to a Phase II/III trial, which could serve as the basis for future regulatory filing. We are also currently enrolling patients in the AUGMENT-102 trial designed to assess Revumenib in combination with standard salvage chemotherapies for patients with relapsed/refractory NPM1 mutant or KMT2A rearranged acute leukemias. We also expect to have initial data available from this trial in 2023. And finally, the INTERCEPT trial. This trial was recently initiated as part of the INTERCEPT Master Clinical Trial led by The Australasian Leukaemia and Lymphoma Group. This trial is a creative approach to treating patients early in their disease course as it is focused on investigating novel therapies to target early relapse and clonal evolution as pre-emptive therapy in AML.

It is designed to explore the activity of Revumenib, the first menin inhibitor to be included as monotherapy in patients with AML who have MRD-positive disease following initial treatment, a group of patients at very high risk of relapse. We are also in the process of planning a trial in combination with standard of care intensive chemotherapy, used to treat fit patients in the frontline setting. We plan to initiate that study in the second half of this year. As is detailed on Slide 8, unlocking the full potential of Revumenib beyond the relapsed/refractory acute leukemia setting by moving it earlier in treatment and in combination with other approved agents has the potential to add meaningful value both for our shareholders and even more importantly, for patients in need.

With these expansion opportunities, we see the potential to address upwards of 12,000 NPM1 mutant and KMT2A acute leukemia patients across various edits. These two forms of acute leukemia together represent up to 40% of the overall AML population, which, to our knowledge, will be the largest subpopulation of AML to be addressed by new targeted therapies. There are currently no FDA-approved therapies targeting KMT2A or NPM1 acute leukemias. We anticipate that Revumenib could become the backbone of choice for patients with KMT2Ar and NPM1-mutant acute leukemia and we are also looking to explore Revumenib as a treatment in solid tumors based on the compelling preclinical signs supporting the role of the menin-MLL1 interaction in data continuum driven tumors.

A proof-of-concept signal-seeking Phase I clinical trial in colorectal cancer is open for enrollment, and we expect to report top line data by year-end 2023. Let me now turn to axatilimab, our potentially best-in-class monoclonal antibody therapy targeting the CSF-1 receptor that has the potential to serve as an effective practice-changing intervention in this underserved population. Slide 9 provides an overview of the pivotal AGAVE-201 dose-ranging trial evaluating axatilimab in patients with cGVHD. The trial has completed enrollment of 240 patients whose disease has progressed after two prior therapies. We’re at least two years of age and have met overall entry criteria. Patients were randomized to one of three treatment groups, each investigating a distinct dose of axatilimab, given every once — given either every once or every two weeks or once every four weeks.

The primary endpoint is overall response rate using the 2014 NIH consensus criteria for cGVHD, while secondary endpoints include duration of response and validated quality of life assessments using the modified leases and scale. We continue to expect to report top line data from the AGAVE-201 trial in mid-2023. For us, the terms of our collaboration agreement, Incyte will be leading the regulatory filing in cGVHD, which we expect will occur in the later part of 2023. Slide 10, details the results from the Phase I/II trial, which showed axatilimab’s ability to provide meaningful clinical responses in chronic GVHD patients that have been refractory to multiple prior therapies. This data was presented at the 2021 ASH Annual Meeting and subsequently published in the Journal of Clinical Oncology in December.

These data were well received among thought leaders who recognize axatilimab is having a clinical profile that would benefit — will be a benefit in the treatment of these heavily pretreated patients. The overall response rate in the trial was 68% and the median time on treatment was over six months. The overall response rate in the Phase II portion was 82% and the median time to response was rapid at four weeks. Importantly, clinical responses were accompanied by a reduction in the cGVHD symptom burden and improvements in all cGVHD involved organ systems. Additionally, more than half of the responders reduced their use of steroids. Axatilimab demonstrated a favorable safety profile in this refractory population with the most common adverse events consistent with on-target effects of CSF-1R inhibition.

Slide 11 highlights the broad clinical and commercial opportunity for axatilimab. cGVHD represents a high unmet medical need and an important commercial opportunity with approximately 14,000 patients suffering from cGVHD in the U.S. today. We and Incyte believe the data generated to date with axatilamab suggests it has the potential to play an important role in the treatment of cGVHD, both as monotherapy and given the safety profile in combination with complementary medicines. Thus, in collaboration with Incyte, we are enthusiastic about expanding the axatilimab program into frontline cGVHD in combination with ruxolitinib, and we expect a Phase I combination trial in patients with newly diagnosed cGVHD to begin later in 2023. The successful commercial launches of Incyte’s Jakafi and Sanofi’s are encouraging, both posting meaningful early revenues that begin to speak to the commercial opportunity in cGVHD.

Axatilimab has a differentiated mechanism of action from these products and could potentially offer a unique set of benefits to patients once approved. Beyond cGVHD, we are excited about the opportunity to expand axatilimab into fibrotic diseases where the monocyte macrophage lineage plays a key role. We expect to initiate a robust Phase II trial in IPF in the first half of 2023. If successful, we believe this trial, along with one additional Phase III trial, could form the basis for FDA approval for the treatment of IPF. Through combinations in the frontline setting as well as the opportunity to expand to ex U.S. markets, we envision the cGVHD opportunity growing meaningfully. I will now turn the call over to Keith to review our financial results.

Keith Goldan: Thank you, Michael. Let me take a few minutes to discuss our financial results for the fourth quarter and full year 2022. Turning to Slide 12. The results of our operations for the fourth quarter of 2022 and the comparison to the prior year’s quarter are included in our press release. So I will not repeat them in these remarks. Additional financial details are available in our fourth quarter and full year report, which was filed earlier this afternoon on Form 10-K. I’d like to point out that our net loss for the fourth quarter was $39.2 million or $0.62 per share compared to a net gain of $96.2 million or $1.81 per share for the same period last year. This difference is primarily attributed to the recognition of the upfront payment from Incyte related to the axatilimab collaboration, which we entered into in December of 2021.

For the full year of 2022, our net loss was $149.3 million or $2.46 per share compared to a net gain of $24.9 million or $0.48 per share for the same period last year. Again, the difference is largely due to the upfront payment in December 2021 from Incyte. We ended the fourth quarter with $481.3 million in cash, equivalents and marketable securities, including the net proceeds of $162 million from our follow-on offering completed in December of 2022 and 69.3 million shares and prefunded warrants outstanding. Our current cash is expected to provide a runway into the second half of 2025 and covers our aggressive development and pre-commercialization plans for both the Revumenib and axatilimab programs as well as provides us flexibility should we decide to selectively engage in early-stage business development.

Looking ahead, I’d like to provide financial guidance for the first quarter and full year of 2023. For the first quarter of 2023, we expect research and development expenses to be $30 million to $35 million and total operating expenses to be $40 million to $45 million. For the full year of 2023, the Company expects research and development expenses to be between $160 million to $175 million and total operating expenses to be $225 million to $240 million, including approximately $30 million of noncash stock compensation expense. With that, let me now turn the call back over to Michael.

Michael Metzger: Thank you, Keith. And as you’ve heard during the call, 2022 was an exceptional year of growth and execution, but it represents only the beginning of what Syndax aims to accomplish in the near future. With two pivotal trial readouts and potential registration filings in 2023 for our two lead drug candidates, both of which are first and potentially best-in-class treatments. Syndax is at the beginning of a significant transition into a fully integrated biopharmaceutical company, serving multiple patient populations of high unmet medical need. In addition, both programs offer the potential for broad franchise opportunities beyond their initial registration indications, adding to Syndax’s long-term growth potential.

We have ambitious goals and milestones that I’ve set out for 2023, and I’m confident that we have the right plan and team in place to execute on them. Further, we are in a strong financial position with a balance sheet that allows us to deliver on key near-term milestones. As always, I want to express our deep appreciation to the Syndax team, collaborators and, most importantly, the patients trial sites and investigators involved with our clinical programs. It is all of you who help us to execute on a mission of realizing a future in which people with cancer live longer and better than ever before. And I’d also like to thank our committed long-term investors who continue to share in our vision and support us in building Syndax. And with that, I’ll turn it back over to the operator and open the call for questions.

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Q&A Session

Operator: And we’ll take our first question from Madhu Kumar with Goldman Sachs.

Omari Baruti: This is Omari on for Madhu. So first — our first question is, does the FDA now consider KMT2A rearranged AML and ALL cohort for filing purposes? And then second, what are you looking to see from the two different combo studies of Revu?

Michael Metzger: Yes. Omari, thank you for the question. Yes, I think the answer to the first question, which is the FDA, as far as I heard, does the FDA consider the one cohort for the filing purposes for KMT2A? And the answer is yes. We will be combining both AML and ALL cohorts, the patients and filing them together. That’s the plan. And the second question, I’m sorry, you cut out on the second half of it, so I couldn’t hear it. Can you repeat that, please?

Omari Baruti: Sure. So the second question, what are you looking to see from two different combo studies at Revu?

Michael Metzger: Once again, it cut out — I think you said what we’re looking to see from the two studies. Is that correct?

Omari Baruti: Right. From the two combination studies for Revu.

Michael Metzger: Got you. So the combination studies, we have multiple combination studies ongoing. There’s AUGMENT-102, which is the chemo combo, which we’ll have data on, we expect later in the year. And we have frontline trials going with ven/aza with beta AML, and we’ll be designing other trials in addition to that in the frontline setting. I think we haven’t necessarily set out guidance on what we’re looking to achieve. I think these are early studies, where we’re going to be looking at first of course, safety and early efficacy and trying to establish a recommended Phase II dose. And I think that would be the main objective of those trials, which we’ll hopefully achieve by the end of this year.

Operator: Our next question comes from Phil Nadeau with Cowen and Company.

Philip Nadeau: Congrats on progress. First, a follow-up on the KMT2A population. So for the readout from the 101 trial, well, it sounds like both AML and ALL patients will be commingled in, I guess, now it’s a combined cohort. Will the CR/CRh be analyzed regardless of myeloid versus lymphocytic etiology? Or will there be any stratification for the underlying disease?

Michael Metzger: Yes. Thanks for the question, Phil. And maybe I’ll let Briggs answer that question.

Dr. Briggs Morrison: Yes. So Phil, there — the — you may recall that when we announced the breakthrough therapy designation and back to Omari’s first question, the agency did accept that KMT2A rearranged leukemia is one disease, whether it presents as AML or ALL, adults or kids. And part of the support for that was that the data we presented was a combination of AML and ALL adults and beads. So we did break it out, and we will break it out for the agency to further support that designation, but the analysis is — we’ll be looking at that integrated population altogether?

Philip Nadeau: Got it. Okay. And in terms of the patient numbers necessarily, I know you’ve said that — you’ve already recruited them. Is the number of patients equivalent to what we thought you were going to roll in cohort 2A and 2B in the study? Or because they’re not being combining — not being combined, is the required number of patients actually equivalent to just really one cohort worth of patients?