Syndax Pharmaceuticals Q1 2024 Earnings Call Transcript

Quartr
Provided by Quartr
May 8, 2024

There are 14 speakers on the call.

Operator

Good day, everyone, and welcome to the Syndax First Quarter 2024 Earnings Conference Call. Today's call is being recorded. At this time, I'd like to turn the call over to Sharon Clary, Head of Investor Relations at Syndax Pharmaceuticals.

Speaker 1

Thank you, operator. Welcome, and thank you all for joining us today for a review of Syndax's Q1 2024 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 Menzger, Chief Executive Officer Doctor. Neal Gallagher, President and Head of R and D Steve Coloster, Chief Commercial Officer and Keith Goldand, Chief Financial Officer. Also joining us on the call today for the question and answer session are Doctor.

Speaker 1

Peter Ordentlich, Chief Scientific Officer and Doctor. Angeli 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. Before we begin, I'd like to remind you that any statements made during the call that are not historical are considered to be forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.

Speaker 1

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 made represent our views as of today, May 8, 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.

Speaker 2

Thank you, Sharon, and good morning, everyone, and thank you for joining us on the call today. I'd like to begin by welcoming Steve Kloster to the call. Steve joined us in March as Chief Commercial Officer. He brings over 30 years of commercial experience to Syndax, which includes establishing winning teams and leading successful product launches. Steve is building on the excellent framework that was in place prior to his arrival, and we are already benefiting from his keen insights as we prepare for commercialization.

Speaker 2

In the quarter, we made significant progress on executing against our corporate strategy. As you can see on Slide 3, we achieved several significant milestones this quarter, including securing priority review from the FDA for both the revumentiv NDA filing and the axotilumab, the BLA filing. We also completed enrollment in the MPM-one AML cohort of AULVANT-1 hundred and one pivotal trial, bringing us one step closer to expanding the market opportunity for revimeneb. We look forward to reporting data from the initial trial in the Q4 of this year, which could serve as the basis for a supplemental NDA filing in the first half of twenty twenty five. These accomplishments set us up for an eventful 2024 that we expect will include 2 full U.

Speaker 2

S. Regulatory approvals, NPM1 pivotal data readout, additional combination data for revumentiv in KMT2A and NPM1, initiation of a pivotal trial for revumentib in frontline KMT2A and NPM1 acute leukemia in combination with venetoclax, as well as the initiation of 2 combination trials for axitilumab in frontline chronic graft versus host disease. As we approach our expected approvals, we are working to ensure that we are fully prepared to successfully launch at any time during the Q3 with an ability to reach all patients in need as rapidly as possible. Steve will provide additional details on our launch preparations later in the call. Syndax has a differentiated profile as a SMIDCAP Bio Tech with 2 first and best in class drugs on the cusp of their potential first approvals.

Speaker 2

Notably, revimeniv has a potential second significant indication and near term expansion opportunity in relapsed or refractory NPM1 that meaningfully extends the target patient population in acute leukemia. This is unique in the launch year as it quickly broadens the market opportunity for revumeneb in the relapsed or refractory setting to up to 6,500 patients. Multiple opportunities beyond the initial relapse or refractory indication exists for both assets and trials are ongoing that can drive significant long term value for these franchises for years to come. We are well funded with $522,000,000 in cash as of March 31 that we expect will provide significant capital through 2026. Our current balance sheet not only supports our planned commercial launches and clinical trials, but also allows us to expand beyond our core registration indications and pursue select business development opportunities.

Speaker 2

I'll now ask Neil to provide an overview of the pipeline. Neil?

Speaker 3

Thank you, Michael. In the Q1, the NDA filing for rivuamenib, our highly selective menin inhibitor, was granted prior to review by the FDA for the treatment of adult and pediatric relapsed or refractory KM2a rearranged or KM2aR acute leukemia and issued a PDUFA date target date of 26th September 2024. The filing is being reviewed under the real time oncology review, which provides a more efficient review process and has historically led to earlier approval timelines. The submission is based on data from the pivotal AUGMENT-one hundred and one trial outlined on Slide 4, where single agent revumena have induced a high percentage of blast FLIP free responses in heavily pretreated kT2AR acute leukemia patients, thereby enabling many of them to undergo potentially curative mytoplietic stem cell transplant and to continue revimenop monotherapy following transplant. We've also completed enrollment in the final pivotal cohort of the AUGMENT-one hundred and one trial of 64 adult relapsed or refractory MPM-one AML patients in March and expect to report the pivotal results from this population in the Q4 of this year.

Speaker 3

I'll take a moment to review the Phase 1 data on Slide 5 that underlines our confidence in the pivotal results for patients with relapsed or refractory MPM1 AML. Multiple presentations generated by us in both the relapsed or refractory and frontline settings have highlighted the consistency of menin inhibition across NPM1 mutations and KMT2A rearrangements. And we see the enthusiasm building for the revuenibin NPM1. The Phase 1 NPM1 data that we've reported supports our conviction that revumentib could be an important treatment for this AML population. In the Phase 1 part of AUGMENT-one hundred and one, 50% of NPM1 patients achieved an overall response and 36% achieved complete remission or CR with partial hematological recovery.

Speaker 3

And importantly, all patients with the CR CRH were MRD negative. Consistent with the KIN IIIA R population, revumenev also enabled a high percentage of NPM1 responders to proceed to transplant, 43% and responses have been durable. This is despite many of the patients having failed prior venetoclax therapy and prior stem cell transplants. It's worth noting that reviumenib has been well tolerated in patients with relapsed or refractory MPM1 AML. In the Phase 1, there were no Grade 4 or 5 QT prolongation events.

Speaker 3

No patient experienced greater than Grade 2 differentiation syndrome and no patients discontinued due to treatment related adverse events. We believe that RevuMena will form the backbone of treatment for patients with both kM2A R and MPM1 acute leukemias. Our clinical strategy extends beyond the initial relapsed or refractory populations and into the frontline and post transplant maintenance settings, including combinations with approved therapies. We have several combination trials ongoing with different standards of care across the continuum of patients, including in the fit and unfit settings that are listed on Slide 6. Investigators presented data from multiple Phase 1 combination trials including BEAT AML, SAVE AML and AUGMENT-one hundred and one during the American Society of Hematology Conference in December, demonstrating reviomedev's ability to safely and effectively combine with the standards of care.

Speaker 3

We expect to provide updated data from these trials later this year. In the Q1, we initiated another Phase 1 combination trial with standard of care intensive chemotherapy also known as 7+3. Beyond acute leukemia, we are investigating the opportunity to expand to solid tumors. Our proof of concept signal seeking Phase 1 clinical trial in metastatic colorectal cancer is ongoing and we expect to provide an update on the progress of the dose escalation phase of the trial later this quarter. Turning to axitilomab on Slide 7.

Speaker 3

Also in the Q1, the BLA filing for axitilomab or CSF1R antibody was granted priority review by the FDA for the treatment of chronic graft versus host disease or chronic GvHD after failure of at least 2 prior lines of systemic therapy with a PDUFA date of August 28, 2024. The submission is based on data from the pivotal AGAVE-two zero one trial for treatment with single agent axitilomab bled to an overall response rate or OR of 74% with 60% of responders still in response at 1 year. Importantly, axitilumab has a differentiated mechanism of action from currently approved therapies for chronic GvHD. It is the 1st investigational chronic GvHD agent to target inflammation excuse me, inflammation and fibrosis through the inhibition of disease associated macrophages. We're excited about the opportunity to expand exotilab into frontline setting in combination with standards of care and other fibrotic diseases where monocyte macrophage lineage plays a key role, including idiopathic pulmonary fibrosis or IPF, where we are currently enrolling a Phase 2 clinical trial.

Speaker 3

The team has been working hard to increase awareness of the compelling revimen of AUGMENT-one hundred and one and the axitilumab AUGAVA-two zero one data ahead of the respective potential approval. In April, investigators presented pediatric data from AUGMENT-one hundred and one in a plenary session of the American Society of Pediatric Shematology Oncology that further supports the consistency of the data across subgroups. Also in April, investigators presented additional analyses from AGAVE-two zero one at the European Society For Blood and Marrow Transplantation Congress, highlighting axotilumab's impressive clinical activity in fibrosis dominant organs, which as I mentioned earlier, is a key point of differentiation. We have an ambitious publication plan underway and we look forward to detailing more of the clinical benefit of axitolamab and revumeneb to the prescribing community. I'll now turn the call over to Steve to talk about preparation for our planned commercial launches and the market opportunity.

Speaker 3

Steve? Thank you, Neil.

Speaker 4

This is an exciting time to be at Syndax, and we're looking forward to launching 2 1st in class and meaningfully differentiated agents this year. As Michael indicated earlier, we'll be ready to launch both revumetiv and axitilumab in the Q3, and we've made significant progress so far this year to prepare ourselves and the market to realize the full potential of these medicines for patients, for healthcare professionals and the company. Our key focus areas are highlighted on Slide 8. Our pre commercialization strategy has focused on developing an efficient, effective and purpose built infrastructure to support the business and prioritize relationships with important external stakeholders in the healthcare provider as well as the payer space to accelerate uptake at launch. For revumetim, our pre launch activities have been centered around disease awareness, mechanism of disease education and market access, as well as ensuring patient support services are in place at the time of launch.

Speaker 4

The customer facing leadership team has been in the field for some time and focus on disease state awareness and building relationships with healthcare providers. The team is actively profiling accounts, understanding workflows and identifying the patient journey at the largest and most influential academic centers in the country. This has allowed us to have important conversations with healthcare providers and other healthcare organization decision makers and gain valuable insights on the market, which has helped us define our outreach strategy. We launched our non branded campaign last year, focused on improving the knowledge and understanding around the role of menin inhibition across key segments of acute leukemia, including KMT2A rearrangements, as well as follow on indications like NPM1 mutant AML. This effort will expand as we approach a potential launch.

Speaker 4

We've recruited a talented and highly experienced sales team with an average of 22 years of experience, primarily in hematology oncology, with an average of 6 product launches per representative. This is obviously a very experienced group with existing relationships and proven past success. The customer facing field team will play a multidisciplinary role in supporting healthcare professionals and patients. With regard to market access, our team has been educating commercial and Medicare payers on the burden of relapsed or refractory acute leukemia to prepare them to conduct timely and evidence based reviews and ultimately access decisions upon potential FDA approval, while formulary approval builds over time. We have little doubt that revumentum will be covered for reimbursement, while plans review the product for formulary inclusion.

Speaker 4

We've been meeting with pharmacy benefit managers and payers since 2023, sharing relevant market and product information and expect to reach plans covering more than 90% of all lives prior to revumentum's anticipated approval. Payers are telling us that they recognize a significant unmet need in KMT2AR acute leukemia patients and the benefit that revumentum could provide as supported by the AUGMENT-one hundred and one data. This is important due to the acute nature of the disease and the high mortality and morbidity in relapsed or refractory KMT2AR acute leukemia, making the urgency to treat quickly absolutely critical. I'm excited about our progress to date and look forward to sharing more about our ongoing efforts in the future. Turning now to Slide 9.

Speaker 4

KMT2AR and MPM1 acute leukemias represent up to 40% of all AML patients, and there are no FDA approved targeted therapies for this population. We believe relapsed or refractory KMT2AR acute leukemia alone represents a total addressable market of approximately $750,000,000 in the U. S. The annual incidence of KMT2AR acute leukemia is about 2,000 600 patients and the majority are refractory to frontline standard fare treatments. We estimate a median duration of therapy across the treated population of approximately 9 months and we believe the clinical data supports pricing competitively to other targeted therapies in AML such as the FLT3 or IDH inhibitors.

Speaker 4

Physicians we've spoken with indicate an eagerness to prescribe revumentiv early during an eligible patient's treatment journey to bring more patients to transplant and then extend responses by continuing through revumentum monotherapy following transplant engraftment. We that our first mover advantage and the early experienced physicians will gain treating patients with revumentib will be vitally important to the long term success of our brand. Our significant market share is likely to extend meaningfully beyond KMT2 AR, especially as we will be the first to deliver meaningful pivotal data in other indications such as NPM1 AML. We estimate that the 2 distinct market segments in acute leukemias, KMT2AR and MPM1, avail a total accessible population of 5,000 to 6,500 patients in the relapse or refractory setting and an addressable market opportunity that approaches $2,000,000,000 in the U. S.

Speaker 4

Turning now to Slide 10. Approximately 14,000 U. S. Patients suffer from chronic GVHD, 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. There are no cures for this advanced chronic GvHD patient population.

Speaker 4

Patients initially treated with corticosteroids are then cycled through a variety of additional therapies based on the physician's experience and manifestations of the disease being addressed. The successful commercial launches of Jakafi and Resiroc and importantly, the speed by which both these agents gained adoption really speak to the unmet need in chronic GVHD. We also know that despite these recent advances, the disease is still inadequately treated and physicians are looking for an agent that can better address the underlying fibrosis that ultimately leads to organ damage. Further, they are excited to have a drug with such a fast onset of action and impressive durability of response. These key points of differentiation should enable axitilumab to carve out a sizable commercial opportunity within the estimated $1,000,000,000 U.

Speaker 4

S. Refractory chronic GvHD market. As you know, Incyte is our partner for axitilumab and really the leader in the GvHD space. As of last year, we exercised their option with Incyte to co commercialize axitilumab in the United States and provide 30% of the commercial efforts as we believe there is a considerable benefit to promoting 2 products simultaneously to a highly overlapping and targeted physician prescriber universe. We're working closely with Incyte to develop our go to market strategy for axotilumab and plan to align more fully with Incyte before sharing additional details.

Speaker 4

However, we expect to follow a similar set of strategic imperatives as we've just outlined for RepuMentum. Now I'll turn the call over to Keith to review our financial results.

Speaker 5

Thank you, Steve. Turning to Slide 11. As Michael mentioned earlier, the $522,000,000 in cash, equivalents and short and long term investments on our balance sheet at March 31 expected to provide runway through 2026. Our financial strength allows us to appropriately invest to maximize the value of our pipeline and importantly to transition into a commercial stage organization this year. Turning to the income statement.

Speaker 5

Operating expenses in the Q1 were $79,500,000 comprised of $56,500,000 of research and development expense and $23,000,000 of selling, general and administrative expense. Keeping in mind that we've always embraced a disciplined approach to resource allocations, we'd like to provide financial guidance for the Q2 and full year of 2024. For the Q2, the company expects research and development expenses to be $50,000,000 to $55,000,000 and total operating expenses to be $80,000,000 to $85,000,000 For the full year 2024, there is no change to the existing guidance and the company continues to expect research and development expenses to be $240,000,000 to $260,000,000 and total operating expenses to be 355

Speaker 2

$1,000,000

Speaker 5

to $375,000,000 Note that the guidance range for operating expenses for the full year 2024 is inclusive of an estimated $43,000,000 of non cash stock compensation expense. In preparing for launch, I wanted to take a minute to lay out how we plan to recognize revenue for axotilumab. Slide 12 includes an illustrative example of accounting for sales of axitilumab and is not intended to provide any margin or other guidance. Commercially, our partnership with Incyte is a fifty-fifty split of the economics in the U. S.

Speaker 5

We will report 50% of revenues earned net of cost of sales and commercial expenses. During a period where there is a net commercial profit for axitilimab, as in the top example of the slide, our 50% share of the net profit will be recognized on our P and L as collaborative arrangement revenue. During a period where there's a net commercial loss for axitilumab, as in the bottom example on the slide, our 50% share of the net commercial loss would be included in operating expenses designated as a separate line item called share of collaboration loss. We also have various future U. S.

Speaker 5

Commercial and regulatory milestones owed to us from Incyte that would be recorded as partnership or milestone revenue on our income statement. Development expenses are shared at $55,000,000 in the U. S. And our 45% share is included in the income statement as part of R and D expense. Outside of the U.

Speaker 5

S, Incyte is responsible for 100% of the development and regulatory expenses and we are entitled to receive a milestone milestones plus royalty on ex U. S. Sales. With that, let me now turn the call back over to Michael. Thank you, Keith.

Speaker 2

As you've heard during the call, 2024 is shaping up to be a historic year for Syndax as we prepare to launch 2 1st in class products, and I'm confident that we have the expertise, resources and determination to bring these products to market. As an organization, we are truly excited to evolve into commercial organization and we are laser focused on bringing these important treatment options to patients in need. On Slide 13, we lay out our key upcoming milestones for the balance of the year and I look forward to updating you on our progress in the coming months. As always, I would like to express my sincere appreciation to the Syndax team, our collaborators and most importantly, the patients, trial sites and investigators involved with our clinical programs. Through your work and dedication, we are getting ever so close to delivering on our mission of improving the lives of patients with cancer.

Speaker 2

I'd 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'd like to open the call for questions. Operator?

Operator

Our first question is from Peter Lawson at Barclays. Your line is open. Please go ahead.

Speaker 6

Just first question is just around how important NCCN guidelines will be for additional indications after you get the initial approval of revivinib?

Speaker 2

Peter, thanks for the question. Maybe I'll ask Neil to comment on the importance of the guidelines.

Speaker 3

Yes. Thanks, Peter. So as you know, the first approval we're anticipating that the first approval for rivuMANAB will come in the Q3 and that will be for K2A rearranged acute leukemias in adults and children. So the approval will be should be sufficient actually have that indication included in the guidelines. And in addition to that, we've also guided to the fact that we will fact, I referenced or Ursula referenced during the prepared remarks that we anticipate reporting pivotal data from the NPM1 cohort by the end of the year.

Speaker 3

So suffice it to say that we have a plan. I mean, prior to approval, presentation at a medical Congress along with publication of the data could position us to at least start conversations with the NCCN committee regarding inclusion in the guidelines. As you're aware, the committee meets twice a year. The disease specific committees meet at least once a year, but they also meet ad hoc once important new data become available. So we're considering all of that.

Speaker 3

And clearly, we want to make sure that the best possible information is made available to the committee as well as to prescribers when we publish our data.

Speaker 6

Got you. Thank you. And then as we think about expansion of the MENA inhibitor into solid tumors, kind of just if you could detail the kind of the expectations around CRC data, if that's still 2Q, when we should expect to see that data at this medical conference and kind of the number of patients?

Speaker 2

Thanks, Peter. Thanks for the follow-up. So question was related to solid tumors and our plans there. And as we've disclosed and mentioned in the prepared remarks, we are continuing to work in the area of colorectal cancer. This is metastatic colorectal cancer, 3rd line plus.

Speaker 2

So these are and we are conducting a Phase I trial. We had said that we had planned to disclose some information, update everyone on our progress there in the Q2 and that remains to be the case. Let me remind everyone, this is a dose escalation trial. So this is roughly 10 to 20 patients heavily pretreated. And what we're essentially looking for looking to see is activity of revumentib, again, in this patient population, looking for prolonged stable disease in the 4 to 6 month, so call it, range with perhaps around 15% of the patients in that stable disease category.

Speaker 2

So that's sort of the signal that would be, we think, impactful. Of course, patients don't do very well in this setting, and certainly standard of care doesn't yield prolonged stable disease of that nature. So we'll obviously update when we're ready to do so in the Q2.

Speaker 6

Perfect. Thank you so much.

Speaker 2

Thank you, Peter.

Operator

Our next question is from Anupam Rama at JPMorgan. Your line is open. Please go ahead.

Speaker 7

Hey, guys. Thanks so much for taking the question. Maybe a quick one for Steven. Just wondering, before you joined Syndax and you were doing your assessments of the opportunities for rivumimab and naxitolimab, what really attracted you to these products? And then the second one is also actually for Steven.

Speaker 7

You mentioned very broadly what some of the levers for success in Slide 8 are for both of these launches, but anything more specific to revimatib and KMT2A that you'd highlight? Thanks so much.

Speaker 4

Yes. Thanks for the question. I'll answer both. First is, why did I probably come here? And it's really a combination of things.

Speaker 4

I've been pretty careful over the course of my career. I think this is my 4th organization in 30 years. So the bar is pretty high. I look at all opportunities in 3 different factors. The first is there needs to be great products, products that address unmet need, products that have a great amount of clinical data and really provides differentiated attributes, and I think both Rev and AXA have that.

Speaker 4

I knew that coming in. And as I've seen the data and as I've reviewed lots of market research and actually engaged with KOLs, that's only been amplified. I think the second thing that I really think about is really who I work with, right, wanting to be at companies with great people and great leaders, and that's exactly what we have here. Michael, the entire Elti, the Board are all top tier, very supportive. And even walking in, the commercial leadership team that was in place was strong as well.

Speaker 4

And the third thing for me is really the willingness to invest and plan for success, and we have that here too. So I'd say my expectations have been exceeded coming in, and I'm more excited now than I was even before I started. I think I'm in week 8. The second question is really around levers for success on RevuMETA. There's a lot we're building as a commercial organization and all of that will be in place.

Speaker 4

I think as Neil mentioned and Michael mentioned, his remarks will be ready in Q3. So infrastructure processes, all those things will be done. I think from a strategic point of view, the three things that I think about that we are very focused on, Really, the first is the population of patients is limited. We know that, right? And that will that opportunity will grow over time, but finding them is critical.

Speaker 4

Patients are fragile. They need treatment immediately. So we've got focus there. I think the second thing is just the landscape of healthcare delivery. There are multiple stakeholders out there that deliver care to patients, physicians, nervous sorry, nurses, advanced practice providers, pharmacy, reimbursement, pathology, you name it, we have a customer facing footprint that will address and directly engage with that dynamic.

Speaker 4

And the 3rd pace third point is really access, right? Neil mentioned NCCN guidelines, which will be important. Payers are looking for that. They're looking for other published data, but patients need access to treatment. So we've been deployed against the payer space for some time, making calls directly with payers and that is in an effort to really expedite formulary review.

Speaker 4

And in addition, we've built a support program to meet the needs of patients, which we know their need. So thanks for the question. Hopefully, that was a good answer.

Operator

Our next question is from Brad Canino at Stifel. Your line is open. Please go ahead.

Speaker 2

Hi, good morning. Relating to the plan for the pivotal VENAZA combo trial to be initiated by year end, This will move the emphasis of clinical endpoints from CR towards remission durability in OS. And I want to ask how does the company plan to evaluate data from the uncontrolled trial updates later this year, both from the combos and also the NPM1 pivotal monotherapy in order to gain confidence in the randomized time to event endpoints for the frontline pivotal? Thank you. Brad, thanks for the question.

Speaker 2

I'm going to turn it over to Neil to address that.

Speaker 3

Yes. Thank you for the question. Specific I mean, all of the combination studies that we reported on, the one specific to this scenario, in other words, initiating the Phase 3 revimenopinasec study by the end of the year is the BEAT AML study. And as you're aware, we the group reported data around the ASH meeting last year and anticipate updating those data during the course of this year. Those data are exciting, not only to the company, but also to the investigators and actually not just the beat AML investigators, but the broader community.

Speaker 3

So people are highly enthusiastic by initiating the Phase 3 study. Just to remind you, the response rates, including the CRCRH rates that were observed in the beta AML study to date have exceeded the historical controls observed in VLEA, including in terms of CR. In particular, molecular MRD negative CR was much, much higher in the beta AML study compared to VLEA. So the emergent data, including the observation that revumentib is highly combinable, it's not adding, it doesn't appear to be adding toxicity to the backbone therapy, as well as being providing incremental efficacy in the target patient population. And that's bolstered also by the observations from, for instance, the SAVE study, which is a combination is a combination of reviomedov with venetoclax and oral decitabine in the relapsed refractory setting, as well as our own Ocment 102 trial, the combination trial with in a relapsedrefractory population in combination with chemotherapy.

Speaker 3

So the body of the evidence is that revumeneb is combinable with backbone standards of care is not adding toxicity in the target population for the Phase III trial for the Phase 3 trial in the newly diagnosed unfit population. The BAML data are providing evidence that revimenev is also adding notable efficacy to the backbone therapy. So obviously, we will be having conversations with health authorities as we design the trial and don't typically comment on those, but we look forward to presenting more details around the study prior to initiation later in the

Operator

Our next question is from Phil Nadeau at TB Cohen. Your line is open. Please go ahead.

Speaker 8

Good morning. Congrats on progress. Thanks for taking our questions. A few from us. First, in terms of the Phase II doses in the combo trials or validating the Phase II doses in the combo trials.

Speaker 8

This morning's press release notes that some of the trials have been expanded to validate the Phase 2 doses. I was curious whether you'd be willing to disclose whether the full monotherapy dose of revimatinib is being used in those combinations at this point?

Speaker 3

Neal, go ahead. Yes. Thanks for the question. So just to remind everyone, the 3 studies that I just referenced in the answer to

Speaker 8

the previous

Speaker 3

question are the studies under discussion. So I won't repeat what those are. In all three of those trials, there were 2 doses of revimab that were investigated, 113 milligrams and 163 milligrams. 163 milligrams is the presumptive monotherapy dose in combination with the STRONG-two forty four that will be included in the label. So revimenop has been given at full dose in all three trials by the time we talked about them at the event around ASH last December.

Speaker 3

In all three, the dose limiting toxicity windows for both doses have been cleared. And both doses are being expanded in all three trials at this point in time. So we haven't when we talk about RP2D, we're continuing to characterize the 2 doses. But in general, our anticipation is that revumentiv or our observation to date is that reviumenib is combinable at full monotherapy dose with backbone standards of care.

Speaker 8

That is very helpful. Thank you. And then second question, based on the milestone tables that you just presented, it doesn't seem like you're anticipating an advisory committee review for either rivimeneb or axitilumab. Is that accurate? And can you remind us, did the FDA explicitly say in the acceptance letters that ADCOMs would not be necessary for both drugs?

Speaker 2

Yes, Phil, thanks for the question. I think our expectation is that neither axitilumab nor revimatinib will require an AdCom, but we haven't explicitly sustained or nor do we comment on regulatory correspondence from the agency relative to things like that. So but that is our expectation that neither will need an AdCom.

Speaker 8

Up. Perfect. And then last question from us. You referenced the 9 month expected median duration of use for KMT2A patients. Can you remind us what proportion of patients going to transplant is assumed in that 9 month figure?

Speaker 2

Phil, thanks for the question. It's roughly about a third of that half, right? Sorry, of the patients that go transplant.

Speaker 8

So a third of patients who get in the relapsed refractory line would go to transplant is the assumption?

Speaker 9

Yes. Sorry, Phil, it's Angelie. I think what we've been saying is there's basically 3 groups of patients that seem based on the trial seem to all be about an equal size population. There were a third of patients that did not respond. Of the 2 thirds of patients that responded, half went to transplant.

Speaker 9

So overall, of the entire population, a third go to transplant.

Speaker 8

Got it. That is very helpful. Thanks for taking our questions.

Speaker 2

Thank you, Phil.

Operator

Our next question is from Michael Schmidt at Guggenheim. Your line is open. Please go ahead.

Speaker 10

Hey, guys. Good morning. Thanks for taking my questions. I just had one on the axotilumab launch now that we're obviously closing in on the PDUFA date later this year. And as we think about the sort of $1,500,000,000 to $2,000,000,000 opportunity in the relapsed refractory setting, Just wondering how we should think about perhaps the early launch trajectory subsequent to approval?

Speaker 10

Are there any good proxies we should look at, for example? And then what are your expectations for potential off label use in the NPM1 subset? Obviously, we will have data later this year. Could that help next year to accelerate the launch early on? Thanks so much.

Speaker 2

Yes, Michael, thank you for the questions. I'm going to ask Angela to comment on the launch.

Speaker 9

Yes. Thanks, Michael. No, we're really excited about this opportunity. I think it's what revimetiv has in front of us is a very unique situation. As you know, we got through the clinical development in record time, 1st patient dose to NDA filing in 4 years.

Speaker 9

We've generated data that support indications across AML and ALL, adults and pediatrics. And as you said, we're anticipating an approval in the Q3 of this year, And we'll have data for another very important patient population treated by the exact same healthcare set of healthcare providers in a disease where physicians can choose the best options for their patients. So and then on top of that, we also talked about all the combination data we've generated with Rigmeniv that allow them to think about multiple ways to use this drug and fit it into their treatment plans as they think best. So I think we have a very unique launch curve that we're going to be generating in real time. I don't think there's a perfect analog that addresses all of these aspects of what's coming in the next 12 months.

Speaker 9

But we have seen very significant excitement around revumentiv, around this new class of agents and how they can utilize it to bring care to patients that have had nothing. And I think you'll recall the last two meetings have been very focused on the data that we've been generating. And I think that shows how much education is already out there. And as Steve talked about, there's a lot more that we're doing to make sure everybody is aware of the drugs, that's all the support and patient support is in place to allow utilization. And we're really excited to have a really strong launch of revumetim.

Speaker 10

Maybe just a follow-up. Can you just remind us what percentage of the AML market is under Medicare and how do you think about pricing in the Medicare population, any sort of expectations for free drug programs as we sort of think about that early launch again later this year? Yes. Let me ask thanks, Michael. I'm going to

Speaker 2

ask Steve to comment on those questions.

Speaker 4

Yes. I mean, it's a good question. And the payer space is different for KMT2 AR versus NPM1. It will be more of a commercial patient for the KMT2A launch just based on the age of the patient. We'll expect coverage honestly at launch.

Speaker 4

Formulary acceptance will happen over time, right, typically takes 6 to 9 months for that to happen. But in the meanwhile, healthcare providers, their staff are very fluent on how to get through the medical exception process. That's where the NCCN guidelines are helpful and other published data. Medicare payers will be less important for KMT2AR, but for NPM1 due to the patient population, which is a little bit older, it's going to change. So our approach has been really over the last 9 months, even a year, is really to approach all plans.

Speaker 4

We've been delivering PIE information exchanges, that's the pre approval information exchange. So we've had some very good interactions with payers. They recognize the unmet need, the criticality of patient care. And I think as Anjali said, it's a unique launch where you've got a launch followed by, we'll just say another launch within a year. So we're preparing for both at the same time.

Speaker 4

It takes time to build coverage, so we've got the whole payer space. And I think in my prepared remarks, we will talk to payers that cover 90% of covered lives in this country, which is as good as it gets in advance of approval. So we're prepared for success.

Speaker 10

Okay, great. And then maybe just a housekeeping question as we think about the aflatolumab filing and potential approval, are there any milestones due from Incyte for that, that we should incorporate our models this year?

Speaker 5

Yes. Thank you, Michael. Teeth? Yes, Michael, we do as disclosed in this Q and as we've disclosed in past Qs and Ks, we do have not only development and regulatory milestones, but commercial milestones do us from Incyte. Total milestones for development and regulatory under the agreement were $220,000,000 Total commercial milestones were 2 $30,000,000 So a total of $450,000,000 do us.

Speaker 5

You can expect those to come at major certainly major regulatory events such as approval. I think that's a reasonable expectation, but we haven't been more specific as to the amounts.

Speaker 2

Thanks, Luca. Thank you, Mike.

Operator

Our next question is from Yigal Nochomovitz at Citigroup. Your line is open. Please go ahead.

Speaker 11

Yes. Hi. Thanks very much for taking the question. Just curious on the NKM-one regulatory pathway, if you may follow R2R pathway or even TRICARE or given sNDA, is that are those options not really necessary?

Speaker 2

Yigal, thank you for your question. You broke up a little bit, but I think I captured it. So as you know, we have we've had breakthrough therapy designation for KMT2A. For MPM-one, we have the opportunity to potentially get breakthrough therapy, probably most important for your first indication. And I think the engagement around KMT2A and the molecule and the submission package has been very strong.

Speaker 2

We have priority review as well. I think for NPM1, we'll look to leverage some of the same access points with the agency, but we're, I'd say, pretty well advantaged by what we've what's come our way already. But we'll see, we don't generally comment on regulatory strategy, but the opportunity to submit for BTD at a point in the future is open to us. So I think it's a obviously a program that will have data on later this year. We'll have a submission, we hope, in the not too distant future beyond that.

Speaker 2

And then, look to get the drug approved in 2025. So that will be through an sNDA process. So it's all, I'd say, call it an expedited pathway through some of the designations we have in hand already or some of the things that we may avail ourselves in the future.

Speaker 11

Okay, thanks. And then when you think more broadly about the revumentib in terms of the spectrum of care and AML both in the frontline and in the relapsed refractory and given the fact that there's a good chance that you're going to be initiating a pivotal trial in the frontline in combo with venetoclax. When you start to think about the commercial build there, are you making assumptions around the potential retreatment revumented for patients that received revumented in the frontline in a combination setting, whether it be with METATXOR or perhaps even with the 7 plus 3, including those patients in the build for revimed in a relapsed refractory setting or once they're treated in the frontline, then that wouldn't be part of your assumption set? Thank you.

Speaker 2

Yes. Thanks, Yigal. I think the I think our assumption is that once you're treated with a meninib or at least from our vantage point the way we see it today, I think once you're treated with in the frontline setting, it's less likely that you're going to be treated in the relapsed refractory setting again with another methan inhibitor. And Neil, if you want to make a comment.

Speaker 3

Yes, I agree with Michael's comments there that I think that it is a little bit nuanced because I think longer term there I can foresee situations where patients could, for instance, have been treated and relapsed a long time later or MPM-one positive or came into a positive, might get might be re exposed. But I think in general, I agree with Michael's points. We shouldn't be sort of expecting a lot of patients to fall into that category.

Speaker 11

And just one on AXA. Do you have any timelines for the IPF trial in terms of enrollment and data?

Speaker 2

Thanks, Yigal. No, not at this point. I think we are enrolling. As you know, we started recently bringing up sites and enrolling patients and it's going nicely. And so we'll have more to say in terms of milestones, both for enrollment as well as data as we get further into the year, maybe into next year.

Speaker 11

Okay. Thank you, Michael.

Speaker 2

Thank you all.

Operator

Our next question is from Kalpit Patel at B. Riley Security.

Speaker 2

Can you comment on what proportion of patients that you estimate might be eligible to receive revumentum as a maintenance treatment after induction and consolidation? I'm trying to understand if that median duration of treatment in that specific frontline setting would be higher than the 9 months that you expect in the relapse refractory study? Thank you. Alpa, thanks for the question. I think, if I interpret your I think, if I interpreted your question correctly, I think in terms of patients who would be eligible for maintenance going in the relapsedrefractory setting, I think, if you're getting if you had a successful transplant, there's no reason that all patients wouldn't necessarily be eligible.

Speaker 2

They need to have be stable and engraft well. And I think that's usually the first step in patients and physicians remind us of that, that there's an engraftment period. But for all intents and purposes, all patients should be eligible for maintenance. So I think that's our assumption and that's, I think, been discussed with physicians on an ongoing basis. I think when you get to the frontline setting, the assumptions for long term maintenance and how that would play out in the FIT population could very well differ if you were able to get to patients earlier and treat them successfully through transplant and put them back on therapy.

Speaker 2

I think the expectation is treat patients earlier, they stay on do better and they stay on longer. And so that should change how the assumptions work on the time on maintenance in the frontline compared to relapsedrefractory. We don't have a good estimate of that yet. Obviously, we're generating that data. But over time, we'll understand that a little bit better.

Operator

Our next question is from Jason Zymanski of Bank of America. Your line is open. Please go ahead.

Speaker 12

Perfect. Thank you. Good morning and congratulations on the progress. Appreciate you taking our questions. Regarding the commercialization plans for revumentib and your initial outreach, I have to imagine there's already quite a bit of excitement across at least the more academic focused community.

Speaker 12

But what sort of division between rapid adopters and non do you expect? How quickly do you expect maybe the more community based prescribers to come on board as far as awareness and education goes? And maybe bolus isn't quite the right descriptor given patient dynamics this late in treatment, but do you expect an initially large bump in patient numbers or more of a straight line uptake?

Speaker 2

Jason, thank you for the question. I'm going to turn it over to Steve to address your questions. Yes. Hey, Jason, thanks for the question.

Speaker 4

I mean, there's a lot of excitement. I think predating me coming to the company, the company has done quite a bit of research, market research, advisory boards, met with KOLs, the field medical team has been out there. So there's a lot of, we'll just say, demand that's there because of lack of treatment options. I've recently actually was out in New York yesterday at Cornell and Sloan and meeting with KOL. So they're ready for the drug, literally cannot wait till it hits the market.

Speaker 4

So I think certainly the academic centers, Jason, there will be quick uptake, they are ready for this product. Awareness is already fairly high for whether it's revumadivore or menin inhibitor. I think downstream in the community, it's going to take a little bit of time. Part of it is just they may not see a lot of patients initially, so it's up to us to be there. So from a commercialization standpoint, we'll have an adequately sized team that's going to cover 95 plus percent of the opportunity.

Speaker 4

We'll have a non personal promotional program that will reach folks in places that we may not be at as frequently. So I think you'll see a quick uptick across the board. And a lot of it is just patients in the office ready to be treated, which I think leads to your second question. And there's not going to be much of a bolus, right. We have an EAP that's in place.

Speaker 4

It's I'm going to give the number, but it's a certain number of patients. No one's withholding treatment for eligible patients to your point. The criticality is just too high. So there'll be a little, we'll say, extra use initially from EAP That will burn out over the beginning months of the launch. And then after that, we'll expect a typical uptick just based on our assumptions and available patients.

Speaker 12

Got it. Makes sense. And then maybe just a quick follow-up on your Phase 1 in metastatic colorectal cancer. In terms of the gono go decision, I know you mentioned disease stabilization as important, but was curious, is there a specific signal, I don't know, maybe a biomarker that you're looking for in terms of Menin's potential or hypothetical role in driving solid tumors that would just make you feel confident about investing significantly in this potential expansion opportunity?

Speaker 3

Jason, thanks for the follow-up on CRC. I'm going to

Speaker 2

turn it over to Neel to address.

Speaker 3

Yes, thanks. So in the part of the study that has been conducted to date, just to reiterate Michael's point, I mean, this is primarily the safety a safety part of the study. We are looking at in addition to clinical responses, I mean primarily it's a safety study. We're also looking at clinical responses. We're also looking at biomarker data.

Speaker 3

And our anticipation is that as we get to a point in the future where we could make a decision on future development in this space, the totality they have to be taken into that taken into consideration. We haven't specifically said what correlative data we're looking at, but at some point in the future, we will provide more details around that. I wouldn't expect necessarily too much data in our update in the Q2 on, for instance, correlative data. But rest assured that we are pursuing correlative studies. And as I said, we'll take the totality of the evidence into consideration.

Speaker 12

Got it. Well, thanks for the color.

Speaker 2

Thank you, Jason.

Operator

Our next question is from Justin Zelman at BTIG.

Speaker 2

So ahead of 2 launches this year, I wanted to ask how large of a sales force you're looking to build here? And could you talk to the overlap of providers who treat both leukemia and chronic graft versus host disease for promotion of both products? Sure. Maybe I'll let Steve take that question. Thanks, Josh.

Speaker 2

Yes. I appreciate the question, Josh. In terms

Speaker 4

of sales force size, we're not prepared to provide the exact color and size of the team. But it will be

Speaker 5

a team that I think

Speaker 4

can really address customer needs. Our goal, whether it's providers, anybody within the healthcare delivery system, that it's a great customer experience. So we're prepared to link up to all different aspects of healthcare organizations to make sure we're meeting the needs and supporting providers in their treatment of patients. So I think I use the term plus 95 percent coverage. So that will cover the opportunity.

Speaker 4

There's no doubt about that. In terms of overlap between GVHD and rev, there's high overlap. I mean, we're likely, along with Incyte, calling on the same treatment centers, right, whether it's treatment of AML or treatment of transplant. And we'll leverage that call point. There's probably a third overlap right now of our rev audience with the AXE audience.

Speaker 4

We'll obviously provide 30% of the effort. So we'll leverage our footprint and we will cover the market opportunity in really both opportunities.

Speaker 2

Thanks for taking the questions. Thank you, Justin.

Operator

Our next question is from Chris Shibutani at Goldman Sachs. Your line is open. Please go ahead.

Speaker 2

Thank you. Good morning. A lot of questions on the

Speaker 13

focus have already been asked. So perhaps if I can ask a bigger picture longer term question, it ties a little bit to your guidance in terms of operating expense spend on R and D. The near term question is it looks as if to reach your full year guidance, we'll have a considerable step up in the second half. Is that primarily attributed to the combination studies? Just to give us a sense there, Keith.

Speaker 13

And then secondly, Anjali, I think you've done a tremendous amount of work in building this portfolio and the company is now very focused on trying to launch 2 products. But as you know, investors are impatient to try and figure out what could come next. What is your thought on capital allocation priorities, further business development? What are you seeing out there? What's your appetite?

Speaker 13

Thank you.

Speaker 2

Great. Thank you, Chris. Good questions. Maybe, Keith, you want to take the first one on the longer term? Yes, sure.

Speaker 2

So, Chris,

Speaker 5

I wouldn't necessarily agree that it's a big step up to use your words. We did total operating expenses in 1Q, approach $80,000,000 The guidance range for the 2nd quarter is $80,000,000 to $85,000,000 So if we were just to stay on that trajectory, we'd be, dollars 320,000,000 ish. So there is some increase that I think we would anticipate in the back half of the year. And I think, yes, certainly as ramps as the first line 7+3 combination trial with REV continues to accrue and as we get ready to launch the pivotal Phase 3 benasa combo trial with Rev, that's certainly going to add to some of our R and D expenses in the back half of the year. But also don't forget, we're building out a commercial organization.

Speaker 5

So on the SG and A side, we would expect some growth there for the sales force, all the customers facing individuals that Steve commented on earlier as well as the G and A support for those for that field force.

Speaker 2

And in terms of your second question, Chris, on business development, maybe I'll start and turn it over to Angelie. So look, I think our strategy has been and we've been pursuing the same business model for quite some time, which is to in license and develop new molecules with differentiated profiles. I think we've been fortunate to have great success with our in licensing strategy and having these 2 molecules that are nearing approval. And so the bar is always quite high with regard to new opportunities. I think it's incumbent upon us to be thoughtful about how we allocate capital.

Speaker 2

And so we do think that additional molecules bringing them into the pipeline, backfilling the earlier part of the pipeline is quite important. And we are interested in doing that. And so, I don't know if Angeline want to make a on our activities, but we remain quite disciplined about what we're doing.

Speaker 9

Yes. No, I think you said it well, Michael, We're very actively engaged in the market looking across a variety of sources for new opportunities and spending a lot of time on diligence and hopefully we'll have some exciting news to share, but there's definitely a lot to look at.

Speaker 2

Exciting times. Thank you, Chris.

Operator

Our next question is from George Farmer at Scotiabank. Your line is open. Please go ahead.

Speaker 2

Hi, good morning. Thanks for taking my question. A competitor of yours has talked about combining their menin inhibitor with other targeted therapies like FLT3 inhibitors and the like. There hasn't been too much conversation on the call about that this morning. Is that something that you're thinking about as well in greater detail?

Speaker 2

George, thanks for the question. So in terms of combinations, maybe I'll let Neil comment on what else is going on with targeted therapies. Obviously, we have the trials ongoing, the pillars of our strategy being the benasa in the unfit population and then in CoV, if you will, as another interesting option for patients in relapsed refractory, perhaps in earlier patients as well. So just think about it in terms of then combos and then on the FIT side of the equation in combination with chemotherapy, we've already demonstrated that the drug's ability to be combined with chemotherapy and relapsed refractory study. We'll have data updates on that.

Speaker 2

We'll also have additional data as we talked about on the Ben combos this year, which so far looks extremely good. But I think there's options open to us. And Neil, I don't know if you want to comment on some of those.

Speaker 3

Yes, sure. So we have investigator initiated trials either planned or ongoing, which will in which revumentiv in combination with gilteritinib or mitostorm will be investigated either are or will be investigated. To Michael's point, conducting, for instance, a pivotal program in the frontline FIT population in patients with both MPM1 and FLT3 mutations is technically very challenging. It's not really core to our strategy. Of course, we haven't revealed overall what our strategy is, but it's not core to our strategy.

Speaker 3

What we've said is that obviously in addition to the unfit Phase 3 that we'll initiate, we plan to initiate by year end, that we're dose ranging in combination with 7+ 3, which will position us then to initiate a Phase 3 during 2025. You can anticipate that, that will not be in dual mutation patients because that's a very large and complicated study. So we prefer to generate evidence in that population as opposed to potentially pursuing a registration strategy.

Speaker 2

Okay. That's very helpful. Thanks. Thank you, George.

Operator

This concludes our question and answer session. I'll now turn the floor over to Mr. Michael Metzger for any additional comments or closing remarks.

Speaker 2

Thank you, operator, and thank you all for your questions. Appreciate you tuning in today, and we look forward to seeing you all at our planned investor events, including the Bank of America Conference in May and the Goldman Sachs Conference in June. And with that, we wish you a great day.

Operator

The meeting has now concluded. Thank you for joining. You may now disconnect.

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Key Takeaways

  • Regulatory progress is on track with the FDA granting priority review for both the revumenib NDA and axitilumab BLA—PDUFA dates are set for September 26 and August 28, 2024—and pivotal trial enrollments are complete, positioning Syndax for two U.S. approvals in 2024.
  • Phase 1/2 data for revumenib in relapsed/refractory KMT2A-R and NPM1 AML show high overall response rates and MRD-negative complete remissions, enabling many patients to proceed to stem cell transplant, with pivotal NPM1 cohort results expected in Q4 2024.
  • Multiple Phase 1 combination trials with revumenib (including venetoclax, 7+3 chemotherapy and decitabine) demonstrate favorable tolerability and enhanced efficacy, and a pivotal frontline trial is planned to initiate in the second half of 2024.
  • Commercial preparations are underway for a Q3 launch, featuring a seasoned sales force, targeted disease-awareness campaigns, deep engagement with academic centers and payer outreach covering over 90% of lives to ensure rapid patient access.
  • Syndax’s strong balance sheet—$522 million in cash at March 31, 2024—provides runway through 2026, with 2024 R&D and operating expense guidance of $240–260 million and $355–375 million, and a 50/50 co-commercialization revenue-sharing model with Incyte for axitilumab.
A.I. generated. May contain errors.
Earnings Conference Call
Syndax Pharmaceuticals Q1 2024
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