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spk04: Good day, everyone, and welcome to the CINDEX fourth quarter and full year 2020 earnings conference call. Today's call is being recorded. At this time, I would like to turn the call over to Ms. Megan Myers of Argo Partners.
spk01: Please begin. Welcome, and thank you to those of you joining us on the line and the webcast this afternoon for a review of CINDEX's fourth quarter 2020 financial and operating results. I'm Megan Myers with Argo Partners. And with me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morickson, Chief Executive Officer, Daphne Kouridis, Chief Financial Officer. Also joining us on the call today for the question and answer session is Michael Metzger, President and COO, Dr. Michael Myers, Chief Medical Officer, and Dr. Peter Ordentlich, Chief Scientific Officer. This call is being accompanied by a slide deck that has been posted to the company's website, so I would ask you to please turn to our forward-looking statements on slide two. Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements, as a result of various important factors, including those discussed in the risk factor section on the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements represent our views as of today, March 8th, 2021 only. A replay of this call will be available on the company's website, www.syndax.com, following this call. With that, I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer of Syndex.
spk06: Thanks very much, Megan, and thank you to everyone for joining us on today's call and webcast. Slide three provides a high-level summary of our current corporate priorities as we strive to realize a future in which people with cancer live longer and better than ever before. 2020 was a transformational year for Syndex. Over the course of the year, we've made great progress in our two clinical stage programs, both of which are on track to be in registrational programs this year. Thanks to the support of our many committed investors, we ended the year well financed to vigorously pursue both of our existing programs and to aggressively look for additional opportunities to bring targeted oncology drugs into our pipeline. Let's now turn to slide four in S&DX 5613. are genetically targeted agent for the treatment of leukemia. As we've noted previously, there's extensive validation of both MLLR and NPM1 mutations as molecular targets in leukemia. And well-established diagnostic tests routinely identify patients with these genetic mutations. Premier publications provide the scientific rationale and preclinical validation of our ongoing clinical trial. and historic precedents support a rapid regulatory path for such targeted agents in acute leukemias. Slide 5 briefly summarizes the ongoing AUGMNT 101 trial, the first in human phase 1-2 trial in the accelerated understanding of MENIN or AUGMNT program. Consistent with what we communicated on our last call, we are on track to present the completed phase 1 portion of the trial in the near future. and to start the Phase II expansion cohorts soon thereafter. We have received several questions about the upcoming data disclosure, and so I just want to provide some guidance. Our intent is to present the completed Phase I trial. The primary objectives of Phase I are to determine the safety, tolerability, the maximum tolerated dose, and the recommended Phase II dose, of S and DX5613 in patients with relapsed or refractory acute leukemia. We anticipate addressing these primary objectives in our data presentation. We will also have characterized the PK parameters of 5613. We anticipate having data for at least 30 patients with relapsed refractory leukemia. There will be patients whose leukemia has an MLR rearrangement. There will be patients whose leukemia has an NPM1C mutation. and there will be patients whose leukemia has neither of these genetic lesions. Although clinical efficacy is not an objective of the Phase I trial, we anticipate summarizing the efficacy that has been observed. We anticipate that the data will be presented by the principal investigator of the Augment 101 trial, Dr. Eitan Stein from the Memorial Sloan Kettering Cancer Institute, an extremely well-respected international expert in the field of adult leukemias, who has extensive experience developing novel targeted agents. Dr. Stein's presentation will be similar in content to a typical presentation at a scientific congress, such as ASH, and the opportunities for Q&A. We are working with Dr. Stein to find a suitable date, but anticipate securing a date prior to the end of April. We have, of course, been busy preparing for the phase two portion of the trial, which will enroll three distinct expansion cohorts, each of which consists of a specific genetically defined relapsed or refractory acute leukemia, and which is on track to initiate over the next couple of months. The three cohorts will include patients with MLLR acute lymphoid leukemia, ALL, patients with MLLR acute myeloid leukemia, AML, in patients with NPM1 mutant AML. The phase two portion will further characterize the safety of 5613 and will provide a robust estimate of the complete response rate as the primary measure of therapeutic benefit. The phase two portion will enroll both pediatric and adult patients, thereby providing us a potential path to regulatory approval with a broad label including both adults and pediatrics. I should note that if the results are positive, this phase two portion of Augment 101 could potentially support a regulatory filing, giving existing regulatory precedents. Over the last period, we've also been conducting extensive research into the broad landscape of clinical opportunities for 5613 beyond the initial approval and relapse refractory acute leukemias, as illustrated on slide six. While we are not in a position today to lay out the specific next steps in building out the 5613 franchise, I can say that we are using this ongoing analysis to inform specific combination regimens that we anticipate starting to study later this year. Several investigators and leading companies have already reached out to us with novel, exciting ideas for future development of S&DX 5613, and we are evaluating those opportunities. Let me now turn to slide seven, and axotilamab, formerly known as SNDX6352, are potentially best-in-class monoclonal antibody therapy targeting the CSF1 receptor. As you know, we recently presented our phase one chronic graft-versus-host disease data at ASH and have initiated our pivotal trial for axotilamab in chronic graft-versus-host disease. This trial is the axotilamab for graft versus host disease trial called Agave 201, and it's outlined on this slide. The trial will enroll patients with chronic graft versus host disease whose disease has progressed after two prior therapies. Patients must be at least six years of age and have met overall entry criteria. This is a pivotal dose-ranging trial in which patients will be randomized to one of three treatment groups, each investigating a distinct dose of axotilamab given either every two weeks or every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronic graft-versus-host disease. Secondary endpoints will include duration of response and validated quality of life assessments using the Lee symptom scale. Enrollment to the study is underway. and we are on track to deliver top-line data in 2023. We believe that chronic graft-versus-host disease represents a high unmet medical need and an important commercial opportunity, with approximately 14,000 patients suffering from a chronic graft-versus-host disease in the U.S. today. With the recent positive pivotal results from both Insight's JAKA-Fi and Cadman's KD025, we may seem soon see regulatory approvals and commercial launches that will begin to delineate the commercial opportunity to chronic graft-versus-host disease. Despite recent advances in this area, to our knowledge, axotilumab is the only agent in clinical development that specifically targets the monocyte macrophage lineage. We believe the data generated state with axotilumab suggests it has the potential to play an important role in the treatment of chronic graft-versus-host disease, both as monotherapy and given its safety profile, potentially in combination with complementary medicines. We've also been working extensively with experts in the field of fibrotic diseases, and have found a strong consensus that the scientific rationale for the efficacy of axotilamab in chronic graft-versus-host disease firmly supports its potential in a wide variety of fibrotic diseases, such as idiopathic pulmonary fibrosis and scleroderma. We are actively evaluating options by which to build the Axotelamab franchise beyond chronic graft-versus-host disease and take advantage of what we believe are a significant set of opportunities that could material enhance shareholder value. Finally, slide eight summarizes the transactions that led to the acquisition of the Mennon MLR and Axotelamab programs. We believe that we will be able to continue to expand our pipeline through the acquisition or in-licensing of quality, differentiated assets. We believe that we have the necessary skills to evaluate and identify high-quality assets and the clinical development experience to bring these campaigns through valuable inflection points. We expect to remain among preferred partners for such transactions. I'll now turn the call over to Daphne to review our financial results. Daphne.
spk02: Thank you, Briggs. Thank you, Briggs. The results of our operations for the fourth quarter of 2020 and the comparison to the prior year quarter are included in our press release, so I won't repeat them in these remarks. Additional financial details will be available in our fourth quarter and full year report on Form 10-K, which will be filed later this week. I would like to point out that our net loss for the quarter was $20.4 million, or 44 cents per share, compared to $14 million, or 44 cents per share for the same period last year. Turning to slide nine, we ended the fourth quarter with $293.1 million in cash and cash equivalents, including net proceeds of approximately $135 million from our public offering completed in December of 2020 and 51.4 million shares and pre-funded warrants outstanding. This cash balance provides us cash runway well into 2023, and importantly, covers the full development cost of both Axotelimab and the 5613 registration-ready programs, as well as provides us flexibility for continued business development. Looking ahead, I'd like to provide financial guidance for the first quarter and full year of 2021. For the first quarter of 2021, we expect R&D expense to be $25 to $30 million, and total operating expense to be 30 to 35 million dollars, including approximately 2 million dollars of non-cash stock compensation. For the full year of 2021, we expect R&D expense to be 90 to 100 million dollars, and total operating expense to be 110 to 120 million dollars, including approximately 2 million dollars of non-cash stock compensation expense per quarter. We expect first half expenses to be more heavily weighted than the second half due primarily to the ramp up in CMC activities for both programs during the first two quarters of the year. With that, I would now like to turn the call back over to Briggs.
spk06: Thanks very much, Daphne. Let me close the call by again noting that 2020 was a transformational year for our company, and we anticipate that 2021 will be no less exciting. We've begun the registrational trial for axotilamab and chronic graft-versus-host disease and are eager to present our Phase I data from the Augment 101 trial in the coming weeks and to start the registrational program for SNDX5613 shortly thereafter. We are also getting increasingly excited about the broad franchise opportunities for both programs beyond their initial registrational indications. We believe that 5613 could have broad utility across a wide range of clinical settings in acute leukemia, and acetilumab could represent a broad franchise opportunity in fibrotic diseases. We are comfortable, given our cash on hand, that we have the financial resources to aggressively advance our programs and achieve key upcoming milestones. We also remain optimistic that we can continue to identify and bring in novel molecules to deepen our portfolio. We have a proven track record of delivering on this pillar of our strategy, and I believe this is a core strength of our company. As always, I would like to thank the wonderfully talented team here at Syndex, our collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical programs. In addition, I would like to thank our committed long-term investors who are helping us to build this great company. With that, I'd like to open the call for questions.
spk04: Ladies and gentlemen, if you have a question at this time, please press star, then the number one key on your touch-tone telephone. Again, that's star, then the number one key on your touch-tone telephone. Your first question comes from the line of Phil Nadeau from Cohen and Company. The line is open.
spk00: Good afternoon. Congratulations on the progress, and thanks for taking my questions. There's a few for you just on some of the parameters you laid out for the data we should expect late this month or next month. In terms of Arm A versus Arm B, you actually didn't give any color there. Should we have any expectations for relative weighting of those arms?
spk06: Hi, Phil. Yeah, thanks for your question. I don't think I've given any guidance on the relative weighting. I think what we anticipate is that we will have a recommended Phase II dose for each of the individual arms.
spk00: Got it. Okay. And then second, I'm not sure you want to comment on this either, but in the past you've suggested that MLLR could be more heavily represented in NPM-1 in light of the history of the trial, particularly at some of the heavier enrolling centers. Is that still your expectation, or could MLLR and NPM-1 be more evenly balanced?
spk06: No, that's still our expectation, that there'll be more MLLR. Again, just to clarify for people, otherwise known as KMT2A rearrangements, but more of the MLLR or KMT2A than NPM1.
spk00: Great. And then just a last question on the data. How will you present the safety data? I guess specifically, will you give us the safety results for all the patients who are enrolled or specifically for the Phase II dose?
spk06: Both, actually. So we'll present the full safety profile for the entire population that was enrolled, and we'll break out the safety profile for the recommended Phase II dose.
spk00: Perfect. Then one question for Daphne. Daphne, you mentioned H1 expenses are going to be more heavily weighted than H2. Do you expect Q2 to kind of look similar to Q1, or is Q1 really going to be the heaviest dose? expense quarter of the year.
spk02: Thanks, Phil. So, yeah, just to clarify, the comment was we expect the first half expenses to be more heavily weighted than the second half, and we would expect the first two quarters to be similar in cadence.
spk00: Perfect. Thanks for taking my questions, and congrats again on the progress. Thanks, Phil.
spk02: Thanks, Phil.
spk04: Your next question comes from the line of Bert Haslett from BTIG. Your line is open.
spk07: Thanks. Thank you for the update and taking the question. Could you just describe a little bit more, Briggs, please, a little bit more about the Phase II expansion part of Augment 101? Do you have any sense for the size and scale of each of the individual arms at this point? Do you have any sense for the potential pace of enrollment or the length of enrollment that that Phase 2 might take?
spk06: Yeah, thanks for the question, Bert. So the precise size of each of the independent Phase 2 expansion cards, again, will be sort of sized on what the sort of null hypothesis is on response rate and what's the alternative That's still, I think, a final discussion we have to have with FDA. There's sort of a related question of, you know, what's the total number of patients that we need from a safety point of view across the three cohorts, including the phase one data. I will emphasize that each of the three are independent, essentially parallel independent phase two cohorts. We could potentially register one or two or all three And then the second part of your question?
spk07: I guess it's dependent upon the first, but the potential length of time enrollment it might take.
spk06: Yeah, we haven't given guidance on the timing exactly to your point. Until we know the precise numbers, it's a little hard to give precise definition of timing. What I would say is thus far at least the phase one trial has progressed very, very nicely. And so, you know, it's really just a question of knowing how many patients we need, and then we'll give you guidance on how long we think it'll take to enroll.
spk07: Okay, thank you. And then just a more strategic question with regard to the slide that says multiple commercial opportunities and acute leukemia, multiple pathways. How are you thinking strategically about potential expansion here? Is this Is this an in-licensing effort which you've been successful at previously? Is this corporate collaboration at some point? Just general framework for how you're thinking about prosecuting these additional efforts.
spk06: Yeah, so I think the first part is just to lay out where we believe that the drug can be used, and in some cases that might entail a combination with you know, established therapies that are, you know, generic and available such as chemotherapy might require or might be enabled by a corporate partnership with somebody who has, you know, a drug that we think makes sense combining. But the strategy is first let's lay out where we think the best, where the largest unmet medical need is. where there's a trial that we can get done reasonably quickly, and then decide is there a corporate partner who would want to work with us on that, or is it single agent, or is there a combination regimen that we can sort of do ourselves?
spk07: Okay. Thank you for that. That's all I had. Thanks.
spk04: Your next question comes from the line of Konstantinos Aprileks from Stifel. Your line is open.
spk05: Hey, good afternoon, guys. Thanks for taking my question. So for the sake of clarity on the size of the 5613 update we're looking forward to later this quarter or early next, does the 30 patients include the six patients presented last year, meaning should we expect 30 additional patients or 30 total patients? And where do the compassionate use patients fit in? Yeah, hi, Constantine. Thanks for your question.
spk06: So I said that. At least 30 patients, that's 30 patients total, so that includes the six that were presented last year. That's the number of patients from the Augment 101 trial, so that does not include the compassionate use patients, and we're discussing with Eitan whether we focus completely on the Phase 1 trial or we also present some of the data from the compassionate use patients.
spk05: Okay. Perfect. Thanks for that clarification. And then, and one more quick one, just, you mentioned it in your prepared remarks, 56, 13 combinations, you know, at this juncture, if you had to say, what do you think is sort of most promising? It sounds like we're going to get something on that in the near term, but any thoughts at this juncture would be helpful.
spk06: Yeah, again, relative to Bert's question, I think that, you know, the first order of business from our point of view is just to lay out where's the right place to further develop the drug. and then see if that requires a combination. Clearly, I think if you were going to do first line with this agent, there's the so-called population of patients who can tolerate intensive chemotherapy. And so there might be a regimen where you combine with standard upfront chemotherapy. And then there's the population of patients, the so-called unfit, where they don't get chemotherapy. you know, other agents, and so combining the agents in that space makes sense as well. So we're looking at both the patients who are candidates for intensive therapy and patients who are not.
spk05: All right, perfect. Thank you. Congrats on the progress.
spk04: Your next question comes from the line of David Lebowitz from Morgan Stanley. Your line is open.
spk08: Thank you very much for taking my question. Looking at the 30 patients we'll be seeing towards the end of this quarter, I know there's going to be a certain number of patients that don't have either the MLLR or NPM1 as the initial trial that have all comers with leukemia. And I guess my question is, will there be patients beyond the initial cohort that we saw that did not have mutation, and if so, do you know how many at this point? And can the number of, I guess, non-NPM1s and MLRs be disclosed at this point? Or, I guess, to what extent, how large is the number of the numbers should we expect?
spk06: Yeah, hi, David. Thanks for your question. So, as you correctly pointed out, when the trial first started, It was an all-comers trial, and the data we presented at AACR last year, three of the patients had neither NPM1 nor MLLR. And the trial, as it continued, did allow continued enrollment of that population. I think last summer on our August call, we had mentioned that we had refocused the trial to focus only on enrolling NPM1 and MLLR. So there will be patients who have neither We haven't said specifically how many of those patients there'll be, but there will be some because of that early design of the trial.
spk08: Thank you for that. And on the initial description of the call, you were referring to the population as acute, as leukemias. I know we've seen ALL patients, and we're going to see MPM1 patients. Are we going to also see AML patients in the trial?
spk06: Right. So we will see both ALL and AML. And as you may remember from our AACR presentation, one of the patients had what is known as mixed phenotypic acute leukemia, where the leukemia actually has markers consistent with both AML and ALL. So there'll be ALL, AML, and at least one mixed phenotypic.
spk08: And I guess my last question would be, I know that there's a competing menin inhibitor out there, and would you be able to, I guess, compare and contrast what you know and understand about your molecule with their molecule?
spk06: Yeah, I mean, I don't think, I'm not quite sure which competitor you're referring to. But I don't think we're in the position to do a lot of comparing and contrasting. The other molecule that's in the clinic, there's actually very little known about the molecule itself. So, you know, I don't think we can say too much about that at this point.
spk08: Thanks for taking my question.
spk04: Your next question comes from the line of Justin Walsh from B O'Reilly Securities. Your line is open.
spk09: Hi. Thanks for taking the question, and congrats on the progress. The CGVHD opportunity is quite intriguing to me. Can you provide any color on how you view that space evolving over the coming years? Specifically, I'm wondering if you think the opportunity is growing with the trend towards increased number of stem cell transplants, or could it be getting crowded with RUX and other drugs going to approval?
spk06: Yes, I'd like our head of new product planning, Angela Ganguly, to take that question.
spk10: Thanks, Frank. Thanks, Justin, for the question. Yeah, you know, I think there's a lot of change in that space. As you mentioned, there's a couple new drugs that are under review for the FDA for potential approval. But, you know, I think there's two parts to that answer with the advent of new leukemia drugs that are very promising and helping patients get to transplants. There could be an increase in overall number of patients who unfortunately then develop chronic GVHD as a consequence of that transplant. And there's also, I think, a lot of underserved patients that exist today with chronic GVHD who have been treated with therapies that weren't developed to treat that disease and haven't done as good a job as we think exotilamab could do and maybe perhaps some of the other agents in controlling their disease. So we think that is really going to be a displacement of some of the, you know, non-labeled agents, the agents used off-label to treat chronic GVG, and there'll be ways to actually maybe better help these patients, better serve these patients, and help them live longer and better with their disease.
spk09: Got it. And I have one follow-up. I know that we aren't expecting the top-line Agave 201 data until 2023, but could we see any data redoubts before that, anything this year or maybe next year for the earlier trial?
spk06: Right. So you may remember we had started a Phase II expansion cohort as part of our Phase I trial at one MIG per gig. And it is, you know, the team is still allowing that trial to enroll while we get agave up and running. So if a site doesn't yet have agave up and running but still has patients they want to put on trial, we can put a few more on. And it's not clear yet when we're going to present that data, but there may be data on that updated Phase II court at the 1 mg per kg later this year.
spk09: Perfect. Thank you. That's all for me.
spk04: Once again, to ask a question, you will need to press star one on your touchtone telephone. Again, that's star, then number one on your touchtone telephone. Your next question comes from the line of Peter Lawson from Barclays. Your line is open.
spk03: Hey, thanks for taking my question. Thanks for the update. Riggs, just on the side effect profile you've seen so far for 5613, does that preclude or point to any particular combination agent that you'd want in presumably frontline?
spk06: Yeah, so obviously we'll present the safety data, I think as somebody asked earlier. From what we've seen, it doesn't preclude combining with any of the agents that we would be interested in combining with.
spk03: And that applies for both kind of Arm A and Arm B?
spk06: Well, it applies to the so-called combination chemo-eligible patients and the unfit.
spk03: Gotcha. Okay. And then as you move from phase one into phase two, do you expect any changes in endpoints or how should we think about the, I guess, the inclusion, exclusion, and how that could potentially change from phase one to phase two or endpoints? Yeah, no, we don't.
spk06: Again, obviously, the phase one trial, the primary objectives, as I alluded to, were PK safety and defining a recommended Phase II dose. The Phase II portion, the primary endpoint, is a CR rate for efficacy. But the overall inclusion and exclusion don't change. Obviously, the Phase I trial has changed over time. We've amended the protocol many times to, you know, allow pediatric patients in to focus on NPM1 and MLR. But overall, the general population of patients that we're enrolling in terms of relapse refractory leukemia doesn't significantly change from phase one to phase two.
spk03: Gotcha. Thank you. And then in that kind of third group of patients you mentioned about presenting, so the non-MLR and the non-NPM1 patients, would you expect to see any kind of response in those patients?
spk06: Well, I think that's why the FDA asked the companies to enroll a broader population. So I think their perspective was we're convinced that your drug potentially could work in NPM1 and MLLR. There's been extensive preclinical validation. We're convinced that your drug probably would not work in BCR-ABL. We've always used that as a negative control in our preclinical models. but there are other forms of leukemia that we, you know, it might be of interest for you to study. So I think that was why the FDA asked us to enroll in all comers population.
spk03: Okay. And so we could get kind of patient vignettes in that group that could be of interest.
spk06: Well, as I said, I think the FDA asked us to enroll a broad population of patients to begin to look at that. It's obviously not a definitive assessment of that population. You know, we focus much more on the MLLR and NPM1 for the simple reason that we can diagnose those patients today and, you know, it's clear unmet need in a population of patients that, from a regulatory point of view, you can identify and you can get an indication for.
spk03: Gotcha. Okay. Thanks so much. Thanks for the answers.
spk04: Once again, to ask a question, you will need to press star, then the number 1 on your touchtone telephone. Again, that's star, then the number 1 on your touchtone telephone. Once again, to ask a question, that's star, then the number 1 on your touchtone telephone. There are no further questions at this time. I would now like to turn the call over back to Mr. Briggs Morrison, Chief Executive Officer of Syndax.
spk06: Thank you very much, Operator. And, again, thank you, everybody, for joining us on our call. As I said, I think, you know, 2020 was a transformational year, and we anticipate that 2021 will be no less exciting. And, you know, the first piece of news, of course, will be the presentation of our Phase I data from the Augment 101 trial. And, you know, I think we're really quite excited to present that data and then to take additional questions from everybody once we have a chance to see that. So thanks so much for joining the call.
spk04: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.
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