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spk02: Hello and welcome to the EpiVine fourth quarter and full year 2021 Financial Results Conference call. At this time, all participants are in a listen-only mode. Following the prepared remarks, there will be a question and answer session. Please be advised that today's call is being recorded. I would now turn the call over to Kristen Hilton, Investor Relations. You may begin.
spk03: Thank you, operator. This morning, Epizyme issued a press release providing a business update in addition to fourth quarter and full year 2021 financial results. That press release can be found in the investor section of the company's website at epizyme.com. On the call today are Grant Bogle, President and CEO of Epizyme, and Dr. Shefali Agarwal, Executive Vice President and Chief Medical and Development Officer. Joe Bollier, Vice President and Corporate Controller and Treasurer, will join us for the Q&A. As a reminder, today's discussion will include forward-looking statements related to Epizyme's current plans and expectations, which are subject to certain risks and uncertainties. Actual results may differ materially due to various important factors, including those described in the risk factors section of our most recent forms 10Q, 10K, and other SEC filings. These forward-looking statements represent our views as of this call and should not be relied upon as representing our views as of any subsequent date and we undertake no obligation to publicly update these statements. At this time, I would like to turn the call over to Grant Vogel.
spk08: Grant? Thank you, Kristen, and good morning, everyone. It's great to be here with you and to provide an update on our fourth quarter and full year 2021 results. On today's call, I will review company results, including commercial performance of TASVERIC, and provide additional business commentary insights on our cash position, and updated guidance for 2022. Shefali will speak to our clinical development progress for Tazimetastat and EZM0414, our investigational CETD2 inhibitor, in more detail. Following our remarks, we will open the line for questions. During the fourth quarter, we reported TASVERIC net product revenue of $11.6 million, including 4.2 million related to the sale of TASVARIC commercial product for third party pharmaceutical company use in clinical trial. TASVARIC commercial net sales for the fourth quarter of 2021 were 7.4 million, representing an increase of approximately 42% when compared with the third quarter of 2021. For the full year, ended December 31st, 2021, We reported TASVERIC net product revenue of $30.9 million, including $7.4 million related to the sales of TASVERIC commercial product for the third-party pharmaceutical company used in clinical trial. TASVERIC commercial net sales for the full year 2021 were $23.5 million. Free goods from our patient assistance program represented approximately 29% of total end-user demand. for the fourth quarter of 2021 and approximately 24% for the full year of 2021. Total end-user demand in the fourth quarter increased approximately 14% over third quarter 2021 levels, driven primarily by increased follicular lymphoma patient sales. We continue to make progress on our commercial efforts to drive prescription growth for TASVIRIC as a monotherapy, as well as advancing our combination clinical studies, which we believe have the potential to significantly expand the value and reach of TASVERIC among physicians and patients as the data matures. As we announced in our press release this morning, we continue to make necessary operational changes to reduce our expenses and extend our cash runway, all while strategically deploying our resources to areas we believe to be the highest impact for the company and its stakeholders. We've implemented a plan that reduces our workforce by approximately 12%, along with external spending. As part of this effort, we have also reprioritized our pipeline, including discontinue enrollment in select studies, Symphony 2 and EZH 1301. As Shefali will review in detail, we continue to study tazometastat in combination with numerous other therapies for both hematological and solid tumor cancers through our ongoing company-sponsored studies and investigator-initiated studies. I want to recognize the contribution of the EPIZON employees that are being impacted today and to thank them for all their efforts to advance our company's mission and vision. Their transition from the company is being handled appropriately to ensure that it is as smooth as possible. For those epizymers who remain with the company, I also wish to thank them for their commitment and support as we continue to focus and streamline the organization for the benefit of all stakeholders and the future of our company. These initiatives, along with the organizational and operational changes implemented when I joined as CEO last August, are designed to advance our vision of transforming the lives of patients living with cancer and helping establish TASVARIC as a foundational therapy in FL and other cancers. Looking ahead to 2022, we plan to continue to educate providers and to align systems of care to support the growth of TASVARIC monotherapy while further advancing key clinical trial programs. We are pleased with the progress we are making in our development program including the global initiation of the Phase III portion of our Symphony I study, the near-complete enrollment in the Lysa study, and the progress we are making in our Phase II prostate cancer study, CHELA I. We look forward to providing updates on these important programs, as well as other activities throughout the year. At this time, I'd now like to turn the call over to Shefali, who will speak to our clinical development progress. Shefali?
spk01: Thank you, Grant, and good morning, everyone. With the initiation of our SET101 study, we now have two molecules in clinical development, Tazometastat and EGM0414, our novel SETD2 inhibitor. During the fourth quarter, we made key progress across our development pipeline. I'll begin with Tazometastat. As we have previously discussed, we believe that Tazometastat has the potential to become a backbone of therapy in FL and potentially other hematological malignancies and solid tumors. Our clinical development program has been built with the aim of demonstrating the clinical utility of using tazometastat across a variety of hematological and solid tumors, both as monotherapy and when combined with other therapies. We are excited that much of the work that began several years ago is beginning to mature and we look forward to a steady stream of data in 2022 and beyond. Speaking as a clinician, we are very encouraged by the Symphony 1 data we disclosed at the ASH annual meeting in December, and I'm pleased to report that we have completed the waiting period for the protocol amendment submitted to the FDA in December, specifying 800 milligrams twice daily as a Thesmetastat dose for the study. which allows us to open the randomized portion of the study in the U.S. As a reminder, the Phase III portion of the study will evaluate tazometastat in combination with rituximab and liridamide, which we call R-square, in patients with relapsed refractory follicle lymphoma who previously had been treated with at least one systemic therapy, including those who are rituximab refractory and or have experienced progression of disease within two years, Part 24. We are actively engaged in global startup activities, including sites in Great and China with our collaboration partner, HutchMed. We are screening patients for the phase three portion and expect to enroll the first patient in the first quarter of 2022. We expect to enroll approximately 500 patients in total across approximately 180 sites globally. In addition, we continue to follow the 40 patients in the phase one B safety run-in portion of the study and anticipate longer-term follow-up data to be presented at a medical conference later this year. Turning to the LISA study, which is the Phase 1b2 study of chasmatostats in combination with RCHOP for newly diagnosed DLBCL or high-risk FL patients, enrollment is now nearly complete for both FL and DLBCL study cohorts. This is a large Phase 2 study, and as of February 23, We have 111 out of 122 patients enrolled in the DLBCL arm and 61 out of 62 patients enrolled in the FL arm. The primary endpoint of the study is to evaluate complete response rate of chasmatostat in combination with ARCHAR. We, in conjunction with Lysa, anticipate presenting interim results from the study in DLBCL and FL patients in 2022. Moving to our solid tumor program, TELO1, an open-label randomized phase 1b2 study evaluating chasmatostat plus enzulutamide compared to enzulutamide monotherapy in metastatic castration-resistant prostate cancer patients is progressing nicely. The study is approximately 75% enrolled in the randomized portion toward a target of 80 patients, and we expect to complete enrollment in 2022. We anticipate presenting the updated data from the completed safety run-in portion and interim data, including radiological PFS and PSA50 from the phase two portion of the study in the second half of 2022. We also recently initiated our TazMedistat Hematological Basket Study, EZH1501, a phase one 1B signal finding basket study designed to investigate potential signals of safety, tolerability, and activity of TazMedistat with various combinations of patient with relapsed refractory hematological malignancies, specifically FL, diffuse large B-cell lymphoma, mantle cell lymphoma, and multiple myeloma. We have entered into a clinical supply agreement with Roche for the bispecific cohort of EZH1501. This cohort will evaluate the investigational use of Tazmetastat in combination with mozuntuzumab, Roche's investigational CD20-CD3 T-cell engaging bispecific antibody for patients with the relapsed refractory follicle lymphoma who have received at least two or more prior lines of therapy. We plan to provide updates on EZH 1501 as it reaches key enrollment milestones. We also plan to provide preliminary data from EZH 1501 in the second half of 2022. Additionally, as Grant mentioned, today we announced reprioritization of our pipeline programs. Given the breadth of Epizem's current desometastat clinical development program, we have made the decision to discontinue enrollment in two studies, including Symphony 2, which is the study of tazometastat in combination with rituximab in third-line plus setting, as well as EDS 1301, the solid tumor basket study. The decision to discontinue these studies was based on evolving market dynamics and continued focus on optimizing our investments and eliminating potentially overlapping studies. The company will continue to follow the patients who have already been enrolled in these studies. We remain committed to the development of Tazomatastat in combination with other therapies for both hematological and solid tumor malignancies, both in ongoing company-sponsored studies as well as investigator-initiated studies. Turning to our novel, first-in-class oral CetD2 inhibitor development candidate, EZM0414. During the first quarter, we initiated CET101 study our Phase I-1B study of EZM-0414 in adult patients with relapsed refractory multiple myeloma and relapsed refractory diffuse large B-cell lymphoma. EZM-0414 has been granted fast drug designation by the FDA in adult patients with DLBCN and has also granted orphan drug designation by the FDA for multiple myeloma. We shared preclinical data on EZM-0414 along with SET-101 Phase I-1B clinical trial design at the 2021 ASH Annual Meeting. We plan to provide updates as the study reaches key enrollment milestones, along with preliminary safety data expected from the study in 2022. As you can see, we continue to advance the development program for TazMetastat and EZM 0414 and expect a steady cadence of data through the coming years. The data yielded will be important as we develop TazMetastat beyond FL and ES given its pipeline inner drug potential, as well as potentially addressing high inmate need in multiple myeloma and DLBCL with a SEDD2 inhibitor. At this time, I'd like to pass the call back to Grant.
spk08: Thank you, Shefali. We ended the fourth quarter with $176.8 million in cash, cash equivalents, and marketable securities. In January 2022, we raised an additional $79.5 million in net proceeds and a public offering of common stock. This raise, as well as the cost reduction measures outlined earlier, extends our runway into the back half of 2023. Total GAAP operating expenses were $62.9 million for the fourth quarter of 2021, and $275.4 million for the full year ended December 31st, 2021. Total non-GAAP adjusted operating expenses were $54.7 million for the fourth quarter of 2021, And $243.4 million for the full year ended December 31st, 2021. We have revised our full year 2022 operating expense guidance due to the expense reduction measures and operational efficiencies discussed today. We now expect 2022 total non-GAAP operating expenses of between $160 to $180 million compared to the prior guidance of 170 to 190 million disclosed in January of this year. In closing, I want to emphasize that all the activities discussed today, both from a clinical development perspective, as well as an operational and organizational perspective, continue to be guided by the four pillars of our strategy. These include maximizing commercial adoption of TASVERIC, building on TASVERIC's pipeline and a drug potential, expanding our pipeline and portfolio, and finally collaborating to expand our reach to patients and building incremental value. We are making difficult but necessary decisions to help ensure that we can deliver on our corporate imperatives. I'm pleased by the progress we've made and look forward to the growth and progress yet to come this year. With that, operator, you may now open the line for questions.
spk02: Thank you. To ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key. Our first question comes from Joseph Tomei with Cowan. Your line is open.
spk05: Hi there. Good morning and thank you for taking our questions. Maybe the first one just on TAS in terms of the commercial setting. As you look over the next year, maybe what are sort of the key drivers that will kind of determine increasing sales and As you're seeing it right now, compared to launch, are physicians using the drug in a different set of patients, maybe for longer duration, earlier in the treatment paradigm? How is that shaking out? Thank you.
spk08: Thank you, Joseph. So, in answer to your question, we continue to execute on the plan that we've laid out, and I'm seeing steady progress. I mean, in terms of really focusing on engaging with healthcare providers and the means that they want to engage. And that has changed as a result of the pandemic and many clinics and hospitals that used to be open now want to engage in a more digital way, which is fine. However, we are seeing clinics in other parts of the country and so forth open up. So we've adjusted our strategies to align with that reality, and as we've talked previously, we've brought on new associates into our organization that have skill sets more on the system side of care delivery. So we are really aligning and working with leadership within these systems to ensure that if a provider wants to use TASVERIC, according to the label, that it's easier to do so by inclusion in, for example, order sets that support appropriate prescribing for patients in different settings. So those drivers of sales will continue to, I believe, strengthen our position and help you know, lead to continued growth within our current label. All the while, the clinical development program continues to move forward, and we're obviously going to talk and have talked a fair amount about that. So I'm excited about that because that, again, we can't promote on that, would not promote that information, but it does help inform clinicians that attend medical meetings and so forth what the future potential of TASVARIC may be.
spk05: Perfect. And then maybe just a follow-up, probably for Shefali, but one of the basket studies, the SALAD was discontinued, but the other one's ongoing. I guess, can you give a little bit more information into this decision? Is it just based on kind of how the current standard of care is evolving, or do you think Tesveric is better suited for heme tumors in terms of probability of success? What went into that decision?
spk01: Sure. Thank you, Joseph. So in terms of the studies, you know, the reason to discontinue these studies was based on changing marking dynamics. It also, we want to optimize our investment as well as the main, one of the big reasons is MNA potentially overlapping toxicities. If you remember the solid tumor basket study that was in combination with PARP, we do have an ISD that we are combining in PARP in those indications. So our goal is to get that data, and we'll be able to get that data from that ISD. And that will actually be important because once we know how it combines, we can think about next steps and starting a different trial in combination with PARP. Overall, we are very committed both in solid tumors and heme malignancies with TASVAC. That's why we have the prostate cancer study as well. So we are committed to that and we believe that Tasveric is important both for solid and heme malignancies.
spk05: Perfect. Thank you very much. Thank you, Joseph.
spk02: Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open.
spk04: Great. Thanks for taking my question. Just thinking about revenues, what's the average duration of use of Tismetastatin? I guess where do you think it could get by the end of the year?
spk08: So, Peter, we've not guided to that in the past, and here's what I can say about duration of use. It is in a general trend increasing quarter over quarter, and we would expect that mainly for two reasons. One is the data matures, so the more patients we get on TAS and the longer we follow them, obviously the duration of therapy increases. The second is we do see trends, and this is Sorry, Joe, I didn't answer this question directly when you asked it, but we do see trends in our tracking studies, the ATU studies that help us guide market shares, projections, and so forth. We do see trends where physicians are tending to use TASD. earlier in lines of therapy. Most of our use is third line plus, but we're seeing even growing use within the second line setting, albeit it is a small portion of the use today. So as they move it to earlier lines of treatment, we would expect that those patients would stay on therapy longer. So it's a journey. The trends are moving in the right direction. And so I believe, you know, there's no reason we would think that it would not continue in that direction for a period of time. Thank you.
spk04: And then a question for Shivali really around the basket study that's been shut down. Should we read into that for particular indications that aren't showing a benefit from Tezmatastat? Anything you can kind of help us, kind of guide us to where you potentially see a beneficial activity for TazNavistat?
spk01: Sure, thank you, Peter. Yeah, so in terms of looking at TazVaric, I think based on the mechanism of action, and we have presented some preclinical data, we believe TazVaric, you know, can combine with many of the agents both in heme and solid tumors. We have shown that in combination with R-CHOP. You know, we've shown that with R-Square. We have shown that with doxorubicin. in heme malignancies, and then in solid tumors we have shown with Abbey and Enza as well in prostate. In terms of that BASCA study, it was more an effort to, you know, how we optimize our development. And if there is an overlapping study, how do we get data irrespective? And that's why, as I mentioned, we have an ongoing study that is enrolling patients in combination with PARP, and we would get data from that study as well. But I believe that based on the process study as well as the other ISTs and our heme studies in combination, there's a potential in both indications.
spk08: Peter, if I might add, because this is, I think, really important for those on the phone to take away, The changes we've made to our operating expense guidance really have been done with the goal of streamlining the organization, removing complexity, removing some layers of management where appropriate, But that also involves simplifying certain things that are underway, especially when we can get the data in a more efficient way, which is what really drove us in the heme, I mean, excuse me, in the solid tumor basket study, as well as, quite frankly, Symphony 2. And if you look at the use of single agent Rituxan in the third light setting, Plus, it is not significant. In fact, it's going down. So we felt that this was the most efficient decision and should no way be viewed, especially in the solid tumor area, that we're not excited about TAZ's potential there. But we've got not only a large Phase II trial underway in terms of CHELA1 that we'll continue to read out in prostate cancer. We've got other work underway in that with ISTs and so forth. So I hope that puts it a little bit more into perspective.
spk04: Great, yeah, thank you. That really helps. Just on SymphonyOne, final question. We get updated data this year. Is that kind of a year-end update that we should be thinking about?
spk01: So in terms of SymphonyOne, as you know that we presented data in ASH last year, for the safety-run portion of the study. And as you know, it's in second line and beyond. So we'll continue to follow those patients and we provide data this year. We haven't really guided on exactly the timing, but we'll continue to provide in conferences this year as the data matures for Symphony 1 for the safety-run portion of the study. I think the important part is, Peter, that I want to highlight is that we have gotten clearance in terms of submitting the protocol amendment for 800 milligrams PID in the phase three portion of the study, and we are actively in the global startup and screening patients for the randomized portion of the study as well.
spk04: Perfect. Thank you so much. Thanks for the updates.
spk02: Thank you. Our next question comes from Michael Yee with Jefferies. Your line is open.
spk07: Good morning. This is Sid Harthorn from Michael Gee. Thank you for taking our questions. And I know it's challenging to move a company forward in this environment. I have two questions. The first is going to be on EZM0414. You guys initiated the first in human study. What do you expect will be or should be good data in DLBCL and multiple myeloma? And do you fully expect responses in those two pathologies? And what's the bar that you're looking for that would be you know, pleasing to move the study forward.
spk01: Yeah, sure. So, I mean, just kind of reminding where we are for EZM-0414. As you know, we are starting our first in-human study. It's a dose escalation part of the study where we will escalate in both multiple myeloma and DLBCL. We initiated the study last year. We are screening patients and hoping to enroll the patient very quickly. The goal in the first in-human portion this year is to get to a dose that is safe. and get preliminary activity in biomarkers. And once we have that dose, then we plan to expand into cohorts where we would like to evaluate, especially the T414 translocation. We have shown some preclinical data in ASH last year, which showed specifically our activity in T414 multiple myeloma, which is a big unmet need in myeloma. And so our goal is to evaluate in that particular biomarker, which could be a faster path for gestation, in that portion of the study. Additionally, we look at non-T414 multiple myeloma as well as looking at how we do in the LBCL look at biomarkers and things like that. So the goal is first to get to a dose which is safe and then eventually expand in myeloma and evaluate the LBCL if needed.
spk07: Okay, great. Thank you. And then you had mentioned that you had updated data from Cello at some point in 2022. Could you give a little bit more guidance as when we can expect that? Was that going to be, you know, at ASCO? Is that going to be at, you know, a GU conference? When can we expect that?
spk01: So the Cello one, just in terms of the status, we had presented the data for the safety run in the 21 patients at ESMO last year. We continue to follow those patients, including radiological PFS, PSA50, time to PSA50 progression. Our goal is to provide that data second half of this year. Additionally, we also mentioned that we have enrolled about 75% of the patients in the randomized portion of the Phase II study. Our goal is to provide some interim data second half of this year as well. So as we continue enrolling patients, as we have more follow-up, we'll guide more further on the timing, exact timing of the presentations.
spk07: Gotcha. Thank you. And just one small last question. You mentioned that you initiated the global phase three study in collaboration with HutchMed. Were there any milestone payments given to Epizyme at the start of that enrollment? No.
spk00: Go ahead.
spk01: So I think in terms of the startup activities, we are in the process of starting activities both globally in terms of opening sites. As you know, it's a big trial, and it's about, you know, our goal is to get the sites up, and we are screening patients right now. So that is the status both in China globally and in U.S., but let me pass on to Grant in terms of milestones.
spk08: So in terms of the collaboration, remember we received a $25 million upfront payment of which that was at signing of the agreement. We're working on the global phase of phase three startup within China, and there are further milestones and also expense offsets that would occur upon commencing of that. But that's really where we're at right now.
spk07: Wonderful. Thank you for taking our questions.
spk08: Thank you.
spk02: Thank you. And as a reminder, if you would like to ask a question, press the star, then the one key on your touchtone telephone. Our next question comes from David Nearinggarden with Wedbush. Your line is open.
spk06: Thanks for taking the questions. I have two. First off for Lysa, have you surveyed doctors or had discussions with with folks on what would be, I hate to say a quote unquote convincing, but kind of a convincing overall response rate that would maybe increase acceptance or use in earlier lines of therapy. And then for Symphony 1, could you just remind us if you had an interim look planned on that as part of the trial design? Thanks.
spk01: So answering your first question, David, The first question in terms of Lysa, as you know, this is a frontline trial in high-risk FL and DLBCL patients. In terms of looking at the endpoint, we normally look at CR rate in upfront trials. And so, you know, as based on the data published with Lysa, the CR rate in high-risk DLBCL is about between 60% to 70%, and that's how we have designed the trial. So the goal is to enroll, as you know, we are almost enrolled, nearly completely enrolled in that trial. So the goal is to be able to get that data, interim data this year, and report on that. And we have talked to, ELISA has a big database where they, you know, look at patients who are high risk in FL and DLBCL because they both are big unmet need. And so the goal is to be able to inform physicians about that data and think about the next steps in terms of frontline high risk patients and put the indications. In the second question regarding Symphony 1, We do have two interims planned in the study. The first interim, as we've guided, is basically based after 100 responders, which is about 100 patients based on how we are seeing our response rate, which is a futility interim. The second interim is based on 65% of PFS events. And the second interim actually is important because you have an opportunity to claim efficacy as we've aligned with the agency as long as you meet the protocol-defined criteria.
spk06: Got it. Thank you.
spk02: Thank you, and there are no other questions in the queue. I'd like to turn the call back to Grant Bogle for any closing remarks.
spk08: I just would once again like to thank everyone for joining us today, and I'd like to thank the colleagues, both Shefali and Joe, as well as the entire Epizyme team for their hard work and dedication to moving our organization forward. We look forward to providing updates in the coming months and speaking with many of you at the upcoming Common Conference next week. Have a great day. Thank you, operator.
spk02: Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.
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