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spk02: to Cirrus Pharmaceuticals' first quarter 2023 financial results conference call. All participants are in a listen-only mode. This call is being webcast live on the Investors and Media section of Cirrus' website at www.cirrus.com. Please be advised that today's call is being recorded. At this time, I would like to turn the call over to Karen Hunity, Director of Investor Relations and Corporate Communications at Cirrus.
spk00: Thank you. This morning, we issued a press release announcing our first quarter 2023 financial results and business updates. The full release is available on the investor and media sections of Cirrus' website at www.cirrus.com. We will begin the call with prepared remarks by Dr. Nancy Simonian, our Chief Executive Officer, Dr. David Roth, our Chief Medical Officer, and Jason Haas, our Chief Financial Officer. We will then open the call for questions. Kristen Stevens, our Chief Development Officer, Dr. Eric Olson, our Chief Scientific Officer, and Kylie Chee, our Chief Commercial Officer, are also on the call and will be available for Q&A. Before we begin, I would like to remind everyone that the statements we make on this conference call will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the risk factors section of our annual report on Form 10-K, and our quarterly report on Form 10-Q that we filed this morning and any other filings that we may make with the SEC in the future. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements. I would now like to turn the call over to Nancy.
spk07: Thank you, Karen. Good morning, everyone, and thank you for joining us today. 2023 is off to a strong start as we focus on clinical execution and move closer to our goal of delivering new standards of care for the frontline treatment of hematologic malignancies. Today, we will be sharing progress with you across our programs in MDS, AML, and APL. We are excited about our continued progress on enrollment in our Select MDS-1 trial, and we remain on track to complete enrollment of the 190 patients in the fourth quarter of this year and to announce pivotal complete response data from Select MDS-1 trial in the third quarter of 2024. We recently amended the protocol for the Select MDS-1 trial to include overall survival as a key secondary endpoint. The primary endpoint of the trial remains complete response in 190 patients. By including overall survival as a key secondary endpoint, we have the potential to convert an accelerated approval based on CR to a full approval based on OS, if warranted, using an efficient one trial design. Importantly, this amendment does not impact the timing of our pivotal CR data from select MDS1. David will provide additional details on the amended protocol shortly. Turning to our efforts in AML, following promising data from the safety lead-in, we initiated the randomized portion of the Phase 2 trial last quarter. We continue to expect initial data from this trial in the fourth quarter of this year, followed by additional data in 2024. We also remain on track to provide an update on the dose confirmation study of 2101 in APL as well as the next steps on a registration pathway in the second half of this year. Taken together, these upcoming milestones lay the groundwork for multiple catalysts over the upcoming 12 to 18 months in which we will progress in turnover cards on each of our lead programs and move closer to our ultimate goal of delivering effective, well tolerated, and convenient therapies to targeted patient populations in need of better options. We believe MDS, AML, and APL each represent significant market opportunities in the frontline setting, which we are well positioned to address through our own commercial efforts in the United States. With that, I'd like to turn the call over to David to provide a more detailed update on our ongoing clinical programs.
spk04: David? Thank you, Nancy. Today, I will focus on the amended protocol for the select MDS1 phase three trial, which is evaluating the combination of tamibaratine and azacitidine in newly diagnosed higher risk MDS patients with RARA overexpression, which we believe represents approximately 50% of patients with higher-risk MDS. As a reminder, the study is a double-blind, placebo-controlled trial evaluating tamibaratine plus azacitidine versus placebo plus azacitidine. As Nancy mentioned, we recently amended the study protocol to include overall survival as a key secondary endpoint while continuing to use complete response as the primary endpoint for potential approval. Recent FDA feedback continues to support our use of complete response rate as an appropriate primary efficacy endpoint for either full or accelerated approval with supporting data on durability of complete response. And CR rate will remain the primary endpoint in our study. That said, if Tamibaratine receives accelerated approval, the addition of overall survival as a key secondary endpoint in the same study could allow select MDS-1 to also confirm the clinical benefit to support full approval in the future, potentially avoiding the need for a separate confirmatory study. The use of a single randomized controlled trial to support potential accelerated approval and subsequent conversion to a full approval if needed is also consistent with recently issued draft FDA guidance on the clinical trial considerations to support accelerated approval of oncology therapeutics. This one-trial approach offers many advantages over a separate confirmatory trial, allowing us to include the 190 patients enrolled to support the primary CR endpoint to also support the confirmatory endpoint. This ensures consistency of the patient population that support the primary and secondary analyses since they are all enrolled in the same protocol at the same sites by the same investigators and with identical eligibility criteria. It also provides the FDA assurances that we are well underway with the delivery of our confirmatory data to provide them with increased confidence when evaluating our primary endpoint data for regulatory decision making. In addition to this being a more efficient way to confirm clinical benefit, a one trial design has additional advantages for potentially speeding the delivery of confirmatory data and limiting trial-related costs and expenses. Under the amended protocol, SelectMDS1 will enroll a total of 550 newly diagnosed higher-risk MDS patients, including the initial 190 patients supporting the primary endpoint, to power the study for the key secondary endpoint. Importantly, and as Nancy mentioned, we continue to expect that we will complete enrollment of the initial 190 patients necessary to support approval, either accelerated or full, using a CR endpoint in the fourth quarter of this year, and then report pivotal CR data in the third quarter of 2024. As we discussed last quarter, in January 2023, the FDA granted fast track designation to tamibaratine for the treatment of higher risk MDS. This designation provides us with several advantages, including priority review timelines, and further underscores the critical need for new treatment options for this patient population, a group that has been underserved by available therapies. Again, the existing standard of care hypomethylating agents offer only a 17% complete response rate and a median survival of 18.6 months. And no more therapies beyond HMAs have been approved since 2006. Turning to our study of temubarotene in AML, we've previously announced that we had initiated the randomized portion of the study in newly diagnosed unfit AML patients with RARA overexpression. Like higher-risk MDS, AML represents a significant unmet medical need. Of the patients diagnosed with unfit AML, approximately a third do not respond to upfront treatment with venasa, and a majority of those with initial responses ultimately relapse. These patients have a very poor prognosis, with median overall survival rates of only 2.4 months. As we announced late last year, in the safety leading portion of select AML1, the triplet combination of tamibaratine and venasa demonstrated an 83% CR-CRI rate, with a rapid onset of action, and no evidence of increased toxicity relative to historical data with venasa. including rates of myelosuppression. These data underscore the potential of Tamibaratine in combination with existing standard of care to deliver improved outcomes to the approximately 30% of AML patients who are positive for RARA overexpression. As a reminder, the randomized portion of the trial is designed to evaluate the safety and efficacy of Tamibaratine in combination with Veneza compared to Veneza in approximately 80 newly diagnosed unfit AML patients with RARA overexpression randomized one-to-one with the composite CR rate or the CR-CRI rate as the primary endpoint. We continue to remain on track to report initial data in the fourth quarter of this year with additional data expected in 2024. Lastly, I'll turn to 2101. our novel oral form of arsenic trioxide, or ATO, which is currently being evaluated in an ongoing dose confirmation study for the frontline treatment of acute promyelocytic leukemia. The current standard treatment regimen with intravenous ATO creates a significant burden for patients, involving up to 140 treatment infusions, each over two to four hours for nearly a year, We believe 2101 has the potential to offer a reduced treatment burden by providing patients an all oral regimen that is effective while also increasing access and reducing healthcare costs and utilization. We look forward to providing an update on the dose confirmation study in the second half of this year to describe the planned development path and timing for further evaluation of 2101 in a registration enabling study in EPL. With that, I would like to turn the call over to Jason to review our first quarter financial results. Jason?
spk08: Thank you, David. Now turning to our first quarter financial results. We recognized $3 million in revenue in the first quarter of 2023, consisting entirely of revenue recognized under our collaboration with Pfizer. Cirrus recognized $5.5 million of revenue in the first quarter of 2022, consisting of $5.1 million in revenue recognized under our collaboration with Pfizer and $400,000 under our collaboration with Insight. R&D expenses were $28.8 million in the first quarter of 2023, as compared to $25.2 million for the first quarter of 2022. This increase was primarily due to the advancement of the company's late-stage clinical programs. Based on our current operating plans, we expect that our future R&D expenses relating to our drug discovery stage programs will continue to be reimbursed by our collaboration partners. G&A expenses were $7.4 million in the first quarter of 2023, as compared to $6.9 million for the first quarter of 2022. The increase relates to supporting the advancement of our late stage clinical programs. We reported a net loss for the first quarter of $23.8 million, or $0.85 per share, compared to a net loss of $25.1 million, or $3.99 per share, for the same period in 2022. Cash, cash equivalents, and marketable securities as of March 31, 2023, were $166 million, as compared with $202 million on December 31, 2022. We believe our current cash position will be sufficient to fund our anticipated operating expenses and capital expenditure requirements into 2025, which is beyond Phase III data from the Select MDS-1 trial and initial data from the randomized portion of the Select AML-1 trial. With that, I will turn the call over to the operator for questions.
spk02: Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the one on your touch-tone phone. You will hear a three-tone prompt acknowledging your request. Questions will be taken in the order received. Should you wish to cancel your request, please press the star followed by the two. The first question is from Phil Nadeau from TD Collin. Please ask your question.
spk03: Good morning. Thanks for taking our questions and congrats on the continued progress. First, on the addition of the OS endpoint to select MDS, I'm curious if you'd be willing to disclose the powering on the OS endpoint. Seems like there's quite a few people that you're gonna enroll additional in the trial, so it seems like it's likely to be well-powered. I'm just curious if you'd disclose exactly what the powering will be.
spk07: Hey, Phil, thanks for the question. David will answer that.
spk04: Yeah, thanks, Phil. So just to remind everyone, the study remains a study focused on a primary endpoint based on the complete response rate. And as we previously shared, that power assumption is over 90% power to demonstrate a difference in the CR rates between the two arms. With respect to the key secondary endpoint, the powering assumptions are 80%. And 550 patients provides enough power to detect a difference in the median overall survival between the two arms.
spk03: In terms of the increment, is the assumption for the control arm the 18.6 months that you referenced in the prepared remarks? And if so, what is the assumption for the testing arm?
spk04: Yeah, so we haven't specifically stated what the actual statistical assumptions are, but, you know, you're correct that, you know, those are the tried and true, you know, data for azacitidine as a single agent in high-risk MDS, you know, in the high teens. So, I think that's a reasonable assumption.
spk03: Perfect. And then, are there interim analyses along the way?
spk04: So, you know, we haven't stated that there are interim analyses, but, you know, obviously the, you know, the initial analysis for the primary endpoint, the CRM, um you know could be interpreted as an interim analysis along the way to the final analysis when the study is completed then the secondary key secondary is reported out uh subsequently great and then last question on this um appreciating that it's it's really early any uh any estimates on when the overall survival data could be available so yeah we haven't um you know yet guided to when you know when that data would be available at you know as you know Survival is an event driven endpoint. So, you know, that's certainly something that we're going to have to, you know, project in the future. But right now we're focused on delivering the key data, which is the pivotal data upon which we anticipate the drug we hopefully will be approved. And that's the CR rate. And just to remind everybody, we remain on track for fully enrolling the 190 patients needed. for the CR primary analysis by the end of this year. And we expect to have that data available in the third quarter of 2024. So, you know, these are the things about which we're really, you know, greatly excited. And obviously, the key secondary endpoint based on survival will come after that.
spk03: Great. And then last question from us. On 2101, have you had preliminary FDA discussions about recent FDA discussions about the trial redesign? And if not, would you expect to hold those discussions?
spk04: So I'll answer the question by saying that we've been guiding and we continue to say that in the second half of this year, we'll provide an update on the dose confirmation study. And at that point, we'll also share information about our plans for you know, moving into the registrational trial, you know, the phase three trial for which the approval will be sought. And I think it would be best to, you know, reserve all of the details around that and things around, you know, regulatory interactions, et cetera, for that update.
spk03: Perfect. Thanks for taking our questions.
spk02: Thanks, Phil. Thank you. The next one is from Ted Tannehoff from Piper Center. Please ask your question.
spk06: Great. Thank you. I think Phil had his Wheaties this morning. So, only thing really left to ask about is Select AML. And with respect to the Phase 2 data, just remind us what expectations are and what would really define a go and no-go. Thanks.
spk07: Thanks, Ted. I'm going to have David to address that.
spk04: Right. So, for the Select AML 1 study, again, just to make sure everyone's up to speed, you know, we reported at the end of last year you know, great progress on the study. We shared the data coming from the safety lead-in, demonstrated tolerability of the drug. We did not see increased toxicity when adding tamibaratine onto the backbone of venasa, so we're really excited about that, and that enabled us to move into the randomized portion of the trial that we initiated in the first quarter. We also were pleased to see an 83% CR-CRI rate, reminding everyone that is the primary endpoint for that study. So, it's a randomized trial. It's currently enrolling two arms, the triplet versus the doublet, tamivineza versus veneza, and we expect to have an update on that in the fourth quarter of this year.
spk02: Thank you. Your next question is from Jason Belther from JMP Securities. Please ask your question.
spk05: Hi. Thanks for taking the question. I guess I just have a follow-up on the AML study. Can you give us a sense of the number of patients and maturity of data we'll get later this year? And I guess ultimately the question is, do you think you can come to some kind of go-no decision based on this first cut of data or will it be based on ultimately the final data set?
spk04: Yeah, so, you know, just to follow up as well on the prior question and as well on this one, you know, we haven't specifically guided to the numbers of patients that would be part of our update at the end of the year. And also in terms of the data maturity, so we reported initiating the randomized portion in the first quarter. So, you know, that can give you a sense as to, you know, the potential for how mature the data might be toward the end of this year. And then, you know, specifically the go-no-go criteria, again, you know, we haven't specifically guided to, you know, what the bar would be for triggering the next phase of investment moving into a registrational trial. This is, again, a randomized phase two, and it will, you know, be the very first prospectively collected data on the performance of ven plus aza in RARA-positive patients compared to our triplet. So, again, we're very excited about that, but we'll have to see the totality of the data in order to really answer that question more specifically.
spk05: Great. Thank you.
spk02: Thanks, Jason. Thank you. Once again, ladies and gentlemen, as a reminder, should you have a question, please press the star followed by the 1. The next question is from Mark Bridenback from Oppenheimer. Please ask your question.
spk01: Hey, good morning, guys. Thanks for taking our questions. Just a couple from me. First, in the prepared remarks, I think I heard that there's still a possibility that tamivirutine could be approved in MDS, fully approved based on the CRN point alone. or it could be an accelerated approval. I was hoping maybe you could just expand on what would be the gating factors that would influence a full versus accelerated approval on that endpoint. And then a second question, I noticed you had a couple of poster presentations at ASCO, or coming up at ASCO for CER 5609. I'm just wondering, are these going to include new clinical data or trials still being enrolled around testing this drug? Maybe just give us a quick status update and what to expect at ASCO from 5, 6, and 9. Thank you.
spk07: Great, Mark. I'm going to have David take the first question, and I'll take the 56 and 9 one.
spk04: Sure. So the FDA has really reiterated even more recently to us that the complete response rate is an appropriate primary efficacy endpoint that could support either the full approval or the accelerated approval, obviously in the context of the duration of the remission. And as always with regulatory evaluation, the totality of the data will also inform their decision making. The specifics around what's going to sway the pendulum in favor of a full approval versus an accelerated approval, you know, really remains, you know, dependent on what our data package provides them to give the evaluation. But it's pretty clear that CR is an excellent surrogate for meaningful clinical benefit. There's multiple studies that have correlated the CR with overall survival And so I think that it's really going to depend on the totality of our data. And really, just to remind everyone, the acknowledgment that the potential for an accelerated approval exists has always meant that there might be a need for a confirmatory trial if we got the accelerated approval. So we've really known all along that one might need to do that and encouraged now by really the great progress we've been making in the enrollment, the expansion of our trial to a global footprint that includes 13 countries and over 100 actively enrolling sites, coupled with the increasing awareness that FDA really likes to understand that a sponsor is committed to delivering the confirmatory data as they make their decisions. This provides them with reassurance when they're thinking about how to award the approval. So we thought that it was very sensible to take advantage of the ongoing progress in one study and use that to potentially fulfill both objectives if it was needed. Of course, if it's just a full approval, then it wasn't required, but certainly it's an important thing to do and we'll continue to do that anyway.
spk07: Great, Mark. And then on the 5609 question that you have, yes, we do have two. or posters at ASCO on 5609. Just as a reminder, we are, you know, actively looking for a partner for that program. We are presenting these data because we think they're very supportive of this being a best in class PDK7 inhibitor where we have a great dose and schedule. And we see clinical activity and very difficult to treat patient populations. And I think these two presentations, one on our experience in breast cancer with fulvestrin, and the other kind of focusing more on our data in PDAC in combination, I think will be, you know, really will be compelling to show the potential for this agent. But as you know, we are not ourselves putting further capital into the development of this program and instead looking for a partnership.
spk06: Great. Thank you.
spk02: Thank you. There are no further questions at this time. I will now hand the call back to Nancy for closing remarks.
spk07: Thank you, operator, and thank you, everyone, for joining us today and for your continued support of Cirrus. Please reach out to us with any further questions and have a great day.
spk02: Thank you. Ladies and gentlemen, the conference has now ended. Thank you all for joining. You may all disconnect.
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