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spk05: Good morning, and welcome to Ciros Pharmaceuticals' fourth quarter and full year 2021 financial results conference call. At this time, all participants are in listen-only mode. This call is being webcast live on the Investors and Media section of Ciros' website at www.ciros.com. Please be advised that today's call is being recorded. At this time, I would like to turn the call over to Courtney Solberg, Manager of Corporate Communications and Investor Relations at Ciros.
spk02: Thank you. This morning we issued a press release with our fourth quarter and full year 2021 financial results, along with anticipated future milestones and recent accomplishments. The release is available on the Investors and Media section 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. Dr. Eric Olson, our Chief Scientific Officer, Kristen Stevens, our Chief Development Officer, and Conley 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 statements we make on this 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 that we filed this morning, and any other filings that we may make with the SEC in the future. In particular, the extent to which the COVID-19 pandemic continues to impact our operations and those of the third parties on which we rely will depend on future developments, which are highly uncertain and cannot be predicted with confidence. Any forward-looking statements made on this call represent our views 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 return the call over to Nancy.
spk11: Thank you, Courtney. Good morning, everyone, and thank you for joining us today to review our fourth quarter and full year financial results and recent updates. 2021 was a pivotal year for Cirrus, driven by the expertise, commitment, and capabilities of our team at Cirrus. Last year, we initiated three clinical trials and one expansion cohort across our targeted hematology and CDK inhibitor portfolios. including the Select MDS-1 Phase III Trial, our first pivotal study of Tamibaratine in RARA-positive patients with higher-risk MDS, the Select AML-1 Phase II Study of Tamibaratine in RARA-positive patients with AML, a dose confirmation study of SY-2101 in APL patients, and finally, an expansion cohort of SY-5609 in combination with chemotherapy in pancreatic cancer patients. These initiations highlight our advancement towards becoming a fully integrated biopharmaceutical company with a diversified pipeline with the potential to make a profound difference for patients. Additionally, in September, we reported promising clinical data from our phase one dose escalation trial of 5609. our highly selective and potent oral CDK7 inhibitor. Based on the results, as well as mechanistic rationale and preclinical data, we are now planning to evaluate 5609 in three distinct opportunities, pancreatic cancer, BRAF mutant colorectal cancer, and hematologic malignancies. To support the continued progress, as well as advance serous to the next phase of our growth, we appointed two new key leadership team members. In September, we named Conley Chee as our first chief commercial officer, who has been hard at work laying the groundwork to set us up for commercial success. And Jason Haas, appointed as our CFO in October, has been spearheading our financing efforts. Cirrus is looking forward to an exciting year in 2022. with three anticipated data readouts across our clinical portfolio. First, we will be sharing PK and safety data from our dose confirmation trial of 2101 in APL mid-year. Then in the second half of this year, we plan to report clinical activity data from the safety lead-in portions of the select AML1 phase two trial of Tamivirutine and the expansion cohort of 5609 in pancreatic cancer. and these results may unlock important insights into the potential of each of our programs and inform our development strategy moving forward. Additionally, we are looking forward to presenting an e-poster at the AACR meeting in April that shows our oral selective CDK12 inhibitor has potent single-agent activity in vitro and in vivo in multiple cancer models, as well as enhanced anti-tumor effect in combination with DNA damaging agents. These data support our decision to nominate our next development candidate from our CDK12 program, which we expect to do in the second half of this year. This program, as well as our other preclinical oncology programs, CDK11 and WRN, reflect the productivity of our gene control discovery engine. a key driver of our long-term goal to discover and develop highly potent and selective small molecules that target gene regulatory systems. I would now like to turn the call over to David, who will review our ongoing clinical programs. David?
spk10: Thank you, Nancy. Today, I will discuss our clinical stage pipeline and review the upcoming important readouts we're anticipating this year. We have a lot to look forward to as these milestones will set us up for rich clinical and regulatory catalysts in the next two years. I'm excited to report that our select MDS1 pivotal trial for RARA-positive, newly diagnosed, higher-risk MDS patients is progressing well, and we expect to have data either late 2023 or early 2024 with a potential NDA filing in 2024. If the trial is successful, Tamibaratine has the potential to offer higher-risk MDS patients a well-tolerated and effective treatment option. Aside from hypomethylating agents, there have been no new therapeutics approved for this indication in over a decade. The unmet medical need is high for the approximately 21,000 newly diagnosed higher-risk MDS patients in the U.S. and EU estimated annually. We believe Tamibaratine, an oral drug with a novel mechanism of action, promising clinical activity, and a favorable tolerability profile could change the standard of care for approximately 30% of these higher risk MDS patients who are RARA positive. In addition to the progress we are making, we're pleased that in February, we received orphan drug designation from the FDA, representing an important milestone for the development of Tamibaratine in MDS and providing certain benefits, including a seven-year period of market exclusivity if the drug is approved. As we look ahead to a potential commercial launch, we entered into a master collaboration agreement with QIAGEN in March to develop and commercialize a companion diagnostic test for our proprietary RARA biomarker to identify RARA-positive higher-risk MDS patients who may benefit from using Tamibaratine. Under the terms of the agreement, QIAGEN will also be responsible for obtaining and maintaining regulatory approvals for the commercial companion diagnostic test. Since hematology physicians often treat both AML and MDS, they are familiar with using diagnostic testing to determine the optimal targeted treatment for blood cancers. We anticipate that following potential approval physicians will readily integrate the RARA companion diagnostic test for routine evaluation of their MDS patients and subsequently turn to our targeted therapy as the standard of care for RARA-positive higher-risk MDS. Turning to our efforts in AML, our Select AML-1 Phase II study is ongoing and evaluating tamibaratine in combination with vaneza in RARA-positive patients with newly diagnosed unfit AML. We estimate that there are approximately 25,000 newly diagnosed unfit AML patients in the U.S. and EU each year, of which about 30% are RARA positive, representing one of the largest targeted populations in unfit AML. We believe there's a substantial market opportunity for Tamibaratine in AML, as our translational and clinical data support the potential for the RARA biomarker to enrich for patients more likely to respond to Tamibaratine and for whom the standard of care may be suboptimal. As Nancy mentioned previously, we're on track to report clinical activity data from the safety lead-in cohort of the select AML1 trial in the second half of this year. As a reminder, this cohort is expected to enroll approximately 15 newly diagnosed RARA-positive unfit AML patients. If successful, we will then advance into a randomized portion of the trial which will evaluate our triplet regimen of tamivaratine plus veneza compared to veneza alone, and the primary endpoint will be the composite complete response rate. In addition, we're also developing 2101 as a novel oral form of arsenic trioxide, or ATO, for acute promyelocytic leukemia, or APL, patients. 2101 has the potential to replace the IV form of ATO which is standard of care for APL. We believe 2101 could significantly improve upon IV ATO by reducing the treatment burden, increasing patient access, and limiting healthcare costs and utilization. The ongoing dose confirmation trial is designed to evaluate the pharmacokinetics and food effect of 2101 using Cmax and AUC, as well as tolerability. with the goal of identifying an optimal dose for the phase three trial. We plan to report data from the dose confirmation trial mid-year. From the feedback we received from the Type C meeting with the FDA in November, we have a clear development path for 2101 in frontline APL. Importantly, at this meeting, the agency reaffirmed its support for using molecular complete response rates as the primary endpoint for accelerated approval and event-free survival rate at two years as the primary endpoint for full approval. In each case, the clinical data generated in patients treated with 2101 will be compared to historic data with IV ATO. We expect to enroll approximately 215 patients in the Phase III study randomized two-to-one to receive 2101 or IV ATO. with the IV ATO arm allowing us to make safety and tolerability comparisons to assist in assessing the overall outcomes of the 2101 arm. We plan to initiate the Phase III study in the first quarter of next year with pivotal data expected in 2025. Now, turning to 5609, our highly selective and potent oral CDK7 inhibitor, in September, we announced promising data from our Phase I dose escalation study in patients with select solid tumors. We identified a dose and schedule for 5609, which achieved proof of mechanism and was generally well-tolerated with predominantly low-grade AEs and a low rate of treatment discontinuation due to AEs. Importantly, we saw the highest level of single-agent clinical activity in the relapsed refractory pancreatic cancer patients we enrolled. In this highly refractory patient population, we observed stable disease, tumor regressions, as well as tumor marker reductions. Based on these data, as well as supportive preclinical 5609 in vivo data, we initiated in the fourth quarter our expansion cohort evaluating 5609 in combination with chemotherapy for patients with relapsed refractory pancreatic cancer. We expect the cohort to enroll approximately 50 patients who have progressed following first-line treatment with fulferinox in first or second relapse. Starting with a biologically active dose of 5609 below the MTD of the seven-day-on, seven-day-off regimen, patients will be treated with 5609 in combination with gemcitabine or 5609 in combination with gemcitabine and nabpaclitaxel using the approved doses of the combination agents. We plan to report clinical activity data from the safety lead-in portion of the trial in the second half of this year. We're also pursuing a second combination strategy with 5609 in BRAF mutant colorectal cancer. In August 2021, we entered an agreement with Roche to evaluate 5609 in combination with their PD-L1 inhibitor, atezolizumab. Roche expects to begin enrolling patients in this arm of their ongoing Phase 1-1B intrinsic trial in the first half of this year, which will mark the first clinical investigation of a CDK7 inhibitor with an immunotherapy. Since we are supplying 5609 and Roche is sponsoring the trial, Roche will be responsible for communicating subsequent data updates. Finally, and as we announced in January, we plan to pursue 5609 in hematologic malignancies. Based on mechanistic rationale and preclinical data, which support the potential of CDK7 inhibition across a range of blood cancers, we plan to initiate a trial of 5609 in relapsed refractory hematologic malignancies to identify a maximum tolerated dose for this population and assess clinical activity. In preclinical studies, CDK7 inhibitors, including 5609, demonstrated a high level of activity across diverse hematologic cell lines and showed robust single-agent in vivo activity. In addition, we've seen synergy with a BTK inhibitor and with venetoclax in vitro. These data give us confidence in our clinical development strategy, and we look forward to initiating a phase one trial in the second half of this year. We are incredibly encouraged by recent progress across our portfolio and are looking forward to reporting data from all three of our clinical programs this year with the potential to provide valuable insights into clinical activity, safety, tolerability, and dosing. With that, I'll turn the call over to Jason to review our fourth quarter and full year financial results.
spk04: Thank you, David. Turning now to our fourth quarter and full year 2021 financial results, we ended 2021 with $143.4 million in cash, cash equivalents, and marketable securities, compared with $174 million at the end of 2020. Based on our current plans, we believe we have sufficient capital to fund our planned operating expenses and capital needs into the first quarter of 2023. We recognized $7.8 million in revenue in the fourth quarter of 2021 from our collaboration with GBT and Insight. For the full year of 2021, we recognized $23.5 million in revenue. For the fourth quarter and full year of 2020, we recognized a total of $5.7 million and $15.1 million under our GBT and Insight collaborations, respectively. R&D expenses were $26.8 million in the fourth quarter of 2021 and $100 million for the full year 2021, as compared to $29 million for the fourth quarter of 2020 and $76 million for the full year 2020. The increase for the year ended December 31st, 2021, was primarily due to the increase in costs associated with the continued advancement of our clinical and preclinical programs and employee-related expenses. G&A expenses were $6.4 million in the fourth quarter of 2021 and $23 million for the full year 2021. For 2020, our G&A expenses were $5.9 million for the fourth quarter and $21.3 million for the full year. Finally, we reported a net loss for the fourth quarter of $23.8 million, or 38 cents per share, compared to a net loss of $30.1 million, or 62 cents per share, for the same period in 2020. Our net loss for the full year 2021 was $86.6 million, or $1.38 per share, compared to a net loss of $84 million or $1.82 per share for the full year 2020. With that, I'll turn the call over to the operator for questions.
spk05: If you'd like to ask a question at this time, please press the star, then the number 1 key on your touch-tone telephone. To withdraw your question, press the pound key. Again, that is star, then 1 if you'd like to ask a question. Our first question comes from Ted Tentoff with Piper Sandler.
spk08: Great. Thank you very much for taking my question. And a lot of progress that I don't think is necessarily being recognized as a stock price, but I know that's the market that we're currently in. And a lot of data that hopefully is going to be recognized. My first question really has to do with and select. And I just want to get a sense for sort of what the thresholds are that you might be looking for you know, to determine next steps and kind of what we should expect from the data readout system. Thank you.
spk11: Hey, Ted. Great to hear from you. I'm going to turn that over to David.
spk10: Thanks for the question, Ted. So with respect to the AML study, which is the Select AML-1 trial, we're in the process of what we're referring to as a safety lead-in, and we're looking forward to reporting data on sharing clinical activity, as well as safety of the triplet combination, tamibaratine plus venetoclax plus azacitidine. And one of the things we'll be looking for, well, obviously the safety will be an important parameter to assure we can combine all three drugs and use them to move forward. But we'll be looking at the clinical activity, and in particular, we have benchmarks for that came from the same patient population in our phase two, where we saw an approximate 61% composite complete response rate. So we'll certainly be looking for responses that are, you know, north of that to justify adding venetoclax into the regimen. That would be a starting place.
spk08: Well, and I guess that's exactly where I wanted to go. And I guess the question is, are you also sort of looking at how that compares to Veni's current response rates and sort of seeing where the opportunity is? Or because there are positive patients don't respond as well, you think you have an opportunity there? Thanks.
spk10: Yeah, I think, well, we think we have great opportunity with tamibaratine in this population for multiple reasons. It's an orally administered, generally well-tolerated drug. The population clearly needs improvements on available therapy. We know the venetoclax regimen really has not benefited significantly about a third of patients who don't achieve an initial response, and the majority of patients who do ultimately lose their response. So, you know, we are hopeful that our regimen will deliver value to these patients and Now, the translational data that we shared at the prior ASH meeting, where we were very excited to show that the majority of the patients who are positive who had entered our study had these features consistent with monocyticness or refractoriness to things that are known to be associated with refractoriness to venetoclax, holds yet additional potential for this therapy to address unmet needs. And so, you know, we're very excited about the program. We see great enthusiasm from the investigators who are participating and the patients, you know, who are signing up. So, you know, look, second half of the year is going to be a very exciting year. We're going to share upcoming information about that and you'll get insights into how this is performing.
spk08: That's really helpful. And then just one last question, if I may, on this topic. When it comes to the data that you get, will that help in terms of responses? Will that help with any powering or sizing of the Phase 3, or is the Phase 3 already pretty much largely set? Thank you very much for all the questions.
spk10: So if you're talking about the Phase 3 in AML?
spk08: Yeah, yeah, yeah. So the data that you get later this year, will it help you design or size the Phase 3 Select AML? Thank you.
spk10: So we haven't spoken yet specifically about the next plan beyond this study. This is a randomized phase two. And we will be presenting the data that's available to us toward the end of this year. So right now it's a bit early for me to forecast whether that specific information is going to inform the future phase three design or not. But all told, I think it should be interesting information to learn about. Great.
spk08: Thank you, guys, for the time.
spk05: Thank you, Ted. Our next question comes from Phil Nadeau with Cowan & Company.
spk09: Good morning. Thanks for taking our questions as well. One follow-up to Ted's on the select AML trial. As you look at the adverse event profile, are there specific adverse events that you're worried Timiberitone could exacerbate that Venaza already have? Are there any toxicities that could potentially be overlapping that you're going to pay attention to? particular attention to.
spk11: Phil, thanks for your question.
spk10: I'm going to turn it over to David. Yeah, so the general safety profile of Tamivaratin and AZA, you know, we previously described that, and we have not noted any exaggeration of toxicities that have been seen by AZA cytogen. Very specifically, we have not increased myelosuppression or the cytopenias that are commonly associated with with use of venetoclax. And so we don't really anticipate that there'll be any exaggerated toxicities from the venasa regimen when we add timobarotene to that. Of course, that's part of our clinical experiment, but we really don't expect that to be the case.
spk09: Great. That's helpful. And then second, on 2101, You mentioned that you're going to collect the PK data, including C-max and AUC, as well as food effect. Are there specific characteristics of the pharmacokinetics that you need to see in order to advance 2101, or is this simply kind of a dose-finding study where there's no specific hurdles for any of those parameters? You simply need to know what dose to move forward.
spk10: Yeah, so that's a good question. Now, just to provide you with the important context, we already have good insight into the fact that we believe we have a dose. We acquired this drug and there already was a phase one study that characterized the dose and the exposures. So what we're doing here is we're testing that dose in direct comparison to IV arsenic trioxide to confirm in a single contemporaneously generated data set that the blood measures are consistent. And that way, we will be assured of taking the right dose forward into phase three. The most important thing we can do right now to assure the technical success of the phase three is to go forward with the right dose. Everything else, you know, this is the same drug substance. There's already a clinical proof of concept with an oral arsenic that had been used in China that shows this methodology will work And so we have high confidence that this will be a successful program. The last piece of the equation for us is just to have confidence that the right dose is being selected. And so we respect the information we reviewed when we decided to acquire this drug, but we just want to prove this to ourselves and go forward on solid footing. And the last point I'll make is that this patient population is largely cured by the currently available therapy. So really the burden of proof is on us to make sure we protect their safety and welfare as we go into this trial. But I think we're doing all the right things with all of our collective experience to assure this program will succeed, and we feel good about our approach.
spk09: When you're comparing an oral to an IV, I guess the shape of the PK curve must be different. Correct me if I'm wrong. So what is the key parameter to... showing equivalence. Is it area under the curve? Does C-max matter? Can you give us some sense of how you determine comparability when you're looking at two very different routes of administration?
spk10: Yeah, you're actually correct about that. I mean, clearly, an intravenously administered drug, the C-max occurs immediately at the end of the infusion, and the area under the curve largely reflects the exposure over time, which is influenced by metabolism and removal from the blood So, you know, the specifics of those parameters may vary with oral, which will be absorbed a bit more slowly, but the exposure over time is going to be critical. And so we're going to be characterizing both the CMAX and the AUC and using our best judgment to pick a dose that represents a comparable exposure. And keep in mind, these patients are treated over prolonged periods of time. They're given this drug daily, the IV drug daily, for nearly 10 months, you know, two months for induction, eight months for consolidation, every other month. And so, you know, it sort of makes clinical intuitive sense that the overall exposure over time is going to make a difference.
spk09: Great. And then last question from Oz on 5609. You mentioned hematologic malignancies as being the target for one of the populations there. In the past, you specifically called out mantle cell lymphoma as perhaps being one hematologic malignancy that's particularly amenable to treatment with 5609. Is that still your thinking? Or now are you more focused on just the broader hematologic malignancy group and you'll let the data narrow down exactly which population you investigate?
spk10: So let me start off by saying that mantle cell lymphoma still is a priority in many ways. I'll remind you of the really exciting data we shared at ESMO in pancreatic cancer and in advanced solid tumors where we saw the highest response rates in pancreatic cancer. We also saw very high response rates in patients who had RB pathway abnormalities. And we know the mechanism of action of a CDK7 inhibitor is very important in places where cell cycle dysregulation occurs. And that plays into the large and important role that cyclin D has in mantle cell lymphoma. So we see a very strong mechanistic connection to mantle cell. That said, as we evaluated the breadth of data that we've generated across a range of hematologic malignancies, we also see other specific vulnerabilities and sensitivities that suggest a much broader opportunity than just mantle cell. So As we dug in on this initial foray in the heme cancers, first, by the way, for CDK7 inhibitor, we thought that we would be well served to explore a variety of tumor types, including mantle cell, and then let the data determine where we go. So what we've done is we've really capitalized on all the information we've been generating, and we're taking a nice broad approach to initiate this program. Perfect.
spk09: That is very helpful. Thanks for taking my questions.
spk05: You're welcome. Our next question comes from Jason Butler at JMP Securities.
spk07: Hi. It's Roy for Jason. Thanks for taking our questions. Just a couple quick ones. I guess apologies for the crystal balling here, but about the pivotal study for 2101 and newly diagnosed ATL, I guess we're wondering about that. Potential for an earlier efficacy read. It seems like the median time is a complete response is about a month, a month and a half. Just wondering if maybe there might be the potential for an earlier look at molecular CR prior to the 2025 readout. And then had a quick one of CDK12.
spk11: Thanks for your question, Roy. I'm going to ask David to address the timing in the phase three, maybe based on FDA feedback.
spk10: Yeah, so we did meet with the agency in November We had a very productive meeting, and they reaffirmed their interest in seeing this compared to historical benchmarks. And keep in mind, we're developing this under, you know, the 5053B pathway, which, you know, relies on the pre-existing data set for the IV arsenic trioxide. So the approval benchmark for molecular CR, it was assessed at the end of the third consolidation cycle. So that would probably be the timing that we would utilize for our molecular CR. And they've also said that the molecular CR could serve as a potential for accelerated approval with the event-free survival at two years for full approval. So we think we've really got all of the guidance we need with respect to the endpoints, when they would be measured, and how they would be assessed versus the benchmarks to determine, you know, how to proceed. So we're very excited about having a clear path forward. You know, it really doesn't get any better in drug development when you have crystal clear guidance from the regulatory agency to help them make a regulatory decision.
spk07: Okay, great. Thank you very much. And just a quick one on CDK-12. So the data at AACR That's going to be using the same clinical candidate that you probably announced in the second half, and I guess just what remains dating to declare the clinical candidate. Thanks.
spk11: Okay, we're going to have Eric address that question.
spk00: Yeah, thanks for the question. Yeah, we're going to be presenting data at AACR on our CK12 program, and we'll be highlighting a molecule and a You know, I think it's safe to say that the profile of our development candidate that we name in the second half of the year is likely to be similar to the one that we show at AACR.
spk07: Okay, thank you.
spk05: Our next question comes from Zeg Bejala with Roth International.
spk03: Good morning. Thanks for taking my question. I think I just wanted to ask a quick one here regarding 5609. You know, you're already in pancreatic cancer, so I was just wondering how quickly can you dose escalate in the heme malignancies, since you've already kind of seen some of that data, and then do you expect to perhaps use the same dose in the solid tumor versus that liquid tumor setting?
spk11: Hey, Zegba, I'm going to have David answer that question.
spk10: Thanks, Zegba. So we've learned a lot about how to dose 5609 in patients with advanced solid tumor malignancies, and we are going to leverage that knowledge as we move forward in the heme cancers. So our plan in the heme program will be to move forward with the regimen that we've optimized the safety for. And we'll be initiating just around the MTD, the maximum tolerated dose for that. And then we'll be combining with gemcitabine or gemcitabine plus Navpax with Haxel using the standard of care approved levels for those combination partners. So we think that this is going to move quite swiftly. And I think that'll be an efficient design.
spk11: and heme. Yeah. I think you also want to know about how we were using the dosing for the heme study? Exactly. Thank you. Yeah, the dosing we're starting in the heme study.
spk10: Oh, I'm sorry. I must have misheard you. Forgive me. Yeah, so in the heme study, we haven't really provided detailed guidance on the specifics of that trial design. But with regard to the heme study, we'll also be starting at around the area of the biologically active dose. So, you know, we actually have incorporated a really nice biomarker for the PD effects, the Polar 2A, and we know where we can tickle the pathway with our drug over time. So we're going to be leveraging that knowledge as well. And so we're not starting at the beginning, if that's what you're asking. I'm sorry, I didn't quite answer your question correctly the first time around.
spk03: No worries. Very helpful, David. And then the last one here, I guess, is just trying to figure out whether or not you will also be needing to look at perhaps more doses, you know, for the heme malignancies, just out of, you know, safe curiosity, trying to figure out if you are at the right dose. And then the last bit here is about your CDK-12 program. Wanted to know if there's anything that you've seen preclinically that that could suggest that it could be combined with your CDK7, and we're looking forward to the data at AACR.
spk11: Great. I'll have David answer the first and then Eric the second question.
spk10: So in terms of the heme malignancies with more doses, again, as I was mentioning, we are going to be starting close to the MTD and the solid tumors, clearly at a biologically active dose. We are prepared to modulate that dose to achieve maximum therapeutic effects in these patients while maintaining safety. So there is some exploration that's going to be going on so we can, you know, clearly define the right dose and utilization of the drug in patients with heme malignancies. But we don't expect that to be a pretty complex clinical trial experiment. You know, and then we're obviously setting the stage to move forward in that context, you know, either as a single agent or in combinations as is so commonly done. So So we're collecting our data and analyzing it to set ourselves up appropriately for future success. And for the CDK12 study, I guess, Eric.
spk00: Yeah, thanks for the question. There's certainly our focus for the CDK12 combinations have really been our thinking around that is really based on the role that CDK12 plays in regulating DNA damage response. So, you know, our CDK7 inhibitor is not you know, directly a DNA damaging agent, so that hasn't been our primary focus. But in cells where there's kind of a susceptibility or dependency on DNA damage repair, that's really where we're thinking about CDK12 combination work, whether that's a genetically defined tumor such as BRCA tumors in combination with other agents, like DNA-damaging agents or other agents that impact other pathways involved in DNA repair, like PARP inhibitors. So that's really been our focus in the combination.
spk05: Thanks, Eric.
spk11: Thanks, Jacob.
spk05: As a reminder, if you'd like to ask a question at this time, that is star, then one. Our next question comes from Matthew Cross with Alliance Global Partners.
spk06: Hi, all. Good morning, and thanks for taking a couple of quick confirmatory questions from me. I wanted to start off, first, congrats on the arrangement with Keyogen around the companion diagnostic. I was curious, because you had called out the terms of that being around MDS in particular, given that you're also looking, obviously, at... rarer positive patients in AML settings. I was just curious if that partnership can be expanded or if you can do something separate there, if that's even necessary, and then kind of the development commercialization strategy you're pursuing for Tamabaratine. And then secondly, you know, I was curious, David, you gave a good or great coverage of kind of the rationale for the confirmatory study in APL, but I was curious between the kind of timing of initial confirmatory data and the initiation of the phase three in 2023. That couple quarters gap was curious if you need to discuss those results with the agency, or as you said, it's really just kind of confirmation for your own sake, making sure you're confident of the dose going into the phase three. But do you need to talk with the agency and review that confirmatory data before moving into the phase three? Does that explain the couple quarter gap there? I just want to make sure we understand that the kind of limiting steps on those timelines. Thanks.
spk11: Thanks, Matt. I'm going to have Kristen Stevens take the first question on the QIAGEN. Kristen?
spk01: Yeah, thanks for the question. So we have been using a centralized clinical trial assay that was developed for use on our original Phase II AML study. And that assay had input from the CDRH division of the FDA and was operated under IDE requirements. And so this is the same assay that's been used across all of our studies with Tamivaritine and it serves as a foundation for the development of the commercial CDX. So, while we haven't provided further detail beyond our agreement with QIAGEN, you can imagine where that will lead.
spk06: Great. Okay. Very helpful. Appreciate it.
spk11: And then on 2101, David, do you want to take that? Yeah.
spk10: So, I think that, you know, we've guided to reporting the the data on the PK and safety from the ongoing trial, you know, mid-year. And, you know, we're going to be initiating the phase three, you know, first quarter of 2023. That's our current plan. You know, we haven't specifically explained the details of what, you know, what is transpiring. But, you know, we're activating, you know, a global phase three. You know, it requires some effort. And I didn't think that there was any particular – you know, challenge to getting that done over the period of time between collecting that data and initiating the trial.
spk11: Yeah, I'll just say, Matt, we're obviously moving as swiftly as we can. There's multiple things necessary to initiate the phase three, which includes the dose, the phase three material, and then all the things that we need to activate a large global study. So, I mean, we think that this is sort of the best timing related to having all those things ready to go And the nice thing is we can work in advance now to kind of get ready for all those things because we actually know the feedback that we've gotten from the agency, and we know exactly the trial that we need to do. So that's going to give us a great way to launch this very quickly when we initiate it.
spk06: Understood. No, didn't mean in any way to imply that that was a long timeline. Just wanted to confirm that you wouldn't need to run that data, I guess, by the FDA again, and that it sounds like, based on what you just said, that they're pretty clear with the plan moving into the pivotal study and that it's really just more of an internal confirmation of dose.
spk08: Yep.
spk06: Okay. Yeah, that covers it. Appreciate it, guys. Thanks for all the answers. Okay.
spk05: Yep. That concludes today's question and answer session. I'd like to turn the call back to Nancy Simonian for closing remarks.
spk11: Thank you, operator, and thank you, everyone, for joining us today. We appreciate your continued support and look forward to providing further updates on our progress as we continue to advance to becoming a fully integrated biopharmaceutical company. Please reach out to us if you have any additional questions and have a wonderful day.
spk05: This concludes today's conference call. Thank you for participating. You may now disconnect.
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