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spk05: Good morning and welcome to CIROS Pharmaceuticals' fourth quarter and full year 2022 Financial Sales Conference call. At this time, all participants are in this synonym mode. This call is being webcast live on the Investors and Media section of CIROS' website at www.ciros.com. Please advise that today's call is being recorded. At this time, I would like to turn the call over to Karen Hunery, Director of Investor Relations and Corporate Communications at CIROS.
spk02: Thank you. This morning, we issued a press release announcing our fourth quarter and full year 2022 financial results. The full release is available on the Investors and Media section of the CIROS website at www.ciros.com. We will begin the call with prepared remarks by Dr. Nancy Simonian, our Chief Executive Officer, Dr. David Ross, our Chief Medical Officer, and Jason Haas, our Chief Financial Officer. We will then open the call up for questions. Christian Stevens, our Chief Development Officer, Dr. Eric Olson, our Chief Scientific 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 the statements we make on this conference call will include forward-looking statements. Actual events or results may 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 filing 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.
spk03: Thank you, Karen. Good morning, everyone, and thank you for joining us today. 2022 marked a meaningful year for Cirrus. in which we made important advances towards our pursuit to deliver new standards of care for the frontline treatment of hematologic malignancies. Today, we are focused on our late-stage programs in MDS, AML, and APL, three diseases in which there is significant need for more convenient and well-tolerated treatment options that improve clinical outcomes while still maintaining patients' quality of life. We believe that MDS, AML, and APL markets are attractive with business synergies that we plan to address through our own commercial efforts in the U.S. Over the past year, we reached important milestones in our heme programs. In December, we announced positive data from the safety lead-in portion of the Select AML-1 study, enabling us to move into the randomized portion of our Phase II study this quarter. In August, we announced promising preliminary data from our dose confirmation study of SY-2101, which, if additional data are supportive, we believe could enable an efficient go-to-market strategy. We continued progressing the ongoing Select MDS-1 pivotal trial And in recent months, we've seen momentum in site activation and enrollment across our global sites. And in January, we were delighted to receive FDA fast track designation for Tamiberitone for the treatment of higher risk MDS, underscoring the critical need for new treatment options for this patient population. I am also pleased to announce that in December we extended our collaboration with Global Blood Therapeutics for another year with the term now scheduled to end in December 2023. In addition, we strengthened our balance sheet and extended our cash runway into the second quarter of 2025 with a successful close of our September 2022 financing in which we secured approximately $190 million in capital. Importantly, we believe these proceeds are sufficient to fund our cash requirements past phase three data from the Select MDS-1 trial and data from the randomized portion of the Select AML-1 trial, while also allowing us to begin investing in pre-commercial activities important in bringing our therapies to market. Together, these accomplishments provide a tremendous foundation as we look ahead and prepare for multiple upcoming catalysts. Specifically, we expect to complete enrollment in the Select MDS-1 Phase III trial in the fourth quarter of 2023 and to announce pivotal data in the third quarter of 2024, share initial data from the randomized portion of the Select AML-1 trial in the fourth quarter of 2023, followed by additional data in 2024. and share an update on the dose confirmation study of 2101 and APL and next steps on a registration pathway in the second half of 2023. I would now like to turn the call over to David to provide a more detailed update on our ongoing clinical programs. David?
spk06: Thank you, Nancy. Today, I'll provide an update on our clinical stage pipeline and walk through the upcoming readouts we anticipate over the next 18 months. First, I'll begin with Tamibaratine in MDS. As Nancy mentioned, we're pleased by the FDA's recent decision to grant fast track designation to Tamibaratine for the treatment of higher risk MDS, allowing us the opportunity to potentially expedite the delivery of Tamibaratine as a new standard of care for people living with this progressive disease. As we've discussed before, today, newly diagnosed higher risk MDS patients have limited available treatment options. The existing standard of care hypomethylating agents offer only a 17% complete response rate and a median survival of 18.6 months. And no new therapies beyond HMAs have been approved since 2006. The FDA grants fast track designation to help speed the approval of new drugs for which non-clinical or clinical data demonstrate the potential to address a significant unmet medical need. Therapeutic candidates that receive fast track designation may be eligible for more frequent interactions with the agency, as well as priority review and accelerated approval if supported by clinical data. In recent discussions, the FDA has reiterated its support for our phase three design, including using complete response rate as an appropriate endpoint for regulatory decision-making, along with supporting data on durability of remission. We continue to see steady progress in our pivotal SelectMDS1 trial, the only actively recruiting registration-enabling trial in frontline higher-risk MDS that we're aware of. We now have over 90 sites activated in 13 countries, and we are encouraged by physician enthusiasm at the open clinical sites. We continue to expect to complete enrollment in the fourth quarter of this year and look forward to sharing pivotal CR data in the third quarter of 2024. Now, turning to our study of tamibaratine in unfit AML or the approximately half of AML patients who are not eligible for intensive chemotherapy due to their age or an underlying medical condition. Today, the standard of care for unfit AML patients is venetoclax with azacitidine or veneza, which has shown a 37% CR rate and a median overall survival of 14.7 months. Unfortunately, approximately one-third of patients do not respond to frontline venasa, and nearly all relapse. And when these patients relapse, they have a very poor prognosis, with median overall survival rates of only 2.4 months. At ASH in December, we announced positive data from the safety lead-in portion of our select AML1 study. The triplet combination of Tamibaratine and Veneza in newly diagnosed unfit AML patients with RARA overexpression demonstrated an 83% CR-CRI rate with a rapid onset of action. The data also showed that Tamibaratine in combination with approved doses of Ven and Aza showed no evidence of increased toxicity relative to historical data with the doublet combination of Veneza in this population. This includes rates of myelosuppression. So based on these data, we moved into the randomized portion of the select AML1 study, which we initiated in the first quarter of this year. The randomized portion of the trial is designed to evaluate the safety and efficacy of tamibaratine in combination with vaneza compared to vaneza in approximately 80 newly diagnosed unfit AML patients with RARA overexpression who are randomized one-to-one with composite CR rate as the primary endpoint. We look forward to announcing initial data from the randomized portion of the trial in the fourth quarter of 2023 and additional data in 2024. Lastly, I will 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 APL. Approximately 2,000 people are diagnosed with APL in the U.S. and EU annually, and the current standard of care is IV ATO combined with oral ATRA. While effective, IV ATO is very burdensome for the patient, involving up to 140 treatment infusions, each over two to four hours for nearly a year. We believe an oral ATO therapy could significantly reduce this treatment burden while also increasing access and reducing healthcare costs and utilization. We believe 2101 could provide exactly this, offering patients an all oral regimen that is both effective and allows for a better quality of life. We're making good progress in the dose confirmation study. As Nancy mentioned, in August, we announced initial data from the trial demonstrating high oral bioavailability of approximately 80% with exposures comparable to IV ATO based on both Cmax and AUC. Based on these emerging data, we believe there may be an opportunity to explore a more efficient registration pathway to potential approval. We plan to share an update on the dose confirmation study and next steps on a registration pathway in the second half of this year. In all programs, we continue to make excellent progress across our hematology pipeline. We're advancing three programs through late stage development, each with the potential to become standard of care and to dramatically improve the lives of patients. We have multiple catalysts upcoming this year and next, and look forward to providing additional updates soon. I would now like to turn the call over to Jason to review our fourth quarter and full year 2022 financial results. Jason?
spk08: Thank you, David. Now I'll turn to our fourth quarter and full year 2022 financial results. As Nancy mentioned, we extended our collaboration agreement with Global Blood Therapeutics this past December for another year. As a result, we extended the amortization period of the upfront payment that GBT made to us at the start of the agreement in 2019. This required us to make a one-time cumulative catch-up adjustment to true up the revenues recognized in the fourth quarter. Therefore, we recognized negative $800,000 of revenue from the GBT collaboration in the fourth quarter. For 2023, we will continue to recognize the revenue from GBT as we have in the past. For the full year, we recognized $14.9 million in revenue, consisting of $13.6 million under our collaboration with GBT, and 1.3 million under our collaboration with Insight. For the fourth quarter of 2021 and full year 21, we recognized a total of $7.8 million and $23.5 million of revenue, respectively, from our collaborations with GBT and Insight. R&D expenses were $27.9 million in the fourth quarter and $111.9 million for the full year, as compared to $26.8 million for the fourth quarter of 2021 and $99.9 million for the full year of 2021. Both the increases for the fourth quarter of 2022 and full year 22 were primarily due to increased costs associated with the continued advancement of our clinical programs and employee-related expenses. Based on our current operating plans, we expect that our future R&D expenses relating to our preclinical and drug discovery stage programs will be reimbursed by our collaboration partners. G&A expenses were $7.3 million in the fourth quarter of 2022 and $29.3 million for the full year 2022, as compared to $6.4 million for the fourth quarter of 2021 and $23 million for the full year 2021. Transaction-related expenses of $9.5 million for this past year primarily consisted of incurred costs allocated to the warrants issued in connection with the pipe financing that were accounted for as liabilities, and severance paid to former Time employees following our acquisition of Time, which closed in September 2022. We reported a net loss for the fourth quarter of $4.8 million, or 17 cents per share, compared to a net loss of $23.8 million, or $3.78 per share, for the same period in 2021. For the full year ended December 31st, 2022, Cirrus reported a net loss of $94.7 million or $7.49 per share compared to a net loss of $86.6 million or $13.84 per share for the same period in 2021. Cash, cash equivalents and marketable securities as of December 31st, 2022 were $202.3 million as compared with $143.4 million at the end of 2021. We believe our current cash position will be sufficient to fund our anticipated operating expenses and capital expenditure requirements into the second quarter of 2025 beyond Phase III data from the Select MDS-1 trial and initial data from the randomized portion of the Select AML-1 trial.
spk01: With that, I will turn the call over to the operator for questions. Thank you.
spk05: Ladies and gentlemen, we will now begin the question and answer session. If you want to ask a question, please press start, followed by the number one. If you want to withdraw your question, please press start. Your questions will be pulled in the order they are received. Sorry, should you please leave the handset before pressing end keys. One moment, please, for your first question. Your first question comes from Phil Nadiel from TV Danra. Please go ahead.
spk06: Good morning. Thanks for taking our questions. A couple from us. First, on the data from select AML1 and Q4, can you talk a little bit more about the quality of data that you'll be able to release at that time? Approximately how many patients with how much follow-up and what endpoints do you think you'll be willing to disclose?
spk03: Great, Phil. I'm going to ask David to take that.
spk06: Sure. Thank you, Phil. So, you know, as we've just reported, we've initiated enrollment into the randomized portion of the trial, and we anticipate reporting data coming out of the randomized portion of the study. We haven't yet specified the total number of patients that would be available. Keep in mind, it'll be balanced randomization, one-to-one into each of the two arms. So we look forward to getting good insights into the performance of the triplet combination versus the doublet in patients who have RARA overexpression. It's going to be very important. to provide us with context as to how to interpret the data. And as usual, we'll report on the response rates and available other information, durability and any available safety to help continue to understand how the triplet is working. So I think we should all look forward to that data presentation as an important update. That's helpful. And then second, on 2101, could you... Maybe share with us some possible designs of a more efficient registration path to approval. What type of efficiencies do you think you could realize after you have discussions with the FDA? So the answer is no. We haven't yet disclosed specific alternative design options. So it's premature for me to comment on that. But I do think it's fair for me to give you some insights into that. As we initially designed that study, which we vetted with the global regulatory agencies, we had really important and encouraging data coming out of arsenics, which demonstrated the exposures relative to historical data with IV arsenic. And we are really the first to ever test directly in patients the oral versus IV to provide properly collected data. you know, data that could support a PK evaluation to really hone in on the exposures and the appropriate dosing. That's what this has been all about. It's a dose confirmation study. And so we, as you know, we previously shared, you know, later last year, earlier last year, that is, that we have data emerging that really supports encouraging outcomes, both based on CMAX and AUC and high bioavailability that really supports you know, new ways of thinking about how to streamline the development strategy. And, you know, I guess streamlining could mean fewer patients or, you know, shorter times to delivering the data. And, you know, that's what we're all about is bringing this forward as quickly as possible. So without specifically giving you great details, I think, you know, you could look forward to that update in the second half of the year and you'll have more insights into how we're thinking about things. That's helpful. Thanks again for taking our questions.
spk03: Thanks, Bill.
spk05: Thank you. Your next question goes from Mark Reisenbach from Oppenheimer. Please go ahead.
spk00: Hey, good morning. Thanks for taking our questions. Just a couple of quick ones for me as well. First of all, can you just remind us if there are any utility analyses built into the select MDS1 protocol that we could see between now and top line data in the third quarter of next year? And then the second question is just housekeeping for Jason. I'm wondering if share count has stabilized now. I think it's around 20.3 million in the 10K. Is that number expected to fluctuate much or is it kind of settled around there following the merger with time? Thanks for taking the questions.
spk03: Hey, Mark. I'll take the first one. So on the futility, we have not guided to any expectations for, you know, futility analysis. So I think really the focus should be on the pivotal CR data in the third quarter of 2024. Okay.
spk08: And markets, Jason, on the share count, we have 20.3 million basic shares outstanding, and that audit remains relatively stable. We also have 7.5 million pre-funded warrants. So the way I would think about our share count is a total of 27.8 million shares outstanding. So to the extent some of the investors who took pre-funded warrants convert those warrants into common shares, we'll just have a different distribution between the common and the pre-funded. but the aggregate number of shares ought to remain relatively constant at 27.8, you know, in round numbers. Understood. Okay, that's super helpful.
spk01: Thank you. Thanks, Mark. Thank you.
spk05: Jason Yeoman, as a reminder, should you have a question, please press star 1. Your next question comes from Jason Butler from JMP Securities. Please go ahead.
spk07: Hi, thanks for taking the question. Two for me also. Just on select AML, can you just remind us if you're stratifying patients by monocytic expression score? And then for 201, have you already had interactions with FDA that support the potential for an expedited path? Or if not, can you talk about what plans you would have to interact with FDA before we get the update later this year? Thanks.
spk03: So I'll have David take the first, and just to clarify, the second question was related to 2101.
spk06: So with respect to the AML, you're asking about whether the AML trial is stratified by... Or whether selecting based on any selection based on the monocytic phenotype. Yeah, no. So we're not. The criteria are consistent with the design of the original phase two, newly diagnosed unfit, provided they have RARA overexpression using the you know, same test we've used all along. You know, obviously we are going to be collecting that data and looking at that, and that's going to be very important, you know, for us to understand, you know, that correlation. We did report from the ASH presentation, you may recall we had six patients who were evaluable for clinical activity, and we saw an 83% CR-CRI rate, which was really encouraging. And of five of the patients at that time who we had the monocytic expression score evaluated for were positive. So that's, again, 80% positivity rate, which was spot on for the prior analysis from the phase two. So we have reason to predict consistency of data across the trials and look forward to giving you an update later this year. And then with respect to the 2101 trial, you're asking if we've had regulatory interactions. And I think it's a little premature for us to discuss that we haven't disclosed specifically. We do, in the course of our ordinary development, communicate with the regulators globally regarding our plans to make sure we're on the right path. But I think that will be part of what we look forward to discussing in the second half of the year when we give you more clarity on our next steps.
spk01: Okay, thank you. Thank you. There are no further questions at this time.
spk05: You may proceed.
spk03: Thank you, Operator. Thank you, everyone, for joining us today. We look forward to an exciting and productive year ahead, and thank you for your continued support of Cirrus. Please reach out to us with any further questions. Have a great day.
spk01: Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.
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