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spk01: Good day and welcome to the Q3 2022 Cirrus Pharmaceuticals, Inc. Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising that your hand is raised. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker, Ms. Karen Honody, Director of Corporate Communications and Investor Relations. Please go ahead.
spk04: Thank you. This morning, we issued a press release announcing our third quarter 2022 financial results and a broader business update. The release is available on the Investor and Media section of the CEROS website at www.ceros.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 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 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. Thank you, Karen. Good morning, everyone, and thank you for joining us today.
spk05: The third quarter was transformative for CIRA. In September, we announced the concurrent close of our merger with Time Technologies and our oversubscribed PIPE financing. Together, these transactions netted approximately $190 million, providing us the necessary cash to continue investing in the clinical development of our late stage targeted hematology programs while also supporting initial launch readiness. Our goal has always been to build Cirrus into a commercial company. With this additional capital, we believe we are an important step closer to achieving this foundational vision and ultimately to delivering our portfolio of medicines to people living with cancer. Now I'll turn to the initial data we announced this morning from the safety-leading portion of our ongoing phase one trial, evaluating SY5609. As David will review shortly, these data provide further evidence that CDK7 inhibition is a potentially important therapeutic approach for treating pancreatic cancer, one of the most devastating and difficult to treat malignancies, as well as other difficult to treat tumor types. We're encouraged by 5609's emerging safety profile, both as a single and combination agent, and by the clinical activity we've observed in pancreatic cancer, with several patients achieving stable disease and one patient achieving a confirmed partial remission. We've yet reached a maximum tolerated dose as a single agent or in combination, and given the emerging exposure response relationship plan to continue dose escalation with both single-agent 5609 and in the doublet combination with gemcitabine. At the same time, we've always said that data from this Phase I trial, evaluated in the context of our own strategic priorities, will inform the best course for further development of this program. While we believe there is a strong rationale to advance 5609 in pancreatic cancer, as well as in other difficult to treat solid tumors, we believe this will be best done in the hands of a partner who has the resources to maximize the opportunity both in pancreatic cancer as well as additional combination regimens in tumor types. To that end, we plan to explore partnership opportunities while we continue to dose Escalate. We look forward to providing an update at the appropriate time in the future. Importantly, we are excited to continue to support Roche's ongoing arm, evaluating 5609 in combination with a kesalizumab in patients with BRAF mutant colorectal cancer in their Phase 1, 1B intrinsic trial. Turning to our hematology portfolio, as you know, tamiberitine is our selective and potent oral RA or ALTA agonist, which has the potential to offer a new standard of care to be approximately 50% of MDS and 30% of AML patients who are positive for RARA gene overexpression. We are currently evaluating camiberitin in two clinical trials. Select MDS1, a pivotal phase three trial in higher risk MDS patients, and select AML1, a phase two trial in newly diagnosed unfit AML patients. As we announced in a press release last week, We will be sharing initial data from the safety leading portion of the Select AML-1 trial at the ASH Annual Meeting in early December. We are highly encouraged by the initial clinical activity observed in this study to date. We initiated both the Select MDS-1 and Select AML-1 trials based on the belief that temibarotene in combination with hypomethylating agents alone and with venetoclax has the potential to improve clinical outcomes for MDS and AML patients with RARA overexpression. We previously reported Phase II data with temiberitone and azacitidine in newly diagnosed unfit AML patients with RARA overexpression, which showed a high CR-CRI rate with a rapid onset of action. And now we are excited by the early data from Select AML-1 trials, which, together with the data from our prior Phase II trials, support the potential for Tamiviridine to augment existing standards of care and meaningfully improve outcomes for both AML and higher-risk MDS patients. We look forward to presenting updated data from the Select AML-1 trial at ASH and request that you save any questions on data from our trial until our presentation on December 10th. Looking ahead, we continue to expect data from the Pivotal Select MDS-1 trial in late 2023 or early 2024, and to initiate the randomized portion of the Select AML-1 Phase 2 trial with data expected in 2023 or 2024. In addition, we are making good progress in our ongoing dose confirmation trial of FY2101, our novel oral form of arsenic trioxide, or ATO, for the treatment of frontline patients with acute promyelocytic leukemia, or APL. We are on track to identify the optimal dose to advance into our planned phase three trial, which we expect to initiate in the second half of next year. And as we announced on our based on feedback from both the FDA and EMA, we believe we will be able to use a single registration trial to support the approval of 2101 in both the United States and Europe. We are excited by the potential of each of our product candidates and confident in our ability to execute with excellence across each of our ongoing clinical studies. And we are grateful for the support of our new and existing investors, which we believe will enable us to bring forward these new medicines that redefine the standard of care for patients with difficult-to-treat tumors. We look forward to our upcoming catalyst and continuing to work towards our mission of making a profound difference in patients' lives. I would now like to turn the call over to David. David?
spk08: Thank you, Nancy. Today, I will focus my discussion on SY5609. Earlier this morning, we announced initial safety data as well as early clinical activity data from the safety lead-in portion of our ongoing phase one trial of 5609, which is evaluating our highly selective and potent oral CDK7 inhibitor in combination with chemotherapy in patients with relapsed refractory pancreatic cancer. We also provided updated data from the ongoing single-agent portion of the trial in advanced solid tumor patients. Pancreatic cancer is one of the most devastating and difficult to treat malignancies. Today, the only approved agent for second-line pancreatic cancer is Onivide in combination with 5-FU and Leucovorin, which offers a median progression-free survival of approximately three months. In September, we received orphan drug designation from the US FDA for 5609 for the treatment of pancreatic cancer, underscoring our urgency to develop 5609 for pancreatic patients whose tumors have otherwise eluded therapeutic intervention. As a reminder, our phase one trial is evaluating 5609 in combination with chemotherapy in pancreatic cancer patients who progressed following treatment with Fulferinox. Patients are being enrolled to receive either 5609 in combination with gemcitabine in first or second relapse, or 5609 in combination with gemcitabine and nabpaclitaxel in first relapse at the approved doses of the combination agents. The study is assessing safety and tolerability, as well as efficacy measures such as disease control rate and progression-free survival. As Nancy mentioned earlier, we're encouraged by the data we shared today. First, on characterizing the safety and tolerability of 5609, both as a single agent and in combination with chemotherapy. We're very pleased to report that as of an October 12th cutoff, 5609 was observed to be generally safe with enhanced tolerability being maintained in the 7-day on, 7-day off regimen at the highest doses tested. To date, we've evaluated 5609 at up to 10 milligrams when administered as a single agent, up to 5 milligrams when administered in combination with gemcitabine, and up to 4 milligrams when administered with both gemcitabine and nabpaclitaxel. This underscores the importance of our careful dose optimization strategy that resulted in our development of an intermittent dosing regimen that allowed for promising advances in our ongoing trial, as I will describe now. The single agent 10 milligram dose did not result in any DLTs, further supporting the tolerability of the seven day on, seven day off regimen, which has now been evaluated in 30 patients across five dose levels, ranging from four to 10 milligrams. with only one DLT observed at the 4-milligram single-agent dose level. Across all arms of the study, an MTD has not yet been reached in the seven-day-on, seven-day-off regimen. The adverse event profile of 5609 in combination with chemotherapy was consistent with the safety profile of single-agent 5609 or gemcitabine monotherapy or gemcitabine naphthaclotaxel. And the majority of adverse events, were low-grade and reversible with no new safety signals identified. The most common related adverse events in the cohort with 5609 and gemcitabine, where the highest 5609 doses were evaluated in combination with chemotherapy, included fatigue, nausea, decreased appetite, and decreased platelet count, all low-grade. with one patient experiencing a DLT of grade three diarrhea at the five milligram 5609 dose level. No DLTs were reported in patients treated with 5609 in combination with the gemcitabine nabpaclitaxel. Turning now to clinical activity, as of an October 20 data cut, two of three enrolled patients in the 10 milligram single agent cohort were response-evaluable, including one patient with pancreatic cancer and one with colorectal cancer. Both patients achieved stable disease, and notably, the patient with pancreatic cancer also experienced a 10% tumor reduction. In the cohort evaluating the doublet combination of 5609 and gemcitabine in patients with pancreatic cancer, one of four, or 25%, of response-evaluable patients treated at the 4-milligram 50-609 dose level experienced a confirmed partial response, or PR, with a 98% reduction in the CA-19-9 tumor marker from a baseline of 60,357 units per milliliter to 968 units per milliliter, which is impressive considering this patient was not responsive to prior treatment with frontline fulfirinox. Three of four or 75% of responsive valuable patients treated at the five milligram SY569 dose level had stable disease for an overall disease control rate of 50%. Importantly, data from the doublet and 10 milligram single agent dose cohorts support an emerging exposure response relationship. The patient from the doublet who achieved a confirmed PR demonstrated higher than average exposure relative to other patients at that dose level. In the cohort evaluating the triplet combination of 5609 and gemcitabine nabpaclitaxel in PDAC patients, one of two responsive edible patients treated at a four milligram dose level achieved stable disease. Based on these data, and as Nancy mentioned earlier, we plan to continue dose escalation of 5609 to 15 milligrams as a single agent and to 10 milligrams in the gemcitabine combination cohort in hopes of leveraging the emerging exposure-response relationship to enhance clinical activity with higher doses and to better characterize the therapeutic index. In parallel, we will explore partnership opportunities to advance 5609 to patients, allowing us to devote our resources to our late-stage hematology programs. As Nancy alluded to earlier, we're making tremendous progress across our hematology portfolio where we are advancing Tamibaratine and SY-2101 as potential standard of care therapies for the frontline treatment of MDS, AML, and APL. We look forward to presenting our initial select AML-1 data at ASH in December and to sharing additional details with you there. I would now like to turn the call over to Jason to review our third quarter financial results.
spk02: Jason? Thank you, David. We continue to operate from a position of financial strength. In September, we closed our merger with Time Technologies, through which we acquired Time, including its pipeline assets and net cash of approximately $60 million. Concurrently, we closed our previously announced oversubscribed type financing through which we raised $130 million. The pipe was led by life sciences-focused investment funds and included new and existing CIRA shareholders, such as Flagship Pioneering, Avidity Partners, DeepTrack Capital, Bain Capital Life Sciences, Indus, Bamsara, Adage, Ally Bridge, and Cowen Healthcare Investments. These transactions, together with the amendment to our senior secured loan facility, with Oxford Finance significantly extended our cash runway. We ended the third quarter with approximately $245 million in cash and cash equivalents, which we believe will be sufficient to fund our planned operating expenses and capital expenditure requirements into 2025, approximately a year past our expected pivotal data readout for select MDS I. Now, turning to our third quarter financial results. we recognized $3.9 million in revenue in the third quarter of 2022, consisting of $3.7 million from the collaboration with GBT and $200,000 from our collaboration with Insight. For the third quarter of 2021, we recognized $5.7 million of revenue under our collaborations with GBT and Insight. R&D expenses were $25.8 million in the third quarter of 2022, compared to $27.3 million for the third quarter of 2021. This decrease was primarily attributable to a decrease in external costs associated with our preclinical programs. G&A expenses were $8.1 million in the third quarter of 2022 compared to $5.3 million for the third quarter of 2021. This increase was primarily attributable to an increase in employee related expenses and an increase in recruiting fees. Transaction related expenses were $9.5 million in the third quarter of 2022. These expenses principally relate to the pipe financing, which are allocated to warrants, classified liabilities, and severance paid to former time employees. We reported a net loss for the third quarter of $30.3 million or $3.21 per share compared to a net loss of $26 million or $4.14 per share for the same period in 2021. Finally, following the 10 to 1 reverse stock split, which we implemented in September, as well as the close of the merger and type transactions, we ended the quarter with approximately 28 million shares of common stock and pre-funded warrants to purchase common stock. This includes 20.2 million shares of common stock and 7.5 million pre-funded warrants. With that, I will turn the call over to the operator for questions.
spk01: Thank you. As a reminder, to ask a question, you will need to press star 1-1 on your telephone. Please stand by while we compile the Q&A roster. Our first question will come from the line of Edward Tenthoff with Piper Sandler. Please go ahead.
spk06: Hi, guys. Thanks so much for the update and congrats on all the progress. Really looking forward to the data at hematology. Just want to see if you can kind of give us a little bit more of an expectation of what we should expect there. Thanks.
spk08: Thanks, Ted. So we're very excited about the upcoming ASH presentation, and we're looking forward to presenting updated data at that time. You know, right now we're planning to take further questions about that at the meeting when we'll be able to dig in and give you a lot more color and context around what the presentation has to show.
spk06: Great. And I think, as you said in the press release, expectations are to initiate the Phase 2 portion. When could that happen? Thanks.
spk05: Hey, Ted. I think you cut out, but I think your question was around the randomized portion. So we're Our plan is to provide Ed Ash an update on kind of the next steps with the trial.
spk06: Great. Looking forward to seeing you in New Orleans.
spk05: Great. Thanks, Ted.
spk01: Thank you. As a reminder, if you would like to ask a question, please press the star 1-1. Our next question will come from the line of Philip Nadu with Cowan. Please go ahead.
spk07: Good morning, let us out our congratulations on progress. A couple questions on 5609 to start. You mentioned that you hope to better define the therapeutic index with 5609. Can you give us some sense in both the monotherapy and combination arms, what response rate or disease control rate you hope to see to give you confidence that there's efficacy over background in this population once you do hit an MTD?
spk08: Sure. Phil, for that question. So, as you can gather, we're very excited about the data that we've generated, which we've just shared with you. You know, we've already demonstrated in the doublet with 56.9 plus gemcitabine at relatively low doses of 56.9, mind you, that we have an aggregate disease control rate of about 50%. with four out of the eight patients having disease control, which is CR plus PR plus stable disease. So we feel that's very exciting at this early stage, in particular because that, you know, is clearly in line with other benchmarks for combination therapies in this type of population with pancreatic cancer. Now, the other comment I would make is our emerging data have clearly to us demonstrated what we are referring to as an emerging exposure response relationship, where we're able to show with the single agent that when we increase the dose of the drug, we get a proportional increase in the circulating levels of the drug in blood. And that's very exciting because that gives us reason to believe that more drug will give you more exposure. And we saw a similar phenomenon even in the doublet, where the patient who was dosed with four milligrams of 56.9 plus gemcitabine at standard doses, 1,000 milligrams, had a durable, confirmed, resist partial response with a dramatic reduction in the tumor marker, CA1990. It went from over 60,000 down to below 1,000. I mean, that was really significant. So the notion that we haven't seen any maximum tolerated dose yet at any of the regimens with the seven-on, seven-off schedule, and we can push the dose even further, gives us reason to hope that, you know, more may be better with respect to the clinical activity, which we think could provide a really meaningful impact for patients with pancreatic cancer. So I hope that sort of answers your question, but in aggregate, we find the data quite compelling.
spk07: That does help. And then maybe a question on the partnership. Can you give us some sense of in your mind, who would be the ideal partner? And then kind of conversely, if no one signs on now, would you start a phase two trial on your own while the partnership discussions continue?
spk05: Hey, Phil, I mean, we're going to be looking at a variety of strategic partnership opportunities for 5609. You know, I think you've heard from David, we're, you know, very excited about the clinical activity that we're seeing, the tolerability, including in combination, the emerging exposure-response relationship. And we think that selective CDK7 inhibition is an opportunity in a broad range of tumors, a really big opportunity. So we're, you know, excited about the opportunity to speak to folks about, you know, partnering to take the drugs forward. We think that's sort of in the best interest of maximizing the value for the program while we focus our resources on our targeted hematology portfolio. You know, at this point in time, we've are going to continue to dose escalate, but right now, no plans for further moving beyond the safety lead-in portion of the trial.
spk07: That's very helpful. And then, last question. I know you don't want to discuss more about the data or the plans forward for Select AML-1. Can you remind us, according to the design, what was the hurdle for the safety lead-in portion to permit moving on to the randomized portion? Was there a specific safety profile that had to be achieved?
spk05: Phil, I think, you know, in general, you know, the safety lead-in is designed to make sure that you have a sort of a dose and schedule that you're comfortable moving forward with into the randomized portion. But obviously also, you know, we're looking at clinical activity as well. And as you know, some of the doublets of TAMI-AZA and then-AZA in a similar patient population have composite CR rates in the kind of low to mid 60% range. So, you know, clearly we're also looking for the opportunity to have something higher than that as we think about moving into the next phase of the trial. And, you know, we're excited about the initial data that we have and we look forward to discussing it at ASHE.
spk07: That's very helpful. Thanks for taking our questions.
spk01: Thank you. One moment for our next question. And that will come from the line of Alexander Hsu with Oppenheimer. Please go ahead.
spk03: Hi, this is Alex calling on behalf of Mark at Oppenheimer. I just have a few questions, first off, with your CDK7 program. So, you know, we noticed that the, like, 56 of 9 using combinations of PEMS-CIVI. What was the logic behind not continuing the testing for it?
spk08: sure um you know thanks alex for that question so we are we're again very excited about the data we're seeing across all of the arms where we've not yet demonstrated a maximum tolerated dose uh and i do want to just remind you you know we've dosed up to 10 milligrams in the single agent up to five in the gem doublet and up to four in the in the um gem nab 5609 triplet, you know, obviously it's very important to focus on the single agent arm to define a maximum tolerated dose. That's really critical in general in drug development because it helps to define our ceiling for dosing. And I think that clearly has a research priority. And then it's very straightforward to understand the contribution of 5609 to the activity of gemcitabine when you add the two together. you can clearly interpret the doublet on the backbone of that single agent. So those have garnered our interest with priority for next steps. That said, we also feel that it's important to help to define the doublet because it's on the basis of the doublet that we'll interpret the outcomes of the triplet. So the doublet enables the triplet to move forward. And we haven't explicitly said we're not going to retain interest in the triplet at some point in the future, but we think the next immediate steps should really just focus on those two. They'll be foundational for moving the whole program forward.
spk03: No, no, that's fascinating. Thank you. My next couple questions, so I have a question about your AML program. So we read your abstract, and we noticed that one of the four responders discontinued treatment due to physician decisions. Do you mind, like, just elaborating on kind of what the factors contributing to this decision?
spk05: Yeah, you know, as we said earlier, we're looking forward to presenting data at ASH, and we'll kind of discuss details of the data at that time.
spk03: Okay, no worries. Thank you.
spk01: Yep. Thank you. I'm showing no further questions in the queue at this time. I would now like to turn the call back over to Nancy Simonian for any closing remarks.
spk05: Thank you, operator, and thank you, everyone, for joining us today and for your continued support of Cirrus. The remainder of 2022 will be an exciting period, and we look forward to updating you again soon. Please reach out with any further questions. Have a great day.
spk01: This concludes today's conference call. Thank you for participating. You may now disconnect.
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