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spk02: Greetings. Welcome to Octernal's first quarter 2024 financial results call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note, this conference is being recorded. I'll now turn the conference over to your host, Richard Vincent, Chief Financial Officer. You may begin.
spk03: Thank you. It's my pleasure. Good afternoon, everyone, and thank you for joining us today. Joining me on the call this afternoon are our President and CEO, Dr. James Breitmaier, and our CMO, Dr. Salim Yazgi. Today's call includes a business update and discussion of our first quarter-ended March 31, 2024 financial results that were filed earlier today. Today's press release and a replay of today's call will be available on the investor relations section of Alternals website for at least the next 30 days. Please note that certain information discussed on today's call is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. We will be making forward looking statements during this call about future events, such as our business and product development strategies, the timing of our clinical studies, planned interim data updates, regulatory filings, and our cash runway. Our actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with our business. These forward-looking statements should be considered in conjunction with and are qualified by the cautionary statements contained in today's press release and our SEC filings, including our Form 10-Q filed today and our previously filed Form 10-K for the full year ended December 31, 2023. This call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 9th, 2024. We undertake no obligation to revise or update any forward-looking statements to reflect events or circumstances occurring after the date of this call. With that, it is my pleasure to hand the call over to our CEO, Dr. Jim Breitmaier.
spk04: Thank you, Rich, and good afternoon, everyone. At Oncternal, we are advancing two first-in-class clinical programs targeting cancers for patients with significant unmet medical needs. Onc534, our novel dual-action androgen receptor inhibitor, or DARI, is advancing rapidly through the dose escalation portion of the Phase 1-2 study, and we continue to see high demand and engagement from KOLs, investigators, and patients. We believe that by interacting with both the ligand binding domain and the N-terminal domain of the androgen receptor, and by inducing degradation of the AR, Onc534 may address many prostate cancer escape mechanisms to approve AR pathway inhibitors, such as enzalutamide and abiraterone, including many LBD mutations and splice variants, such as ARV7. We have recently opened several top academic centers to join the Phase I-II study, and the investigators are enthusiastic. We are also happy to announce that the fourth dosing cohort of the study is now fully enrolled. Patients in this cohort are receiving 300 milligrams of ARN534 once per day orally. The decision to move to this dose level was made by the study's Safety Review Committee after reviewing data from the patients treated to date including those at the third dose level of 160 milligrams on 534 daily. Based on preclinical analyses, we are optimistic that study participants are receiving doses along 534 that may be within the active dose range for anti-tumor activity. We plan to share an initial clinical data update for this program late in the second quarter of this year. Now switching gears to 808, our ROAR-1 targeting ontologous CAR-T, we are also happy to announce that the Phase 1-2 study in patients with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR treatment, is again open and enrolling patients. We'd like to thank the team and our investigators for the swift implementation of protocol amendments which include modified eligibility criteria, increased monitoring for infection, and evaluating lower doses. As a reminder, we recently shared an encouraging initial response signal at the one times 10 to the sixth CAR T cells per kilogram dose, with two of the three patients achieving complete metabolic response, and the third achieving a partial response. as of the December 4th cutoff date. We expect to report updated clinical results, including data from patients treated with the new dosing schedule in mid-2024. With this, I will now turn the call back to our CFO, Rich Vincent. Rich?
spk03: Thank you, Jim. Our revenue is currently derived from research and development grants received from the NIH. Our grant revenue was 0.6 million for the first quarter ended March 31, 2024. Our total operating expenses for the first quarter ended March 31, 2024 were 9.3 million, including 1.4 million in non-cash stock-based compensation expense. In the first quarter, research and development expenses totaled 6 million. In general and administrative expenses totaled 3.3 million. Net loss for the fourth quarter was 8.4 million. for a loss of 2.83 per share, basic and diluted. As of March 31, 2024, we had approximately 3 million shares of common stock outstanding, 27 million in cash, cash equivalents, and short-term investments, and no debt. We believe these funds will be sufficient to fund our operations into the first quarter of 2025. With respect to upcoming milestones, we remain on track for both programs moving forward towards significant data points. For ONC 534, our lead DARI product candidate, we expect to present initial clinical data in the latter part of this second quarter of 2024 with additional readouts in the fourth quarter of 2024. For ONC 808, our ROR1 autologous CAR T, we expect to report a clinical data update in mid 2024 with additional data readouts in the fourth quarter of 2024. With that, I will turn things back to the operator for the Q&A portion of this afternoon's call.
spk02: Thank you. At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. One moment, please, while we poll for questions. Our first question comes from the line of Carl Burns with Northland Capital Markets. Please proceed with your question.
spk07: Thanks for the question, and congratulations on your progress. With respect to 534, in terms of the 300 dose, in the dose escalation study. Do you expect to get, I think you mentioned that you had full enrollment in that cohort. How many were in that cohort? And then also, would you suspect that you would go to the higher 600 milligram dose, you know, prior to the mid, excuse me, year end update? Thanks.
spk04: So, we'll have Saleem answer that question.
spk00: Yeah, so actually we already fully enrolled and dosed this cohort, three patients in this cohort. We're still in a DLT period, and we expect to have SRC happening mid-this month, towards the end of this month, actually, and then if everything's fine, we'll escalate to the next dose cohort, which is the 600 milligram.
spk04: Yeah, so Carl, assuming that everything runs on track, we would have some data from the 600 milligram cohort by the time we announce results.
spk07: Great, thanks so much.
spk02: Thank you. Our next question comes from the line of Haritaj Singh with Oppenheimer and Company. Please proceed with your question.
spk05: Great, thank you. I just got a couple of questions. One is, again, just going back to prostate cancer. You know, amateur receptor signaling, the current, you know, when these molecules are given redosed, Jim, it seems with an ARSI, after first line, the second line ARSI is given, you've got about 25% responses, you know, maybe a little bit higher. But that's what the academic literature seems to suggest. Is that the way to think about how, you know, the update could happen in the second quarter with 534? Is it too early to see, you know, data in depth like that? And I just got a quick question on follow-up on Aurora 1.
spk04: Sure, and I'll take that question. So I think that the published data on switching from one existing androgen receptor signaling inhibitor to another would be at the low end of what we're expecting. Because, for example, if you switch from enzalutamide to abiraterone, the failure to respond to the abiraterone includes the fact that mutations in the ligand binding domain have developed that the second agent cannot address. So in our case, 534 is active against, for example, prostate cancer that is resistant to enzalutamide. So it would be active in more cases than you would expect from switching from one ARSI to another. We're also active against splice variants, which have lost the ligand binding domain entirely, and those do not respond to conventional hormone-related therapies at all.
spk05: Great. Thank you, Jim. And then the other question is, just on rule one, is there any color or updates you can provide on the durability of those two, you know, CRs that you saw in December. And thanks for the question.
spk04: Sure. Salim, do you want to comment? Hartaj has to wait, I know, but you can speak in generalities.
spk00: Sure. So, you know, we're not going to go into the details, but as you know, the patients that we've been treating in the cohort one those patients who failed multiple prior therapy, including prior CD19 CAR-T, as well as some of them CD79 and bispecific treatments. Those are very heavily pretreated patients, and usually the expectation of those patients is very, very low and short in progression-free survival. So to answer your question, I think we are enthusiastic about what we are seeing about the durability of this response, but taking into consideration that we have very sick, very heavily treated patients.
spk05: Great. Thank you. Really appreciate that. Thanks for the question.
spk02: Thank you. Our next question comes from the line of Robert Burns with HC Wainwright. Please proceed with your question.
spk01: Hi, guys. Thanks for taking my questions. I can grasp on the progress. Just two questions for me regarding 808. So I know that in the current trial design, it's only phase one in which you're looking at the CD19 failed CAR T patients or those who are ineligible for CAR T, CD9 targeted CAR T. I was curious whether you would also try to explore that in phase two, or are you trying to go for a more broader population? And then secondly, with regards to the modified eligibility criteria, how do you think that that is going to help from a safety profile perspective?
spk04: So let me – I can start from the – with the safety question, Rob. So we had – we are – we're responding to the unfortunate – case of a grade five toxicity in a patient earlier in the dose escalation. And we think we learned some things about that patient that we can use to improve overall safety for the rest of the study, which is what you're asking. So for example, we're no longer allowing bulky disease which that patient had. We're lowering the upper age limit. That patient was 80 years old. And we're taking a number of measures to try to detect and have treated any kind of occult infection, which as I'm sure you know well, infection is the number one cause of non-tumor death in patients who have undergone CD19 CAR T therapy because they've had their B cells obliterated by the therapy. So with these, these are the three measures that we do feel will add to the many safety measures that were already built into the study. So, and your first question I'm going to have – was suitable for Salim, except I've forgotten what it was. So if you could repeat it, please.
spk01: Yeah, so I know in the first – in the phase one portion, you're allowing for G19 failed CAR T patients, but that's only for the phase one. Are you also thinking about considering looking at that population specifically, given the unmet need there?
spk00: Yeah, so actually we – You know, as you know, we are still in the phase one, but we are learning as we go. I think at the phase two, we're probably going to expand the patient population based on what we see in the phase one. And yes, to answer your question, I think if we see signals from those patients in phase one, we're probably going to expand that population.
spk04: Yeah. Yeah. And the protocol allows CD19 failures in phase two, while FDA required us to have either people who had failed CD19 CAR T or patients who were ineligible or had refused it in phase one. So we're removing that restriction for phase two.
spk01: Awesome. Thank you.
spk04: Thank you, Rob.
spk02: Thank you. And our next question comes from the line of Kent Dolliver with Brookline Capital Markets. please proceed with your question.
spk06: All right, thanks. And just to continue with the 808 discussion around the enrollment criteria, and admittedly, you know, this is early on, but based on the changes you've made and whatever other data you looked at in making those decisions, how are you thinking, does that have any noticeable difference on the addressable market that you'd previously estimated?
spk04: Kemp, thanks for the question. And no, we don't think that the modified eligibility criteria changes the addressable market.
spk06: Great. Thank you.
spk02: Thank you. Thank you. And we have reached the end of the question and answer session, and I'll now turn the call back over to CEO James Breitmaier for closing remarks.
spk04: Thank you, Shamali. Overall, we are very encouraged and pleased with the pace of execution in both our clinical programs, 534 and 808, and the enthusiasm of our investigators for these studies. We're looking forward to potentially significant clinical data updates for both programs in the coming months. Thank you for joining us today and we look forward to updating you throughout the year.
spk02: And this concludes today's conference and you may disconnect your lines at this time. Thank you for your participation.
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