Oncternal Therapeutics, Inc.

Greetings and welcome to Octurnal Therapeutics Third Quarter 2023 Financial Results Conference Call. At this time, all participants are on 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. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Mr. Richard Vincent, Chief Financial Officer. Please go ahead.

Thank you, Rob. 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 third quarter-ended September 30, 2023 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 Ontario's 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 initiation of our preclinical and clinical studies, the timing of planned interim data updates, the timing of our 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 previously filed Form 10-K for the full year ended December 31, 2022. This call contains time-sensitive information that is accurate only as of the date of this live broadcast, November 9, 2023. 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.

Thank you, Rich, and good afternoon, everyone. At Oncturnal, we are now advancing two first-in-class clinical programs targeting cancers for patients with significant unmet medical needs. In October 2023, we dosed our first patient in our Phase I-II dose escalation study of Onct534, our novel dual-action androgen receptor

Hello. Hello. You're back.

Okay. Thank you. I apologize, everybody. I'm calling in internationally. Onc534 is for patients with metastatic castrate-resistant prostate cancer who have progressed after treatment with approved AR pathway inhibitors. In October, we also received FasTrac designation from FDA. further supporting our belief that ONC534 may be an important therapeutic alternative for patients with advanced prostate cancer. We expect our initial clinical data readout in the first half of 2024. With respect to ONC808, our ROR1 targeting autologous CAR-T program, we continue to execute on enrollment of the Phase I-II study in aggressive B-cell non-Hodgkin's lymphoma patients. We have now dosed the first few patients and plan to announce initial clinical data in December of this year with additional clinical readouts in 2024. The manufacturing process is delivering large numbers of high-quality CAR-expressing T cells and may offer reduced vein-to-vein times. Overall, we are delivering on our plan to advance our two clinical programs, 534 and 808, through potential significant value inflection points by the first half of 2024, all while maintaining our cash runaway guidance into 2025. With that, I'd like to now turn the call to OncTernal CMO, Saleem Yazji, to expand on our clinical progress with 534 and 808. Saleem?

Thank you, Jim. As Jim mentioned, we are excited to have dosed our first patients in the study of Onc 534-101. A Phase I-II dose escalation study that's enrolling patients with metastatic, castration-resistant prostate cancer with progressive disease that have relapsed or are refractory to prior androgen receptors pathway inhibitors, such as enzalizumide or abiraterone. Based on preclinical studies and its noble mechanism of action, we believe that UNK534 can provide an important treatment alternative to these patients by addressing a key tumor escape mechanism that results in resistant to currently available AR pathway inhibitors, including AR mutation, AR amplification, and splice variants such as ARV7. Enrollment is advancing according to plan, and we continue to expect to report initial data in the first half of 2024. In September, we announced the establishment of our Prostate Cancer Scientific Advisory Board, which includes distinguished academic and industry leaders in the prostate cancer field, such as Professor Johan de Bono from the ICR in London, Dr. Matthew Smith from Mass General, and Dr. Evan Yu from the Fred Hutch. We look forward to working with our SAB to develop our future clinical and registrational strategy for ONC 534. With respect to ONC 808, our autologous ROAR-1 targeting CAR-T, we continue to dose patients in the dose escalation portion of our study. ONC 808-101, a phase 1-2 study for patients with relapse or refractory aggressive B-cell lymphoma, including those who have failed previous CD19 CAR-T therapy. We have seen encouraging expansion and persistence of CAR-expressing T cells in the study, which has been demonstrated to be positively correlated with clinical response in previous CD19 CAR-T studies. I now turn the call to our CFO, Rich Vincent. Rich?

Thank you, Celine. Our revenue is currently derived from research and development grants received from the NIH. Our grant revenue was $0.2 million for the third quarter ended September 30, 2023. Our total operating expenses for the third quarter were $10.6 million, including $1.7 million in non-cash stock-based compensation expense. Research and development expenses totaled $7.5 million, and general and administrative expenses totaled $3.1 million. Interest income for the quarter was $0.5 million. Net loss for the third quarter was $9.9 million for a loss of 17 cents per share, basic and diluted. As of September 30, 2023, we had 59 million shares of common stock outstanding, $40.3 million in cash and investments, and no debt. We believe these funds will be sufficient to fund our operations into 2025. With respect to upcoming milestones, we remain on track. BRONC 808, our ROR1 autologous CAR T, we expect to report initial clinical data in December 2023 with additional data readouts in 2024. BRONC 534, our late DARI product candidate, We expect to present initial clinical data in the first half of 2024. Now I will turn the call back over to Jim. Jim?

Thank you, Rich. We are very pleased with the recent progress in our two clinical programs while reiterating our cash runway guidance into 2025. We are excited to be advancing the clinical development of novel pathways in areas with very high unmet medical need, such as CD19 relapses in aggressive lymphoma, and metastatic castrate-resistant prostate cancer harboring AR mutations and splice variants. Thank you for joining us today, and we look forward to updating you during upcoming medical and banking conferences. With that, I will turn things back to Rob for the Q&A portion of this afternoon's call.

Thank you. At this time, we'll be conducting a question and answer session. If you'd 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'd 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 keys. One moment, please, while we poll for questions. Our first question is from Carl Burns with New Orleans Capital Markets. Please proceed with your question.

Thanks for the questions, and also congratulations on your progress. I'm wondering if you can provide a little more detail with respect to the velocity of patient recruitment in the 534 dose escalation study. And this is obviously considering the urgent unmet medical need indication. And then I have a follow-up.

Go ahead, Salim.

Yeah. You know, as you know, we designed the study based on the Boeing design, which has allowed us to move forward with the first two cohorts with only one patient each if there is no toxicity or side effect during those cohorts. So, so far, I mean, you know, I think the enrollment and everything goes as expected.

And, Carl, there are a lot of these patients out there.

Yeah, and that's where I was going. It seems like these trials, as you progress and advance, they should be relatively easy to populate and enroll.

We hope so. You never know. But what we're finding is that for most studies, the investigators are enthusiastic, and the number of patients who are in their systems with these kinds of unmet needs seem to be ample for a good enrollment pattern.

Excellent. And then shifting gears a little bit on 808, do you have any thoughts there in terms of the potential efficacy signal with the data readout in December, considering the dose level being relatively close to recommended base two doses of other CAR T therapies? Thanks.

Yeah, I'll take that one, Salim. I think that... As you probably know, with aggressive lymphoma, responses to CAR-T have pretty quickly. And CAR-T, the median time to a response was between one and two months. So if there's any, you know, similarity between this and CAR-T,

I'm sorry, Jim, I think you broke up a bit.

Yeah, I did. I'm sorry. Can you hear me better now?

Yes. Yes.

Okay, I just switched phones. So given that other CAR T programs have shown that complete responses can develop quickly, we're optimistic that we may have some efficacy to talk about in December.

Great. Again, congratulations on the progress.

Our next question comes from with Oppenheimer and Company. Please proceed with your question.

Great, thank you, and thanks for the couple of questions and really nice updates. Things are moving along pretty quickly, Jim and Colleen and team. I guess on 808, just one question there is following up on the previous questions. You know, what would you like to see, you know, whether it's dose level one, two, or three, you know, a minimum amount of efficacy in order to move forward? And then, you know, when you do move forward and you're thinking about dose expansion, what are we thinking in terms of what would be an acceptable durability that you'd like to see as you sort of follow these patients onwards? And then, you know, on the other program with 534, again, you know, just similar questions. You're going to have a lot of data being presented there, you know, early stage. What should we be looking for, you know, that signals to us that you're getting close to a sort of a, you know, moving to dose expansion from the dose escalation part of the system. Thank you.

Jim, do you want me to take some? Okay. So, Hartej, I can start, actually, while Jim is probably establishing the connection. You know, as you know, we really – dealing with very sick patients, especially patients who are after relapsed from prior CD19 CAR-T. Unfortunately, I mean, you know, these patients, the progression-free survival and overall survival is very short, which is usually in months, not even in years. And what we would expect, we would expect to see some objective response and also durability of response. And that's a big question here. What would be good as a durable response in those patient populations that already failed prior CAR-T? I think it's a very objective question and we need to still see some of that data and evaluate it because usually medium progression-free survival there is no more than three months currently, and the survival rate is no more than six months. So I think we are really dealing with very aggressive and very sick patients, but we're hoping for the best. So I'll stop here and I'll take any questions if there's any additional ones from you, Hirtash.

No, that's really good. And then just on five, three, four, um, you know, how do we, I guess, what do you expect to see? I mean, you've got all the way can go to 600 milligram oral daily, right? It seems like, um, and, uh, but you know, when, when, when you, where do you think you could get to before you would expect DLT? Did you need to go all the way to 600? Do you think it could be before that? And back to the question.

So, um, I think it is also, you know, it all depends, I mean, you know, on the dose escalation and how fast we can go there. But we will actually believe that therapeutic dose or the efficacy dose maybe start from the 300 above, which is that would be the fourth cohort. We may start seeing things earlier than that, and, you know, we're hoping to do that. But I think time will actually be on our side to see if we'll be able to see any early responses in earlier cohorts.

And let me add something. Yeah, so there was a very interesting panel discussion at the CITSE conference last week where several members of the FDA addressed Project Optimus. And what they made clear and emphasizing what's in the FDA guidance here is that FDA is looking for developers to establish a balance between efficacy and safety. And they are not, in oncology in particular, they're encouraging early development to learn more than just the maximum tolerated dose and to explore doses below MTD to look for that perfect balance between efficacy and safety. And so this was what was particularly helpful about this panel was that it was being discussed in the context of cell therapy, such as 808, but the same principles will apply to the choice of dose for OCT534 as well.

And Jim, you know, I guess I was just thinking, I know you've probably mentioned this before. Just remind us again, why do you have two dose levels, dose level A and dose level B, when you move forward from the dose escalation part of the study?

It's exactly for that reason, Arntaj. It's what FDA is looking for. in this Project Optimus and they made clear that whenever possible, they expect to see randomization between the two dose levels so that before you start a registration intent study, FDA will have the opportunity to examine efficacy and safety and the risk benefit ratio for more than one dose.

Yeah. No, these are all very helpful. Thank you for the question.

Thank you.

Our next question comes from Kemp Dulliver with Brookline Capital Markets. Please proceed with your question.

Great. Thank you. So, the question relates to 534. And, you know, Novartis recently presented the data from PSMA 4. which, as you know, is the pre-taxane setting. And we're expecting data any day now from the SPLASH trial, which is also in that same patient population. And based on what you've seen so far and the commentary regarding how these drugs would be used in that setting, how are you thinking about the opportunity for 534?

Yeah, good question, Kemp. So the challenge from the PSMA-4 study is that there is a slightly worse overall survival in the active treatment group in the intent to treat analysis. And so we know that FDA will be looking at their safety data in a very close manner. And what we believe is that there is still a very high desire for both the patients with prostate cancer and their physicians to have another treatment option available, an oral treatment option available that doesn't require referral to a different specialist. to treat after resistance to enzalutamide or abiraterone develop. So we're remaining confident that we have a commercially viable and clinically important indication here in the prostate cancer continuum.

Got it. Thank you.

We have reached the end of the question and answer session. I would now like to turn the call back over to Dr. James Breitmaier for closing comments.

Thank you, Rob. We appreciate everybody's time and attention and the good questions this afternoon. We are looking forward to an exciting end of this year and the first half of next year and look forward to staying in touch with you. So with that, Thank you for your time, and we will sign off.

This concludes today's conference. You may disconnect your lines at this time, and we thank you for your participation.