Oncternal Therapeutics Inc (ONCT) 2023 Q1 法說會逐字稿

Greetings, and welcome to the Oncternal Therapeutics first-quarter 2023 financial results call. (Operator Instructions) As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Richard Vincent, Chief Financial Officer.

Thank you, Joe. Good afternoon, everyone, and thank you for joining us today. Joining me on the call this afternoon are our President and CEO, Dr. James Breitmeyer; and our CMO, Dr. Salim Yazji. Today's call includes a business update and discussion of our first quarter ended March 31, 2023 financial results that were filed earlier today, which will be followed by Q&A. Today's press release and a replay of today's call will be available on the Investor Relations section on Oncternal'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 and our 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, May 4, 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 Breitmeyer.

Thank you, Rich, and good afternoon, everyone. At Oncternal, we are advancing a focused and robust product pipeline with clinical and preclinical product candidates that target cancers for patients with unmet medical need. We recently announced a strategic reprioritization to focus on advancing our ROR1-targeting cell therapy, ONCT-808, and our novel dual-acting AR inhibitor, ONCT-534, towards significant clinical catalysts within the next 12 to 18 months.

At the same time, on April 3, we decided to close with our Phase 1/2 and Phase 3 studies of zilovertamab in combination with ibrutinib due to major shifts in the Bruton's tyrosine kinase inhibitor landscape, which was followed by an announcement by our partner of their plans to withdraw ibrutinib's FDA accelerated approval in mantle cell lymphoma. This decision allowed us to extend our expected cash runway into 2025 and reinforces our mission to address important unmet needs for patients with hematologic malignancies and prostate cancer.

Looking to the future, we are very excited about the clinical potential of our ROR1-targeting autologous CAR-T, ONCT-808, which is being investigated in a recently initiated Phase 1/2 clinical trial. ONCT-808 leverages our extensive clinical experience with zilovertamab, which was found to be safe in several Phase 1 and 2 studies. Specificity for tumor cells is also (technical difficulty) by data from clinical testing of zilovertamab vedotin, an antibody drug conjugate using the same targeting antibody, which has shown that ROR1 can be targeted without unwanted off-tumor on-target activity.

Our preclinical models show robust and specific cytotoxic activity of ONCT-808 against ROR1-expressing cells from multiple tumor types. Our manufacturing process is reproducible, scalable, and only eight days in duration. As previously guided, we expect our initial clinical data readout in late 2023, with additional clinical data readouts in 2024. Our ONCT-808-101 Phase 1/2 study will enroll patients with relapsed or refractory aggressive B-cell lymphoma, including those who have failed previous CD19 CAR-T therapy. In Phase 1, increasing doses of ONCT-808 CAR-T cells will be evaluated to help us determine the recommended Phase 2 dose using a standard three plus three dose escalation design.

The starting dose will be one-times 10 to the six CAR-expressing T cells per kilogram. And this dose has potential to exert anti-tumor effects considering that other CAR-T products can be effective at similar doses. Phase 2 of the study will investigate the recommended Phase 2 dose using a Simon two-stage design, which will help us to further evaluate the safety and efficacy of ONCT-808. As a reminder, patients who have failed CD19 treatment have extreme unmet medical need with little likelihood of responding to the next treatment, and median progression-free survival of only three months, and overall survival of only five months.

We are also very enthusiastic about our novel and first-in-class dual-action androgen receptor inhibitor, ONCT-534, which both inhibits AR activity and induces its degradation. We have now concluded IND-enabling studies, and we are assembling the IND and are on track for submitting it in mid-2023. Preclinical models suggest activity directed to both the N-terminal and ligand binding domains of the AR.

ONCT-534 is active against preclinical models of the most common forms of resistance to current standard of care, AR directed therapies, including AR amplification, LBD mutations, and AR splice variants that are [constitutively] active, even though lacking the LBD. Our Phase 1/2 clinical trial in patients with metastatic castration-resistant prostate cancer who are resistant to AR inhibitor treatment is expected to open shortly after the IND has cleared. We expect to present initial clinical results in mid-2024.

Let me now turn the call back to Oncternal's CFO, Rich Vincent.

Thank you, Jim. Our revenue is currently derived from research and development grants from the NIH. Our grant revenue was $0.2 million for the first quarter ended March 31, 2023. Our total operating expenses for the first quarter were $12.3 million, including $1.9 million in non-cash stock-based compensation expense.

Research and development expenses totaled $9 million, and general and administrative expenses totaled $3.3 million. Net loss for the first quarter was $11.5 million, or a loss of $0.20 per share, basic and diluted. As of March 31, 2023, we had approximately 58.7 million shares of common stock outstanding and $54.3 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, to recap again, we remain on track for ONCT-808, our ROR1 autologous CAR-T. We expect to report initial clinical data by the end of 2023 with additional data readouts in 2024. For ONCT-534, our lead DAARI product candidate, we expect to submit an IND with the US FDA in mid-2023, and we expect to initiate our Phase 1/2 study in the second half of 2023, and to present initial clinical data in the first half of 2024.

Now I will turn the call back over to Jim.

Thank you, Rich. We are very enthusiastic to be focusing our efforts on these two programs for patients with lymphoma and prostate cancer, who have such high unmet medical need where we believe our product candidate can make the greatest difference for patients.

With that, I will turn things back to Joe for the Q&A portion of this afternoon's call.

(Operator Instructions) Hartaj Singh, Oppenheimer.

Great. Thank you. Thanks for the updates, Jim and team. And again, those are very hard decisions, I'm sure, you had to make and make the company a little bit stronger going forward in this environment.

A couple of questions. One is just on the experience you've had with zilovertamab, the antibody. Of course, you have had experienced zilovertamab vedotin before Merck bought that ADC. But how does experience with the binder of that antibody help you with ROR -- with ONCT-808? And then, in terms of how that helps you in your dosing profile going forward for the trials you're initiating, how does that help? And I just got a couple of quick follow-ups after that.

Sure, Hartaj. So zilovertamab is -- the binding domains of zilovertamab are what we're using as the targeting moiety on the CAR-T. So, we do know now from treating a lot of patients with the whole antibody that we can target ROR1 using an antibody targeting exactly that way, with a very encouraging and safe toxicity profile.

Another thing that zilovertamab offers is, if a patient is getting into trouble with excessive activation of T-cells, that we could infuse the zilovertamab antibody. And we've shown in vitro that that can cool off the cytotoxic reaction. And so, we think that it might be able to serve as an emergency off switch.

And then the relevance of the ADC experience, since it's also using zilovertamab, is that the toxicities with that ADC were typical for that class MMAE antibody drug conjugate without any apparent toxicity, suggesting that other organs were damaged through ROR1 targeting.

Great, Jim, thank you. And then just in terms of what's the dosing level you're going to start at. If you can give a little bit -- give us some specificity there? And that again, having a binder on your CAR-T that you've already had experience with through the antibody, how does it help you as you go through your dose titration phase of your trial?

So we proposed to the FDA, and they agreed, that we would start at 1 million CAR-expressing cells per kilogram. So that means for an average adult, that we'd be giving 60 million or 70 million CAR-T. The reason that's exciting for us is if there are CAR-T out there, where that kind of a dose is associated with substantial efficacy. We also proposed to escalate with a fairly quick escalation scheme.

And so, we will be moving up in doses every time -- based on three plus three rules which you're familiar with. And so, the increasing doses will be monitored by a safety review committee, who will make the decision to move from one dose to the next. And so we're starting at a good dose. That's what's exciting about it. And then we will move up and find the right dose during Phase 1.

Great, Jim. And sorry, last question for me is your initial data readout by the end of the year -- I know we're always asking for more as [I'll expect you], but if you can just give us the contours of what that looks like. I mean, you think you could have a few patients, five to 10 patients, more than 10 patients. And then what are you looking for, response and some duration, or just response? Any thoughts there? Thank you.

Sure, Hartaj. So, for this year, few patients and initial response and early duration. So it would -- it's not likely to be much more than that. As you know, FDA wants to be conservative in the early going in a clinical trial. And so, they've asked us to have 30 days between each patient that is treated.

Great. Thank you, Jim. Thanks for all the questions.

All right.

Carl Byrnes, Northland Capital Markets.

Great, and thanks for the question. I think most of my questions have been answered here. But just going back to 808, if I recall correctly, the subjects of 1 and 2, they are eligible for bridging therapy in those segments. Is that correct?

Yes, that's correct, Carl. But with our -- and bridging therapy is sometimes needed when there's a long period of time where patients are waiting to get their CAR-T product. So, one of the things we are very enthusiastic about is that our CAR-T manufacturing goes pretty quickly. It's an eight-day manufacturing process. And so, we're hoping that our patients are most likely to need bridging therapy.

Great. Thanks, very helpful.

Li Watsek, Cantor Fitzgerald.

Hi, there. Thanks for taking our questions. This is Rosemary Li on for Li Watsek. Just firstly, on ONCT-808, could you give us a sense of how enrollment is tracking, and where you might be in terms of dose escalation? And then for 534, would you be able to guide anything about the bar of success for the Phase 1 portion? Thank you.

Thank you, Rosemary. So we're not going to talk specifically about enrolled numbers. But we do believe, as Hartaj asked, that we'll have data on a few patients by the end of the year.

Salim, would you -- Salim Yazji, our CMO, can answer the question about the bar for prostate cancer in Phase 1.

Yes. Thank you, Jim. Thank you for your question, Rosemary. Yes. I think what we're trying to do here specifically in the Phase 1, we're using a very well-known [bind] design to get to the therapeutic dose as fast as possible. And the Phase 1, I think PSA reduction as this is what we're looking for as a primary marker for antitumor activities. And I think this is what we'll be looking for. Of course, we're going to look into other surrogate markers, including PFS and others.

Got it. Thank you --

And I'll add, Rosemary, that the patients will have failed standard-of-care androgen receptor signaling inhibitors like enzalutamide and abiraterone, and so a hormone-based treatment for patients after that yields very low response rates, probably in the 15% range. So, if we see something in the 30% to 40% range for these patients with advanced disease, we'll be very happy.

Great. Thanks so much.

Kemp Dolliver, Brookline Capital Markets.

Thank you. A question about zilovertamab and potentially pivoting it toward the other BTKs based on additional preclinical work. I know it's only been about a month, but do you have any further thoughts on that process and how it shakes out in the priorities of the pipeline at this point?

Yes, good question, Kemp. So of course, the decision by AbbVie to withdraw its FDA accelerated approval of ibrutinib for mantle cell lymphoma was a blow to our plan for registration in that indication with ibrutinib. And so, we are talking to other BTK inhibitor companies, and there is some interest here. And we are of course interested in generating additional data.

We do believe that zilovertamab will be synergistic with all of the approved BTK inhibitors, and mechanistically, at least, expect it to be synergistic with others that are still in earlier stages of development. So, short answer is that we're keenly interested in another BTK inhibitor as a potential path forward.

And I guess it's too early to give any thoughts on the timetable.

Yeah, it's too early.

Okay. Fair enough, thank you.

Thank you, a good question.

Thank you. Ladies and gentlemen, there are no further questions at this time. I'd like to turn the call back to Jim Breitmeyer for any closing remark.

Thank you all for your time and attention today. We look forward to reporting our initial clinical data for ONCT-808, our ROR1-targeting autologous CAR-T in patients with lymphoma who have failed CD19 CAR T treatment; and for ONCT-534, our novel first-in-class dual-action AR inhibitor for metastatic castrate-resistant prostate cancer patients who are refractory to current AR inhibitor therapy.

Thanks again for joining us. And we look forward to updating you during upcoming medical and banking conferences.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.