Greetings. Welcome to Oncternal's First Quarter 2024 Financial Results Call. [Operator Instructions] Please note, this conference is being recorded. I will now turn the conference over to your host, Richard Vincent, Chief Financial Officer. You may begin. .

Thank you, Shamali. 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. This 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 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 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 9, 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 Breitmeyer. .

Thank you, Rich, and good afternoon, everyone. At Oncternal, we are advancing 2 first-in-class clinical programs targeting cancer for patients with significant unmet medical needs.

ONCT-534, our novel dual action and receptor inhibitor, or DAARI, is advancing rapidly through the dose escalation portion of the Phase I/II 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 terminal domain of the androgen receptor and by inducing degradation of the AR, ONCT-534 may address many prostate cancer escape mechanisms to approved AR pathway inhibitors, such as enzalutamide and abiraterone, including many LVD mutations and splice variants such as AR-V7..

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 ONCT-534 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 ONCT-534 daily.

Based on preclinical analysis, we are optimistic that study participants are receiving doses of ONCT-534 that may be within the active dose range for antitumor 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 ONCT-808, our ROR1 targeting autologous CAR-T, we are also happy to announce that the Phase I/II study in patients with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T 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 1x10^6 CAR T cells per kilogram dose. With 2 of the 3 patients achieving complete metabolic response and the third, achieving a partial response as of the December 4 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?.

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 noncash stock-based compensation expense.

In the first quarter, research and development expenses totaled $6 million and 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 ONCT-534, our lead DAARI product candidate, we expect to present initial clinical data in the latter part of the second quarter of 2024, with additional readouts in the fourth quarter of 2024. ONCT-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. .

Thank you. [Operator Instructions] Our first question comes from the line of Carl Byrnes with Northland Capital Markets. Please proceed what's your 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 into the higher 600-milligram dose prior to mid -- excuse me, your end update. .

So we'll have Salim answer that question?.

Yes. So actually, we're already fully enrolled and dosed this cohort 3 patients in this cohort. We're still in a DLT period, and we expect to have SRC happening mid-this months towards the end of this month actually. And then if everything is fine, will escalate to the next dose cohort, which is the 600 milligram. .

Yes. So Carl, assuming that everything runs on track, we would have some data from the 600-milligram cohort by the time we announce results. .

Our next question comes from the line of Hartaj Singh with Oppenheimer & Company. .

I just got a couple of questions. One is, again, just going back to prostate cancer.

And is your receptor signaling the current -- when these molecules are given redosed, Jim, it seems with that ARSI after first line, second line ARSI is, given you've got about 25% responses maybe a little bit higher, but that's what the academic literature seems to suggest.

Is that the way to think about how the update could happen in the second quarter with 534? Is it too early to see data and death like that? And then I just got a quick question on follow-up on ROR1. .

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, we are -- 534 does -- 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. .

Great. And then the other question is just on ROR1.

Is there any color or updates you can provide on the durability of those 2 CRs that you saw in December?.

Sure. Salim, do you want to comment? We're -- Hartaj has to wait, I know, but you can speak in generalities. .

Sure. So we're not going to go into the details. But as you know, the patients that we've been treating in the cohort 1, those patients who failed multiple prior therapy, including prior CD19 CAR-T as well as some of them CD79 and bispecific treatments. So these are very heavily pretreated patients.

And usually, the expectation of those patients is very low and short and progression-free survival. So to answer your question, I think we are enthusiastic about what we are seeing about the durability of the response, but taking consideration that we have very sick, very heavily tritiated patients. .

Our next question comes from the line of Robert Burns with H.C. Wainright. .

Congrats on the progress. Just 2 questions for me regarding 808. So I know that in the current trial design, it's only Phase I in which you're looking at the CD19 failed CAR-T patients or those who are -- are ineligible for CAR-T -- CD19 targeted CAR T.

I was curious whether you would also try to explore that in Phase II? 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?.

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 5 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 were 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 a cult infection, which, as I'm sure you know well, infection is the #1 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 3 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 -- were suitable for Salim, except I've forgotten what it was. So if you could repeat it, please. .

Yes. So I know in the first -- in the Phase I portion, you're allowing for CD19 failed CAR-T patients. And that's only for the Phase I.

Are you also thinking about considering looking at that population specifically, given the unmet need there?.

Yes. So actually, we -- as you know, we are still in the Phase I, but we are learning as we go. I think as the Phase II, we're probably going to expand the patient population based on what we see in the Phase I. And yes, to answer your question, I think if we see a signal from those patients in Phase I, we're probably going to expand that population. .

Yes. And the protocol allows CD19 failures in Phase II, while FDA required us to have either -- people who had failed CD19 CAR-T or patients who are ineligible or had refused it in Phase I. So we're removing that restriction for Phase 2. .

And our next question comes from the line of Kemp Dolliver with Brookline Capital Markets. .

And just to continue with the 808 discussion around the enrollment criteria.

And admittedly, 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 notice of a difference on the addressable market that you had previously estimated?.

Kemp, thanks for the question. And no, we don't think that the modified eligibility criteria changes the addressable market. .

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 Breitmeyer for closing remarks. .

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. .

And this concludes today's conference, and you may disconnect your lines at this time. Thank you for your participation..