Q4 2022 Oncternal Therapeutics Inc Earnings Call
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Speaker 2: Greetings, and welcome to the Oncternal Therapeutics Inc. 4th Quarter 2022 Financial Results Conference Call. At this time, all participants are in a listen-only mode. A brief question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star-0 on your telephone keypad.
Speaker 3: Thank you, John . Good afternoon, everyone, and thank you for joining us today. Joining me on the call this afternoon are our President and CEO , Dr. James Breitmayer, and our CMO, Dr. Selim Yazzchi. Today's call includes a business update and discussion of our results for the fourth quarter and full year 2022, 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 of Long
Speaker 3: We filed our 10K for the full year 2022 earlier today. 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.
Speaker 3: 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 submissions, and our cash runway.
Speaker 3: Our actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainty associated with our business.
Speaker 3: These forward-looking statements should be considered in conjunction with and are qualified by the cautionary statements contained in today's press release and RSAC filings.
Speaker 3: including our Form 10-K for the full year ended December 31, 2022.
Speaker 3: This call contains time-sensitive information that is accurate only as of the date of this live broadcast, March 9, 2023.
Speaker 3: We undertake no obligation to revise or update any forward-looking statements to reflect events or circumstances occurring after the date of this call.
Speaker 3: With that, it is my pleasure to hand the call over to our CEO , Dr. Jim Breitmeier.
Speaker 3: Thank you, Rich, and good afternoon, everybody. At Ockturnell, we are advancing a focused and robust product pipeline with clinical and late-stage preclinical product candidates that target cancers for patients with unmet medical needs. In 2022, we transitioned Ockturnell into a multi-product clinical stage company.
Speaker 3: with the initiation of our phase three study ZILO301 in mantle cell lymphoma and the initiation of our phase one to dose escalation study of ONC808 our autologous CAR-T product targeting ROR1 in advanced B-cell malignancies. Our third product ONC534.
Speaker 3: our dual action androgen receptor inhibitor is completing IND-enabling studies, and we expect it to become our third clinical product later this year. Zilivertamab continued to demonstrate encouraging clinical activity in our phase one study in MCL and CLL.
Speaker 3: The data presented in December at the American Society of Hematology Annual Meeting were encouraging and continue to improve over prior reporting.
Speaker 3: The results in relapse refractory MCL patients further validated our phase 3 rationale with efficacy and safety data that compare favorably to historical results with Ebrutinib alone. The data in CLL patients with TP53 mutation or 7TP deletion treated with Ebrutinib and cilab feeling Bhackett quite positively. bucks
Speaker 3: are particularly encouraging with a landmark PFS of 100%.
Speaker 3: at 42 months in this difficult-to-treat population.
Speaker 3: months and it's difficult to treat population.
Speaker 3: On the corporate front, we continue our focus on execution as we remain vigilant regarding our cash and resource usage, and we estimate we can fund our operations into the first quarter of 2024 with funds currently available. Let me now turn the call over to our internal chief medical officer.
Speaker 4: We continue to activate sites around the world and the feedback we are receiving from investigators in those sites supports our thesis that there is a high unmet medical need in patients with mental cell lymphoma that relapse after the first line of therapy.
Speaker 4: We presented exciting data from our phase 1-2 trial of Zilovertumab in combination with Abrucinec at the ASH meeting in December . We reported an overall response rate of 89% for patients with MCL treated with Zilovertumab plus Abrucinec. We also reported a response rate of 89% for patients with MCL treated with Zilovertumab.
Speaker 4: which continue to improve from prior reporting and compares favorably to the historical overall response rate of 66% for abrutinib monotherapy.
Speaker 4: The complete response rate also continued to improve to a 43% for MCL patients treated with the combination. The medium-PFS has not been reached for relapse refractory MCL patients with TP53 mutation treated with ZilloburteMap plus of Brutonip.
Speaker 4: with a landmark of PFS approximately 85% at 15 months, which is compared favorably to historical operative monotherapy
Speaker 4: Further, strengthening our belief that we can achieve rapid and deep responses in this area of high and medical need.
Speaker 4: The data presented for CLL patients with deletion 17p or p53 mutation are also very encouraging. We demonstrated landmark PFS of 100% at 42 months in patients treated with the combination, which is compared considerably to the recent data updates from the Alpine study.
Speaker 4: which had showed landmark PFS of 55.7% at 24 months for abrutinib monotherapy and 77.6% at 24 months for zenabrutinib monotherapy in this difficult-to-treat CLL subpopulation.
Speaker 4: As you may know, mutation of the TP53 gene is the most commonly acquired mutation in cancer including hematological malignancies.
Speaker 4: TP53 abreation are associated with markedly decreased survival and predicts inadequate therapeutic response, those being among the strongest predictive and prognostic factor guiding treatment decisions in CLL and MCL.
Speaker 4: The combination of Ziloverte map and AbruTINib continue to be well-tolerated with a safety profile consistent with or improved compared with the historical data for AbruTINib monotherapy.
Speaker 4: Now let me turn to Unst 808, our ontologist CAR T, targeting role 1.
Speaker 4: In January of this year, we obtained our first IRB approval for our phase 1-2 study in advanced hematological malignancies and we expect to share initial data by the end of 2023.
Speaker 4: As a reminder, the UNCT808 phase 1, 2 trial will be a 3 plus 3 dose escalation study in patients with aggressive B cell lymphoma, including those that have failed prior CAR see treatment.actly.
Speaker 4: and both safety and efficacy results will be taken into account to select the recommended phase 2 dose.
Speaker 4: After the initial dose escalation, additional dose exploration and evidence of anti-tumor activity will be evaluated in the expansion cohorts.
Speaker 4: and we expect to be able to provide an initial update on key efficacy, safety, and PK results.
Speaker 4: Finally, with respect to UNK 534, our novel dual action androgen receptor inhibitor, we are glad to report that we received helpful feedback from the FDA from our pre-IND meeting in December .
Speaker 4: And we are now completing the final IND-enabling studies.
Speaker 4: Our plan is to submit an IND in the mid-2023 and initiate a phase 1-2 dose escalation study in metastatic-resistant prostate cancer patients shortly thereafter.
Speaker 3: I will now turn the call over to our CFO , Rich Benson, to review our financial results and upcoming milestones. Rich? Thank you, Selim. Our revenue is currently derived from two research and development grants from the National Institutes of Health, or NIH.
Speaker 3: Our grant revenue was $0.2 million for the fourth quarter ended December 31, 2022, and $1.5 million for the full year 2022.
Speaker 3: Our total operating expenses for the fourth quarter ended December 31, 2022, were $12.1 million, including $1.8 million in non-cash, stock-based compensation expense.
Speaker 3: Total operating expenses for the full year 2022 were $46.4 million, including $7.4 million in non-cash, stock-based compensation expense. In the fourth quarter, research and development expenses totaled $8.8 million and general and administrative expenses totaled $3.3 million.
Speaker 3: For the full year 2022, research and development expenses totaled $33 million and general and administrative expenses totaled $13.5 million.
Speaker 3: Net loss for the fourth quarter was $11.4 million for a loss of 20 cents per share, basic and diluted.
Speaker 3: For the full year 2022, our net loss is $44.2 million for a loss of 84 cents per share, basic and diluted.
Speaker 3: As of December 31, 2022, we had $63.7 million in cash, cash equivalents, and short-term investments and we had no debt. We believe these funds will be sufficient to support our operations into the first quarter of 2024.
Speaker 3: We have and will continue to manage expenses carefully and will explore all potential sources of capital to enable us to reach value-driving milestones.
Speaker 3: for our Zillow-Vertimat program. We continued open sites outside of the US for our global clinical, registrational phase three study Zillow 301.
Speaker 3: And for ONC-808, our autologous War-1 CAR-T cell therapy, we plan to report initial clinical data from our phase one, two study in patients with aggressive B-cell lymphoma late in 2023.
Speaker 3: And for ONS 534, our DARI product candidate, we expect to submit a 90 to the USFDA in mid-2023.
Speaker 3: With that, I will turn the call back over to Jim. Thank you, Rich. We are excited to have several programs in clinical development that can make a difference to patients suffering from hematologic malignancies and prostate cancer.
Speaker 2: 2023 will be a year of execution with the continued rollout of our Phase 3 study, ZELA301.
Speaker 3: the initial data readout of our ONC808 ROR1 CAR-T study, and the study initiation of our novel AR inhibitor, ONC534. We will continue to use our capital and resources thoughtfully and efficiently as we advance our focused pipeline of research and development.
Speaker 3: towards significant value inflection points.
Speaker 2: Thank you for joining us today and we look forward to updating you throughout the year.
Speaker 3: With that, I will turn things back to John for the Q&A portion of this afternoon's call.
Speaker 2: Thank you, sir. We will now 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 that your line is in the 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 keys.
Speaker 2: One moment, please, while we poll for questions. And our first question comes from the line of Hartaj Singh with Oppenheimer. Please proceed with your question. give your wrap and we're users and and open to your audience.
Speaker 5: Great, thank you. Thanks for the questions and really nice update, Jim and team. I have a couple of questions on just Zillivertamab and then one I'll follow up with onc808. On Zillivertamab, Jim or Celine, can you just talk a little bit about, you know, the scientific rationale behind why you're seeing this TP.
Speaker 5: 53, you know, efficacy in combination with ibupnib. And then how do you seek to kind of translate that into potential clinical trials, maybe in CLL, or where are you there, you know, where exactly are you there? And then with ONC-808, the second question is, you know, what could a potential readout look like at the end of the year?
Speaker 5: You know, we've got other autologous therapies, not necessarily in B-cell and H-L, but just what you expect to show us, you know, by the end of the year if that data does read out then. And I just have a quick P&L follow-up question after that. Thank you.
Speaker 3: Thank you for the question, Hartaj. And I'll take the first one. So our TP53 finding, it's one of those really fun and exciting things that happened in drug development where we've gone from bench to bedside.
Speaker 3: And now we're going back from the bedside to the bench to dive into what the mechanism of action is between TP53, ROR1, and the BTK inhibitors. At this point, we do believe that there is a common pathway.
Speaker 3: between these three systems. And that the... we don't know what it is yet. We're performing research in several laboratories for it right now. And what's particularly exciting is that as you know, TP53 is...
Speaker 3: prognostically important, not just in hematologic malignancies, but in a wide variety of solid tumors with unmet medical need as well. So this might open up a whole fresh area of clinical research for zilivertamab and ROR1 inhibition.
Speaker 4: So I'll let Salim speak about how it could translate into potential clinical trials in the hemolygnancies. Yeah, thanks Jim. So I mean, as Jim said, we really are having very encouraging clinical data with regards to the TP53 and CLL.
Speaker 4: TP53 deletion 17p. And for patients who are specifically relapsed in a fracture, I mean, as they go through a multiple line of therapy, they could be acquiring more of TP53 mutation and deletion 17p in CLL.
Speaker 4: So we're actually thinking if we're going to go in that route to maybe combine that with the BTKI as a physician choice and to see the effect of the combination versus monotherapy. And Selim, just one question before if you can.
Speaker 5: specific, you know, patients with this kind of mutation. Do regulators view that as sort of a higher bar for therapies, meaning that, you know, potentially having, you know, accelerated approval type potential or Sanger-Ahn study approval, or you just don't know yet?
Speaker 4: We haven't talked to the regulator or specifically FDA or other health authority about the T63 specifically, but we're planning to do that. I think there's a huge unmet medical need there. And because of that, I think we are very, you know.
Speaker 4: We are very excited and believe that regulatory agency will be actually giving us good advice on how we will be able to go in that path.
Speaker 5: Great. And then if you can just give us a quick update on what the ROR1 CAR-T results could look like at the end of the year, just sort of a broad perspective.
Speaker 4: Yeah. Yeah. I'll talk. Go ahead, Roger. No, that's fine, Celine. Go ahead. No, no. I just want to say it's just like probably we starting our trial in a very good, though this could be therapeutic, even in an early cohort. We don't know yet, but we would expect to give at least a little bit of a
Speaker 4: and early safety and maybe some hints of efficacy by end of 2023. So it all depends, you know, how actually high the dose is and how therapeutic it is and also how many patients we can enroll by the end of the year. Jim, please go ahead.
Speaker 4: No, Celine, that's exactly what I would have said. And Hartag, you said you had one other question.
Speaker 5: Yeah, thank you, Jim. Just P&L. Rich, you know, your spend, Opex spend in this quarter was very much in line with what we were expecting. Usually, fourth quarters tend to be a little bit heavy. Just any thoughts on, I mean, you've given us an idea of where your cash run rate goes till, but can you just give us any idea as to how Opex kind of trends over the next two to four quarters roughly?
Speaker 3: So Hartage, historically we have not provided guidance on a prospective basis. Historically we burned about $12 million in the third quarter. We burned about $4 million in the fourth quarter of 2022. And as stated, we have $63 million in the bank that's not in the bank.
Speaker 3: We believe we'll get us into the first quarter 2024. So we definitely expect things to ramp up. We've got the Zillow 301 program on fade away that's pulling up real time. And hopefully, the IND.
Speaker 3: activities on the 534 program will be nearing the clinic by the end of 2023 there as well. So, spend will definitely be ramping up sequentially as we go quarter by quarter. Great. Thank you, Rich. Jim, Celine, thank you all for the questions.
Speaker 3: Thank you, Hartaj.
Speaker 2: And our next question comes from the line of Carl Burns with Northland Capital Markets. Please proceed with your question.
Speaker 5: Great, thanks for the question and congratulations on your progress. I was wondering if you might be able to give us a little more commentary on the site activation for ZELO 301 in the US and then what your expectations are in terms of site activation in Europe or outside of the United States for the balance of 2023. Thanks. Thank you very much.
Speaker 4: Sure. Go ahead. Yeah, I mean, I think what what we have did we did we did actually contact a big number of sites, not only in the US, but also outside of the US. And as you know, I mean, you know, due to the post COVID situation, as well as geopolitical, political, political geolocation of the world.
Speaker 5: Great. Thank you. And then just a follow-up question on 808. At the end of the year, if you're expecting, you know, maybe some preliminary efficacy and PK data, what would be a reasonable expectation in terms of progression, all things considered, when you would be able to identify a recommended phase 2 dose for that candidate, 808? Thanks. So, we are actually...
Speaker 4: on efficacy and safety, I think that's where we need to, you know, decide what will be the recommended phase to those. So, I mean, it's all depends what we see and when we see it. I think it's very early on now to speculate, but we have a big hope that this...
Speaker 5: carefully and we're well aware that FDA is hoping to have new product development occur in a way that is more thoughtful about arriving at a phase two and ultimately phase three dose. So I would expect that and they've offered to be more communicative.
Speaker 3: with early data here. And so we are building in the Project Optimus kind of thinking into both of our early stage programs, both 808 and 534.
Speaker 2: And our next question comes from the line of Lee Watsack with Cantor Fitzgerald. Please proceed with your question. Hi, this is Rosemary. Thank you so much for taking our questions. Just two for me. Yes, please.
Speaker 6: How are you thinking about the next program for this program? And then for 5.4, could you talk a little bit about your potential Phase 1 trial design and how quickly you might be generating initial data? Thank you. So the topic of today is How Sure Annie Helms 4 Excellence
Speaker 6: How are you thinking about the next program for this program? And then for 5.4, could you talk a little bit about your potential Phase I file design and how quickly you might be generating initial data? Thank you. This is a great question.
Speaker 5: Thanks Rosemary, your first question broke up a little bit. Could you repeat it?
Speaker 6: Oh, sorry. So for Zillow in CLL with TP53 mutations, how are you thinking about next steps for this program? Yes, you did.
Speaker 4: Go ahead, Celine. Yeah. So, we are evaluating all the aspects of the potential unmet medical needs for patients with TP53 deletion 17P and CLL specifically. And as you may know, as patients go into multiple lines of therapy, I think they get a lot of
Speaker 4: BTKIs or was the physician choice of a BTKI versus you know, this physician choice of the monotherapy in the second arm.
Speaker 5: And the N534 trial design? Yes.
Speaker 4: Yeah, and the Fox C3-4 trial design, we're using a base on design, which will get us actually to dose escalate faster if there's no safety concerns. So we're hoping that that would get us into the therapeutic dose.
Speaker 4: as soon as possible. And as Jim said, we are actually expanding into a cohort to be in line with the project optimus that the FDA is promoting now to look into a recommended phase two dose or actually two doses and then choosing one of them to go into the phase three.
Speaker 2: Thank you. You're welcome. There are no further questions at this time. Now I would like to turn the floor back over to James Brightmire for any closing comments.
Speaker 5: Thank you very much for joining us today for Ockturnell's earnings call. Enjoy your evening and we look forward to staying in touch with you.
Speaker 5: Thank you very much for joining us today for Ockturnell's earnings call. Enjoy your evening and we look forward to staying in touch with you. Good night.
Speaker 2: This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation and have a great day.