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spk05: Greetings and welcome to internal therapeutics and third quarter 2022 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 a conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Richard Vincent, Chief Financial Officer. Thank you. You may begin.
spk01: Thank you, Doug. Good afternoon, everyone, and thank you for joining us today as we cover our first quarter 2022 earnings. 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 2022 first quarter financial results, 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 Oncturnal's website for at least the next 30 days. We filed our 10Q for the first quarter of 2022 earlier today as well. 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 potential for our Zillow 301 study to support a BLA submission, the timing of planned interim data updates, and the timing of our regulatory filings and submissions. 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-K for the full year ended December 31, 2021. This call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 5th, 2022. 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 Uncternal, we are advancing a focused and robust product pipeline with clinical and preclinical product candidates that target cancers for patients with unmet medical need. During the first quarter of 2022, we further sharpened our focus on the achievement of key pipeline catalysts in hematologic malignancies in prostate cancer as we navigated an unprecedented, challenging macroenvironment, which is obviously continuing in the second quarter, including today's stock market events. We made significant progress toward the initiation of our global phase three registrational study, ZELO301, for zelovertamab in patients with mantle cell lymphoma, which is planned to be initiated in the third quarter of 2022. Zelovertamab is our investigational, potentially first-in-class humanized monoclonal antibody that inhibits receptor tyrosine kinase like Orphan Receptor 1 or ROR1, function by binding with high affinity to a biologically important epitope on the receptor. We continue to evaluate additional countries and study sites for the Phase III study to ensure robust enrollment as we mitigate disruptions caused by the situation in Ukraine. As a reminder, we reached consensus with the FDA on the design and major details of the ZILO 301 study plan, which is supported by encouraging data from our ongoing Phase I-II clinical trial of zolivertimab in combination with ibrutinib, the SURL study. We look forward to providing a data update on that study at this year's American Society of Clinical Oncology meeting in Chicago in June 2022. Our autologous CAR T-cell program targeting ROR1, ONCT808, also continues to advance and is on track for an IND filing in mid-2022. In our initial Phase I study, we plan to enroll patients with relapsed or refractory hematologic malignancies, including those who have failed CD19 CAR T-cell therapy. We established a clinical manufacturing agreement with the Dana-Farber Cancer Institute to conduct collaborative CGMP process development and manufacturing activities for use in our upcoming first in human studies. Our partners at the Dana-Farber have some of the best cell manufacturing facilities in the world and proved to be a perfect fit with the cell processing technology we selected for our ROR1 CAR-T program. Research collaborations with Cellularity and with the Karolinska Institute continue to generate encouraging data for our other next-generation off-the-shelf RoR1-based cell therapy program. Next, ONCT534, the lead candidate of our dual-action androgen receptor inhibitor, or DARI program, continues to advance toward IND-enabling studies. ONCT534 may be a highly differentiated and novel treatment alternative for patients with advanced prostate cancer, as we believe it interacts with both the N-terminal and the ligand binding domains of the androgen receptor, inhibiting its function and inducing its degradation. Preclinical data have shown that OCT534 exerts anti-tumor activity in clinically relevant prostate cancer models, including those with AR amplification and zalutamide resistance, or tumors expressing androgen receptor splice variants, such as ARV7, all of which represent significant unmet medical needs for patients with prostate cancer. Finally, we announced the deprioritization of development of our E26 transformation-specific, or ETS, inhibitor, OCTU16, along with the discontinuation of enrollment in the Phase I-II study evaluating ONC-216 in patients with relapsed or refractory Ewing sarcoma. This resource reallocation will allow us to further focus on hematologic malignancies and prostate cancer, while deploying our capital toward meaningful catalysts, especially those related to our lead asset, Z-loverdomast. Let me now turn the call back to our internal CFO, Rich Vincent.
spk01: Thank you, Jim. Our grant revenue is derived from a California Institute for Regenerative Medicine, or CIRM, grant subaward and two research and development grants from the National Institutes of Health, or NIH. In October 2017, CIRM awarded an $18.3 million grant to researchers at the UC San Diego School of Medicine to advance our CIRL study. We are conducting this study in collaboration with UC San Diego and expect to receive approximately $14.4 million in development milestones under research subawards throughout the award period that was substantially completed from a revenue perspective in the first quarter of 2022. In the third quarter of 2021, The NIH awarded the company two research and development grants for up to $2.2 million to support preclinical activities for the company's ONCT 534 and ONCT 216 programs, including $0.7 million that is payable to subawardees. Our grant revenue was $0.7 million for the first quarter ended March 31, 2022. Our total operating expenses for the first quarter ending March 31, 2022, were $10.7 million, including $2 million in non-cash stock-based compensation expense. Research and development expenses totaled $7 million, and general and administrative expenses totaled $3.7 million. Net loss for the first quarter was $9.9 million for a loss of 20 cents per share, basic and diluted. As of March 31, 2022, We had $82.2 million in cash and cash equivalents and no debt. We believe these funds will be sufficient to support our operations well into the third quarter of 2023. We have and will continue to manage expenses deliberately and will explore all potential sources of capital to enable us to reach our milestones. As of March 31, 2022, we had 49.4 million shares of common stock outstanding. With respect to upcoming milestones, for our Zolivertamab program, we expect to initiate the global registrational phase three study, Zolo 301, in the third quarter of 2022. We expect to report an interim clinical data update for patients with MCL and CLL treated with Zolivertamab plus ibrutinib from our ongoing Searle study at the June 22 ASCO meeting. We also expect to have a Phase 1B investigator-sponsored trial of zilivertimab plus docetaxel enrolling patients with metastatic castration-resistant prostate cancer in mid-2022. On the cell therapy front, we are on track to submit our first IND for ONCT 808, our autologous ROR1 CAR T cell candidate in mid-2022. For ONCT 534, our lead DARI product candidate, We are on track to initiate IND-enabling GLP toxicology studies and GMP manufacturing in the second quarter of 2022. Now, I will turn the call back over to Jim.
spk04: Thank you, Rich. We look forward to multiple catalysts in 2022, especially the initiation of our global phase III zolivertimab study, and submitting our ROR1 CAR-T IND application and advancing our DARI program toward the clinic. Our sharp focus on resource allocation, prudent cash management, and a strong balance sheet are enabling us to navigate this historically challenging macro environment. We plan to continue to focus our resources on areas of the highest unmet patient need where we believe our product candidates can make the greatest difference for patients. 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 Doug for the Q&A portion of this afternoon's call, and remind you that CMO Salim Yazji is also on with us for the Q&A.
spk05: Thank you. Ladies and gentlemen, at this time, we will be conducting a question and answer session. If you'd like to ask a question, you may 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. Our first question comes from the line of Hartaj Singh with Oppenheimer. Please proceed with your question.
spk06: Great. Thank you. Thanks for the update, Jim and team. And just a couple of quick questions. Jim, I know that when you presented and Celine and everyone had presented the phase three design for Zolivertumab 301 a couple of months ago, you'd also talked about Zolivertumab 302 aspect to that. How are you thinking about that? You know, that's the, I guess that's the arm for the patients that have progressive disease, the run-in patients on ibrutinib. So just what are you thinking about that? And I just got a couple of quick follow-up questions after that.
spk04: Sure. I'll start, and Celine can comment as well. The 302 study you're referring to is one of the really novel aspects of our registration study design because during the four-month run-in or enrichment portion of the study where patients receive single-agent ibrutinib, a percentage of those patients will progress on ibrutinib. And so they're already in our study. They're already well documented with disease parameters, medical history, and everything. And so to give them the opportunity to see if their disease can be resensitized to ibrutinib with zolivertamab therapy, it's a very convenient and incrementally inexpensive way to test for impact of Xelavir in this resistant disease. So we're still planning to conduct that part of the study as well. And since it's open label, that would also give us an opportunity to talk about the results in real time or at medical conferences without having to wait for the blind to be broken in the main 301 study. Salim, do you want to add anything to that?
spk00: Great, great.
spk06: And then the other question I would have is just, you know, on 808, the CAR-T therapy, you know, Jim, if you can just kind of describe, you know, once you file the IND in mid-2022, what's the sort of clinical program, you know, setups that we can look forward to? I mean, basket studies, certain tumor types, you know, hematology versus solid tumors. Just what are your thoughts on what that could look like in the second half of this year?
spk04: Go ahead, Slane.
spk00: Yeah. So, Herthage, this will be mainly in hematological malignancies as a first in human study. And specifically, we're going to do a dose escalation in lymphoma, B-cell lymphoma patients. Once we reach our recommended phase two portion, then we can expand to other cohorts as well.
spk06: Okay. Got it, Salim. So, I mean, just so I'm clear, it'll be hematologic malignancies with the cohorts, meaning you'll have a basket of patients with different types of tumor types and then pick the ones you want to dose expand into after you get into your recommended phase two dose?
spk00: So, in the dose escalation, we would have only B-cell lymphoma, including diffuse large B-cell lymphoma, MCL, and maybe other aggressive lymphomas. That's in the dose escalation. Now, in the expansion cohort, we will expand in those patient populations for sure, but also we may open other indication and hematological malignancies, like maybe, for example, multiple myeloma or others.
spk06: And, Celine, is there any sort of pathway that you see with the CAR-T program whereby there's some tumor type you're looking at where the unmet need is high enough that, you know, if you see a good signal in dose escalation and you get into dose expansion, that that could actually form the basis for potential accelerated approval type scenario? I know that's low probability, but just any thoughts there?
spk00: Yeah, absolutely. I mean, I think we will, as you know, since this is going to be, again, dose escalation and open label, we're going to be looking into signal as we go. And, you know, if we see that something could be a possibility to get a quick, maybe quick approval or escalated approval, we will go after that for sure.
spk06: Yeah, and these would be patients that are later in general therapy than what the ROR1 antibody would have seen, right? Dilivertamab would have seen.
spk00: Yeah, absolutely. And as Jim mentioned, this will be in relapsed refractory hematological malignancy, which is probably a little bit later line of therapy, including patients who have failed CD19, CAR-T, where there's a huge medical need there as well.
spk06: And then last question is just when do you see filing the IND for ONCT 534?
spk04: So we haven't guided to the timing of that IND yet, Hartaj. And the reason is that, like other people, we're experiencing some supply chain uncertainty, including things such as slots for manufacturing activities and availability of animals and equipment for toxicology studies. So this is an area where there's still some continuing impact from COVID. So we just haven't been specific yet. And when we have greater clarity around that, timing of the IND enabling work, then we will lay that out.
spk06: Great. That makes sense, Jim. Thank you all for the update. Really appreciate it.
spk04: Thank you.
spk05: Our next question comes from the line of Carl Burns from Northland Capital. Please proceed with your question.
spk03: Thanks for the question and congratulations on your progress. With respect to ZLO 301 and 302 studies, How many sites do you anticipate recruiting or participating in those studies? I think before you were looking at around 50. And I guess my question is, has that changed given what's going on in Eastern Europe? Thanks.
spk04: Go ahead, Salim.
spk00: Yeah, Carl, I think we're monitoring the situation very closely. And, you know, the short answer, yes, we're trying to look into additional sites and especially monitoring Eastern Europe now is kind of a little bit, you know, difficult to recruit there. So, yeah, we may go a little bit beyond that, yeah.
spk04: Great, thanks. That's helpful. Thank you, Carl.
spk05: Our next question comes from the line of Kavari Pullman with BTIG. Please proceed with your question.
spk02: Hi, yeah, thanks. Good afternoon. This is Brian for Caveri, and thanks for the update, and thanks for taking our question. Just one for me regarding the use of Zolivertumab and CRPC. Is the WENT5A signaling pathway providing the main biology and rationale for this trial, and is it really ROAR1-driven? Our understanding is that ROAR2 is also a receptor for WENT5A. Thank you.
spk04: Hi, Brian, and thank you for standing in for Kaveri today. So the ROR1 and ROR2 can actually form a heterodimer, which can act as a receptor for Wnt5a. And so the ROR2 is, for us, kind of in the background. We're not targeting it because First of all, our antibody doesn't target ROAR2, and it's also harder to target ROAR2 selectively on tumors because it has a broader distribution on normal tissues. So the ROAR1 is highly expressed on prostate cancer. That's part of the rationale. The other is some very interesting data out of UC San Diego that shows that in the bone tumor microenvironment, the prostate cancer bone metastasis, that Wnt5a is one of the absolutely most highly overexpressed proteins. And so we see the receptor for Wnt5a, we see the Wnt5a, and that forms a nice rationale for prostate cancer.
spk01: Excellent.
spk02: Thank you so much for the very thorough answer, and thanks for taking the question.
spk04: You're welcome, Brian.
spk02: Thank you.
spk05: Our next question comes from the line of Kumar Raja with Brookline Capital Markets. Please proceed with your question.
spk07: Hi, I'm for Kumar. Thanks for the update. Could you provide some color to the 216 program? What is the strategy there to take it further? I mean, are you exploring collaborations or partnerships? And also, there were two patients that demonstrated CR. I mean, how are they doing now? And are there any other patients that are showing a similar response? Thank you.
spk04: I'll let Celine comment on the patients first.
spk00: Yeah, so we still have two patients that are still in CR. One has been off treatment and continues to be in CR after eight months of therapy. And the other patient is still on still CR on therapy. And we're going to continue giving the drug to this patient and maybe a compassionate use program since the CR is still durable.
spk04: Yes, and so as far as the program is concerned, we have, as we've announced, we're focusing our clinical programs, particularly on the zolivertumab phase 3 study, However, we do have an NIH grant with which we are collaborating with some academic investigators, including the discoverer of this form of AIDS inhibition, Jeff Turetsky, to do further work on the mechanism. The puzzle for us is that we are inducing these dramatic responses but only in a very small percentage of cases. And so we feel that it's necessary to know more about the mechanism. And so we have a non-diluted source of funding for that research. There is an open IND to continue to study TK216, OX216 in China through our collaborator, Shanghai Pharma. and we expect that study in Ewing sarcoma to open soon, and we expect they'd be doing some additional biomarker work and such to try to understand mechanistically what's occurring.
spk07: Thank you. That is useful. And also, what's the cutoff date going to be for the Phase I to ASCO data readout, and how many patients do you expect to include in that And what are the expectations in terms of pointed points like progression-free survival and so on? Thank you.
spk04: Were you asking the cutoff date?
spk07: Yeah.
spk04: Yeah. So as you can imagine, the posters are due to ASCO on May 16th. And so... We've tried to go as late as we can and still process the information. The contents of what we're going to present are still embargoed by ASCO, but there would be updated information compared to the ASH meeting for both CLL and mantle cell, including a more mature look at progression-free survival and also further look at... interesting subset analyses.
spk07: Okay, thanks. And finally, with regards to the Dana-Farber collaboration, could you please provide some color to the kind of agreement this is? And, you know, any other details with regards to the kind of capacity they have and the timelines of manufacturing? And when do you think you'll have the first batch ready? Thank you.
spk04: Thank you. So it is a collaboration and manufacturing agreement. You may recall that we're using a benchtop processing system called the Miltigny Prodigy, and that's technology that the group at the Dana-Farber have quite a bit of experience with, and they own their own Prodigy equipment. And so... We expect that by the time that we submit our IND that several performance characterizing runs will have been performed at the Dana-Farber and that they will be ready to manufacture as soon as sites are open and able to enroll patients. There will be, they have indicated that they can handle capacity both from sites in the Harvard system and sites outside of Massachusetts. And so we're very happy with their apparent capacity here for our phase one program.
spk07: Thank you so much for getting my questions.
spk04: Thank you for your questions. We appreciate your call today.
spk05: There are no further questions in the queue. I'd like to hand the call back to management for closing remarks.
spk04: Thank you, everybody. This is Jim Breitmaier. And so on behalf of Richard Vincent, Celine Yazgi, and everyone at Internal, I thank you for your interest and participation today. Have a good day, and we look forward to catching up with you in the future.
spk05: Ladies and gentlemen, this does include today's teleconference. Thank you for your participation. You may disconnect your lines at this time, and have a wonderful day.
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