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spk01: Greetings and welcome to the internal Therapeutics Inc. Q3 2022 financial results 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 zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Mr. Richard Vincent, Chief Financial Officer. Please go ahead, sir.
spk02: Thank you very much, Ryan. 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. Selene Yazchi. Today's call includes a business update, and discussion of our results for the third quarter ended September 30, 2022, which will be followed by Q&A. Today's press release and the replay of today's call will be available on the investor relations section of Moncturnal's website for at least the next 30 days. Our 10Q for the third quarter 2022 is also available 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, such as our business and product development strategies, the timing of initiation of our preclinical and clinical studies, the potential for our Zillow 301 Phase III study to support a BLA submission, the timing of planned interim updates, the timing of our regulatory filings and submissions, and expected pre-IND feedback. 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, November 3rd, 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.
spk07: Thank you, Rich, and good afternoon, everyone. At Acturnal, we are advancing a focused and robust product pipeline with clinical and preclinical product candidates that target cancers for patients with unmet medical needs. The third quarter of 2022 was a pivotal one for Acturnal. First, we announced that we initiated the Xela-301 study, our Phase III clinical trial of Xelavertimab, aduabrutinib in patients with mantle cell lymphoma. As a reminder, Xela-301 is the first registrational study for a therapeutic targeting the important RoR1 pathway, which we believe can play a key role in addressing unmet needs in multiple hematologic and solid tumor indications. Second, we announced the receipt of a study may proceed letter from FDA just 30 days after submitting our IND application for a phase one, two dose escalation study of OCT808, our lead autologous CAR-T product candidate targeting RoR1. This study will be conducted in the U.S. in patients with aggressive B-cell lymphoma, including those who have failed previous CD19 CAR treatment, which represents a significant medical unmet need. Also this morning, we announced that results from our ongoing Phase I-II clinical trial with zolivertimab plus ibrutinib in patients with mantle cell lymphoma or chronic lymphocytic leukemia were accepted as an oral presentation at the American Society of Hematology annual meeting in New Orleans in December of this year. We are very honored by this selection, and we look forward to presenting updated study results, including extending the encouraging progression-free survival data for patients with CLL and p53 alterations receiving Xelabertamab and Abrutinib that we first presented at ASCO 2022. Finally, OCT534, our lead candidate for the Dual Action Androgen Receptor Inhibitor, or DARI program, continues to advance towards an IND filing, and we expect to have pre-IND feedback from the FDA in December of this year. We are optimistic that OCT534 may be a differentiated and novel treatment alternative for patients with advanced prostate cancer, as we believe it interacts with both the end-terminal domain and the ligand binding domain of the androgen receptor, inhibiting its function and inducing its degradation. Preclinical data has shown that OCT534 exerts anti-tumor activity in clinically relevant treatment-resistant prostate cancer models, including those with AR amplification and zalutamide resistance or androgen receptor splice variants, such as ARV7. each of which represents a significant unmet medical need for patients with prostate cancer. On the corporate front, we continue our focus on execution as we remain vigilant on our cash and resource usage, and we estimate we can fund our operations into the first half of 2024 with funds currently available. Let me now turn the call over to Uncterno's CMO, Salim Yazgi, to discuss the status of our Phase III study, ZELO-301, and the plans for the first inpatient study of our autologous CAR-T ANCT-808. Salim?
spk04: Thank you, Jim. Good afternoon, everyone. We are very excited that our Phase III study, ZELO-301, is now underway. We are focusing on activating sites around the world. As we are estimating, we will open between 50 to 100 sites to meet our enrollment target. We believe sites outside of the United States will play a key role in achieving this goal, and we expect to open the first sites in these regions in the first quarter of next year. We are also very excited to announce that our abstract from the ongoing Phase I-II study, CIRM001, was accepted for all representation at the upcoming ASH this year in December. Now, turning to Onc808, the lead candidate of our autologous ROR1 targeting CAR-T program. We are excited that our IND submission was cleared by the FDA in 30 days. And I would like to thank our partners, Lentigen, Multani Biotech, and the Dana-Farber Cancer Institute and its cell manipulation core facility for their support in helping us achieving this important milestone. The UNC808 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 previous CAR-T treatment. And both safety and efficacy results will be taken into account to select the recommended Phase 2 dose. After the initial dose escalation, additional dose exploration, and the evidence of efficacy will be evaluated in the expansion cohorts. And we expect to be able to report on key efficacy, safety, and PK endpoints. We expect to initiate the Phase 1-2 study for our UNC808 in the first quarter of 2023, and expect to share initial data later next year. I will now turn the call over to our CFO, Rich Vincent, to review our financial results and upcoming milestones.
spk02: Rich? Thank you, Celine. Our revenue is derived from two research and development grants from the National Institutes of Health, or NIH. 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. Our grant revenue for the third quarter ended September 30, 2022 was 0.4 million. Our total operating expenses for the third quarter ending September 30, 2022 was 11.7 million, including 2 million in non-cash stock-based compensation expense. Research and development expenses totaled 8.4 million, and general and administrative expenses totaled $3.3 million. Net loss for the second quarter was $11.1 million for a loss of 0.21 per share, basic and diluted. Cash flows from financing activities through the nine months ended September 30, 2022, totaled $7.6 million, which was generated from the issuance of approximately 6.1 million shares of common stock under our ATM program with Jeffries as our sales agent. As of September 30, 2022, we had $70.6 million in cash and cash equivalents and no debt. We believe these funds will be sufficient to support our planned operating activities in this first half of 2024. We have and will continue to manage our cash and all other resources deliberately. As of September 30, 2022, we had 55.5 million shares of common stock outstanding. With respect to upcoming milestones, For our Zilabertamab program, we expect to open sites outside of the U.S. for our global registrational Phase III study, ZILA 301, in the first quarter of 2023, and to provide an interim clinical data update from our Phase I-II study of Zilabertamab plus ibrutinib in patients with MCL and CLL as an oral presentation at the 64th American Society of Hematology Annual Meeting and Exposition in December 2022. For ONC 808, our lead autologous War 1 CAR T cell therapy candidate, we plan to initiate our Phase 1-2 study in patients with aggressive B-cell lymphoma in the first quarter of 2023 and to present an initial clinical data readout in 2023. For ONC 534, our lead DARI product candidate, we expect to receive pre-IND feedback from the US FDA in December of 2022. With that, I will turn the call back over to Jim.
spk07: Thank you, Rich. This past quarter, the Uncturnal team continued to meet or exceed its goals. We are excited to have one Phase III program active and a second exciting Phase I clinical program for Unct 808 opening, cementing our leadership in the promising ROAR I space, along with a very promising asset for patients with prostate cancer, which is in late IND enabling studies. We plan to continue to use our capital and resources efficiently, as we have, and we will advance our focused pipeline towards significant value inflection points that we believe will make a difference for patients suffering from hematologic malignancies and prostate cancer. We look forward to key events in the coming quarters, especially the continued rollout of our global phase three study and advancing our prostate cancer program toward the clinic. 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 Ryan for the Q&A portion of this afternoon's call.
spk01: Thank you. Ladies and gentlemen, at this time, we will 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 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 keys. Ladies and gentlemen, we will wait for a moment while we poll for questions. Our first question comes from the line of Hartaj Singh from Oppenheimer and Company. Please go ahead.
spk05: Great. Thanks for the updates, Jim, Rich, and everyone. And just a couple of questions. One, you know, with the announcement now on 808 going into clinical trials, just a little bit more color around it, you know, around B-cell lymphoma, dose escalation, dose expansion. I mean, what, you know... with the three plus threes, it's sort of on a monthly basis, you know, the car to your tolerance product. I imagine there's a vein to vein time, just, you know, what could be the centers, just some more meat on those, on those bones, Jim. And then I just got a couple of follow-up questions off that.
spk07: Thank you, Hartaj. So we are, we're pretty excited about our manufacturing process. And we have, we've selected a, automated benchtop processing system called the Prodigy that a lot of people are getting excited about. And we have found that we get very good yields of exactly the kind of T cell that we're hoping for in an eight-day process with normal volunteer cells. Now, of course, we don't have experience yet with harvesting and making CAR T cells from patients. But if we duplicate our preclinical work here, we would have eight days of manufacturing, and then we're getting our product release as short as possible. So we'll be somewhere in the 14 to 21-day range for vein-to-vein, which is pretty good for a Phase I study. And we will be enrolling patients who have either failed CAR-T therapy previously or were not candidates or refused the available CD19 CAR-Ts.
spk05: Yeah. No, that's great, Jim. And Jim, you know, Zolivertimab is going up for MCL, CLL. You know our ROR1 is our target very well. What other potential cancers could you envision with the autologous CAR-T product in the future?
spk07: It's a great question. And so our initial thought, our first additional candidate, we think could be CLL. And there's been some work in the CLL field with CAR-T. but not as much as there has been in the aggressive lymphomas. And ROAR1 is very highly expressed and essential to the biology of CLL. Multiple myeloma is another possibility. AML, another possibility. So there's really quite a few liquid tumor options available. And then we intend to expand into solid tumors probably with the addition of some co-treatments or some additional technology in the car. And we are particularly excited about lung cancer and prostate cancer for ROR1 expressing targets.
spk05: Great. Thank you, Jim. And my last question there is you kind of foreshadowed a little bit, which is that you've mentioned previously that ROR1 is a good target for combining with other you know, other modalities also, zilivertimab, you know, combined with ibrutinib and seen some good, you know, even a decrease in toxicity of BTK inhibition. Could you do that with the autologous with ONCT-808? Is that possible? And also then move up in earlier lines of therapy?
spk07: Yeah, I think combining the antibody with the CAR-T could be tricky because the antibody might block the axis of the CAR-T to the ROR1 on the cell surface. So you could do it with a different ROR1 binding antibody. We have a couple of those in the freezer. But there's also, there's some interesting work being done combining other agents with CAR-T. We've taken particular note of studies that are adding ibrutinib to CAR T therapy. Not only would the ibrutinib have an effect on the tumor, but it also has an interesting effect on T cells itself through a form of tyrosine kinase that's expressed in human T cells.
spk05: Great. Thank you, Jim. I'll jump back in the queue.
spk07: Thank you, Hartaj. Always nice to catch up with you.
spk01: Thank you. Our next question comes from the line of Carl Burns from Northland Capital Markets. Please go ahead.
spk06: Thanks for the question, and congratulations on your progress with three candidates advancing here. In addition to the prepared comments that you made, do you have any updates with respect to the investigator-sponsored studies? I know those are largely out of your control, and then I have a follow-up as well. Thanks.
spk07: Salim, go ahead about the ISDs.
spk04: Yeah, sure. So we actually have an active IST that just recently opened at UCSD using ROR1 in combination with docetoxel for patients with castration-resistant metastatic prostate cancer. And so far, actually, the IRB, we have an IRB approval, but we don't have any patients yet. So hopefully we get patients actually soon. But as you said, this is out of our control. It's an investigator-sponsored study.
spk06: Great. Thank you. And obviously there's a lot of excitement around all the programs, but just focusing a bit on 534, what might be a realistic expectation in terms of a timeline into the clinic? and when there might be first aid on that program. Thanks.
spk07: Thank you, Carl. I'll start with that. And so we haven't been guiding to that yet. And we had an interesting COVID-related experience where the type of beagle dog that is used in toxicology studies for prostate cancer drugs was suddenly unavailable. And so we think what happened was that the breeders stopped breeding during COVID and then didn't catch up. And so the team has worked around that, and the final toxicology studies are getting underway right now. And so we are optimistic that we're going to have We're going to have some back and forth with the FDA, a virtual pre-IND meeting in the fourth quarter, and then intend to get the IND in and the study open just as soon as we can. So, and Salim, you might mention some of the reactions we got from prostate cancer experts at the Prostate Cancer Foundation meeting.
spk04: Yeah, yeah, absolutely, Jim. So last week, actually, we were in the Prostate Cancer Foundation meeting where, you know, we met some of our advisors and key opinion leaders that's very well known in the world to be prostate cancer experts. And, you know, we went through the program and through the synopsis and what we're trying to do. And there was excitement around what we're trying to do and also around the program from, you know, people who are very well known as one of the top-notch key opinion leaders in the process of cancers.
spk06: So that's great. It also seems that given the urgent medical need for the indication that it would be very likely that it would be, you know, potential breakthrough with priority review status involved, I mean, I know you probably don't want to comment on that at the moment, but a very exciting program. Thanks.
spk07: Thank you, Carl.
spk06: Absolutely. Thanks.
spk01: Thank you. Our next question comes from the line of Robert Burns from HC Wainwright. Please go ahead.
spk03: Hey, guys. Thanks for taking my questions, and congrats on the quarter. I guess a little color around sort of what you view as the benchmark for ONCT 808 in that CD19 directed CAR T experience patient population. And then second question, obviously, you know, we saw the data from VILOS BIOS, VLS 101 in 2020 with that 80% objective response right in DLBCL, and I was just curious whether those five patients, did they receive CD19 directed CAR T therapy in that data set?
spk07: So, Rob, can you repeat the second question? Which patient specifically?
spk03: Yeah. Remember the data set for VLS 101 at ASH 2020? In BLBCL, there were five patients. They had 80% objective response rate. I was just curious whether those patients had CD19-directed CAR T therapy prior to receiving BLS-101, because I'm just trying to get a sense of what the benchmark is going to be in the CD19, post-CD19 CAR T patient population.
spk07: Yeah, that's a great question. And so I'm, you know, I'm... stressing my memory here to remember that first presentation of data. I do know, I do recall that when the data from the VLS 101 program was updated at the ASCO meeting, that the response rate in DLBCL was lower. I think it was closer to 40 or 50% in a larger patient set. while you're right, it had been four out of five patients or 80% the six months before. I think all of those patients were BTK experienced and I don't recall if they were also CAR T. But to answer your question, we do think that once you pass CD19 treatment, the progression-free survival and overall survival are very low, both measured in months. And so we believe that a significant clinical response rate will be, that people will pay attention to it and that it will support going forward with the program exactly what that percentage is It's a little hard to predict because, of course, we'll be exploring various doses at the same time we're getting a look at the potential efficacy outcomes.
spk02: Awesome. Thank you.
spk01: Thank you. Our next question comes from the line of Kenny Stodge from CTIG. Please go ahead.
spk00: Hey, internal team. This is Kenny on for Kaveri. Thanks for taking my question. I guess maybe to drill down on the ZLO 301 trial, I'd love to maybe get an update in terms of, you know, how many clinical trial sites are up and running, and if you could share any color in terms of what you're seeing, you know, for early enrollment trends. It'd be great to sort of get a sense of, you know, the pacing of enrollment there. Thanks.
spk07: Yeah, thank you, Kenny. Kenny, I'll turn you over to Salim.
spk04: Yeah, yeah. Thank you, Kenny. I mean, I think at this moment, we are not guiding for such a, you know, operational details. As you know, we're trying to do everything possible to open those sites and get enrollment goal met.
spk00: Got it. Thank you. And then I guess just one quick follow up. So on the 302 study, Is that a study that you plan to conduct in parallel and at the same sites, or is it mostly going to be a separate trial, you know, based on patients that don't screen into the 301 trial? Thanks.
spk04: Yeah, so the initial thoughts would be actually for the patients who enrolled in 301 and trying to capture those early progressors during the monotherapy brucinib.
spk06: Thanks a lot.
spk02: Sure.
spk01: Thank you. Ladies and gentlemen, we have reached the end of the question and answer session. And now I would like to turn the conference over to Mr. I'm sorry, Dr. James Breitmaier, President and CEO for closing comments.
spk07: Thank you, Ryan. And I would like to thank everybody. for your time and interest in joining us today for our third quarter update on our business and earnings. We appreciate your interest in the company and look forward to staying in touch with you. We hope you all do well. And with that, I will say thank you and goodbye.
spk01: Thank you, sir. The conference has now concluded. Thank you for your participation. You may now disconnect your line.
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