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spk08: Welcome to the Guardies of Oncology First Quarter 2024 Financial Results and Business Update Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone and you will hear an automated message advising, your hand is raised. Please be advised that today's conference is being recorded. I would now like to turn the conference over to Kiki Patel of Gilmourter & Group. Please go ahead.
spk09: Thank you, Operator. Joining us on the call today from Guardies of Oncology are Chief Executive Officer Mark Erlander and Chief Financial Officer Jamie Levine. During this conference call, management will make forward-looking statements including, without limitation, statements related to guidance, results, and the timing of data readouts for advanced clinical trials. These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties. Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. Factors that could cause results to be different from these statements include factors the company describes in the section titled, Risk Factors, in our annual report on Form 10K filed with the SEC for the year ended December 31, 2023. Cardiff Oncology undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations. With that, I turn the call over to Chief Executive Officer Mark Erlander. Mark?
spk12: Well, thank you, Kiki, and good afternoon, everyone, and thank you for joining our conference call for the first quarter of 2024 business update. It was less than a year ago that we announced that our clinical development plan for advanced intensive would focus on the first-line treatment of rat mutated metastatic colorectal cancer, or MCRC. The data we shared last August supported this move, and our focus on first-line MCRC addresses a large patient population, almost 50,000 new patients a year in the United States, for whom there have been no new therapies approved in 20 years. In the first quarter of 2024, three data sets added to the body of evidence supporting our first-line focus strategy. First was the Ensemble Data, which served as an independent and randomized data set that replicated the efficacy signals in Bavna-y patients observed in our Phase 1b2 trial. Second was our five posters presented at the annual meeting of the American Association of Cancer Research for AACR. And finally was the publication of data in the peer-reviewed journal, Clinical Cancer Research, from the Phase 1b portion of our Phase 1b2 K-RAS mutated MCRC trial. I want to emphasize our conclusion that the collective data released in Q1 strongly supports our findings that adding on vancetib to standard care, ovarian, and bevacizumab, which I will refer to as BEV, has significant efficacy in RAS-mutated MCRC patients that are Bavna-y, that is, patients that have had no prior treatment with BEV. Now during today's call, we have three topics to cover. First, I will provide a summary of the promising data we presented last month at AACR. Next, we will discuss our lead program in MCRC and provide updates around our ongoing CAR-TEP 004-5. And finally, we'll talk about our financial position that we disclosed today in our Form 10-Q. So let's begin. Last month, the American Association for Cancer Research held its 2024 annual meeting in San Diego, in which CAR-TEP oncology presented a total of five posters, all of which are available on our website. One poster described the design of our ongoing CAR-TEP 004-5. A second poster presented data that supports our first-line strategy in MCRC by providing new translational data from our Phase 1b2 trial and second-line K-RAS mutated MCRC. Three additional posters shared promising preclinical data in other cancer indications, including RAS wild-type MCRC, small cell lung cancer, and ovarian cancer, demonstrating the broad opportunity we see for our answer tips. I would like to highlight some of the important data we presented in the poster on our lead program in RAS mutated MCRC. In this poster, we presented both clinical data from the Phase 1b2 trial and subsequent data from preclinical studies that forms the basis of the scientific rationale for our clinical findings. We also demonstrated that BAB-NI patients within this trial had a higher objective response rate and a longer progression through survival. The additional preclinical data disclosed at AACR provides further evidence that on vancers of embed have their pharmacological effect at two different nodes of the hypoxia pathway. We hypothesized that on vancers of embed work in a synergistic manner, giving a one-two punch to the tumor. Our hypothesis was further strengthened by our preclinical in vivo data and three K-RAS mutated MCRC xenograft models. Combination treatment with on vancer tip plus bed resulted in significant superior anti-tumor activity compared to monotherapy with either agent. And importantly, the combination treatment also resulted in a greater decrease in tumor vascularization compared to either agent alone. This finding provides rationale for further exploration of the combination of on vancer tip and bed in additional indications where bed is FDA approved. Collectively, the clinical and preclinical data presented at AACR in RAS mutated second line MCRC provides further validation of our ongoing -DAP-004 trial. We believe on vancer tip will have a significant impact in the first line setting given that all patients are as naive. Now let's move on to our additional posters presented at AACR in therapeutic areas outside of our core focus of RAS mutated MCRC. Today, most of the data we have generated in an MCRC has been in RAS mutated patients and we are often asked if our therapy could work for patients who do not have a RAS mutation. At AACR, we shared encouraging preclinical data in RAS wild type MCRC, meaning these models were derived from patients who did not have a RAS mutation. Our preclinical study in RAS wild type MCRC patient derived venegraph or PBX model aimed to assess the efficacy of on vancer tip as monotherapy and in combination with the EGFR inhibitor, the tuximab, which is the standard care for RAS wild type MCRC patient. We evaluated models that were both sensitive to the tuximab and resistant to the tuximab. In summary, on vancer tip displayed robust anti-tumor activity as a single agent in tuximab sensitive and resistant PBX model. As for combination therapy, efficacy was enhanced when on vancer tip and tuximab were combined compared to monotherapy of either agent alone. In combination, on vancer tip and tuximab induced tumor stages of regression in 90% or 18 of the 20 PBX models. Overall, we are exceptionally pleased with our RAS wild type preclinical data presented at AACR as it emphasized that on vancer tip has broad spectrum activity in MCRC independent of RAS computational set. This provides sound rationale for us to consider future clinical trials in RAS wild type MCRC. I now would like to share the data we presented at AACR demonstrating on vancer tips anti-tumor activity across multiple tumor types outside of MCRC. If you recall, last September we shared clinical data from our investigator initiated trials in extensive stage small cell lung cancer where on vancer tip as a single agent demonstrated a confirmed partial response with 50% shrinkage of patient's tumor among the first seven patients treated on the trial. While we were impressed by on vancer tip single agent activity, we believe a combination strategy would be the optimal approach to treating this aggressive disease. At that time, we disclosed that our clinical path forward in small cell lung cancer would be the combination strategy of on vancer tip and pachyletaxel, which is one of the standards of care for second line small cell lung cancer. At AACR, we presented preclinical evidence that supports this clinical plan. In vitro, the combination of on vancer tip plus pachyletaxel synergistically inhibited tumor proliferation in cell lines for small cell lung cancer. In vivo, the combination was well tolerated and highly effective in cis-flatin sensitive and resistant PDX models for small cell lung cancer. These findings support the scientific rationale for a planned investigator initiated trial providing on vancer tip with pachyletaxel as a promising treatment strategy for extensive stage small cell lung cancer patients. Our final poster presented at AACR evaluated the combination of on vancer tip plus carboplatin or gem cytobine in high grade serious ovarian cancer models, where both of these agents are standard of care. In vitro, on vancer tip was synergistic in combination with carboplatin as well as with gem cytobine in an ovarian cell line. In vivo, both combinations demonstrated anti-tumor activity and platinum resistance ovarian cancer PDX models and were well tolerated. Overall, we believe that these data support the potential of on vancer tip to improve standard care treatment for platinum resistant ovarian cancer patients. At the moment, we are still determining our path forward in this indication. So in summary, the data we presented at AACR this year provided strong scientific rationale for the clinical development of on vancer tip across multiple tumor types and various combinations. And our Ras mutated MCRC data provided further validation of our lead program and our ongoing CARDICT 004 clinical trial. Now turning to our second agenda item, CARDICT 004 is our ongoing phase two trial evaluating first line patients with Ras mutated MCRC. On vancer tip is being added to the current standard care, which is either full berry plus bed or full full box plus bed. We plan to enroll a total of 90 patients who will be randomized to receive either 20 migs of on vancer tip plus standard care, 30 migs of on vancer tip plus standard care or standard care alone. We are working closely with our partner Pfizer Igniter who is conducting the clinical execution of the trial and we are highly confident in Pfizer's ability to operationally given their track record of success. Currently we have 24 activated clinical trial sites. In August of 2023, when we decided to move forward with the CARDICT 004 trials, we forecasted that they would be able to share additional data from the trial in the Q2 Q3 2024 time frame. As of today and based on the actual enrollment trends at our activated sites for the past few months, our expectation for the timing of an initial readout is now in the second half of this year or Q3 Q4. I want to make it clear that this timing for the readout is solely based on the pace of enrollment. We together with Pfizer Ignite feel confident in our ongoing site activation enrollment efforts and we believe that we have all the resources to meet this timing. We anticipate this initial top line data release will include objective response rate for approximately half of the 90 patients we expect to enroll in the trial. Now I would like to turn the call over to Jamie to discuss our third agenda item, our first quarter 2024 financial update.
spk05: Thank you, Mark. Earlier today we issued a press release summarizing our financial results for the first quarter ending March 31, 2024. You can also find additional information in our Form 10-Q for the first quarter filed with the SEC earlier today. Turning to our balance sheet, cash and short-term investments as of March 31, 2024 totaled $67.2 million and our cash used in operating activities was $7.7 million in Q1 2024. We believe that our current cash resources provide us with cash runway into the third quarter of 2025 which is well beyond the updated timing for the initial readout from the CARDIF 004 trial Mark just discussed. With that I'll turn the call back over to Mark.
spk12: Thank you, Jamie. Let me close the call by emphasizing our conviction in our clinical development strategy to add on Vancertib to the standard care in first line RAS mutated MCRC. We followed the data that was available at the time and with the ensemble clinical data and the AACR data announced this quarter our confidence continues to grow. And that brings us to where we are today, our ongoing CARDIF 004 trial for the treatment of first line RAS mutated MCRC. Overall, we believe that the initial data readout of CARDIF 004 has the potential to be an important value inflection point for CARDIF oncology and for the nearly 50,000 patients diagnosed with RAS mutated MCRC each year. We look forward to sharing an update on the trial later this year. With that, I will now open the call up for questions. Operator.
spk08: Thank you so much. And as a reminder, press star 1-1 to get in the queue and wait for your name to be announced. One moment while we compile the Q&A roster. One moment for our first question. It comes from Mark Fram with TD Cowan. Please proceed.
spk02: Thanks for taking my questions. Just start off on the tweak to guidance on when the interim data might become available. Can you just clarify how much of the small push out was really, you know, kind of the enrollment pace once sites are open versus maybe just some delays getting the sites up and running as quickly as you'd hoped?
spk12: Well, yeah, let me just, thanks Mark for the question. And let me just step back for a minute and just talk about the CARDIF 004 trial. Over the last month or so, Dr. Feroz Kibinibar, our chief medical officer, and I have been going across the country and visiting with the principal investigators that are participating in our trial. And Feroz has actually been taking them through the previous data in the phase 1b2 and the ensemble data. And what I would say to you universally is that there is a high amount of enthusiasm with all of the principal death scares we have met. And, you know, that reason for that is not only because of the actual data that they're seeing billied up to the trial that they're participating in now, but also that the on-vancer tip does provide a novel new option for first lines in a first line setting, whereas you know there have been no new therapies for 20 years. Also, one of the key things that makes them enthusiastic is the actual design of the trial because we're adding on-vancer tip, we're building it onto current
spk13: standard
spk12: of care and not replacing
spk13: standard of care.
spk12: And finally, also, there are no competing trials for a first line vasculatated NPRC. So as you know, as I was saying earlier in the call, you know, when we started, when we made the decision in the summer of 23 to basically start CARDIF 004, that's when we then announced in August of 23 prior to the trial started, the forecast to share data in the
spk10: Q2-Q3 timeframe
spk12: of 2024. Now that we've got several months of the enrollment and the pace of enrollment, we are able to now make a more accurate projection of the data share, and that is more in the Q3-Q4. And so I think one thing, last thing I'd say, Mark, is that, you know, why are we so confident of this timing? That's really because we are leveraging Pfizer's resources, Pfizer-Knight's resources, their techniques and their capabilities in multiple areas around the execution of this trial, and we are very confident of their ability to execute.
spk02: Okay, great. That's helpful. And then maybe just as we get to that data,
spk01: can you
spk02: review some of the scenario planning that you and the team are kind of going through in terms of the data? You know, I know it's not a formal statistical analysis there, but, you know, is there a scenario where, you know, it could get shut down either more kind of from a futility perspective or also on the other end of the spectrum, make you want to kind of accelerate LAMS to open up O5 even faster and not have to wait for all 90 patients?
spk12: Yeah, I mean, I think right now, of course, what we are saying is that we will be looking to share data, initial data in the Q3-Q4 time frame, and we should have approximately, you know, half the patients of the trial, approximately that, with at least one quote, baseline scan. I mean, one thing I would say about that time, and it's a great question, Mark, is that, you know, the 004 from the FDA's point of view is really a dose confirmation trial with Project Optimist. And so the faster we can get to the FDA with a dose, of course, the better off we are and better off we are as far as
spk11: our timelines going into our registrational trial.
spk00: Okay,
spk11: thanks.
spk08: Thank you. One moment for our next question, please. And it comes from the line of Joe Catanzaro with Piper Sandler. Please proceed.
spk03: Hey, everybody. Thanks for taking my questions here. Maybe first one with the slight push in the initial readout from 004. I'm wondering if there's a possibility of maybe seeing another cut of the Ensemble cohort before them, just getting longer follow-up and better sense of the durability of responses and how that's shaking out between, you know, the arms of the trial, the BevNaive, BevExperience. So any thoughts there would be helpful?
spk12: Yeah, thanks, Joe, for the question. I mean, as we sit here today, you know, we did announce the data on February 29th for the Ensemble trial, and we felt that that was a very robust data set that propelled us with even greater confidence into our 004. You know, as we sit here now, we don't have plans to have a continued follow-up of the Ensemble data.
spk03: Okay, thanks. And then maybe my follow-up is on the pre-criminal work at AACR and the wild type CRC scenario. You know, I recall years back the synthetic lethality idea of PLK1 inhibition in the context of mutant rats. It seems like you're sort of thinking outside of that, and you mentioned potentially exploring it. Maybe you could just elaborate whether there's opportunity to explore that clinically and think about that population of patients within the context of a potential future pivotal front line trial?
spk12: Yeah, great question, Joe. I'd say, you know, first of all, you know, when you look at rats wild type and rats mutant tumors and colorectal, those are very different beasts, very different animals in the sense of the biology. And so, you know, as you know, we have shown synthetic lethality in the rats mutant background. In rats wild type, I think it's a different biology, and I think that we are seeing a very interesting finding where we are combining with cetuximab. And so, I think as we sit here today, we are evaluating what kind of trial design that would be in the wild type setting, but we have not made any moves yet in that area. Our focus as we sit here today continues to be 004 and getting the data toward the registrational trial.
spk04: Okay, got it. That's all helpful. Thanks for taking my question.
spk13: No, absolutely. Thanks, Joe.
spk08: Thank you. One moment for our next question. It comes from Andy with William Blair. Please proceed.
spk14: Great. Thanks for taking our questions. A couple of quick ones from us, if you don't mind. So, in terms of clinical sites, I believe, Mark, you said 24 sites right now. I believe it was 20 before. And is your end goal being 30 total by the end of the enrollment completion?
spk12: Yeah. Thanks, Andy, for that question. So, you're right. As of today, we have 24. And our goal, actually, in working with Pfizer-Ignite is to activate 35 sites. And we are also looking at some additional sites. But one of the things to keep in mind with this is this is a very dynamic process in the sense that we continue to evaluate sites. And if a site is not performing, then that site will be replaced with another site. So, if the number is not always static, it's really more dynamic as we go through this trial and continue to activate sites.
spk14: Okay. That's helpful. Thank you. And just kind of follow up on Mark's question before. You mentioned about Project Optimus, two doses in the 004 study. Is it conceivable to bring two doses in the pivotal study? Is that a potential scenario? And I guess, you know, from an FDA perspective, beyond kind of confirmation of safety, efficacy, what else are they looking at before giving you the okay to start a pivotal study?
spk12: Right.
spk14: Thanks for
spk12: the question. Just to answer those questions kind of literally, first off, we don't expect to go into the registration trial of the two doses. We plan to have a single dose. And you're right. What the FDA looks for is really, is there a difference between the efficacy between the two doses? And is there a difference in the safety? Both those things, we will be continuing to evaluate not only using our existing data, but also the obviously the 004 data. And like I said to Mark, our goal,
spk06: you know,
spk12: the gate to the registration trial is this confirmation of dose with the FDA. So, of course, we are very focused on getting that as soon as possible.
spk14: Great. And maybe like my last question has to do with catalyst events. So, Jamie, you talked about Q3 2025 being the cash runway. You know, perhaps can you give us maybe a big picture view? Obviously, 004 study happening in second half of this year. Any other potential data readouts that you can expect in the first three quarters of 2025 that could, you know, allow us to better appreciate the clinical activity of Vanserjee?
spk12: That's a great question. We are not prepared at this point to set dates of some of the investigator initiated trials that we do actually have ongoing right now. Those could be potentially, but we're just not prepared to set put out in the public, okay, this is the time that we would announce data on those trials. But clearly, we are looking at those as well as we continue to keep our laser focused on the 004 trial.
spk14: Got it. I understand. All right. Thanks so much for answering all of our questions. Thank you, Andy.
spk08: Thank you. And we'll conclude the Q&A session as I see no further questions and have them back to Mark Erlander. Thank you.
spk12: Thank you, operator. And this concludes our conference call. Thank you once again, everyone, for joining us this afternoon. Have a good day.
spk08: Thank you. You may all disconnect. Update conference call. At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone and you will hear an automated message advising your hand is raised. Please be advised that today's conference is being recorded. I would now like to turn the conference over to Kiki Patel of Gilmourjian Group. Please go ahead.
spk09: Thank you, operator. Joining us on the call today from Cardiff Oncology, our Chief Executive Officer Mark Erlander and Chief Financial Officer Jamie Levine. During this conference call, management will make forward-looking statements, including without limitation, statements related to guidance, results, and the timing of data readouts for un-vancerative clinical trials. These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties. Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. Factors that could cause results to be different from these statements include factors the company describes in the section titled risk factors in our annual report on form 10K filed with the SEC for the year ended December 31, 2023. Cardiff Oncology undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectation. With that, I turn the call over to Chief Executive Officer Mark Erlander. Mark?
spk12: Well, thank you, Kiki, and good afternoon everyone and thank you for joining our conference call for the first quarter of 2024 business update. It was less than a year ago that we announced that our clinical development plan for advantages was focused on the first-line treatment of Rasputin and metastatic colorectal cancer or MCRC. The data we shared last August supported this move and our focus on first-line MCRC addresses a large patient population, almost 50,000 new patients a year in the United States for whom there have been no new therapies approved in 20 years. In the first quarter of 2024, three data sets added to the body of evidence supporting our first-line focus strategy. First was the ensemble data, which served as an independent and randomized data set that replicated the efficacy signals in Bavna youth patients observed in our Phase 1B2 trial. Second was our five posters presented at the annual meeting of the American Association for Cancer Research,
spk11: or
spk12: AACR. And finally was the publication of data in the review journal, Clinical Cancer Research, from the Phase 1B portion of our Phase 1B2 K-Rasputin MCRC trial. I want to emphasize our conclusion that the collective data released in Q1 strongly supports our findings that adding on vancetim to standard care, O'Ferry and Bevaciz-Met, which I refer to as Bev, has significant efficacy in RAS-retreated MCRC patients that are Bavna-y, that is, patients that have had no prior treatment with Bev. Now during today's call, we have three topics to cover. First, I will provide a summary of the promising data we presented last month at AACR. Next, we will discuss our lead program in MCRC and provide updates around our ongoing CARDS 004 trial. And finally, we'll talk about our financial position that we disclose today in our Form 10Q. So let's begin. Last month, the American Association for Cancer Research held its 2024 annual meeting in San Diego, in which Cardiff Oncology presented a total of five posters, all of which are available on our website. One poster described the design of our ongoing CARDS 004 trial. A second poster presented data that supports our first-line strategy in MCRC by providing new translational data from our Phase 1B2 trial and second-line KRAS-reutated MCRC. Three additional posters shared promising preclinical data in other cancer indications, including RAS wild-type MCRC, small cell lung cancer, and ovarian cancer, demonstrating the broad opportunity we see for our answer to. I would like to highlight some of the important data we presented in the poster on our lead program and RAS-reutated MCRC. In this poster, we presented both clinical data from the Phase 1B2 trial and subsequent data from preclinical studies that forms the basis of the scientific rationale for our clinical findings. We also demonstrated that Bavnaid patients within this trial had a higher objective response rate and a longer progression through survival. The additional preclinical data disclosed at AACR provides further evidence that Onvancerative and BED have their pharmacological effect at two different nodes of the hypoxia pathway. We hypothesized that Onvancerative and BED work in a synergistic manner, giving a one-two punch to the tumor. Our hypothesis was further strengthened by our preclinical in vivo data and 3K RAS mutant MCRC denograft models. Combination treatment with Onvancerative plus BED resulted in significant superior anti-tumor activity compared to monotherapy with either agent. And importantly, the combination treatment also resulted in a greater decrease in tumor vascularization compared to either agent alone. This finding provides rationale for further exploration of the combination of Onvancerative and BED in additional indications where BED is FDA approved. Collectively, the clinical and preclinical data presented at AACR in RAS mutated second-line MCRC provides further validation of our ongoing CARDF 004 trial. We believe Onvancerative will have a significant impact in the first-line setting given that all patients are BED-naive. Now let's move on to our additional posters presented at AACR in therapeutic areas outside of our core focus of RAS mutated MCRC. Today, most of the data we have generated in an MCRC has been in RAS mutated patients and we are often asked if our therapy could work for patients who not have a RAS mutation. At AACR, we shared encouraging preclinical data in RAS wild type MCRC, meaning these models were derived from patients who did not have a RAS mutation. Our preclinical study in RAS wild type MCRC patient-derived vena grap or PDX model aimed to assess the efficacy of Onvancerative as monotherapy and in combination with the EGFR inhibitor cetuximab, which is the standard care for RAS wild type MCRC patients. We evaluated models that were both sensitive to cetuximab and resistant to cetuximab. In summary, Onvancerative displayed robust anti-tumor activity as a single agent in cetuximab sensitive and resistant PDX models. As for combination therapy, efficacy was enhanced when Onvancerative and cetuximab were combined compared to monotherapy of either agent alone. In combination, Onvancerative and cetuximab induced tumor stages of regression in 90% or 18 of the 20 PDX models. Overall, we are exceptionally pleased with our RAS wild type preclinical data presented at AACR as it emphasized that Onvancerative have broad spectrum activity in MCRC independent of RAS mutational death. This provides sound rationale for us to consider future clinical trials in RAS wild type MCRC. I now would like to share the data we presented at AACR demonstrating Onvancerative's anti-tumor activity across multiple tumor types outside of MCRC. If you recall, last September we shared clinical data from our investigator initiated trials in extensive stage small cell lung cancer where Onvancerative as a single agent demonstrated a confirmed partial response with 50% shrinkage of patient's tumor among the first seven patients treated on the trial. While we were considering the combination strategy would be the optimal approach to treating this aggressive disease, at that time we disclosed that our clinical path forward in small cell lung cancer would be the combination strategy of Onvancerative and Paclitaxel which is one of the standards of care for second line small cell lung cancer. At AACR we presented preclinical evidence that supports this clinical plan. In vitro the combination of Onvancerative plus Paclitaxel synergistically inhibited tumor proliferation in cell lines for small cell lung cancer. In vivo the combination was well tolerated and highly effective in cis-flatin sensitive and resistant PDX models for small cell lung cancer. These findings support the scientific rationale for a planned investigator initiated trial providing Onvancerative with Paclitaxel as a promising treatment strategy for extensive stage small cell lung cancer patients. Our final poster presented at AACR evaluated the combination of Onvancerative plus Carboplatin or Gem-Citabine in high-grade serious ovarian cancer models where both of these agents are standard of care. In vitro Onvancerative was synergistic in combination with Carboplatin as well as with Gem-Citabine in an ovarian cell line. In vivo both combinations demonstrated anti-tumor activity in platinum resistance ovarian cancer PDX models and were well tolerated. Overall we believe that these data support the potential of Onvancerative to improve standard care treatment for platinum resistant ovarian cancer patients. At the moment we are still determining our path forward in this indication. So in summary the data we presented at AACR this year provided strong scientific rationale for the clinical development of Onvancerative across multiple tumor types and various combinations and our RAS mutated MCRC data provided further validation of our lead program in our ongoing CARDIP 004 clinical trial. Now turning to our second agenda item CARDIP 004 is our ongoing phase two trial evaluating first line patients with RAS mutated MCRC. Onvancerative is being added to the standard care current standard care which is either full berry plus Bev or full Fox plus that. We plan to enroll a total of 90 patients who will be randomized to receive either 20 mgs of Onvancerative plus standard care 30 mgs of Onvancerative plus standard care or standard care alone. We are working closely with our partner Pfizer Igniter who is conducting the clinical execution of the trial and we are highly confident in Pfizer's ability to operationally execute given their track record of success. Currently we have 24 activated clinical trial sites. In August of 2023 when we decided to move forward with the CARDIP 004 trials we forecasted that they would be able to share additional data from the trial in the -Q3-2024 time frame. As of today and based on the actual enrollment trends at our activated sites for the past few months our expectation for the timing of an initial readout is now in the second half of this year or Q3-Q4. I want to make it clear that this timing for the readout is solely based on the pace of enrollment. We together with Pfizer Ignite feel confident in our ongoing site activation enrollment efforts and we believe that we have all the right resources to meet this timing. We anticipate this initial top-line data release will include objective response rate for approximately half of the 90 patients we expect to enroll in the trial. Now I would like to turn the call over to Jamie to discuss our third agenda item our first quarter 2024 financial update.
spk05: Thank you Mark. Earlier today we issued a press release summarizing our financial results for the first quarter any March 31st 2024. You can also find additional information in our form 10-q for the first quarter filed with the SEC earlier today. Turning to our balance sheet cash and short-term investments as of March 31st 2024 totaled 67.2 million dollars and our cash used in operating activities was 7.7 million dollars in Q1 2024. We believe that our current cash resources provide us with cash runway into the third quarter of 2025 which is well beyond the updated timing for the initial readout from the CARDIF 004 trial Mark just discussed. With that I'll turn the call back over to Mark.
spk12: Thank you Jamie. Let me close the call by emphasizing our conviction in our clinical development strategy to add on Vansertum to the standard care in first line grasp mutated MCRC. We followed the data that was available at the time and with the ensemble clinical data and the AACR data announced this quarter our confidence continues to grow and that brings us to where we are today our ongoing CARDIF 004 trial for the treatment of first line grasp mutated MCRC. Overall we believe that the initial data readout of CARDIF 004 has the potential to be an important value inflection point for CARDIF oncology and for the nearly 50,000 patients diagnosed with grasp mutated MCRC each year. We look forward to sharing an update on the trial later this year. With that I will now open the call up for questions. Operator
spk08: thank you so much and as a reminder press star 1 1 to get in the queue and wait for your name to be announced. One moment while we compile the Q&A roster. One moment for our first question it comes from Mark Fram with TD Cowan please proceed.
spk02: Thanks for taking my questions. Let me just start off on the tweak to guidance on when the interim data might become available. Can you just clarify how much of the small push out was really kind of the enrollment pace once sites are open versus maybe just some delays getting the sites up and running as quickly as you'd hoped.
spk12: Well yeah let me just thanks Mark for the question and let me just step back for a minute and just talk about the CAR004 trial. Over the last month or so Dr. Feroz Kibinnibar our chief medical officer and I have been going across the country and visiting with the principal investigators of that are participating in our trial and Feroz has actually been taking them through the previous data in the phase 1b2 and the ensemble data and what I would say to you universally is that there is a high amount of enthusiasm with all of the principal desk heirs we have met and you know that reason for that is not only because of the actual data that they're seeing building up to the trial that they're participating in now but also that the on-vancer chip does provide a novel new option for first lines in the first line setting whereas you know there have been no new therapies for 20 years. Also one of the key things that makes them enthusiastic is the actual design of the trial because we're adding on that to we're building it onto current
spk13: standard
spk12: of care and not replacing
spk13: standard care
spk12: and finally also there are no competing trials for a first line brass mutated mpc. So as you know as I was saying earlier in the call you know when we started when we made the decision in the summer of summer of 23 to basically start a card of 004 that's when we then announced in August of 23 prior to the trial started the forecast to share data in the
spk10: q2 q3
spk12: 3 time frame of 2024. Now that we've got several months of the enrollment and the pace of enrollment we are able to now make a more accurate projection of the data share and that is more in the q3 q4 and so I think one thing last thing I'd say Mark is that you know why are we so confident of this timing that's really because we are leveraging Pfizer's resources Pfizer Ignite's resources their techniques and their capabilities in multiple areas around the execution of this trial and we are very confident
spk11: of their ability to execute.
spk02: All right great that's helpful and then maybe just as we get to that data
spk01: can you
spk02: review some of the scenario planning that you and the team are kind of going through in terms of the data you know it's it you know I know it's not a formal statistical analysis there but you know is there a scenario where you know it could get shut down either more kind of from a utility perspective or also on the other end of the spectrum make you want to kind of accelerate blams to open up 005 even faster and not have to wait for all 90 patients.
spk12: Yeah I mean I think right now of course what we are what we're saying is that we will be looking to share data initial data in the Q3 Q4 time frame and we should have approximately you know half the half the patients of the trial approximately that with at least one post baseline scan. I mean one thing I would say about that timing it's a good it's a great question Mark is that you know the 004 from the FDA's point of view is really a dose confirmation trial with Project Optimist and so the faster we can get to the FDA with a dose of course the better off we are and better off we are as far
spk11: as our timelines going into our registration trial.
spk00: Okay thanks.
spk08: Thank you one moment for our next question please. Any comments on the line of Joe Catanzaro with Piper Sandler please proceed.
spk03: Hey everybody thanks for taking my questions here. Maybe first one with the slight push in the initial readout from 004. I'm wondering if there's a possibility of maybe seeing another cut of the ensemble cohort before them just before then just getting longer follow-up and better sense of the durability of responses and how that's shaking out between you know the arms of the trial the Bev Naive Bev experience. So any thoughts there would be helpful.
spk12: Yeah thanks thanks Joe for the question. I mean as we sit here today you know we did announce the the data on February 29th for the ensemble trial and and we felt that that was a very robust data set that propelled us with even greater confidence into our 004. You know as we follow up of the ensemble data.
spk03: Okay thanks and then maybe my my follow-up is on the pre-criminal work at AACR on the RAS wild type CRC scenario. You know I recall years back the synthetic lethality idea of PLK1 inhibition in the context of mutant RAS. It seems like you're sort of thinking outside of that and you mentioned potentially exploring it. Maybe you could just elaborate whether there's opportunity to explore that clinically and think about that population of patients within the context of a potential future pivotal frontline trial.
spk12: Yeah great question Joe. I'd say you know first of all you know the when you look at RAS wild type and RAS mutant tumors and colorectal those are very different beasts of very different animals in the sense of the biology and so you know as you know we did we have shown synthetic lethality in the RAS mutant background. In RAS wild type I think it's a different biology and I think that we are seeing a very interesting finding where we are combining with cetuximab and so I think as we sit here today we are evaluating what kind of trial design that would be in the wild type setting but we haven't you know we have not made any move yet in that area. Our focus as we sit here today continues to be 004 and getting the data toward the registrational trial.
spk04: Okay got it that's all helpful thanks for taking my questions.
spk08: Oh
spk04: absolutely thanks Joe.
spk08: Thank you one moment for our next question and it comes from Andy with William Blair please proceed.
spk14: Great thanks for taking our questions a couple of quick ones from us if you don't mind. So there are critical sites I believe Mark you said 24 sites right now I believe it was 20 before and is your end goal being being 30 total by the end of the enrollment completion?
spk12: Yeah thanks thanks for that question so you know you're right as of today we have 24 and our our goal actually in working with Pfizer-Ignite is to activate 35 sites and we are also looking at some additional sites but one of the things to keep in mind with with this is this is a very dynamic process in the sense that we continue to evaluate sites and if the site is not performing then that site would be replaced with another site so if you know the number is not always static it's really more dynamic as we go through this trial and continue activating sites.
spk14: Okay that's helpful thank you and just kind of follow up on Mark's question before you mentioned about project optimists two doses in the 004 study is it is it conceivable to bring two doses in the pivotal study is that a potential scenario and I guess you know from an FDA perspective beyond kind of confirmation of safety efficacy what else are they looking at before giving you the okay to start a pivotal study?
spk12: Right thanks for the question it's just to answer those questions kind of literally first off we don't expect to go into the registrational trial of the two doses we plan to have a single dose and you're right what the FDA looks for is really is there a difference between the efficacy between the two doses and is there a difference in the safety both those things we will be continuing to evaluate not only using our our existing data but also the obviously the 004 data and like I said to Mark our goal you know our the gate to the registrational trial is this confirmation of doses with the FDA so of course we are very focused on getting that as soon as possible.
spk14: Great and maybe like my last question has to do with catalyst events so Jamie you talked about Q3 2025 being the cash runway you know perhaps can you give us maybe a big picture of you obviously 004 study happening in the second half of this year any other potential data readouts that you can expect in the first three quarters of 2025 that could you know allow us to better appreciate the clinical activity of on master tip.
spk12: That's a great question we're not prepared at this point to set dates of some of the investigator initiated trials that we do actually have ongoing right now those could be potentially but we're just not prepared to set put out in the public okay this is the time that we would announce data on those trots but clearly we are looking at those as well as we continue to keep our laser focused on the 004.
spk14: Got it I understand. All right thanks so much for answering all of our questions. Thank you Andy.
spk08: Thank you and I will conclude the Q&A session as I see no further questions and hand them back to Mark Erlender. Thank you.
spk12: Thank you operator and this concludes our conference call. Thank you once again everyone for joining us this afternoon. Have a good day.
spk08: Thank you. You may all disconnect.
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