This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk04: Ladies and gentlemen, thank you for standing by. Welcome to the Onconova Therapeutics fourth quarter and full year 2022 financial results and business update conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a question and answer session. To ask a question at that time, please press star followed by the number one on your touchtone phone. If anyone has any difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this call is being recorded today, March 16th, 2023. At this time, I would like to turn the call over to Bruce Mackle of Lifestyle Advisors.
spk06: Thank you, operator, and welcome everyone to Oncanova's fourth quarter and full year 2022 financial results and business update conference call. Earlier this afternoon, Oncanova issued a press release reporting its financial results and business progress. If you have not seen this press release, it is available in the Investors and Media section of the company's website at Ancanova.com. Following my introduction, we will hear from Ancanova's President and CEO, Dr. Steve Fruchman, Chief Medical Officer, Dr. Mark Gelder, and Chief Operating Officer and Chief Financial Officer, Mark Guerin. These prepared remarks will then be followed by a question and answer session. Before we begin, I would like to remind everyone that made during this conference call will include forward-looking statements under the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, which involve and uncertainties that can cause actual results to differ materially. Forward-looking statements speak only as the date they are made, as the underlying facts and circumstances may change. Except as required by law, Ankanova disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances. For more information on forward-looking statements, please review the disclaimer in today's press release and the risk factors in the company's SEC filings. With that, I will now turn the call over to Ankanova's President and CEO, Dr. Steve Fruchman.
spk08: Thank you, Bruce, and thanks to all who have joined the call today.
spk07: We are entering a very exciting time for AnkaNova as our recent progress has us moving toward anticipated milestones that we believe will serve as key value inflection points. I'll begin today by providing the highlights of this progress before turning the call over to Dr. Mark Gelder, our chief medical officer, to elaborate further. Let me begin with a discussion of our lead asset, nerazacyclib, which, as a reminder, is a multi-kinase inhibitor targeting CDK4, 6, and other kinases.
spk08: Important. the tumor growth, and metastasis.
spk07: We are pursuing Neuragic Cyclips development in multiple cancer indications based on both preclinical and clinical science. And we are pleased to say that Neuragic Cyclips Phase 1 to A combination trial with estrogen blockade in endometrial cancer is on track to open for enrollment and screening patients later this quarter. In parallel, our phase one trials of single agent nerazociclib in the US and China have continued to demonstrate the assets favorable safety profile through their fifth dose escalation cohorts. Based on these studies, we'll be able to place patients on a once-daily continuous dosing regimen in endometrial cancer, as well as in future studies. Once-daily continuous dosing differentiates Neurazacyclib from each of the three health already approved PDK4-6 inhibitors. Of these agents, which are multi-billion dollar franchises with approvals only in hormone receptor positive, HER2 negative breast cancer, two of them require a one-week drug holiday and every fourth week mainly due to their bone marrow toxicity leading to neutropenia or a low white blood cell count, while the third requires twice daily dosing due to its shorter half-life. By dosing Neurazacyclib once daily continuously, we can provide patients with a more convenient and safer dosing regimen from a marrow suppression perspective that will not include a one week off drug holiday during which tumor cells could potentially proliferate in the absence of kinase inhibition of their overexpressed pathways. Turning next to our investigator sponsored rego-certum programs, our recent progress here was highlighted by Phase II data reported last month in advanced squamous cell carcinoma, complicating recessive dystrophic epidermolysis bullosa, or RDEB-associated squamous cell carcinoma, for short. I'll let Mark detail these early data. But we'll note that given the results, the magnitude of the unmet need in R-dev associated squamous cell and its ultra-orphid nature, we plan to seek guidance from the FDA on the most expeditious path towards a potential approval for regoacertib in this indication. In addition to highlighting these clinical accomplishments, Mark will preview upcoming posters on the razocyclib, our lead compound, that will be presented at the AACR meeting in Orlando next month. He will also recap preclinical data on regocertum that were presented at the recent AACR Targeting Glass Conference last week. Before I hand the call off to Mark, I'd like to highlight the important and recent appointments of Drs. Peter Retagia and Trafford Clark, who are Board of Directors. Together, Peter and Trafford bring more than 50 years of experience in the pharmaceutical industry to our board, having had key positions with increasing responsibilities at both Novartis and Eli Lilly, respectively. In the short time since their appointments, they've already provided invaluable insights informed by their extensive knowledge of drug development leading to commercialization. Looking forward, I am eager to continue benefiting from their wise counsel as we pursue our mission of discovering, developing, and delivering best-in-class products to patients with cancer. With that, I'll now turn the call over to Dr. Mark Gelder to provide more details and context on our recent clinical and scientific accomplishments.
spk08: Mark? Thanks, Steve.
spk09: I'll start with a quick update on the Razocyclibs Phase I Solid Tumor Program. I'm going to focus on the program's U.S. study, referred to as Study 1901. This study is evaluating the continuous once-daily dosing that we plan to utilize with the razocycline moving forward. The trial recently completed the fifth dose cohort. This was a cohort of patients who took 200 milligrams a day by mouth on a continuous daily basis, days one through 28, each cycle being 28 days. We expect it will advance to the sixth dose escalation cohort, which will evaluate the safety, tolerability, PK and PD of a 240 milligram dose of nerazacyclib orally once daily. We expect to move to the sixth dose escalation cohort after the safety monitoring committee has reviewed the data from the fifth dose cohort. Data from the trial continues to be highly encouraging with anticipated on-target effects of nirazacyclib observed, but in the absence of any clinically meaningful cases of neutropenia or diarrhea. This is important since, as Steve pointed out, neutropenia is the dose-limiting toxicity for two out of the three approved CDK4-6 inhibitors, while diarrhea is the primary dose-limiting toxicity for the third one, abemacycline. These early clinical findings are also notably consistent with nerazacycline's differentiated kinase inhibitory profile as well as its preclinical data that showed reduced neutropenia when directly compared to the most widely prescribed CDK4-6 inhibitor, palvocycline. On our last earnings call, you heard Steve and I speak about how neurazocyclines differentiated inhibitory profiles. positions it as a potentially best-in-class therapy when combined with letrozole in patients with recurrent or metastatic low-grade endometrioid endometrial cancer, or LGEEC. We also announced that we plan to begin exploring this hypothesis in a Phase I 2A trial, which has received IRB approval at New York University Langone Health. We expect the study to be open for enrollment later this quarter as planned and are very pleased that it remains on track for a preliminary data readout in the fourth quarter of this year. Several other sites are on track to be open and up and running in the coming weeks. As a reminder, The scientific rationale for the neurazocycline LGEEC study comes from a randomized placebo-controlled phase 2 study, as well as a couple of different single-arm clinical trials of the currently available CDK4-6 inhibitors, pulvocycline, ribocycline, and abemacycline, in patients with estrogen receptor-positive endometrial cancer. These trials all demonstrated the improved anti-cancer activity of CDK4-6 inhibitors when combined with letrozole, when compared with letrozole plus placebo in the low-grade endometrioid, endometrial carcinoma patients. It was these trials that support the compendia listing of the three currently available CDK4-6 inhibitors that enable their off-label use and reimbursement in this setting today. However, I think it's important to realize that none of the currently available CDK4-6 inhibitors are FDA-approved for the treatment of low-grade endometrioid endometrial cancer, and they are limited by the shortcomings related to safety tolerability, and treatment resistance, as we've discussed before. Given neurazocyclin's ability to inhibit CDK4 and 6 with similar potency to palmocyclin, ribocyclin, and abamacyclin, we believe our Phase I-II trial has a high likelihood of technical and regulatory success.
spk10: Moreover,
spk09: we believe our preclinical and phase one findings suggest that neurazocyclic may offer significant safety advantages compared to currently available agents. And its ability to target additional proteins related to anti-tumor immunity, metastases, cancer cell survival, et cetera, may lead to improved efficacy. We therefore believe that neurazacyclin has the potential to substantially improve the treatment paradigm for patients with recurrent low-grade endometrioid endometrial cancer and look forward to evaluating this hypothesis in our Phase I 2A trial. Looking beyond low-grade endometrioid endometrial cancer, we are planning to initiate a clinical program of nerazacycline in one or more additional indications by the end of this year. And while we can't provide too much detail on these plans since they are still being finalized, I can say that other refractory tumors of the female reproductive tract as well as breast cancer are under consideration. Protocols for these clinical trials are currently being prepared for review, and we have identified key opinion leaders to serve as the principal investigators of the additional studies being planned. To conclude my section on neurazocyclic, I want to briefly preview two posters on preclinical data that will be presented at the upcoming American Association of Cancer Research, or AACR, meeting next month in Orlando. The first of these posters will feature results that demonstrate neurazocyclic single-agent activity against mantle cell lymphoma in vitro and in a chicken embryo choreolactoic membrane xenograft model. And importantly, neurazocyclib's activity against mantle cell lymphoma cell lines was found to be superior to that of pulmocyclib and ribocyclib and similar to that of abemacyclib. Moreover, when neurazocyclib was combined with ibrutinib, a BTK inhibitor approved for the treatment of mantle cell lymphoma, synergistic increases in anti-tumor activity against both BTK inhibitor resistant and BTK inhibitor sensitive cell lines were observed. The second poster that will be presented at AACR next month will compare the differential cellular targets that are engaged by nerazacycline compared to the FDA-approved CDK4-6 inhibitors. In addition, results from a cell-based mammary cell carcinoma models show that stronger induction of apoptosis with neurazocyclic would deserve compared to pulmonocyclic, as will data that will show neurazocyclic combining with autophagy inhibitors to sensitize breast cancer cells to cell death. While the conference embargo policy prevents me from saying much more about the data, featured in these two posters at this time. We look forward to having further discussions with the scientific and clinical community at the ASCR meeting next month. Shifting gears, I'll now discuss our investigator-sponsored regocertum programs with a focus on the exciting early clinical data in the R-DEB-associated squamous cell carcinoma, which was reported back in February. As those familiar with Ankanova may recall, R-DEB is caused by insufficient type 7 collagen protein expression. This deficiency in type 7 collagen leads to extreme skin fragility, chronic blistering, and wound formation in these R-DEB patients, many of whom go on to develop squamous cell carcinomas, frequently metastatic, that are driven by overexpression of PLK1. Unfortunately, all of the currently available treatments, including targeted therapy, immunotherapy, conventional chemo therapy, radiation therapy, et cetera, provide only limited benefit for RDEV-associated squamous cell carcinoma patients who have a cumulative risk of death of 70% by age 45. To address the unmet needs of patients with R-dev associated squamous cell carcinoma, we are working with multiple investigators on a phase two program evaluating the safety and efficacy of regocerative monotherapy in this patient population. Last month, we announced that the trial's second evaluable participant achieved a complete clinical response of all cancerous skin lesions after only four cycles of therapy. This patient remains on study with additional scans scheduled to monitor metastatic disease. The announcement of this second patient followed data that showed a complete clinical response in the program's first valuable participant, who has remained in complete remission with no signs of metastatic disease for more than 24 months while remaining on regocercum. The studies remain open and are continuing to enroll patients, and we are actively looking for additional sites to participate in the program. While data from an ENTIV-2 must always be taken with caution. The results from regoceratib's R-DEV-associated squamous cell carcinome program have far exceeded our expectations as well as those of the trials investigated. They have confirmed regoceratib's activity against PLK1 in the clinic as well as its ability to drive durable clinical responses in patients who have failed prior therapy. As Steve mentioned, the next step for the program is now to engage with the FDA to align on the optimal regulatory path for the program, given our data to date, and the lack of effective treatments that are currently available for patients with RDEV-associated squamous cell carcinoma. In addition, RDEV is a catastrophic pediatric illness And this reality, as well as the potential enrollment of pediatric patients in the clinical program, will be some of the topics to be discussed with the FDA. Taking a broader view, we believe the results from regoceratins are done associated squamous cell carcinoma program may have positive read-through into other, more prevalent cancers characterized by PLK1 overexpression. This is a hypothesis being explored in preclinical studies, though I should note that any effort to advance regoceptive clinical development and additional indications would be enabled by investigator-sponsored trials so that we can continue to dedicate our primary focus and resources on neurazocyclic. Lastly, I'd like to touch on the status of the two investigator-sponsored trials evaluating regocertib in combination with a PD-1 checkpoint inhibitor. These trials are supported by preclinical data published by Dr. Ann Richman's group at Vanderbilt University, as well as results recently presented at the AACR Targeting RAS Conference recently held in Philadelphia, Pennsylvania. This data showed how regocertib can stimulate an anti-cancer immune response via activation of the NLRP3 inflammasome. Collectively, these preclinical data provide a strong mechanistic rationale for the aforementioned trials, which aim to leverage regocertib's immunotherapeutic effects to overcome checkpoint inhibitor resistance. The first of these trials I'll mention is designed to evaluate regocertib plus pembrolizumab in checkpoint inhibitor refractory metastatic melanoma. I am pleased to say that this trial has recently been posted on clintrials.gov, now has an NCT number, 057-643-95, and should be open for patient accrual at Vanderbilt University Medical Center later this quarter. We look forward to providing additional updates as this trial progresses. The second regocertib checkpoint inhibitor combination study I'll mention is the Phase I 2A trial evaluating regocertib plus nivolumab in KRAS-mutated non-small cell lung cancer patients who have failed prior therapy with a checkpoint inhibitor. We remain on track to report additional data from this trial in the first half of this year. This announcement will likely include updated data from the two patients who remained on study as of its readout at ESMO last year, as well as data from additional patients who were not yet enrolled and or valuable for efficacy as of the ESMO data cutoff date. After seeing these data, we plan to discuss them with the study investigator to determine the optimal next steps for this program.
spk08: And now with that, I'll pass the call off to Mark Garrett. Thank you, Mark.
spk01: Onconova finished 2022 in a strong financial position with cash and cash equivalents of $38.8 million as of the end of the year. This compares with cash and equivalents of $55.1 million at the end of 2021. Based on our current projections, we believe our current cash position will be sufficient to fund our ongoing clinical trials and operations into the first quarter of 2024. This cash runway is expected to take us through key milestones, including a first data readout from our combination trial of nerazacyclib and letrozole in advanced endometrial cancer later in 2023. Turning now to our full-year financial results, research and development expenses for 2022 were $11.4 million compared to $7.3 million for 2021. General and administrative expenses were for 2022 were 8.4 million compared to 9.4 million for 2021. Our net loss for 2022 was $19 million or 91 cents per share on 20.9 million weighted average shares outstanding. This compares with the net loss for 2021 of 16.2 million or 96 cents per share on 16.8 million weighted shares outstanding. The increase in net loss for 2022 compared with 2021 was primarily a result of higher spending in the Neraziciclov Development Program and drug manufacturing in 2022. That completes my financial review. I'll now pass the call back to Steve.
spk08: Thanks to both of you, Marks.
spk07: I'll start my closing remarks by thanking all of those who made the progress we spoke about today possible. At the top of this list are our clinical trial participants and their caregivers, whose bravery is a constant source of inspiration to all of us. I'd like to also thank our employees, investigators, partners, and shareholders for their support. which has its advancing towards multiple key milestones that you heard about today that are expected between now and the year end. In our neurazocyclic program, we expect to report preliminary data from our combination trial of neurazocyclic metrazole and advanced endometrial cancer in the fourth quarter of this year. We also expect the continued progress of our phase one trials to enable the selection of a recommended phase two dose in the first half of the year and to initiate a clinical program of Neurazacyclib in one or more additional cancer indications. Regarding rigor assertive, we look forward to discussing our recent RDEB-associated squamous cell carcinoma data with the FDA in order to help determine the optimal regulatory pathway for these exciting clinical outcomes. We also look forward to opening the combination trial of Vigocertab and Pemolizumab in melanoma later this quarter and expect that the Phase I 2A trial of regocertal plus nivolumab in KRAS-mutated non-small cell lung cancer will have additional important data to report in quarter two. In parallel with the progress of our clinical programs, we will continue to evaluate potential opportunities to expand our pipeline and will focus any such efforts on assets that have a strong body of evidence demonstrating their best-in-class potential in an indication with a high unmet medical need. We plan to be very highly selective as we make these corporate development assessments as our current programs are backed by compelling data and provide us with multiple shots on goals and opportunities to generate value for our investors and the patients. With that, we'll begin today's Q&A session. And operator?
spk04: Ladies and gentlemen, if you wish to register for a question for today's question and answer session, you'll need to press star then the number one on your telephone. If your question has been answered or you wish to withdraw your request, you may do so by pressing star 1 again. If you're using a speakerphone, please pick up your handset before entering your request. One moment, please, for the first question. And our first question comes from Charles Zhu from Guggenheim Securities. Please go ahead. Your line is open.
spk05: Hi, guys. This is Edward Onfer for Charles Zhu at Guggenheim. My first question is on Narzocyclib, the monotherapy dose escalation. I'm curious if you can give any more color on how the dose escalation is going beyond the prepared remarks. Do you think you're in the potentially therapeutically efficacious range for the doses and how much higher do you think you could go? And then as a potential and as a follow-up, I know you've guided to the letrozole combo data in 4Q, but so how should we be thinking about the monotherapy scenario? dose escalation data update. Would you, could that come before the 4Q update?
spk08: Thanks, Ed. I'll ask Dr. Gelsis to take that, please. Sure.
spk09: So, more clarity on the phase one dose escalation study. What I can tell you is that we do believe that we're getting close. to a quote-unquote dose that we can use as our recommended phase two dose. We are beginning to see some effects that we would anticipate from a CDK4-6, i.e. we're beginning to see a little more grade one, grade two neutropenia. We're not seeing a whole lot other than that. We're seeing some low-grade diarrhea, but nothing significant. The PD work, the pharmacodynamic work with the 200-milligram cohort is still pending. It's still out. So I can't say anything for certain about that. But just based on what I'm seeing, do I think that we're getting relatively close? Yeah, I do. Does that mean 240 milligrams is going to be the dose? 280 milligrams, you know, 320 milligrams, I don't know. Do I think we're going to have to push this to 500 or 600 milligrams? No, I do not. So I do think we're getting closer, but I can't give you a firm answer to that.
spk07: And, Mark, the second question was the strategy of the monotherapy trials. but we also have already begun the combo trial with letrozole. Make some comments on that?
spk09: So, you know, we're looking at different options right now. You know, whether we do continued work in combination with either letrozole or other anti-estrogens, whether we do work as a monotherapy, whether we do some continued work with neurazocyclob in combination with, say, a checkpoint inhibitor or in combination with, you know, a BTK inhibitor or in combination with a MEK inhibitor. We're looking at several different options now. So I can't give you any more specific details at this time. What I will tell you is that we do have, we believe, we do have several good options in terms of additional development programs to start moving forward with other than the low-grade endometrial cancer. And so exactly what our second program and third program and fourth program will look like at this time I just can't say. Steve, you may want to give a little more away, but I'll hold my comment.
spk07: I think Ed's question, and correct me if I'm wrong, Ed, is how do we start a combination trial with neurazocyclic before we know the recommended phase two monotherapy dose? I think the answer, Ed, the answer is that as Dr. Gelder said, we believe we're close to the recommended phase two dose. And anytime you do a phase one new combination, you always decrease the dose of the experimental agent, in this case, Neurasa cyclin. So since we think we're close, we went back one step, one cohort, pick that dose of nerazacyclib in combination with letrozole. And in a three-by-three design, we'll again continue to increase the dose of nerazacyclib in combination with letrozole based on the safety profile that Dr. Geldo will be observing. So I hope that answers your question.
spk08: That's great. Thank you. Thank you.
spk04: Our next question comes from from . Please go ahead. Your line is open.
spk03: Good evening. Hello, team. Thanks for taking my questions, and congrats on the progress. I have two questions. One of them, we heard you say the NTT was not reached, and also you don't observe the neutrophilia and diarrhea. I am curious to hear if you could provide more color on the similarities or differences between narizocyclic with other CDK4-6 inhibitors? Do you observe similar safety profile, or is it very differentiating? If you could provide some color on that, that would be helpful.
spk08: Mark?
spk09: Yeah, so I think when I look at what really differentiates us, you know, as you're well aware, ALBO and RIBO are the two, quote-unquote, purists CDK4-6 inhibitors, with ribo being the purest, followed closely by palba. Abemacyclib, like nerazacyclib, is truly a multi-targeted kinase inhibitor. It hits several different kinases at low nanomolar concentration. But the kinases that abemacyclib hits are very different than the kinases that nerazacyclib hits. All of them are very potent, very effective CDK4-6 inhibitors. What differentiates nerazacyclib are the other kinases that it hits at low nanomolar concentration, particularly the ARK5 or NUAC1 and the CSF1R. But there are others, the FLIT3. the CKIT, et cetera. So there are actually several kinases that we hit that we think have the potential to be very important in terms of the overall efficacy as well as the safety of neurazocyclic. This is all preclinical data. We're just getting into the clinic. We've now had in our phase one dose escalation study, we've now had 21 patients total who have been exposed to the neurazacycline at escalating doses. And as I said so far, the safety profile looks very, very good, very similar to what we had anticipated based on all of our preclinical data. And we are very excited to as we've said, to be moving into the low-grade endometrioid endometrial cancer study because now rather than using a typical phase one solid tumor population, we will be using a population where we expect, where we anticipate to start to see some really significant activity. So this is sort of where we are. I hope that answers your question, but it all has to do with the other kinases that we inhibit.
spk07: And actually, there will be more data that Mark alluded to. There will be greater detail at the AACR meeting in Orlando.
spk03: That's helpful. Thank you. I have one more question on the lateral gall combination trial. Since both Drugs are administered daily. I am curious if you have looked at the safety profiles. Are there any overlapping toxicities? Are you expecting anything major in the combination trials?
spk09: So when I look at Lekrozol, it's got a very well-established AE profile. And when I look at what we've seen so far with neurazocyclic and what we expected based on the other CDK4-6 inhibitors that are already approved and based on our preclinical data, there really is very little, very little overlapping toxicities of the two. The biggest one is really fatigue.
spk07: And if I can add to that and also add to the previous question, because letrozole is an anti-estrogen and, as Mark just said, a very different safety profile and a very acceptable safety profile, a very different mechanism of action as an anti-estrogen, that's why rather than waiting to wait for the recommended phase 2 dose of mononeurazacyclam a study to read out, we are comfortable combining Neurasa Cycle with Letrozole with a lower dose of Neurasa Cycle to make sure we're safe. But this approach of already opening the combination trial in endometrial saves us two key factors, which are both very important, time and money. So we now will have, as we mentioned in this quarter, the first patient on this combination trial with endometrial cancer studying the combination.
spk08: Thank you. Thanks for taking my question.
spk04: Our next question comes from Joe Pantjanis from HC Wainwright. Please go ahead. Your line is open.
spk02: Hey, guys. Good afternoon. Thanks for taking the question. So this question... might be jumping the gun a bit here. Obviously, you need to talk to the FDA first with regard to Rigocertib's potential in RDEB. But with that said, do you have, I guess, any sort of broad strokes to take right now, both internally and maybe from any external sort of regulatory consultants that might give you an early wish list that you can share with us regarding a potential design?
spk07: Well, the wish list, Joe, won't require a design. The results that Dr. Gelder shared with us, the patients and the experts who see these patients are extraordinary. They have failed everything else. And as we mentioned, we have complete cutaneous responses. This is an ultra-rare disease. and we have already demonstrated complete responses when nothing else works. Our regulatory consultants are the ones saying we should go to the FDA now and ask the question, what will it take to get RegoCertib approved in squamous cell, complicating our debt. We don't know if the current two patients are enough. Will they want an additional two patients? We really don't know what the end is going to be. And as Mark said, hopefully before we meet with the FDA, maybe we'll have one or two additional patients. The incidence of this disease in the U.S. is about 100 odd dead patients a year, maybe 50 live long enough to develop squamous cell carcinoma. But it's very hard to identify these patients, as you know. In addition, the other wish, is because this is a pediatric disease, the RDEB expresses itself in the pediatric age population. We are told that periodically a child is seen with squamous cells, mostly the young adults who develop the squamous cells. The two patients that we treated are, in fact, young adults. This will be presented in greater detail at the International Dermatology Meeting in Tokyo, Japan. that's coming up, but we are continuing to look for additional patients, and if we're very lucky, but it may not be necessary to find a pediatric, it's hard to say lucky to find a cancer in a child, but if there is a child out there anywhere in the globe that we become aware of, we, of course, would be very interested in treating that child with RegoCertib and discussing the possibility of a pediatric voucher for squamous cell complicating RdEV. So those are our wish lists to get rigor assertive approved in this indication and to discuss the possibility of a pediatric voucher with the FDA.
spk02: Very helpful, Steve. Thanks a lot.
spk04: Our next question comes from Robert LaBoyer from Noble Capital Markets. Please go ahead. Your line is open.
spk11: Good afternoon. I had a question that I think was partially answered earlier, but if you're going into a sixth cohort for neurazocyclib, could you give any kind of time frames as to when the sixth might be completed or the seventh or even an eighth if you go that far, and when you might start the phase two?
spk08: Mark?
spk09: So it's impossible to say when... a cohort is going to get completed. You know, you have a three plus three design and it depends on if you get a DLT, it depends on how many screen failures you have, et cetera, et cetera. So, you know, typically it takes, if you don't have any significant problems, don't have a lot of screen failures, et cetera, you can complete a cohort of three in, you know, two to three months. But if you have a DLT and then have to expand it out to six, or if you start having several screen failures, et cetera, it can take four, five, six months to complete a single cohort. So it's really impossible to say. Our fifth cohort, as you're all well aware, took several months to complete because we had several screen failures, et cetera. But that's just the nature of clinical research. The first four cohorts, we all completed. We completed each one of them in two to three months. And in terms of how many cohorts we're going to have to go, I do not have a crystal ball. I can't tell you. In my gut, do I think we're probably getting close? Yeah, I do. The sixth cohort is at 240 milligrams. Will that be as high as we need to go, or do we need to go to 280? That decision won't just be driven by the AE profile. It will also be driven by the PD data, the pharmacodynamic data, because we're going to look for a dose that maybe isn't the MTD or maximal tolerated dose, but look for a dose where we see... you know, maximal biological effectiveness too.
spk08: So it's just hard to say. Okay, thank you very much.
spk04: I'm showing no further questions in queue. At this time, I'd like to turn the call back over to the speakers for closing remarks.
spk08: Thank you all again for joining today.
spk07: to hear about our recent progress and outlook for the rest of the year. We're obviously excited to be nearing several important clinical milestones and appreciate your continued interest in the important, if not crucial, work we are doing. Thanks again, and enjoy your evening. I look forward to seeing many of you going forward. Thank you.
spk04: Ladies and gentlemen, thank you for your participation on today's conference call. This concludes today's event. You may now disconnect.
Disclaimer