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spk06: Ladies and gentlemen, thank you for standing by. Welcome to the October Therapeutics.
spk07: Sarah, excuse me. You're coming in and out. I don't know if other people hear you coming in and out.
spk00: Thank you. Let me restart. Ladies and gentlemen, thank you for standing by. Welcome to the Onconova Therapeutics second quarter 2023 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 one on your touchtone phone. If anyone has difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this call is being recorded today, August 10, 2023. At this time, I would like to turn the call over to Bruce Mackel of LifeSci Advisors. Go ahead.
spk01: Thank you, operator, and welcome everyone to Onconova's second quarter 2023 financial results and business update conference call. Earlier this afternoon, Onconova issued a press release reporting its financial results and business progress. If you have not yet seen this press release, it is available in the Investors and Media section of the company's website at www.oncanova.com. Following my introduction, we will hear from Oncanova's President and CEO, Dr. Steve Fruchtman, Consultant Chief Medical Officer, Dr. Victor Moyo, and Chief Operating Officer and Chief Financial Officer, Mark Guerin. Ancanova's VP of Regulatory Affairs and Quality Assurance, Fred Frullo, will also be available during a Q&A session following their prepared remarks. Before we begin, I would like to remind everyone that statements 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 involves risks and uncertainties that can cause actual results to differ materially. Forward-looking statements speak only as of the date they are made as the underlying facts and circumstances may change. Except as required by law, Onconova 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 Onconova's president and CEO, Dr. Steve Fruchman.
spk07: Thank you, Bruce, and thanks to all our investors and analysts who are listening today. As you know, Onconova is dedicated to developing novel, differentiated therapies for patients with cancer that act by targeting some of the most important pathways that enable cancer cells to grow. We are very encouraged about the outlook for our two lead programs involving nerazacyclid, a differentiated multi-kinase CDK4-6 inhibitor, targeting proteins involved in resistant pathways, and regocertib, a cell signaling inhibitor. Over the last quarter, we have worked diligently to advance the development of both programs in multiple company and investigator-sponsored Phase I and Phase II trials. Data from these studies will guide the clinical and regulatory strategy for each product candidate. Over the course of the quarter, we have also presented encouraging preclinical data on each program at several very prestigious medical meetings, including the AACR and ASCO meetings. Presentation of these data affirms the value proposition of neurazocyclope and regocertum and recognition by a rigorous preclinical and clinical scientific community as warranting the data from these important presentations. In addition, we opened an important and constructive dialogue with the FDA related to the requirements for a regulatory path for regocertib for an approval in the ultra-rare indication of R-DEV-associated squamous cell carcinoma. Looking ahead to the rest of 2023 and early 2024, for neurazocyclib, we will be focused on defining the monotherapy daily phase two dose and advancing the program into one or more randomized studies. For RegoCertib, we will be focused on mapping out a registrational study plan to discuss with the agency Rdamp-associated squamous cell carcinoma based on the very impressive clinical responses that have been seen in previously refractory patients and presented at major medical meetings. We also continue to support the ongoing investigator-sponsored checkpoint inhibitor combination studies with rigor assertive in KRAS-mutated non-small cell lung cancer and advanced malignant melanoma. Importantly, The KRAS mutation in non-small cell lung cancer added in malignant melanoma. Importantly, the KRAS non-small cell lung cancer trial welcomes refractory patients with any KRAS mutation. And the clinical data support our hypothesis that responses should be seen no matter the KRAS mutation present. And in fact, responses are now reported and appear to be KRAS agnostic to the effects of regocertib in combination with nivolumab. Before we dive into the details for each program, I would like to introduce to you Ankanova's Consulting Chief Medical Officer, Dr. Victor Moho. It is an honor to have such a fine global health professional, physician, and successful clinical researcher join Ankenova following the untimely passing of our late chief medical officer, Dr. Mark Gelder, and the extraordinary service of our interim chief medical officer, Dr. Michael Saunders. We thank Michael for his service to Ankenova and to the patients with advanced cancers entering our trials under his leadership. Michael will remain as a consultant to the company. Victor has hit the ground running and is already making an important contribution to Ankenova's clinical development efforts. Victor brings a great depth of experience from his three decades of work in clinical research, including more than 15 years in the biotech industry. He has held responsible leadership roles and led programs at the Center Corps OrthoBiotech subsidiary of J&J, Merrimack Pharmaceuticals, as well as other emerging startups. I personally have known Victor for more than 15 years. Working with him when we were together at OrthoBiotech, and he was leading the erythropoietin-alpha trial in myelodysplastic syndrome, as well as the doxil trial in advanced ovarian cancer. Obviously, both these drugs are approved, and erythropoietin-alpha was a multi-billion dollar franchise for orthobiotics. It is with great confidence that I and we welcome Victor warmly to the AnkaNova team. For our update today, we will focus primarily on two topics. Starting with our CDK4-6 inhibitor, nerazacycline, the first topic will be the progress of our efforts to define a recommended phase two dose, or RP2D. Worldwide sales of the top six drugs in this class top $6 billion in 2020, driven by their ability to improve progression-free survival. We believe that Nerazacyclib has the potential to be a differentiated entrance into this market based on an improved safety profile and, importantly, the low risk of the development of resistance by totally targeting protein involved in these resistant pathways. Our efforts over the last year have been dedicated to completing a phase one program and defining the recommended phase two dose to support evaluation of a combination trial with nerazociclib and metrazole with registrational intent. The clinical program includes two phase one monotherapy studies in patients with solid tumors and one phase one slash two dose escalation trial in combination with letrozole in patients with low-grade endometrioid endometrial cancer, also known as LGEEC. Patients continue to be entered onto the trials and we anticipate reporting top-line results from these studies, including safety, pharmacology, and selection of a recommended phase two dose in the fourth quarter of this year. We will use this information to define and initiate additional combination neurazacyclic studies in other indications once the dose is identified. Based on the progress seen to date, we anticipate initiating a randomized trial in LGEEC in the first half of 2024. Moving on to regocertib. The second topic will be related to the development of a registrational plan for regocertib. As you may know, we had a Type B meeting with the FDA towards the end of June. Based on this constructive meeting and feedback from the agency and the impressive clinical responses in these previously refractory patients with a tremendous unmet medical need, we have seen and presented at major medical meetings our clinical data. We intend to develop a protocol for a potential registrational trial with regocertib in patients with R-DEB-associated squamous cell carcinoma. We will provide an update on next steps in the first half of 2024. With that overview and introduction, I will invite Victor to give you more insight and take you through the latest updates on both nerazocyclib and regocertib.
spk08: Victor, thanks for the introduction, Steve.
spk10: I'm very excited to join Onconova and believe that our two assets have the potential to improve the care of people with cancer. So I'll start by providing you with an update on Narazacyclic. We believe that nirazacyclib has the potential to improve care even more than other CDK4-6 inhibitors because of its unique attributes. Number one, it has differentiated safety profile with potentially less myelosuppression and neutropenia than the other drugs in this class. Number two, we have already demonstrated and feel confident that narazocyclic can be administered once daily and every day. Thus, there is no need for a drug holiday to permit bone marrow recovery that is required by other CD4-6K inhibitors and which may permit replication of cancer cells. Number three, it inhibits multiple kinases. This activity could contribute to enhanced tumor growth inhibition and overcome immunosuppression in the tumor microenvironment. And thus, this overcomes the development of treatment resistance. During our first quarter call, we reported observations from the phase one study of patients with solid tumors that indicated that at a continuous daily dosing schedule of 240 milligrams, Narazacyclib achieved target engagement with an acceptable safety profile. We also reported the initiation of the first Phase I-II study evaluating the combination of Narazacyclib and letrozole in patients with recurrent low-grade endometrioid endometrial cancer, abbreviated LGEEC. And we reported positive preclinical data at AACR 2023 that demonstrated that narazacyclib can be effectively synergistically combined with other agents and in additional indications. So we believe LGE-C is an ideal first indication for neurazocyclists. Compendia data suggests that off-label combination use of CDK4-6 inhibitors and letrozole improve progression-free survival in recurrent LGE-C. However, these regimens, appear to be negatively impacted by issues of safety, tolerability, and treatment resistance, creating an unmet need for new therapies. In addition, beyond inhibiting CDK4-6, narazocyclib uniquely targets a protein called BARB1. Overexpression of BARB1 is linked to poor outcomes in tumors, including breast and endometrial cancer. Together, the compendia data and BARB1 action support the potential for neurazocyclic to make a positive impact on LG, EEC, and other indications. Looking into 2024, we intend to begin at least one additional combination study of narazocyclib and letrozole in a different indication, and we'll provide additional details once a clinical protocol is finalized. Next, I'd like to speak about our plans to define a registrational path for regocertib. We've been evaluating the clinical potential for this compound as a single agent in the ultra-ray lead indication of R-DEB-associated squamous cell carcinoma and separating in combination with checkpoint inhibitors. During our first quarter call, we reported on data presented at the ISID, International Society of investigated dermatology and the International Epidermolysis Bullosa Symposium, showing that patients with refractory R-DEV-associated squamous cell carcinoma achieved complete cutaneous clinical responses of all the cancerous skin lesions. We also observed that patients treated with either IV or oral Rigocertib experienced durable responses and that Rigocertib had been well tolerated with no additional toxicities in this new important indication. The enormous interest from the international experts in the disease supports our enthusiasm to continue to develop Rigocertib for this indication. I'll point out that R-DEP-associated squamous cell carcinoma has a very high mortality, and there are no effective therapeutic options. Patients with R-DEP who develop their first squamous cell carcinoma have a 50% mortality within two and a half years, and this is the most common cause of death in this patient. Because of this high mortality, urgent unmet need, we requested and completed a Type B meeting with FDA in June. As Steve mentioned, the meeting was constructive and based on our discussion, our goal is to develop a protocol for a registration trial and discuss the strategy with FDA and their review. Notably, regocertib's results in R-DEV-associated squamous cell carcinoma may have positive read-through into more prevalent indications. As a key driver of the disease is PLK1, a kinase that is overexpressed in other cancers and potently inhibited by regocertib. We continue to collaborate with Pangea Biomed, an AI company, to identify biomarkers that could predict a response to regocertib. In addition, we continue to evaluate the potential to combine regocertib in combination with checkpoint inhibitors through two investigational sponsored studies, or ISTs. The first IST is being conducted by investigators at the ICANN School of Medicine at Mount Sinai in New York. This Phase I-II study is evaluating the combination of Rigocetib and Nivolumab in patients with KRAS-mutated non-small cell lung cancer who have failed prior therapy with a PD-1 checkpoint inhibitor. As reported last quarter, based on encouraging efficacy data and acceptable safety data, the protocol was amended to allow further dose escalation of regocertib. Patient accrual is intended to be complete at the end of the year. We would expect the investigators to provide an update of the trial in 2024. The second phase two IST is being conducted at Vanderbilt University and initiated enrollment in May. This Simon two-stage design is evaluating regocetib in combination with Keytruda in patients with refractory metastatic melanoma. And with that, I'll conclude my portion of the call and hand it off to Mark.
spk08: Thank you, Victor.
spk04: Onconova closed the second quarter of 2023 with cash and cash equivalents of $29.7 million compared to $38.8 million as of December 31st, 2022. Based on our current projections, we believe that our cash position will be sufficient to fund our ongoing clinical trials and business into the second quarter of 2024. Research and development expenses for the second quarter of 2023 were 2.5 million compared to 2 million for the same period in 2022. General and administrative expenses for the second quarter of 2023 were 2.2 million. This compares with 2.1 million for the same period in 2022. Net loss for the second quarter of 2023 was 4.3 million or 20 cents per share on 21 million weighted shares outstanding. That compares with the net loss for the second quarter of 2022 of $4 million, or 19 cents per share, on 20.9 million weighted shares outstanding. The increase in net loss for the second quarter of 2023 compared with 2022 was primarily a result of Narazic-Cyclib clinical development and manufacturing expenses in the 2023 period. With my financial review complete, I'll now hand the call back to Steve for his concluding remarks.
spk08: Thanks to both Mark and Victor for that review.
spk07: In conclusion, we are very optimistic about the outlook for our two lead compounds because of the promising clinical observations, safety signals, and supporting preclinical data. along with our strategy for eventual health authority approval for our compounds. For neurazocycline, we believe this CDK4 system compound has the potential to provide differentiated efficacy and safety based on reduced bone marrow toxicity, a wider carnage inhibition pattern, and an improved administration scheme To date, we have seen target engagement and the development of mild butrypedia, which permits a once-per-day dosing regimen without the need for a drug holiday that permits bone marrow recovery but may also permit cancer cells to proliferate. We expect to report top-line results from our Phase I monotherapy and phase one slash two combination study with letrozole in the fourth quarter of this year. The readout will include safety, pharmacokinetics, and the definition of a recommended phase two dose. Looking ahead to 2024, we plan to advance the nerazacycline-letrozole combination into a randomized trial in patients with low-grade endometrioid, endometrial cancer in the first half of 2024. We intend to leverage the results of the preclinical studies presented in the second quarter to define further combination studies with Lesterzo or other compounds in an additional indication. For regal sorting, we continue to believe that regocertib's unique mechanism of action on cell signaling pathways, including KRAS mutations, combined with an acceptable safety profile, could position it as an attractive anti-cancer agent. We had a constructive type B meeting with the FDA for the discussion of regocertib monotherapy, in the lead ultra-rare indication of RDEB complicated by squamous cell carcinoma. Based on that meeting, we plan to design a registrational trial and will look to provide an update on next steps after continued dialogue with the agency in the first half of 2024. In addition, we continue to believe that regocertum has the potential to act synergistically with checkpoint inhibitors to enhance response rates and overcome checkpoint inhibitor resistance. We have been using an IST strategy to evaluate this approach. Two studies are thus underway, evaluating regocertib with checkpoint inhibitors in patients with melanoma and KRAS mutated refractory non-small cell lung cancer. While enrollment in the melanoma study started quite recently, enrollment in the lung cancer study is expected to be completed at the end of this year, and the investigators can provide an update on the trial in 2024. In closing, I want to thank our management team employees, partners, and investigators, as well as the brave and dedicated patients who participate in our experimental clinical trials and the investment community for your support of our efforts to bring new medical entities to patients at Ancanova. We look forward to providing you ongoing updates on the company's progress.
spk08: With that, we will begin today's Q&A session.
spk07: Operator?
spk06: Ladies and gentlemen, if you would like to register for a question in today's question and answer session, you will need to press star and then the number one on your telephone. If your question has been answered and you wish to withdraw your request, you may do so by pressing star A star and one again. If you are using a speakerphone, please pick up your handset before entering your request. One moment, please, for the first question. Our first question comes from Charles Zhu with Guggenheim.
spk05: Hi, guys. This is Edward on for Charles. Thank you for taking our questions. I mean, maybe a first question on the narizocyclib, monotherapy, dose escalation. I'm just kind of wondering what remains to be done for you to establish an RP2D. It sounded like on the past call that you were getting pretty close. Are you still enrolling patients? Have you cleared another dose cohort just kind of with the status there? And then as a follow-up question on the combination with letrozole for LGEEC, just any color there on how recruitment, how that trial is going. Thank you.
spk07: So the first question, we are currently, I think we've mentioned this in the past, at 240 milligrams every day for these patients, and we're in the middle of expanding that cohort. And, you know, it's hard to predict. As you know, it depends on the number of DLTs. If no additional DLTs are seen, then the next cohort will be at 280 milligrams. So we believe we're close based on a target engagement of a 2D1 marker that shows us whether or not cells are proliferating, and the proliferation marker is evidence that cells are not proliferating at this current dose of nerazacycline. We're also seeing mild neutropenia, which we could have expected. So based on those two observations, we believe we're getting closer. but how close is close is sometimes hard to predict. We may be at the dose limiting toxicity at 240, in which case the recommended phase two dose would be 200, or we may have to expand to another cohort at 280 milligrams, and we anticipate knowing this in the next few months. The second question, Edward, was what?
spk05: Thanks for that color. Maybe just on the letrozole combo, just how enrollment is going, any color on progress on that combination trial?
spk07: Right. That trial is open at a number of sites across the country, including NYU, MDNs, and others. It took a while to get a crew going. We believe we had to amend the trial our eligibility criteria was a bit strict and we decided, because the key thing about this trial is to get the dose of the combination of nerazacyclic and letrozole. So based on an amendment, we believe accrual should increase. And we anticipate, again, before the end of this year, which has always been our prediction, that the combination of the monotherapy trial and the trial specifically studying LGEEC, that we will have the recommended phase two dose of the combination of nerazacyclin and letrozole before the end of this year.
spk08: Did that answer your question?
spk06: Our next question comes from Ahu Demir from Leidenberg, Tottenham.
spk03: Good afternoon. Thank you for taking my question and congrats on the progress in this quarter. Victor, also congrats on taking the full-time position as a CMO. I have two questions, one on the narizocyclib. Could you comment on the letrozole combination for endometrial cancer In terms of the safety signals, are there any overlapping safety signals and anything that you could actually highlight for us?
spk07: Sure, so I'll take that, Ahu. You know, we're mostly focused on finishing a monotherapy trial with single-agent neurazocycline, but I'll explain to you why, and it has to do exactly with your question. All of the CDK4-6 inhibitors are combined with anti-estrogens, typically letrozole or provestrant, and we plan to do that as well. And there is no cross-toxicity between nerazociclob as a multi-kinase CDK4-6 inhibitor and an anti-estrogen. So we anticipate the combination will be safe, but we'll have a few patients on the trial. But the key thing will be to show the safety of the combination, which will permit us to open a randomized trial in early 2024. So the combination of the monotherapy trial and the study specifically in low-grade endometrial cancer with letrozole, I think those two studies should be finished by the end of this year, which will lead into a randomized trial in low-grade endometrial cancer, and that's our goal.
spk03: Thank you, Steve. And the follow-up question would be, In this folic tumor narzocyclic trial, are there any indications that's dominating the enrollment? Any particular indications we'll see more data on?
spk07: I didn't catch that. You were asking about the monotherapy trial and what type of cancers are being put onto that? Was that your question? Or could you repeat it?
spk03: Yes. That is correct. In the total tumor narizocyclic trial, what indications are you enrolling and also any of the indications that you see more numbers of patients enrolling in the trial, that we will see more data from those indications?
spk07: So the monotherapy trial is open to all end-stage cancers and is very variable. There's no one type of cancer that dominates. It's the typical end-stage patients. It could include lung cancer, prostate cancer, bladder cancer, ovarian cancer. So it's very diffuse and there's no single indication that dominates. I don't think, other than safety, I don't anticipate and we don't expect to have any efficacy signals because the patients are very diverse regarding their indications and their cancers. So the goal is like most phase one studies, is just to establish the recommended phase two dose. And I think the endometrial cancer study that's up and running at the same time to combine the recommended phase two dose of monotherapy of neurazacycline with letrozole will answer the safety of the combination, which I already said we anticipate will be completely safe, just like it is with the competing CDK, the approved CDK4-6 inhibitors, and we don't anticipate any toxicity issues when letrozole is going to be added to the recommended phase 2 dose generated from the monotherapy trial.
spk08: Thank you, Steve. Very helpful.
spk06: Our next question comes from Joe Pagano. from HC Wainwright.
spk11: This is Lander on for Joe. Thanks for taking our questions. I have two questions. The first question for Narasacyclib, are we expecting any initial efficacy data in the readouts anticipated in 4Q?
spk07: So I'll take that one. So the CDK4-6 inhibitors, and that's a great question, by the way. These are very important. so the investment community and the analysts who probably already understand how these drugs work. These are not cytotoxic drugs. These class of drugs prevent tumor proliferation. And if you look at the approvals for the three health authority approved CDK4-6 inhibitors, they were all based on two endpoints. The first is progression-free survival, and the second is overall survival. And the reason for that is because they are not cytotoxic, you do not see many responses. You may periodically see a response, but it's probably in single digits. So the way these drugs work to improve patients' lives is by prolonging PFS and a longing overall survival. And thus, to really evaluate that intelligently, you need a control arm. But you could use historical controls by all means. But really, in the modern era, the way to do that is with a control arm to show improvement in either PFS or OS. And thus, once you establish the recommended phase two trial, the next hurdle will be to open a randomized trial in early 2024 in LGEDC, and that is our plan, and we remain on target for that plan.
spk11: Got it. Got it. And one more question for Rico Serdip in RDD. I may have missed it, but if you could provide us an update on how many patients are still pending to be enrolled in the Phase II trial
spk07: So this is, we have two international sites as ISTs participating in this trial. One at Thomas Jefferson in Philadelphia, where one of the world's experts in Ardeb squamous cell resides, Dr. Andrew South, and also Dr. Johann Bauer in Austria. Those are the two primary sites. Since the results of these trials have been presented, we now have requests to treat patients in Israel, in Chile, in Paris, France, and we're doing it on a compassionate use approach. And in discussions with the agency, specifically they asked us, and we will, transition the trials to an Onconover-sponsored trial And again, because these patients may appear anyway, we may have to do it as once a patient is identified anywhere in the world, because these are ultra-rare patients, then we would open up a site or perhaps a patient can travel to one of the major medical centers that are expert in R-DEV squamous cell. So the responses have been reported at a major medical meeting. We have what we think is Very impressive cutaneous complete remissions. A number of patients since those presentations are now also on the trial in a compassionate use approach. I believe there's another patient more recently put on the trial at Thomas Jefferson, but those patients are too early for an efficacy evaluation, but they continue on either oral or intravenous rego-certum, and we look forward. but the continuation of RegoServe to see an efficacy signal in a larger number of patients. In the interim, we plan, as Victor said, to create a protocol to go back to the agency and get their buy-in on an Ancanova-sponsored trial, potentially in RDEV squamous cell carcinoma.
spk08: Thanks for clarifying, Steve, and thank you for the updates. Pleasure, Landon.
spk06: Our next question comes from Robert Leboyer from Noble Capital Markets.
spk02: Good afternoon. And my question has to do with the melanoma trial going on at Vanderbilt. And I was wondering if you could give any additional details as to the number of patients or the progress that's been made or any particular data points that might be ahead.
spk07: So we've not publicly stated how many patients are on that trial. I will mention that the first cohort is enrolling, and that first cohort is, I believe, almost completed, maybe a little bit too early to evaluate efficacy. So it's up to three patients. So far there's been no safety concerns, and the next cohort obviously would be at a higher dose. of regocerta, but that trial in malignant melanoma is quite early in its progress.
spk08: Okay, thank you very much.
spk06: I'm showing no further questions in the queue. At this time, I'd like to turn the call back to Steve for any closing remarks.
spk07: Thank you again, operator. and thank all of you for participating in today's call. We are pleased to be approaching important milestones, as we mentioned, across our pipeline and look forward to providing additional updates as they are achieved. Thanks again for participating and for your excellent questions, and have a wonderful evening.
spk08: Thank you again.
spk06: thank you all for participating in today's call this concludes today's event you may now disconnect
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