Onconova Therapeutics, Inc. (NASDAQ:ONTX) Q4 2022 Earnings Call Transcript

Onconova Therapeutics, Inc. (NASDAQ:ONTX) Q4 2022 Earnings Call Transcript March 16, 2023

Operator: 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, I would like to turn the call over to Bruce Mackle of LifeSci Advisors.

Bruce Mackle: Thank you, operator, and welcome, everyone, to Onconova’s fourth quarter and full year 2022 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 seen this press release, it is available in the Investors and Media section of the company’s website at onconova.com. Following my introduction, we will hear from Onconova’s President and CEO, Dr. Steve Fruchtman; 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 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 involve 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 Fruchtman.

Steven Fruchtman: Thank you, Bruce, and thanks to all who have joined the call today. We are entering a very exciting time for Onconova 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, narazaciclib, which, as a reminder, is a multi-kinase inhibitor, targeting CDK4/6 and other kinase important for tumor growth and metastasis. We are pursuing narazaciclib’s development in multiple cancer indications based on both preclinical and clinical science, and we are pleased to say that narazaciclib’s Phase I/IIa 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 I trials of single-agent narazaciclib in the U.S. and China have continued to demonstrate the asset’s favorable safety profile through their fifth dose escalation cohorts. Based on these studies, we will 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 narazaciclib from each of the 3 health authority approved CDK4/6 inhibitors. Of these agents, which are multibillion-dollar franchises with approvals only in hormone receptive positive add to negative breast cancer, 2 of them require a 1-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 narazaciclib once daily continuously, we can provide patients with a more convenient and safer dosing regimen from a myelosuppression perspective. They will not include a 1-week off drug holiday, during which tumor cells to potentially proliferate in the absence of kinase inhibition of their over-expressed pathways. Turning next to our investigator-sponsored rigosertib 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 sure. I’ll let Mark detail this early data. So note that given the results, the magnitude of the unmet need in RDEB-associated squamous cell and its ultra-orphan nature, we plan to seek guidance from the FDA on the most expeditious path towards a potential approval for rigosertib in this indication.

In addition to highlighting these clinical accomplishments, Mark will preview upcoming posters on the narazaciclib, our lead compound, that will be presented at the AACR meeting in Orlando next month. He will also recap preclinical data on rigosertib that were presented at the recent AACR targeting RAS conference last week. Before I hand the call off to Mark, I’d like to highlight the important and recent appointments of doctors, Peter Atadja and Trafford Clarke to our 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 have 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. Mark?

Mark Gelder: Thanks, Steve. I’ll start with a quick update on narazaciclib’s 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 regimen that we plan to utilize with narazaciclib 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 1 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 narazaciclib 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 narazaciclib 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 2 out of the 3 approved CDK4/6 inhibitors, while diarrhea is the primary dose-limiting toxicity for the third one abemaciclib. These early clinical findings are also notably consistent with narazaciclib’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, palbociclib. On our last earnings call, you heard Steve and I speak about how narazaciclib’s differentiated inhibitory profile 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/IIa 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 narazaciclib, LGEEC study comes from a randomized, placebo-controlled Phase II study as well as a couple of different single-arm clinical trials of the currently available CDK4/6 inhibitors, palbociclib, ribociclib and abemaciclib in patients with estrogen receptor positive endometrial cancer.

These trials all demonstrated the improved anticancer activity of CDK4/6 inhibitors when combined with letrozole, when compared with letrozole plus placebo in the low-grade endometrioid endometrial carcinoma patient. It was these trials that support the compendia listing of the 3 currently available CDK4/6 inhibitors that enabled our 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 narazaciclib’s ability to inhibit CDK4 and 6 with similar potency to palbociclib, ribociclib and abemaciclib, we believe our Phase I/II trial has a high likelihood of technical and regulatory success.

Moreover, we believe our preclinical and Phase I findings suggest that narazaciclib may offer significant safety advantages compared to currently available agents and its ability to target additional proteins related to antitumor immunity, metastasis, cancer cell survival, et cetera, may lead to improved efficacy. We therefore believe that narazaciclib 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/IIa trial. Looking beyond low-grade endometrioid endometrial cancer, we are planning to initiate a clinical program of narazaciclib 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 service the principal investigators of the additional studies being planned. To conclude my section on narazaciclib, I want to briefly preview 2 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 narazaciclib’s single-agent activity against mantle cell lymphoma in vitro and in a chicken embryo chorioallantoic membrane xenograft model. And importantly, narazaciclib’s activity against mantle cell lymphoma cell lines was found to be superior to that palbociclib and ribociclib and similar to that of abemaciclib.

Moreover, when narazaciclib was combined with ibrutinib, a BTK inhibitor approved for the treatment of mantle cell lymphoma, synergistic increases in antitumor 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 narazaciclib compared to the FDA-approved CDK4/6 inhibitors. In addition, results from a cell-based memory cell carcinoma model show that stronger induction of apoptosis with narazaciclib would deserve compared to palbociclib as well data that will show narazaciclib combining with autophagy inhibitors to sensitize breast cancer cells to cell death. While the conference embargo policy prevents me for saying much more about the data featured in these 2 posters at this time, we look forward to having further discussions with the scientific and clinical community at the AACR meeting next month.

Shifting gears, I’ll now discuss our investigator-sponsored rigosertib programs with a focus on the exciting early clinical data in the RDEB-associated squamous cell carcinoma, which was reported back in February. As those familiar with Onconova may recall, RDEB is caused by insufficient type VII collagen protein expression. This deficiency in type VII collagen leads to extreme skin fragility, chronic blistering and wound formation in these RDEB patients, many of whom go on to develop squamous cell carcinoma frequently metastatic that are driven by overexpression of PLK-1. Unfortunately, all of the currently available treatment, including targeted therapy, immunotherapy, conventional chemo therapy, radiation therapy, et cetera, provide only limited benefit for RDEB-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 RDEB-associated squamous cell carcinoma, we are working with multiple investigators on a Phase II program evaluating the safety and efficacy of rigosertib monotherapy in this patient population. Last month, we announced that the trial’s second evaluable participant achieved a complete clinical response of all cancer skin lesions after only 4 cycles of therapy. This patient remains on study with additional scans scheduled to monitor metastatic disease. The announcement of the second patient followed data that showed a complete clinical response in the program’s first evaluable participant who has remained in complete remission with no signs of metastatic disease for more than 24 months while remaining on rigosertib.

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 must always be taken with caution. The results from rigosertib’s RDEB-associated squamous cell carcinoma program have far exceeded our expectations as well as those of the trial’s investigators. They have confirmed rigosertib’s activity against PLK-1 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 RDEB-associated squamous cell carcinoma.

In addition, RDEB 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 rigosertib’s RDEB-associated squamous cell carcinoma program may have a positive read-through into other more prevalent cancers characterized by PLK-1 over expression. This is a hypothesis being explored in preclinical studies, though I should note that any effort to advance rigosertib’s 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 narazaciclib. Lastly, I’d like to touch on the status of the 2 investigator-sponsored trials evaluating rigosertib in combination with a PD-1 checkpoint inhibitor.

These trials are supported by preclinical data published by Dr. Ann Richmond’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 rigosertib can stimulate an anticancer 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 rigosertib’s immunotherapeutic effects to overcome checkpoint inhibitor resistance. The first of these trials I’ll mention is designed to evaluate rigosertib plus pembrolizumab in checkpoint inhibitor refractory metastatic melanoma. I am pleased to say that this trial has recently been posted on clinicaltrials.gov, now has an NCT number, 05764395, 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 rigosertib checkpoint inhibitor combination study I’ll mention is the Phase I/IIa trial evaluating rigosertib 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 2 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 evaluable for efficacy as of the ESMO data cutoff date. After seeing these data, we plan to discuss them with the study investigators to determine the optimal next steps for this program.

And now with that, I’ll pass the call off to Mark Guerin.

Mark Guerin: Thank you, Mark. 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 narazaciclib 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 $0.91 per share on 20.9 million weighted average shares outstanding. This compares with a net loss for 2021 of $16.2 million or $0.96 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 narazaciclib development program and drug manufacturing in 2022. That completes my financial review. I’ll now pass the call back to Steve.

Steven Fruchtman: Thanks to both of you, Marks. 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 who’s 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 us advancing towards multiple key milestones that you heard about today. They are expected between now and the year-end. In our narazaciclib program, we expect to report preliminary data from our combination trial of narazaciclib and letrozole in advanced endometrial cancer in the fourth quarter of this year. We also expect continued progress of our Phase I trials to enable the selection of a recommended Phase II dose in the first half of the year and to initiate a clinical program of narazaciclib in one or more additional cancer indications.

Regarding rigosertib, 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 of these exciting clinical outcomes. We also look forward to opening the combination trial of rigosertib and pembrolizumab in melanoma later this quarter and expect that the Phase I/IIa trial of rigosertib plus nivolumab in KRAS-mutated non-small cell lung cancer will have additional important data to report in quarter 2. In parallel with the progress of our clinical programs, we will continue to evaluate potential opportunities to expand our pipeline, and we’ll focus any such efforts on assets that have a strong body of evidence, demonstrating their best-in-class potential and 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?

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Q&A Session

Operator: . And our first question comes from Charles Zhu from Guggenheim Securities.

Edouard Mullarky: This is Edouard on for Charles Zhu at Guggenheim. My first question is on narazaciclib, 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 dose escalation data update? Would you — could that come before the 4Q update?

Steven Fruchtman: Thanks, Ed. I’ll ask Dr. Gelder to take that, please?

Mark Gelder: Sure. So more clarity on the Phase I dose escalation study. What I can tell you is that we do believe that we’re getting close to a “dose” that we can use as our recommended Phase II 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 1, grade 2 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? Yes, I do. Does that mean 240 milligrams is going to be the dose, 280 milligrams, 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 today.

Steven Fruchtman: And Mark, the second question was the strategy of the monotherapy trial when we also have already begun the combo trial with letrozole. Make some comments on that.

Mark Gelder: So we’re looking at different options right now, whether we do continued work with — in combination with either letrozole or other anti-estrogens, whether we do work as a monotherapy, whether we do some continued work with narazaciclib in combination with, say, a checkpoint inhibitor or in combination with 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 endometrioid 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 comments there.

Steven Fruchtman: I think Ed’s question — and correct me if I’m wrong, Ed, is how do we start a combination trial with narazaciclib before we know the recommended Phase II monotherapy dose. So I think the answer, Ed — the answer is that as Dr. Gelder said, we believe we’re close to the recommended Phase II dose. And anytime you do a Phase I new combination, you always decrease the dose of the experimental agent. In this case, narazaciclib. So since we think we’re close, we went back one step, one cohort, take that dose of narazaciclib in combination with letrozole. And it’s, by design, we’ll again continue to increase the dose of narazaciclib in combination with that result based on the safety profile that Dr. Gelder will be observing. So I hope that answers your question, Ed.

Operator: Our next question comes from Ahu Demir from Ladenburg Thalmann.