Traws Pharma Q2 2023 Earnings Call Transcript

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August 10, 2023

There are 9 speakers on the call.

Operator

Ladies and gentlemen, thank you for standing by.

Speaker 1

Welcome to the

Speaker 2

Sarah, excuse me, you're coming in and out. I don't know if other people hear you coming in and out.

Speaker 3

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.

Speaker 3

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 Mackle of LifeSci Advisors. Go ahead.

Speaker 4

Thank you, operator, and welcome everyone to Onconova's 2nd quarter 2023 Financial Results and Business Update Conference Call. Earlier this afternoon, Onconova issued a press release reporting 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 atwww.onconova.com. Following my introduction, we will hear from Onconova's President and CEO, Doctor. Steve Fruchtman Consultant Chief Medical Officer, Doctor.

Speaker 4

Victor Moya and Chief Operating Officer and Chief Financial Officer, Mark Yerin. Onconova's VP of Regulatory Affairs and Quality Assurance, Fred Frullo, will also be available during the Q and A session following their prepared remarks. 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.

Speaker 4

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, Doctor. Steve Bruckman.

Speaker 2

Thank you, Bruce, and thanks to all our investors and analysts who are listening today. Onconova is dedicated to developing novel, differentiated therapies for patients with cancer that act by targeting We are very encouraged about the outlook for our 2 lead programs Involving Nirajaciclib, a differentiated multi kinase CDK4six inhibitor targeting proteins involved in resistant pathways and rigosertib, a cell signaling inhibitor. Over the last quarter, we have worked diligently to advance the development of both programs Multiple company and investigator sponsored Phase 1 and Phase 2 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 presentation of these data affirms the value proposition of neragiciclib and rigosertib In addition, we opened an important and constructive dialogue with the FDA Looking ahead to the rest of 2023 and early 2024, For nirazaciclib, we will be focused on defining the monotherapy daily Phase 2 dose We will be focused on mapping out a registrational study plan to discuss with the agency R DAB associated squamous cell carcinoma based on the very impressive clinical responses We also continue to support the ongoing investigator sponsored checkpoint Inhibitor Combination Studies with rigosertib in KRAS mutated non small cell lung cancer Advanced Malignant Melanoma.

Speaker 2

Importantly, the KRAS mutation in non small cell lung cancer 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 mutations present. And in fact, responses are now reported and appear to be KRAS agnostic to the effects of rigosertib in combination with nivolumab. Before we dive into the details for each program, I would like to introduce to you Onconova's Consulting Chief Medical Officer, Doctor. Victor Moho. It is an honor to have such a fine global health professional, physician and successful clinical researcher Join Okanova, following the untimely passing of our late Chief Medical Officer, Doctor.

Speaker 2

Mark Gelder and the extraordinary service of our Interim Chief Medical Officer, Doctor. Michael Saunders. We thank Michael for his service to Onconova 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 Arkinova's clinical development efforts.

Speaker 2

Victor brings a great depth of experience from his 3 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 CentaCore Ortho Biotech subsidiary of J&J, Maramac 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 Ortho Biotech and he was leading the erythropoietin ALPHA trial Obviously, both these drugs are approved and erythropoietin alfa was a multibillion dollar franchise for Ortho Biotech. It is with great confidence that I and we welcome Victor warmly to the Onconova team. For our update today, we will focus primarily on 2 topics, Starting with our CDK4six inhibitor, nurazaciclib, the first topic will be the progress worldwide sales of the top 6 drugs in this class, top $6,000,000,000 in 2020, Nirajaciclib 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 Our efforts over the last year have been dedicated to completing a Phase 1 program defining the recommended Phase 2 dose to support evaluation of a combination trial with miragacyclin and metrazole with registrational intent.

Speaker 2

The clinical program includes 2 Phase 1 mono ongoing Phase III study in patients with solid tumors and 1 Phase Ietwo dose escalation trial 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 We will use this information to define and initiate additional combination niradjacentclin studies In other indications, once the dose is identified, based on the progress seen to date, We anticipate initiating a randomized trial in LG EEC in the first half of 2024. Moving on to rigosertib. The second topic will be related development of a registrational plan for RIGO Certific. As you may know, We had a Type B meeting with the FDA towards the end of June.

Speaker 2

Based on this constructive meeting 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 rigosertib in patients RDEB associated squamous cell carcinoma. We will provide an update on next steps In the first half of twenty twenty four. With that overview and introduction, I will invite Victor Victor?

Speaker 5

Thanks for the introduction, Steve. I'm very excited to join Onconova And believe that our 2 assets have the potential to improve the care of people with cancer. So I'll start by providing you with an update on nirazaciclib. We believe that nirazaciclib has the potential Number 1, it has differentiated safety profile with potentially less myelosuppression and neutropenia And the other drugs in this class. Number 2, we have already demonstrated and feel confident that nirazaciclib can be administered once daily and every day.

Speaker 5

Thus, there's no need for a drug holiday to permit bone marrow recovery That is required by other CD4six ks inhibitors and which may permit replication of cancer cells. Number 3, 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 1 study of patients With solid tumors that indicated that at a continuous daily dosing schedule of 2 40 milligrams, Narazaciclib achieved target engagement with an acceptable safety profile.

Speaker 5

We also reported the initiation of the 1st Phase III study evaluating the combination of nirazaciclib And we reported positive preclinical data at AACR 2023 That demonstrated that naresociclib can be effectively synergistically combined with other agents So we believe LGEC is an ideal first indication for nirazaciclib. Compendia data suggest that off label combination use of CDK4six inhibitors and letrozole improve progression free survival in recurrent LGEC. However, these regimens In addition, beyond inhibiting CDK4six, nirazociclib uniquely targets a protein called BAB1. Over expression of BAB1 is linked to core outcomes in tumors, including breast and endometrial Together, the compendia data and BAB1 action support the potential Looking into 2024, we intend to begin at least one additional combination study of nirazociclib and letrozole in a different indication and we'll provide Next, I'd like to speak about our plans to define a registrational path for rigosertib. We've been evaluating the clinical potential for this compound as a single agent In the ultra rare lead indication of rdeb associated squamous cell carcinoma And separately in combination with checkpoint inhibitors.

Speaker 5

During our 1st quarter call, we reported Dermatology and the International Epidermolysis Bullosa Symposium showing that patients with Refractory rdev associated squamous cell carcinoma achieved We also observed that patients treated with either IV or oral rigosertib experienced durable And that rigosertib 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 I'll point out that RDEB associated squamous cell carcinoma has a very high mortality and there are no effective therapeutic options. Patients with RDEB who developed their first square muscle carcinoma have 50% mortality within 2.5 Yes. And this is the most common cause of death in these patients. Because of this high We requested and completed a Type B meeting with FDA in June.

Speaker 5

As Steve mentioned, the meeting was constructive and based on our discussion, our goal is Notably, rigosertib's result in RDEB 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 rigosertib. We continue to collaborate with Pangaea Biomet, an AI company to identify biomarkers that could predict response to rigosertib. In addition, we continue to evaluate the potential to combine rigosertib In combination with checkpoint inhibitors through 2 investigational sponsored studies or ISTs. The first IST is being conducted by investigators at the I-ten School of Medicine at Mount Sinai in New York.

Speaker 5

This Phase III study is evaluating the combination of rigosertib and nivolumab As reported last quarter, based on encouraging efficacy data and acceptable safety data, Patient accrual is intended to be complete at the end of the year. We would expect the investigators to provide an date of the trial in 2024. The 2nd Phase 2 IST is being conducted at Vanderbilt University And initiated enrollment in May. This Simon two stage design is evaluating rigosertib And with that, I'll conclude my portion of the call and hand it off to Mark.

Speaker 6

Thank you, Victor. Onconova closed the Q2 of 2023 with cash and cash equivalents of $29,700,000 compared to $38,800,000 as of December 31, 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 Q2 Q2 of 2023 were $2,500,000 compared to $2,000,000 for the same period in 2022. General and administrative expenses for the Q2 of 2023 were $2,200,000 This compares with $2,100,000 for the same period in 2022. Net loss Q2 of 2023 was $4,300,000 or $0.20 per share on 21,000,000 weighted shares outstanding.

Speaker 6

That compares with a net loss for the Q2 of 2022 of $4,000,000 or $0.19 per share on 20,900,000 weighted shares outstanding. The increase in net loss for the Q2 of 'twenty 3 compared with 2022 was primarily a result With my financial review complete, I'll now hand the call back to Steve for his concluding remarks.

Speaker 2

Thanks to both Mark and Victor for that review. In conclusion, We are very optimistic about the outlook for our 2 lead compounds Because of the promising clinical observations, safety signals and supporting preclinical data, For neuradagocycline, we believe this CDK4six compound has the potential A wider kinase inhibition pattern and an improved administration scheme. We expect to report top line results from our Phase 1 monotherapy and Phase onetwo combination study with letrozole in the Q4 of this year. The readout will include safety, pharmacokinetics and the definition of a recommended Phase 2 dose. Looking ahead to 2024, we plan to advance the nurazaciclib metrazole combination In the first half of twenty twenty four, we intend to leverage the results We continue to believe that Rigosertib's unique mechanism of action on cell signaling pathways, including KRAS mutation combined with an acceptable safety profile could position it As an attractive anticancer agent, we had a constructive Type B meeting with the FDA discussion of rigosertib monotherapy in the lead ultrarare indication of RDEB complicated bisquamous cell carcinoma.

Speaker 2

Based on that meeting, we plan to design a registrational trial In addition, we continue to believe that rigosertib has the potential to act synergistically We have been using an IST strategy to evaluate this approach. 2 studies are thus underway, evaluating rigosertib with checkpoint inhibitors in patients with melanoma ONCAD- 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, and the investment community for your support of our efforts to bring new medical entities 2 patients at Onconova.

Speaker 2

We look forward to providing you ongoing updates on the company's progress. Operator?

Operator

Ladies and gentlemen, if you would like to register for a question in today's question and answer session. Our first question comes from Charles Zhu with Guggenheim.

Speaker 7

Hi, guys. This is Edward on for Charles. Thank you for taking our questions. I mean, maybe a first question on the narsociclib monotherapy dose escalation. I'm just kind of wondering What remains to be done for you to establish an RP2D?

Speaker 7

It sounded like on the past call that you're getting pretty close. Are you still Enrolling patients, have you cleared another dose cohort? Just kind of what's 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?

Speaker 7

Thank you.

Speaker 2

So the first question, we are currently at I think we've mentioned this in the past 2 40 milligrams every day for these patients that were in the middle of expanding that cohort. 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 So we believe we're close based on target engagement of a 2G1 marker that shows us Whether or not cells are proliferating and proliferation marker is evidence that cells are not proliferating At this current dose of nurazaciclib, we're also seeing mild neutropenia, which we could have expected. So based on those two observations, we believe we're getting closer.

Speaker 2

But how close is closer is sometimes hard to predict. We may be at the dual swimming toxicity at 2 40, in which case the recommended Phase 2 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.

Speaker 7

Yes, maybe just on the letrozole combo, just how enrollment is going? How that any color on progress on that combination trial?

Speaker 2

Right. So that trial is open at a number of sites across the country, including NYU, MD Anderson and others. Accrual, it took a while to get accrual 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 nurazaciclib and letrozole.

Speaker 2

So based on an amendment, we believe accrual should increase. We anticipate again before the end of this year, which has always been our prediction The combination of the monotherapy trial and the trial specifically studying LGEEC that we will have the recommended Phase 2 dose of the combination of nirazaciclib and letrozole

Operator

Our next question comes from Ahu Demir from Ladenburg Thalmann.

Speaker 1

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. 1 on the nerzociclib.

Speaker 1

Could you comment on the betrothal 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?

Speaker 2

Sure. So I'll take that, Ahu. We're mostly focused on finishing the monotherapy trial with single agent Nirazacycline, but I'll explain to you why and it has to do exactly with your question. All of the CDK4six inhibitors are combined with antiestrogens, typically metrazole or fulvestrant, and we plan to do that as well. And there is no cross toxicity between nirazaciclib as a multi kinase CDK4six So we anticipate the combination will be safe, but we'll have a few patients on the trial, The key thing will be to show the safety of the combination, which will permit us to open a randomized trial In early 2024.

Speaker 2

So the combination of the monotherapy trial and the study

Speaker 1

Thank you, Steve. And the follow-up question would be in the solid tumor narsociclib trial. Are there any indications that's dominating the enrollment? Any particular indications we'll see more data on?

Speaker 2

I didn't catch that. You're asking about the monotherapy trial and what type of cancers are being put on to that? Is that your question? Could you repeat it?

Speaker 1

Yes. And that is correct. In the solid tumor narsotaglif trial, what indications are you enrolling? And also any of that you see more numbers of patients enrolling in the trial that we will see more data from those indications?

Speaker 2

So the monotherapy trial is open to all end stage cancers and is very variable. There's no one type of cancer dominates. It's the typical end stage patients that could include lung cancer, prostate cancer, bladder cancer, ovarian cancer. So it's very Diffuse and there's no single indication that dominates. So I don't think other than Safety, who I don't anticipate and we don't expect to have any efficacy signals because Patients are very diverse regarding their indications and their cancers.

Speaker 2

So the goal, like most Phase 1 studies, is just to establish recommended Phase 2 dose and I think the endometrial cancer study, it's up and running at the same time to combine recommended Phase 2 dose of monotherapy of neuragacycline with metrazole 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 and the approved CDK4six inhibitors. We don't anticipate any toxicity issues when metrazole is going to be added to the recommended Phase 2 dose generated from the monotherapy trial.

Speaker 1

Thank you, Steve. Very helpful.

Operator

From H. C. Wainwright.

Speaker 8

This is Lander on for Joe. I have two questions. The first question for narsaciclib. Are we expecting any initial efficacy data in the readouts anticipated in 4Q?

Speaker 2

So I'll take that one. So the CDK4six inhibitors, That's a great question, by the way. These are very important questions. So the investment community and the analysts Who probably already understand how these drugs work. These are not cytotoxic drugs.

Speaker 2

These Class of drugs prevent tumor proliferation. And if you look at the approvals For the 3 health authority approved CDK4six inhibitors, they were all based on 2 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.

Speaker 2

The way these drugs work to improve patients' lives is by prolonging PFS And belonging overall survival. And thus to really evaluate that intelligently, You need a control arm. So you could use historical controls by all means. But really in the modern era, the way to do that With a control arm to show improvement in either PFS or OS and thus Once we establish the recommended Phase 2 trial, the next hurdle will be to open randomized trial in early 2024 in LGEC and that is our plan and we remain on target for that plan.

Speaker 8

Got it. Got it. And one more question for Rigo Serdeep in RDEB. I may have missed it, but if you could provide us an update How many patients are still pending to be enrolled in the Phase II trial?

Speaker 2

So this is we have 2 international sites as ISTs participating in this trial. 1 at Thomas Jefferson in Philadelphia, where one of the world's experts in our dead squamous cell resides, Doctor. Andrew South And also Doctor. Johann Bauer in Austria. Those are the 2 primary sites.

Speaker 2

Since the results of these trials have been presented, we now have request to treat patients in Israel, in Chile, in Paris, France, and we're doing it on a compassionate use approach. In discussions with the agency, it was with the agency specifically they asked us And we will transition the trials to an Onconova 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 RDEB squamous cell. So we do the responses have been reported at a major medical meeting. We have what we think is Very impressive cutaneous complete remissions.

Speaker 2

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 efficacy evaluation, but they continue on either oral or intravenous rigosertib and we look forward the continuation of rigosurf to see an efficacy signal in a larger number of cases. 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 Onconovirus sponsored trial potentially in RDEB squamous cell carcinoma.

Speaker 8

Thanks for clarifying, Steve, and thank you for the updates.

Speaker 2

Pleasure, Adam.

Operator

Our next question comes from Robert line of Loboier from Noble Capital Markets.

Speaker 8

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

Speaker 2

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. This up to 3 patients at the next cohort. So far there's been no safety concerns and the next cohort obviously would be at a higher dose

Operator

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.

Speaker 2

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

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Key Takeaways

  • Nerazaciclib progress: The company is finalizing the monotherapy Phase 1 dose escalation and expects top-line data on safety, pharmacokinetics and the recommended Phase 2 dose (including a letrozole combination in LGEC) in Q4 2023, with a registrational randomized trial planned for 1H 2024.
  • Rigosertib strategy: After a constructive Type B FDA meeting, Onconova is designing a registrational trial in RDEB-associated squamous cell carcinoma with an update expected in 1H 2024, leveraging encouraging durable single-agent responses and tolerability data.
  • Combination studies: Two investigator-sponsored trials are evaluating rigosertib plus nivolumab in KRAS-mutated non-small cell lung cancer and melanoma, with NSCLC enrollment set to complete by year-end and initial data anticipated in 2024.
  • Financial runway: As of June 30, 2023, Onconova held $29.7 million in cash and cash equivalents, which is projected to support operations and ongoing clinical trials into Q2 2024.
  • Executive hire: Dr. Victor Moya joined as Consulting Chief Medical Officer, bringing over 15 years of biotech leadership and three decades of clinical research experience to accelerate the development of Onconova’s oncology assets.
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Earnings Conference Call
Traws Pharma Q2 2023
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