Ladies and gentlemen, thank you for standing by. Welcome to the Onconova Therapeutics Third Quarter 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. [Operator Instructions] As a reminder, this call is being recorded today, November 14, 2022. At this time, I'd like to turn the call over to Bruce Mackle of LifeSci Advisors.

Thank you, operator, and welcome everyone to Onconova's third quarter 2022 financial results and business update conference call. Earlier this afternoon, Onconova issued a press release announcing its plan to conduct a Phase 1/2a clincial trial narazaciclib combined with letrozole in endometrial cancer and reported 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.onconova.com. Following my introduction, we will here from Onconova's President and CEO, Dr. Steve Fruchtman; Chief Medical Officer, Dr. Mark Gelder; and Chief Operating Officer and Financial Officer, Mark Guerin. These prepared remarks will then be followed by a question-and-answer session. Before turning the call over to Onconova's management team, I'd 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'll now turn the call over to Steve.

Thank you, Bruce, and good afternoon to everybody. On today's call, we will focus predominantly on our two most recent and exciting pieces of news. These relate to our newly announced plans to advance our lead assets narazaciclib into a Phase 1-2a trial in second and third line, low-grade endometrioid endometrial cancer and our recent presentation that the ESMO conference featuring updated data from investigator sponsored study of rigosertib. Our CMO, our Chief Medical Officer, Dr. Mark Gelder, who will go into more detail on each of these points, but I would first like to briefly outline the rationale, underlying the upcoming endometrial cancer trial, which will evaluate narazaciclib in combination with the non-steroidal aromatase inhibitor letrozole. Our decision to pursue this clinical program was driven by three key factors. First, we recognize that endometrial cancer, which arises in uterine lining is an indication with a pressing unmet medical need for improved therapies is a large, addressable patient population, and in fact is the most common cancer of the female reproductive organs, low-grade endometrioid endometrial cancer represents the target patient population for our newly announced clinical development program for narazaciclib. Second, we believe a clinical program evaluating narazaciclib in combination with letrozole in endometrial cancer as a high probability of technical and regulatory success. This belief is supported by clinical data that demonstrates the benefits of combining an agent that inhibits the CDK 4/6 pathway with letrozole in this indication. As a reminder, narazaciclib potently inhibits CDK 4/6 alongside additional tyrosine kinases that play important roles in cancer cell growth, survival and metastasis, clinical data, which Dr. Gelder will discuss in more detail substantially de-risks our upcoming trial by providing validation and clinical proof-of-concept for narazaciclib's mechanism of action in endometrial cancer. The third and last driving factor behind our…

Thanks, Steve. And I'll begin by discussing our lead program the narazaciclib, which is advancing towards a Phase 1/2a study of narazaciclib and letrozole as combination therapy in second or third line recurrent metastatic low-grade endometrioid endometrial cancer or otherwise, referred to as LGEEC. The decision to move forward with a full clinical development program in LGEEC has been guided by extensive Phase 2 clinical data, demonstrating the safety and clinical benefit of combining a CDK 4/6 inhibitor with letrozole in this indication. This includes the results of the ENGOT-EN3-NSGO/PALEO study that was presented by Mirza at ESMO in 2020. This Phase 2 study was a randomized double blind placebo controlled trial, evaluating palbociclib plus letrozole versus letrozole plus placebo in patients with estrogen receptor positive or ER positive advanced recurrent endometrial cancer. Participants received letrozole orally on days 1 through 28 with either palbociclib or placebo orally on days 1 to 21 in 28 day cycles until disease progression. Progression free survival or PFS was significantly improved with letrozole and palbociclib compared to letrozole plus placebo with a hazard ratio of 0.56 and a median PFS of 8.3 months in the palbociclib arm versus three months in the placebo arm. This difference in median PFS between groups was statistically significant with a P value of 0.0376. In addition, disease control rate at 24 weeks was also improved in the combination therapy group, compared to the monotherapy or placebo group with values of 63.6% and 37.8% respectively. Safety data from the trial shows that the toxicity of palbociclib and letrozole combination therapy was manageable and most patients remained on treatment until disease progression. As anticipated treatment emergent grade three, four hematologic adverse events with leprozole with palbociclib were the most common AEs observed including neutropenia and anemia. Dose reduction and…

Thank you Mark. I'm happy to report that I'm going to finish the quarter ending September 30, 2022 with cash and cash equivalents of 42.6 million. This compares to 55.1 million as of December 31, 2021. Based on our current projections, we believe our cash position will be sufficient to fund our ongoing clinical trials and operations including the pursuit of corporate development opportunities into 2024, thereby taking us through key catalyst expected across the pipeline. Turning now to our financial results, research and development expenses for the third quarter of 2022 were 3.6 million compared to 1.8 million for the third quarter of 2021. General and administrative expenses for the third quarter of 2022 were 2.1 million and this compares with 2.3 million for the third quarter of 2021. We reported a net loss for the third quarter of 2022 of 5.4 million or $0.26 per share on 20.9 million weighted shares outstanding. This compared with a net loss of the third quarter of 2021 of 3.5 million or $0.22 per share on 16 million weighted shares outstanding. My financial review complete, I'll now turn the call back over to Steve.

Thank you, Mark. Before opening up the call for questions, I like to briefly review the near-term value drivers we are approaching. Looking first at narazaciclib, we expect to initiate our Phase 1/2a study in endometrial cancer in the first quarter of next year and we put preliminary data in the fourth quarter of 2023. In the first half of 2023, we expect to identify a recommended Phase 2 dose for narazaciclib to inform its further development multiple indications. With rigosertib, we're expecting additional data from the investigator sponsored nivolumab combination study in KRAS mutated non-small cell lung cancer in the first half of 2023. We expect to initiate an investigator sponsored study in metastatic malignant melanoma evaluating rigosertib in combination with the PD-1 inhibitor pembrolizumab. We are extremely pleased with the results seen in the squamous cell carcinoma trial complicating or death. These patients have few if any therapeutic options that work and we have already seen a complete response in our trial with single agent rigosertib. We believe this is extraordinary. There is non-dilutive funding to help finance the trial and we planning to report on additional patients already entered onto the current trial at the appropriate time at a major medical meeting. As we seek to generate value with these programs, we will continue to devote our internal resources primarily to narazaciclib while leveraging investigator sponsored studies and collaborations to facilitate rigosertib continued progress. In addition, we will continue to assess opportunities to potentially expand our pipeline, guided by a data driven approach that focuses on assets, backed by robust scientific evidence, demonstrating their potential and indications with high unmet medical needs. We are fortunate to have a robust financial foundation in place as we pursue these various avenues for value creation, and I eager to continue our work developing novel solutions for patients with cancers. Finally, I'd like to briefly thank those behind the progress we reported today. The list starts first and foremost with our clinical trial participants and also includes our employees, partners, investigators and shareholders. With that, we will now open up the line for questions. Operator.

[Operator Instructions] Charles Zhu with Guggenheim Securities. Your line is open.

My first question regarding the narazaciclib combination with letrozole. How should we think about the cadence of dose escalation in this combination relative to what you guys already did for the single agent dose escalation? Would you need to escalate in combination just like he did a single agent or could you possibly start the escalation to hire given your prior experience?

I'll ask to Dr. Gelder. Mark, please.

Yes. So, this has been discussed extensively as you can probably imagine, and because of the experience with the other CDK 4/6 inhibitors in their combination with letrozole in breast cancer, the current protocol that we will initiate, we're going to start the Phase 1 dose of narazaciclib at 200 milligrams a day, which is where we are now in the fifth dosing cohort. And so, we don't see any problems so that we will combine this with letrozole 2.5 milligrams every day, which is the usual approved dose of letrozole.

Got it. That makes sense. Sorry go on.

And dose escalation will proceed in 40 milligram. So, we'll do the 200 plus letrozole assuming that's well tolerated, et cetera. We'll then move to 240 plus letrozole et cetera. We'll not only be looking at PK and safety, but also the PD marker, the DiviTum assay from Biovica and the TK1 assay.

I just want to add and highlight to make sure everybody knows this. Dr. Gelder, we are very fortunate to have him. I want to highlight his background that everybody may know this. Mark is superbly trained and experienced surgical gynecologic oncologists, having worked at some of the major medical centers in our country, leading their efforts and that's why we are so pleased to have Mark be our Chief Medical Officer for his expertise in oncology. Just wanted to highlight that for the people on the call.

Great. And maybe one more follow-up. Given that the other CDK inhibitors have generated proof-of-concept data, but it doesn't appear that they are approved in this particular setting. What do you think you would need to demonstrate? And what in combination, what do think would be considered a win? Thank you.

So, we will look carefully at the data from the Phase 1/2a study. But based on the data with the available agents, we would expect that a median PFS of 8 to 9 months would be a clear win, because when you look at historical data with letrozole or other "antiestrogen" as single agents in this setting, it's generally the PFS is in three to four month range.

Ahu Demir with Ladenburg Thalmann. Your line is open.

Good evening. Thank you so much for taking my question. My question is also on narazaciclib program. Have you shown any data from endometrial cancers as a single agent activity? And what did it look like, if you could comment on that?

So, we don't have any data with nirazaciclib as a single agent in endometrial cancer. And if you look at the work that's been done in endometrial cancer with the other CDK 4/6, they have all combined with an oral mutation inhibitor letrozole.

I see. And my follow-up question is, palbociclib showed promising data, proof-of-concept. It was HR positive endometrial cancer. Are you planning to target that in that particular population or are you going to have a broader endometrial patient enrollment?

So, our patient population will be patient with low grade i.e. grade 1 or grade 2 endometrioid endometrial cancer. And historically, if you look at this population, 97%, 98%, 99% of them are exterior receptor positive. ER positivity is not routinely performed on all patients with endometrial cancer, unlike breast cancer. And the actual -- the threshold for ''endometrial" or estrogen receptor positivity is not well established for endometrial cancer like it is for breast cancer. So this is why we have decided to move forward with this population after consultation with lots of other experts in this area.

Robert LeBoyer with Noble Capital. Your line is open.

My question I thought may have been answered by Dr. [Guerin] (sic) [Gelder]. And I thought I may have heard that the dosing regimen is going to be every day compared with three on and three off. Is that correct?

Yes. So based on the data we have so far, and we believe for reasons we discussed, we prefer not having the one week off scheme that the other drugs required because of bone marrow suppression. In the U.S., our studies every day and to-date, we do not see significant marrow suppression. We believe already targeting the key tyrosine kinase because we do see some lowering of the white count, which is anticipated with this class of drugs but not to the degree that anything needs to be done. So, we believe in anticipate that we'll have well called the optimal dose, which will be every day and also once a day. Everyday dosing to optimize the anti-tumor proliferative effect and because of the safety seen to-date and in preclinical models as well, we do not -- have not seeing significant marrow toxicity.

And just one other financial question is, in the R&D expense line, there was a bit of an increase this quarter over the first half. And I was wondering if you could give some guidance as to what it might look like going forward for the next several quarters?

Mark Guerin?

Sure, thanks Robert. Yes, there was an increase in research and development expenses. As you can see, if you look at our 10-Q, a big chunk of that, compared to last year at this time was related to manufacturing. During the third quarter of 2022, you probably know that our historic quarterly cash burn rate has been around 4 million to 4.2 million. And as we embark on this Phase 1/2a combination study, naturally, that's going to go up. Our current studies are Phase 1, and/or investigator sponsored. So once we get back into sponsored studies, our burn will go up on a quarterly basis. And so, that the only guidance that we're comfortable giving at this point is what we said in the press release and in my comments that we believe based on our current cash and our plans that our cash will get us into 24. Hopefully, that's helpful.

I'm showing no further questions in the queue. At this time, I'd like to turn the call back over the speakers for any closing remarks.

Thank you, Operator. And thanks again to all who are joined us today. It's been our pleasure to update you on the progress and newly announced plans to pursue narazaciclib development, endometrial cancer, and to update you on the very encouraging clinical data we have seen and presented with rigosertib at ESMO. We look forward to providing additional updates in the future. As the Thanksgiving holiday approaches, we have much to be thankful for, special thanks to the brave patients who consent to participating on our experimental studies and to our investors who support our science and helping to bring new therapeutics to those in need. We wish all of you a very lovely evening and thank you again.

Ladies and gentlemen, thank you for your participation on today's conference call. This concludes today's event. You may now disconnect.