Ladies and gentlemen, thank you for standing by. Welcome to the Onconova Therapeutics Second Quarter 2021 Financial Results and Business Update Conference Call. At this time, all participants are in listen-only mode. Following management’s prepared remarks, we will hold a question-and-answer session. As a reminder, this call is being recorded today, August 12, 2021. At this time, I would like to turn the call over to Avi Oler, Senior Vice President of Corporate Development and General Counsel. Please go ahead.

Thank you. Good afternoon, everyone, and welcome to Onconova's second quarter 2021 financial results and business update conference call. Earlier this afternoon, we issued a press release reporting our quarterly financial results and business progress. If you have not seen this press release, it is available in the Investors and Media section of our website at www.onconova.com. On today's call, Dr. Steve Fruchtman, our President and CEO, will give a high-level overview on our recent progress and future outlook and then Dr. Mark Gelder, our recently appointed a Chief Medical Officer will introduce himself and provide a more detailed update on our clinical and scientific progress over the past few months. Finally, Mark Guerin, our Chief Financial Officer will then review our second quarter financial results and we'll move to the Q&A portion of the call. Before we begin, I'd like to remind everyone that statements made during this conference call by management 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, it is my pleasure to turn the call over to Steve.

Thank you, Avi. Good afternoon, everyone and thank you for joining us. As the COVID-19 pandemic continues to progress in the regions of our country and the world, we hope you and your loved ones are remaining safe. As has been the case throughout the pandemic, we remain committed to successfully navigating any challenges that maybe posed to execute on our clinical and corporate objectives. Thanks to the talent and dedication of our employees, partners and investigators, we recently wrapped up a highly productive quarter and have achieved both clinical and corporate milestones since our last earnings call. In our lead program, evaluating ON 123300 or simply called 123, we began dosing patients in our US Phase I trial, evaluating an everyday continuous dosing schedule. As a reminder, 123 is a novel multi-kinase inhibitor targeting CDK4 and 6 and additional kinases involved in tumor genesis including ARK5, which is reported to be involved in cancer cell survival and the mechanisms of how cancer cells metastasize. I'll let Dr. Mark Gelder speak in more detail about our 123 clinical development program and the importance of this Phase I study in a few minutes but we'll say now that the trial is continuing to advance and we remain on track to determine the recommended Phase II dose of 123 by the first half of next year. The recommended Phase II dose will be determined based on data from this clinical trial in the US as well as the ongoing Phase I trial in China, evaluating there a three weeks on, one week off dosing schedule of 123. Both administration schemes under study are based on the two different dosing schemes of the FDA-approved CDK4/6 inhibitors in hormone receptor positive HER2-negative metastatic breast cancer. Outside our lead program, we also saw a substantial…

So thanks Steve, and thanks to all who are listening, as well for joining us here today. For those of you on the call, who don't yet know me, I joined Onconova as the company's Chief Medical Officer in the middle of June of this year. I am trained as an academic GYN oncologist and have more than 35 years of experience in drug development in hematology and oncology, as well as medical affairs and medical marketing. I also have a fair degree of expertise in the development of kinase inhibitors as cancer therapeutics. One of the primary drivers behind my decision to join Onconova was indeed the potential I saw in the company's pipeline and in particular 123's clear differentiation compared to currently approved CDK4/6 inhibitors. 123's ability to simultaneously inhibit both the cell cycle and cellular metabolism through CDK and ARK5, respectively positions it as a compelling approach for treating cancer patients that are refractory or have become resistant to current CDK4/6 inhibitors. I was also highly impressed by pre-clinical data showing that 123 exhibits superior CDK4 inhibition and improved on-target toxicity compared to palbociclib, which is currently the most widely prescribed CDK4/6 inhibitor. 123's potent kinase inhibition profile and safety profile based on mouse models with less neutropenia observed when directly compared to an approved CDK4/6 inhibitor may provide single-agent efficacy and facilitate continuous daily dose. This would be a significant development since palbociclib and another improved CDK 4/6 inhibitor, ribociclib are prescribed in combination with an anti-estrogen in a three weeks on, one week off treatment schedule due to a lack of single-agent activity and issues of tolerability including side effects related to neutropenia. We believe that continuous daily dose combined with 123's ability to potently inhibit CDK4/6 and other kinases may lead to improved efficacy…

Thanks Mark and good afternoon everyone. I'll begin with a quick review of our second quarter expenses. And then, I'll discuss our cash position and runway. Research and development expenses for the second quarter of 2021 were $1.9 million, compared to $4.8 million for the second quarter of 2020. The decrease was primarily related to clinical development and consulting expenses related to our INSPIRE study, in the 2020 period. General and administrative expenses for the second quarter of 2021 were $2.9 million, compared to $2.6 million for the second quarter of 2020. The increase here was primarily related to expenses for investor relations, proxy solicitation and fees related to our special meeting by proxy, in the 2021 period. We reported a net loss for the second quarter of 2021 of $4.2 million or $0.27 per share on 15.8 million weighted average shares outstanding. This compares with a net loss for the second quarter of 2020 of $7.4 million or $0.65 per share, on 11.3 million weighted shares outstanding. Cash and cash equivalents as of June 30th, 2021 were $43.7 million, compared to $19 million as of December 31st, 2020. We believe that this cash position will be sufficient to fund our ongoing clinical trials and business operations for more than 18 months and through the achievement of significant milestones including, pursuing corporate development opportunities. This completes my financial review. I'll now turn the call back to Steve.

Thank you very much, Mark. In summary, we have multiple, key near-term milestones and value drivers ahead of us. One, the continued progression of our, ON 123300 studies in the U.S., and China and the anticipated selection of a recommended Phase II dose in the first half, of next year. Two, the presentation of preliminary data from the investigator-initiated Phase I/IIa study of the rigosertib-nivolumab combination therapy in refractory KRAS-mutated non-small cell lung cancer trial to be presented in late September. Three, finally we continue to actively evaluate strategic licensing opportunities to enhance our product portfolio. As with all of our decisions, any decision we make on this front will be driven by science and the potential for clinical benefit in an indication with an unmet medical need. So with that review of our clinical progress and our financial results, we'd like to open up the call now for questions. Operator?

We have your first question from Dr. Etzer Darout with Guggenheim Securities. Your line is open.

Great. Thanks for taking the questions and congrats on the progress here. So the first question for me. Just wondered if you could provide any additional color on the ongoing China study for 123, maybe the types of patients being enrolled so far. And anything differentiating about the data beyond the lack of grade three plus neutropenia that you highlighted? And then I guess secondly anything further on the protocol amendment for rigosertib-nivolumab trial that's being prepared maybe what doses may be explored? And any other changes that you may be making to the study design. Thank you.

Thank you, Etzer. Dr. Gelder, would you like to take those two questions?

Sure, Steve. No, thank you. So the study with 123 in China, as we mentioned, we are currently enrolling the third cohort. So the first cohort was at 40 milligrams a day, days one through 21 of a 28-day cycle. Second was at 80. And this third cohort is at 120 milligrams. What I can tell you is that all three patients in the third cohort have been enrolled the DLT period for the third patient has not yet been completed. And what the -- in terms of the tumor types that we're seeing its open to all solid tumors. They have seen a fair amount of -- well they've seen a variety of different tumors have seen breast cancer, have seen I believe, colorectal cancer, have seen prostate cancer. So they're seeing the usual types of patients that you would expect in a Phase I trial that is open to all solid tumors. In terms of the safety profile and what we're seeing the tolerability, so far seems to be very, very good. We have not seen any DLTs and we have not seen any grade three or beyond neutropenia. We've seen a couple of patients who have had grade one or grade two neutropenia. The other side effects that we've seen have been low-grade, fatigue weakness, that sort of thing but we have not seen anything to date that is a strike. Is there anything else I can tell you about the study in China?

No. Maybe if we could talk a little bit about the rigosertib protocol amendment and any changes there that you could, kind of, provide incremental color on?

Sure. So as you know the rigosertib trial that's ongoing is -- and this is a combination study with rigosertib and nivolumab, it's in stage 4 non-small cell lung cancer with KRAS mutations who have progressed on "standard of care." The original protocol called for three dose-escalation cohorts. And the first cohort was rigosertib 280 milligrams PO twice a day or BID. The second dosing cohort was 560 milligrams of rigosertib in the morning 280-milligram mid-afternoon. And the third dosing cohort was 560 milligrams twice a day. And what I can tell you is that in the first and second cohort there were no DLTs observed. I should also mention that in all of these cohorts in addition to the rigosertib patients received nivolumab 240 milligrams IV every two weeks. In the first two cohorts there were no DLTs observed. In the third dosing cohort there was one DLT observed. It was grade three hyponatremia. As you know, hyponatremia is commonly observed in patients with non-small cell lung cancer but has also been seen with rigosertib. And so based on a variety of data, I think appropriately a decision was made that this was due to the rigosertib. But there was one DLT an additional three patients were enrolled because it was a three plus three design and there were no further DLTs observed. So the investigator went on and started enrolling six more patients at that dose level. And in -- because this is an ISS an investigator-initiated study, the investigator really makes the decisions in terms of what he wants to do next in discussions with us and in discussions with the folks at Bristol-Myer because remember Bristol-Myers Squibb providing the nivolumab. All of the parties concerned have said they would be interested in seeing further dose escalation. So have we seen the protocol amendment yet? No, I have personally not seen a final copy of it in writing. That will be up to the PI of the study when he presents that to us. What do I anticipate? My suspicion is that this dose level four will probably be -- it will be an escalation of the rigosertib from 560 to 660, 760 probably 840 milligrams in the morning and 560 milligrams in the afternoon in combination with the nivolumab. And if he wants to go with dose level 5 that would then probably be 840 twice a day in combination with nivolumab. But again I have not seen this yet. There have been some discussions, but I haven't seen it in writing. But do we anticipate that we are going to get an amendment for further dose escalations? Yes, we do. But Steven Fruchtman, did you have anything to add to that?

No, Mark. Thank you. Etzer, thank you. I think that is the anticipated based on the tablets that we are currently using is 280 milligrams that's a 560 plus 280 that's how Mark came up with the 840 number. So probably next dose escalation will be 840 in the morning 560 in the afternoon if there are no additional DLTs and the next will be probably 840 in the morning, 840 in the afternoon. We look forward to that amendment being completed.

That makes sense. Thank you.

Thank you, Etzer.

We have your next question from Joe Pantginis with H.C. Wainwright. Your line is open.

Hi, this is Sara on for Joe. Thanks for taking the questions. My first question is I'm just wondering how is the screening process currently going for your squamous cell carcinoma study in the recessive dystrophic epidermolysis patients. If you could just provide any color on how that process is being handled.

Mark?

Yes. So, again, this is a investigator-initiated study that is currently open in Austria. What I can tell you is that a second site in the UK, we anticipate will be opening in the near future. But the exact timing of that I can't tell you for certain today. Additionally, a very similar study, but separate ISS in this same population will open here in the United States shortly. And the screening is -- I mean I can go through the screening criteria inclusion-exclusion criteria et cetera for you. But the -- this is a population of patient with this very unfortunate disease who have developed biopsy-proven squamous cell carcinomas and who have been refractory to standard-of-care. And as you may or may not be aware multiple different therapies have been tried over the ages for these patients none of them to date have been very successful because of the fact that they have large areas of skin that are denuded cytotoxic therapy is very risky in this population because of the fibrosis in webs in the esophagus and limited ability to swallow pills and take things orally. Many of these patients have to receive medications intravenously. And the checkpoint inhibitors have not proven to be very effective in this population. There are no large series with the checkpoint inhibitors in these populations. There are just some isolated case reports. But in talking with the investigator, the results have generally been somewhat discouraging. So, they are very hopeful based on the preclinical work that they have done and the PLK1 over-expression seen in many if not most or all of these tumors they are very hopeful that they will see some activity with rigosertib. I'm not sure inclusion-exclusion criteria I can. But this is a very, very rare disease.

I think the answer to your question is when a patient is identified, they'll be put on the study. These are very rare patients as Mark was saying nothing works. Actually it's proud -- but I shouldn't say this but I will. Anybody wants to go on a weight loss program after eating you can view pictures of these patients it's very tragic. We hope to be able to help them.

Okay. Yes, that's really helpful. And then I had one quick follow-up question. You kind of touched on this briefly before but regarding your 123 program what's your communication strategy for the study in China? Do you have a certain number of patients that you'd want enrolled first before like fully disclosing your data set? Or can early responses in limited numbers also be shared? Or what's your yes what's the strategy for this program in general?

Yes sure. I'll take that one. So, we have standing joint development meetings between Onconova and HanX to make sure that all the data both for the US patients, we review that data with them, and we review the data put on the 123 protocol in China. My approach, my vote, I will do this as a consensus is probably to wait for the recommended Phase II dose to be determined and then at a major medical meeting to present the data from the Phase I and to do it that way as opposed if we get a response to -- just to announce it, we probably would prefer completing the study seeing what patients because as Mark -- Dr. Gelder said, we have diverse patient population. It's all -- there's many different cancer indications. So we probably will do it -- reveal the data at a major medical meeting.

Okay. Thank you.

Thank you.

We have your next question from Dr. Robert LeBoyer with NOBLE Capital. Your line is open.

Good afternoon. I just had a quick question about the second cohort in the 123300 trial, if you could just discuss how many patients and what the timing of that data would be? You mentioned selection of dose in the second half, but if there's any data presentation or any other details you can give that would be helpful?

So I'll take that one as well. So the second cohort as Mark said is 80 -- I'm just making sure you're asking about ON 123300. So the second cohort was treated at 80 milligrams three out of four weeks. And that's the only thing, we revealed in the public domain so far. And as I already said rather than doing it per cohort, the third cohort has already been fully accrued, but we anticipate revealing the data from the entire study at a major medical meeting when we -- following reaching the recommended Phase II dose.

Okay. Great. And did you mention when the trial with rigosertib and KEYTRUDA might start accruing patients?

That trial the protocol is being finalized. It needs the usual IRB approval. So once the protocol is finalized, which I -- we expect quite soon it will be submitted to the IRB, the Vanderbilt IRB. I don't know if they meet every two weeks every month. So following IRB approval, I think we look forward to the initiation of patients being put on to the protocol. It's hard to predict precisely. I would guess in the next few months, as a guess.

Okay. Okay. Great. Thank you very much.

Thank you.

I'm showing no further questions at this time. I'd like to turn it back to Steve Fruchtman for any closing remarks.

Thank you everybody for participating on today's update call. We look forward to executing on our business plan, and to keep you appraised of all of our progress. We appreciate your continued interest in our programs. Thank you again and have a great evening, so long.

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