Ladies and gentlemen, thank you for standing by. Welcome to the Onconova Therapeutics' First Quarter 2022 Financial Results and Business Update Conference Call. At this time, all participants are in a listen-only mode. Following management's prepared As a reminder, this call is being recorded today, May 11,022. At this time, I'd like to turn the call over to Avi Oler, Senior Vice President of Corporate Development and General Counsel.

Thank you operator, and welcome everyone to Onconova's first quarter 2022 financial results and business update conference call. Earlier this afternoon, we issued a press release reporting our financial results and business progress. If you have not yet seen this press release, it is available on the Investors and Media section of our website at www.onconova.com. Today's call will begin with our President and CEO, Dr. Steve Fruchtman providing an overview of our recent progress and corporate strategy. Dr. Fruchtman will then ask our Chief Medical Officer, Dr. Mark Gelder to review our clinical programs. Our CFO, Mark Guerin will then report our first quarter financial results before we move on to a question-and-answer session. Before turning the call over to Steve, I’d like to remind everyone that statements made by management 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, it is my pleasure to turn the call over to Steve.

Thank you, Avi and good afternoon everyone. Our clinical programs continued to make strong progress over the past months as we efficiently executed on the corporate strategy we've spoken about on our past earnings calls. This strategy has us internally focused on our nerazacyclib program, while leveraging relationships with thought leaders from industry and academia to continue the development of rigosertib through investigator-sponsored studies, based on the mechanism of action of rigosertib to target cancer indications of interest. As many listening may recall, nerazacyclib is a orally available multi-targeted kinase inhibitor, it has a low nanomolar affinity for CDK4/6 and other kinases that play an important roles in tumor cell proliferation, metastasis and survival. It can also stimulate anti-cancer immunity through the inhibition of the CSF1 receptor and disrupt several pathways linked to the described mechanisms of drug resistance for this class of drugs. We believe this inhibitory profile positions nerazacyclib to be a highly differentiated and potentially a best-in-class therapy. And we look forward to the publication of an abstract at the upcoming ASCO 2020 meeting that describes this topic further. Currently two ongoing Phase I trials are evaluating nerazacyclib in patients with solid tumors. These trials are collectively designed to inform the development and latest stage studies, and also seek to begin clinically demonstrating the advantages of nerazacyclib’s differentiated pharmacologic profile. Dr. Mark Gelder will be speaking about these studies in more depth. So for now, I'll just remind everyone that they evaluate both a continuous dosing schedule and a three weeks, one week we off schedule. These dosing regimens mimic the drug administration schemes for those of the FDA approved CDK4/6 inhibitors. I'm pleased to say today that each of nerazacyclib’s Phase I trials remains on track and that we expect to identify the optimal recommended Phase…

Thank you, Steve, and good afternoon everyone. It is my pleasure to provide an update on our recent clinical progress and future plans. Starting with a discussion of our lead nerazacyclib program. As Steve mentioned, nerazacyclib is currently being advanced in two complementary Phase I dose escalation studies in patients with solid tumors, one in the United States and one in China where we are collaborating with HanX Biopharmaceuticals. The US trial is evaluating a continuous daily dosing schedule in patients with advanced solid tumors. Enrollment remains ongoing in this trials fourth cohort, which is evaluating a 160 milligram dose of nerazacyclib administered orally each day. The safety findings coming out of this study continue to be very promise. As we have not observed any dose limiting toxicities or clinically meaningful cases of neutropenia. Although, we are beginning to see anticipated on target effects. If the final data from our US study confirm nerazacyclib favorable safety profile with daily dosing, it will provide an important point of differentiation between nerazacyclib and the approved CDK4/6 inhibitors, palbociclib and ribociclib. Due to their associated bone marrow toxicity that leads to neutropenia, these two drugs are administered with a three week on, one week off dosing schedule to a lot of time for bone marrow recovery. We believe that avoiding an interrupted dosing schedule with nerazacyclib could potentially contribute to enhanced efficacy. Alongside our progress in the US, we have also seen nerazacyclib’s Phase I trial in China proceeding as planned. The study continues to enroll patients into its fifth cohort, which is evaluating a 200 milligram oral dose of nerazacyclib administered each day with a three weeks on, one week off dosing schedule. Given the favorable safety data seen in this trial to date HanX is currently preparing a protocol amendment that…

Thank you, Mark, and thanks to everyone who has joined today's call. I'm pleased to say that Onconova remains in a strong financial position. As of March 31, 2022, the company had cash and cash equivalents of $50.8 million, compared to $55.1 million as of December 31, 2021. Based on our current projections, we believe our current cash position will be sufficient to fund our ongoing clinical trials and business operations, including the pursuit of corporate development opportunities for more than 18 months. This runway is expected to take us through the achievement of multiple important milestones. Turning now to a review of our first quarter financial results. Research and development expenses for the first quarter of 2022 were $2 million compared to $1.9 million for the first quarter of 2021. General and administrative expenses for the first quarter of 2022 were $2.2 million and this compares with $2.2 million for the first quarter of 2021. We reported a net loss for the first quarter of 2022 of $4.1 million or $0.20 per share on 20.9 million weighted average shares outstanding. This compares with a net loss for the first quarter of 2021 of $4.7 million or $0.32 per share on 14.6 million weighted common shares outstanding. This completes my financial review. I'll now turn the call back over to Steve to provide a summary of our anticipated milestones before we move on to Q&A.

As always, thank you, Mark. We expect to achieve several important clinical milestones over the upcoming months. Starting with nerazacyclib, we remain on track to establish its recommended Phase II dose in the second half of this year. This then enable the subsequent initiation of a Phase II basket trial and a number of important indications, including hormone receptor positive HER2-negative refractory metastatic breast cancer. With nerazacyclib we expect the investigator-sponsored trial evaluating rigosertib pembrolizumab combination therapy in melanoma to open for enrollment later this quarter. We also expect the continued advancement of the ongoing Phase I/IIA trial of rigosertib plus nivolumab in advanced KRAS mutated non-small cell lung cancer. Updated data from this study are expected with great anticipation by year's end. Finally, we continue to assess opportunities to potentially expand our pipeline through strategic licensing and collaborations. With regards to these assets, I will emphasize two points. First, any action here will be data driven based on the science and market size underlying the opportunity. Second, we intend to take a highly selective approach in these efforts as we continue to have very strong conviction around the therapeutic and commercial potential of our current assets. With that, we will now open the call for questions. Operator?

Our first question comes from Charles Lu with Guggenheim.

Good evening, everyone, and thanks for taking the question. Regarding CDK4/6 inhibition, to what extent is neutropenia an on target effect? And do you need to observe neutropenia in order to also see a therapeutic effect associated with your inhibitor? Thank you.

Mark Gelder, would you like to take that?

Sure. And thank you for the question. So neutropenia is an on target effect of CDK4/6, particularly CDK6 inhibitors. If you look at the Phase I data from palbo, ribo and abemaciclib, you'll see that neutropenia once the dose limiting toxicity or DLP associated with both palbociclib and ribociclib, and it was really the neutropenia that was responsible for the ultimate dose selected to move forward in their Phase II and III clinical trials and it was also responsible for the necessity of a three week on, one week off schedule. Abemaciclib, also a very potent CDK4/6 inhibitor also has some associated neutropenia. But if you look at the Phase I data with abemaciclib, diarrhea was their primary DLT. And because they had some but it was not actually the dose limiting toxicity and the neutropenia that was observed did not necessitate a three week on, one week off dose schedule. Abemaciclib has a continuous daily dosing. So do we anticipate seeing some neutropenia, as we continue with our dose escalation? Absolutely we do, we will not be surprised at all, we expected. Based on our preclinical data do we think that the neutropenia associated with the nerazacyclib will be as severe or profound as that with palbociclib or riboside. No, we do not. And what do we anticipate will be the DLT associated with the nerazacyclib. We don't really know yet what our DLT will be. We have not seen a DLT in our study here in the US, but do we anticipate we will see some neutropenia? Yes we do and I’m hopeful. Are we all hopeful that the neutropenia will not facilitate a three week on, one week off schedule, but the jury is still on.

Got it. Great, thanks for that color and detail.

Our next question comes from Ahu Demir with Ladenburg.

Hello team. Thank you very much for taking my question. My question will be on nerazacyclib as well. I'm curious to hear what is the extent of preclinical models we are expecting to see at ASCO? Any additional color would be much appreciated.

I'll ask Mark Gelder again to take that. Mark?

So we submitted an abstract to ASCO describing the kinase inhibitory profile associated with nerazacyclib, we did not submit an abstract that describes any of its activity in terms of preclinical models, such as PDX or xenograft date.

That's helpful. My follow-up question will be again on nerazacyclib. How many active sites is currently open? And do you plan to open additional sites? Curious on the enrollment status. I'm sorry, I joined late, I hope I'm not asking something you already covered.

Mark?

Yeah. So again, thank you for the question. In our Phase I study here in the US, we have three active Phase I sites who have all been enrolling very well. And do we anticipate opening additional sites for the dose escalation -- the Phase I dose escalation study? No, we do not. As we open additional studies as part of the basket trial, once we achieved the recommended Phase II dose, well we open additional sites for the basket studies? Absolutely, we will. Yes.

That's helpful. My last question will be, are there any rational combination of strategies you could use to pair it with nerazacyclib? Are you considering any of those given the safety profile has to match, of course, but just curious if there are any rationale matches with nerazacyclib?

Mark?

Yeah. So again, thank you for the question. Great question. And I think that if you look at where the currently approved CDK4/6 is, where their approval is, i.e. hormone receptor positive HER-2 negative metastatic breast cancer and you look at the combination therapies employed with the three approved agents, i.e. either a raw mutation inhibitors, surge, et cetera. We will be doing combination studies with one or more raw mutation inhibitors, we'll be doing combination studies with one or more (ph). We will -- we are also planning some additional combination studies that we think make a very good mechanistic sense and we will be outlining those in the future. But yes, we are planning combination studies with at least two other, if not more anti-cancer agents.

And just to give –

Great. Thank you very much.

And I would just to give Mark Gelder a break. As you know, mantle cell based on the mechanism of action of nerazacyclib and as we mentioned it is a great interest to us and based on the anticipated profile and perhaps some preclinical studies planned, drugs like ibrutinib in mantle cell are the standard of cash, so we could anticipate looking at combinations with the typical anti-mantle cell drug use, such as ibrutinib as well.

Very helpful. Thank you very much. Much appreciate you taking my questions.

Our next question comes from Joe Pantginis with H.C. Wainwright.

Hey guys, good afternoon. Thanks for taking the question and the details today. So sticking with nerazacyclib a little bit, obviously everything we're discussing today is the completely classical route and going to identify the RP2D in the second half. So I wanted to ask my question this way, with all the initiatives that FDA, how are you going to look to reconcile, if that's the right word, the initiatives with the FDA to identify the minimal effective dose?

Well, I tried to give Mark a break, but I can’t. Mark Gelder, would you like to handle that.

What I can tell you is that, we have recently completed and finalized a protocol amendment for the ongoing Phase I dose escalation study, where we are going to incorporate a PD, pharmacodynamic marker, so that we will not only be looking at the safety profile with each dose escalation, but we will also be looking with the PD marker. And this will allow us not only to identify the “MTD” or maximally tolerated dose, but also a dose where we achieved maximal biological effect based on the PD market.

Got it.

So that protocol amendment has been finalized, that's been signed and the amendment has been sent to the three sites for submission for their IRB has been submitted to the FDA as well.

Okay. And then -- so you're talking about markers. That's a good segue for my next question. I guess earlier in your prepared comments when you talked about on target effects that you're seeing already and of course, you already have the discussion about neutropenia, any other details about what other on target affects you are seeing? And how you're measuring them?

Go ahead Mark. Please.

So the other on target effects that we're seeing are, again, primarily related to bone marrow and bone marrow precursors. And so looking at hematocrit hemoglobin levels looking at platelet counts, again, looking at white blood cell counts, etcetera. So we are -- this is primarily through looking at different laboratory values and the CBC is the most sensitive indicator of CDK6 inhibition.

Got it. And then my last question, just switching gears, thanks for the patients. When you look at the potential for a Phase II in RDEB, obviously, there is no standard of care really. And I was just wondering at this point could you take any broad strokes as to the design or size of this study one would guess that it wouldn't be that big.

Well, I'll take that. I think actually Joe, it could be tiny. This is such an ultra-rare disease, 100 patients -- new patients per year in the US, most of them die and foresee a wound and infection before they develop squamous cell carcinoma, but the fact that we have one complete remission, rate limiting step in my view is to get more patients, because of the ultra-rare nature of the disease. I don't think we would have to do a controlled Phase II trial. I think if we have few more patients we have the dose, we have the dose for few more patients on the current trial, if the responses are seen the plan would be to go directly to the FDA to ask for approved in this rare indication based on the response rate observed and how durable the response has been to date. So that would be our plan. Get a few more patients has robust response that we've seen to date and then go to the FDA with our data and have a discussion with the FDA about an approval or what next steps would it take to get such an .

Got it. Thanks a lot. And I’m looking forward to the updates later this year.

Our next question comes from Robert LeBoyer with Noble Capital Markets.

I'm opposed to giving Dr. Gelder a break. So I would like to ask a question about the rigosertib trial that's coming up. Based on the discussion earlier, it sounds it's going to do a combination trial of rigosertib with KEYTRUDA and metastatic melanoma. And this is going to start with a phase using a single-arm in a single center and then go to a second stage with additional patients. Could you elaborate as much as you could on the number of patients, treatment time and time for data or starting the second Phase.

Sure.

Steve, do you want me to handle that or do you want to go

No please, Rob, has good taste and he sounds like he prefers you, so go ahead, Mark, please.

So the study is going to be conducted, it’s a Phase II study or Phase I2 study. It's going to be conducted at a single academic center that has a very high volume melanoma patient population. It will -- the inclusion criteria are such that, all patients will have been required to have failed prior checkpoint inhibitor therapy and by that, I mean, progressed on prior therapy. It's not going to include patients who are intolerant, because this is a combination of rigosertib and pembrolizumab. And in Stage 1 there will be 10 patients enroll. If a certain response rate is met, as defined in the protocol, it will then progress on to Stage 2. Currently Stage 2 will take place at the same institution. They feel confident that they have a very adequate patient population to enroll this trial quickly. The Stage 2 will enroll an additional approximately 20 patients. And if all goes well and as planned and looking at the volumes that they do have, we do believe that they can meet the enrollment targets, but if all goes well, we should have data from these first stage by the first part of next year. We believe that we will have Stage 1 fully enrolled by the end of the year and then we should have some response data in the first part of next year. Remember, the primary endpoint is response rate per resist. And so, it's going to take a minimum two cycles, some patients may have responses early i.e. after one or two cycles, but it may be that we don't see responses in other patients with three or four cycles. So we won't -- we don't anticipate having results of the first stage until the first part of next year.

Great. Thank you very much.

But this is a -- this is going to be conducted at an academic center with a very high volume of melanoma.

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

Thank you, operator. I’d like to once again thank all the those participating today and for your very insightful questions. We are excited about our recent progress and look forward to the continued execution of our corporate and clinical plans as outlined today. Please stay safe and have a nice evening and take care.

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