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Edited Transcript of ONTX.OQ earnings conference call or presentation 12-Nov-20 9:30pm GMT

·26 min read

Q3 2020 Onconova Therapeutics Inc Earnings Call Newtown Nov 13, 2020 (Thomson StreetEvents) -- Edited Transcript of Onconova Therapeutics Inc earnings conference call or presentation Thursday, November 12, 2020 at 9:30:00pm GMT TEXT version of Transcript ================================================================================ Corporate Participants ================================================================================ * Abraham N. Oler Onconova Therapeutics, Inc. - Senior VP of Corporate Development & General Counsel * Mark Patrick Guerin Onconova Therapeutics, Inc. - CFO * Richard Charles Woodman Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development * Steven M. Fruchtman Onconova Therapeutics, Inc. - CEO, President & Director ================================================================================ Conference Call Participants ================================================================================ * Ahu Demir NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst * I-Eh Jen Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst * Joseph Pantginis H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst ================================================================================ Presentation -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- Ladies and gentlemen, thank you for standing by. Welcome to the Onconova Therapeutics Third Quarter Financial Results and Business Update Conference Call. (Operator Instructions) As a reminder, this call is being recorded today, November 12, 2020. At this time, I would like to turn the call over to Avi Oler, Senior Vice President of Corporate Development and General Counsel. -------------------------------------------------------------------------------- Abraham N. Oler, Onconova Therapeutics, Inc. - Senior VP of Corporate Development & General Counsel [2] -------------------------------------------------------------------------------- Thank you, operator. Good afternoon, everyone, and welcome to Onconova's Third Quarter 2020 Financial Results and Business Update Conference Call. Earlier this afternoon, we issued a press release reporting our financial results and business progress during the quarter. 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 discuss the company's recent highlights and anticipated clinical and business milestones. And then Mark Guerin, our Chief Financial Officer, will review third quarter financial results. Following Mark's report, we'll move to the Q&A portion of the call and we'll be joined by Dr. Rick Woodman, our Chief Medical Officer. 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. Please see the forward-looking statements disclaimer in the press release issued this afternoon and the risk factors in the company's current and future filings with the SEC. With that, it's my pleasure now to turn the call over to Steve. -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [3] -------------------------------------------------------------------------------- Thank you, Avi. Good afternoon, everyone, and thank you for joining us this afternoon. We hope you and your loved ones are safe and remain healthy. The COVID-19 pandemic has certainly impacted us all in how we live and work together. At Onconova, we are still awaiting word on our funding request to the National Institute of Allergy and Infectious Diseases branch of the National Institutes of Health and the Biomedical Advanced Research and Development Authority, also known as BARDA, for the possible funding of clinical trials with rigosertib in patients with COVID-19 disease. However, cancer and the development of effective new anticancer therapies remains a significant health issue and is our corporate focus. We believe Onconova is well positioned to play an important role in developing differentiated therapeutics for cancer care. During the third quarter, our product pipeline advanced nicely with ON 123300 entering the clinic in a Phase I study in China and oral rigosertib entering a Phase I investigator-initiated study in combination with the PD-1 inhibitor, nivolumab, in KRAS-mutated non-small cell lung cancer. The senior management team in Onconova brings substantial drug development expertise and a previous string of successes in anti-cancer drug development to our company, Onconova. Our core expertise is to identify promising drug candidates, develop and test them and ultimately, to commercialize them. Both Dr. Rick Woodman and I are medical oncologists by training, with careers in academia prior to joining industry. And the Onconova team has developed and brought to market numerous successful oncology products during our careers to date. At Onconova, our lead pipeline product is ON 123300, which is a proprietary first-in-class multikinase inhibitor targeting CDK4/6 and ARK5. ON 123300 simultaneously inhibits both cell cycle and cellular metabolism through CDK and ARK5, respectively. And in vitro has been shown to be cytotoxic to cancer cells, thus killing cancer cells rather than cytostatic or nearly inhibiting the growth of cancer cells. The currently commercially available CDK inhibitors are typically cytostatic. We believe with this mechanism of action targeting both CDK4/6 and ARK5, ON 123300 represents an innovative potential approach for treating solid tumors and hematologic malignancies that are refractory or have become resistant to commercially available CDK4/6 inhibitors. Based on preclinical models, ON 123300 may have utility for patients with certain types of breast cancer and non-Hodgkin's lymphoma. And based on these preclinical models, ON 123300 may also have broader utility potentially for advanced mantle cell lymphoma, multiple myeloma, colorectal cancer, hepatocellular carcinoma and inoperable glioblastoma due to the preclinical evidence that ON 123300 can cross the blood-brain barrier. We are particularly pleased that during the third quarter, ON 123300 entered the clinic in China, with our partner, HanX Biopharmaceuticals. The HanX Phase I dose escalation study began in September. As of today, the first cohort of 3 patients, each who has breast cancer, has been enrolled. The Phase I study in China is a standard 3x3 dose escalation study with each cohort requiring 3 or 6 patients, depending on the number of dose-limiting toxicity observed, if any are observed. This Phase I study is expected to enroll patients with advanced relapsed/refractory cancer at 2 sites in China, and together with our planned Phase I study in the U.S., will inform the future development of ON 123300. In the U.S., we are preparing to file an investigational new drug application with the FDA by the end of this year, with patient enrollment expected to begin in the first half of 2021. We expect that our Phase I dose escalation and dose expansion study will differ from the HanX study in both dosages and treatment cycles, but believe the data from these 2 studies will generate important information to inform anticipated later-stage studies. Our current plan is for the Phase I trial in the U.S. to assess safety, tolerability and pharmacokinetics of ON 123300 administered orally at increasing doses, starting at 40 milligrams daily or higher, for consecutive 28-day cycles in patients with relapsed or refractory advanced cancer including, but not limited to, patients with hormone receptor positive and HER2- metastatic breast cancer with clinical resistance to the approved second-generation CDK4/6 inhibitors. Once the recommended Phase II dose is established, our plan is to enroll at least 36 hormone receptor positive HER2- postmenopausal metastatic breast cancer patients with resistance to the approved second-generation CDK4/6 inhibitors as well as patients diagnosed with advanced non-Hodgkin's lymphoma, with a special interest based on preclinical studies, in mantle cell lymphoma. This trial design differs from the study in China in that HanX will dose patients daily for 21 days; and in the U.S., we will study continuous daily dosing for a 28-day cycle. Notably, of the 3 currently approved CDK4/6 inhibitors, 2 were tested and used for dosing in 21-day cycles, and 1 was tested in a 28-day cycle. All 3 are blockbuster drugs marketed by (inaudible) companies. We expect these 2 Phase I studies, the one in China and the one in the U.S., to collectively increase the number of patients studied and thus, to augment our understanding of the safety profile of ON 123300. Although designed as a classical Phase I study to establish safe -- to establish safety, this study may also provide preliminary important efficacy signals. We believe the result of 2 simultaneous Phase I studies will also inform and enhance the development of subsequent later stage studies to be conducted. Let me now turn to our second pipeline product, oral rigosertib, which is directed to patients with cancer who may carry a KRAS mutation. Following the negative overall survival data readout of our Phase III INSPIRE trial testing intravenous rigosertib in higher risk myelodysplastic syndromes, we are encouraged by investigator-initiated studies aimed at alternative diseases characterized by KRAS mutations that are underway or proposed with oral rigosertib. On our last call, we shared with you that during the third quarter, a Phase I dose escalation study had been already initiated at a leading medical center in New York City, exploring the use of oral rigosertib in progressive KRAS-mutated non-small cell lung cancer patients in combination with a PD-1 inhibitor, more specifically, the immune checkpoint inhibitor nivolumab, or Opdivo. As of today, this study has enrolled 5 patients. It is designed to identify the recommended Phase II dose to further study the combination in future studies and to characterize the safety profile of the combination treatment. Dosing results of this Phase I trial are expected in 2021. Note that the most recent dosing cohort has already received the 560-milligram twice-daily dose of oral rigosertib, which is the highest dose the current protocol is designed to deliver. It is likely this will be the dose we are taking into Phase II testing. However, if no additional dose-limiting toxicities are observed with additional patients entered into the current trial, this [furthest] dose increases of rigosertib may be considered with an amended protocol. More than half of non-small cell lung cancers are classified as lung adenocarcinomas. Of these, the largest subset has a KRAS mutation as the predominant genetic driver of the cancer. Given their utility in multiple cancer settings, checkpoint inhibitors are among the world's top-selling pharmaceutical products, and they continue to gain FDA approval for new indications. In our view, this makes our novel combination approach with rigosertib a potentially meaningful option to pursue in lung cancer and other disorders with KRAS mutations managed with immuno-oncology therapies. We hope these studies will offer patients who have progressed on first-line therapy with a potential efficacious second line approach. In addition, a multi-site investigator-initiated Phase Ib/II study with rigosertib monotherapy has opened. This is studying patients with advanced squamous cell carcinoma associated with recessive dystrophic epidermolysis bullosa, an extremely rare genetic mutation of RAS, an area of high unmet medical need. The first patient is expected to be enrolled in 2021. Additional investigator-initiated preclinical studies with oral rigosertib are being proposed, including melanoma and renal cell carcinoma, which we expect will also be in combination with a PD-1 inhibitor. As I mentioned, our focus at Onconova is on advancing our cancer therapeutic pipeline to help patients. Based on robust preclinical data, we are keen to investigate the potential of ON 123300 in the clinic and to further the promise of oral rigosertib for new indications. We are also actively evaluating strategic opportunities to further advance and enhance our portfolio of proprietary anti-cancer agents. We look forward to keeping all of you updated on our progress with these very important initiatives. And now I'd like to turn the call over to Mark Guerin, our Chief Financial Officer, for a discussion of our financial results for the third quarter of 2020. Mark, please? -------------------------------------------------------------------------------- Mark Patrick Guerin, Onconova Therapeutics, Inc. - CFO [4] -------------------------------------------------------------------------------- Thanks, Steve, and good afternoon, everyone. I plan to start with a quick review of our third quarter expenses, and then I'll discuss our cash position and cash runway. . Research and development expenses for the third quarter of 2020 were $4.2 million, and this compares with $3.5 million for the third quarter of 2019. The increase was primarily related to higher consulting fees and manufacturing costs related to clinical supply for ON 123300, partially offset by lower expenses for the oral rigosertib combination program and the Phase III INSPIRE study. We announced the Phase III INSPIRE results on August 24, and we expect modest wind-down costs for this trial to continue late into the fourth quarter. General and administrative expenses for the third quarter of 2020 were $2.1 million compared with $1.6 million for the third quarter of 2019. The increase was due to higher precommercialization of insurance and corporate, legal and stockholder meeting expenses. We reported a net loss for the third quarter of 2020 of $6.2 million compared to a net loss for the prior year third quarter of $4.6 million. Cash and cash equivalents as of September 30, 2020, were $24.2 million compared to $22.7 million as of December 31, 2019. During the third quarter of 2020, we raised $2.7 million from the exercise of warrants. The company expects that its cash and cash equivalents will be sufficient to fund ongoing clinical trials and business operations into the first quarter of 2022. This completes my financial review. I'll now turn the call back to Steve. -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [5] -------------------------------------------------------------------------------- Thank you, Mark. So with that review of our product pipeline, and our financial results, we'd like to open up this call for questions. Operator, please. ================================================================================ Questions and Answers -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- (Operator Instructions) Our first question comes from Joe Pantginis of H.C. Wainwright. -------------------------------------------------------------------------------- Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [2] -------------------------------------------------------------------------------- So a couple of questions. I'm going to go backwards in the chronology of the way you described them. So first, with regard to the lung cancer study, you mentioned, obviously, there's 5 patients enrolled, and we've already hit the top dose for the protocol. So just curious, besides 2021, since there is a, I'll call it, relatively decent number of patients in the study for an IST by the time ASCO or other conferences roll around, would we be targeting those types of releases? Or is this really up to the investigator? -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [3] -------------------------------------------------------------------------------- Joe, thank you for that question, and I'll ask Rick to take it. Please, Rick. -------------------------------------------------------------------------------- Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [4] -------------------------------------------------------------------------------- Thank you, Steve, and thank you, Joe, for the question. I think there's a couple of considerations. First is the practical one that ASCO abstracts -- I saw an e-mail today announced that abstract deadline is February 17. And so to have an abstract submitted for the -- what I assume will be a virtual meeting next May, June time frame, that's the time line by which we would be operating. I think to submit an abstract, there's also an important consideration of what is the information we would provide in it. I think that if there was a recommended Phase II dose identified and/or DLTs and a maximum tolerated dose identified, that would be important information worthy of submitting an abstract. Whether that happens before February 17 is entirely unknown. Certainly, in addition to that, if you had any early signals, it's unlikely that we'd have any, given the short time frame patients would be on treatment, but that would be another important typical inclusion for an abstract on a study like this. So I think certainly, the investigator would be interested. It is his final decision. And I think some of the things I've described to you would be something that I'm sure he would discuss with us in his decision. -------------------------------------------------------------------------------- Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [5] -------------------------------------------------------------------------------- Great. And then going backwards, so it's very intriguing this new investigator study in squamous cell carcinoma for RDEB patients. So I think one of the, I think, intriguing things to me as well -- sorry to keep using that word, but it really applies, is the safety profile of rigosertib to date because the patients with RDEB are predominantly pediatrics. So I think, to be able to move this IST forward in this patient population that literally spends about $10,000 a month just on bandages, is very intriguing and exciting. So I don't know if you have any additional comments about the conduct of the study. -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [6] -------------------------------------------------------------------------------- So I think, Joe, it's very impressive, first of all, that you know so much about this very rare disease. That is amazing. But Rick, why don't you take that as well? -------------------------------------------------------------------------------- Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [7] -------------------------------------------------------------------------------- Yes. Joe, I'm also impressed. I'm not sure from what I've learned about this rare disease, $10,000 a year might be an underestimate. -------------------------------------------------------------------------------- Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [8] -------------------------------------------------------------------------------- No, a month, unless I misstated, a month. -------------------------------------------------------------------------------- Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [9] -------------------------------------------------------------------------------- A month. I'm sorry. Thank you. I think, first of all, let me clarify, this Phase I study we're doing is in adults, age 18 and over. At this point in time, it's unknown whether we'll be able to move into a pediatric population. I think the important thing to consider is that not only do these patients have terrible skin disease and risk for squamous cell carcinoma, but they also have epithelial webs that form in their -- throughout their gastrointestinal tract. And so in this particular study, we have the need to investigate either oral or intravenous based on individual clinical circumstances for each patient. So I think, again, it won't be a pediatric study initially. But certainly, if there's benefit demonstrated, that's a possibility. -------------------------------------------------------------------------------- Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [10] -------------------------------------------------------------------------------- Got it. Very helpful again. And then, I guess, more quickly because you really did, Steve, delineate the types of dosing differences you're going to be looking at for ON 123300. Is, I guess, based on -- let me ask this way. Based on the preclinical profile for the drug, do you believe you'll see a particular dosing regimen beating the other one? Or you just need to do the experiment at this point? -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [11] -------------------------------------------------------------------------------- Yes. I think, Joe -- and thank you again for the question. I think that's why we're doing that experiment to determine if the 21-day cycle or the 28-day cycle is preferable. As we mentioned, the commercially available has either regimen depending on which drug we're talking about. So we think we're going to get very interesting data, both from the patients in China and the patients in the U.S. And the study in China is going to help us greatly because they started at a low dose of 40 milligrams. If that cohort does not have any dose-limiting toxicities, when we open our U.S. trial, we could already start at the next cohort. And after we put all the data together, then we'll determine what is the best safety approach: is it a 21-day regimen or the 28-day regimen? And until we have the data, I can't -- we can't answer your question, Joe. But thank you. -------------------------------------------------------------------------------- Operator [12] -------------------------------------------------------------------------------- Our next question comes from Jason McCarthy from Maxim Group. -------------------------------------------------------------------------------- Unidentified Analyst, [13] -------------------------------------------------------------------------------- It's Dave on the line for Jason. So when can we expect a data readout from the Phase I Chinese trial? And do you guys plan on exploring any potential combination trials with ON 123300? -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [14] -------------------------------------------------------------------------------- Thank you for that. Rick, would you like to handle that? -------------------------------------------------------------------------------- Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [15] -------------------------------------------------------------------------------- Yes. Thank you, Steve. Thank you, Jason. I think that, to answer your question, I think it depends on what you call data readout. I think that we're anticipating that for one or both studies, by fourth quarter 2021, we would have an understanding of maximum tolerated dose and recommended Phase II dose as well as the safety profile in the monotherapy setting. I think it's -- it will be difficult to have final readout on any efficacy signals given that patients who may be benefiting may be on study for several months or longer, hopefully. And depending when the last patients come into the study on the expansion phases will also determine what we know about efficacy. I want to emphasize again, this is a phase -- both studies are Phase I. And obviously, reading efficacy signals with these studies can be challenging. And that's certainly not the primary objective of the study. -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [16] -------------------------------------------------------------------------------- And if I could expand on Rick's comments regarding the combination approach as a second part of your question. Just to highlight to you, and as you probably know, all the commercially available CDK4/6 inhibitors have limited efficacy as single agents. Typically they're given -- not typically, always, given with an aromatase inhibitor in combination. Because ON 123300 targets ARK5 in addition to CDK4/6, our drug appears to be cytotoxic for refractory CDK4/6 inhibitor refractory breast cancer cell lines. So it is possible we'll have efficacy as a single agent but perhaps in combination with an aromatase mutase inhibitor or some other compound, we'll have even greater efficacy. And clearly, those studies will have to be conducted after Rick's team determines what the maximally tolerated dose for the Phase II shall be. -------------------------------------------------------------------------------- Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [17] -------------------------------------------------------------------------------- I would just add, it also depends what disease we see a response in. What Steve's described this is for metastatic breast cancer. But if we had a response in another tumor type, which there may be because of the ARK5, that may dictate the feasibility of doing combinations. And it's hard to know what those combinations might be until we understand which tumor types are, in fact, responding. -------------------------------------------------------------------------------- Operator [18] -------------------------------------------------------------------------------- Our next question comes from Ahu Demir from NOBLE Capital Markets. -------------------------------------------------------------------------------- Ahu Demir, NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst [19] -------------------------------------------------------------------------------- I want to follow-up on the CDK4/6 and ARK5 targeting. So I am really curious, is ARK5 amplified in any other cancers? Do you believe one of the cancers will respond better, as Rick's comment? And if so, what are the indications you might consider going after stronger than others? Do you have any strategies or any ideas about that to start with? . -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [20] -------------------------------------------------------------------------------- Thank you, Ahu. And Rick, would you like to take that, please? -------------------------------------------------------------------------------- Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [21] -------------------------------------------------------------------------------- Sure. Yes, there are a number of other tumors that have increased expression of ARK5 such as mantle cell lymphoma, hepatocellular carcinoma, multiple myeloma, and obviously, there is some increased expression in breast cancer. Glioblastoma is another example, and this compound does cross the blood-brain barrier. . So there are a number of tumors that potentially have up-regulation of the target. And so it will be of interest as we move through the clinical studies to see what kind of safety and efficacy we observe in those diseases. -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [22] -------------------------------------------------------------------------------- And in addition, unfortunately, women with metastatic breast cancer frequently have metastatic disease to their brain. We hope, based on what Rick said and our evidence of efficacy, targeting ARK5 and thus crossing also the blood-brain barrier, that, that will be a great benefit to women with metastatic breast cancer who are at risk for CNS disease. We're very excited. So we're very excited about the future development of ON 123300. -------------------------------------------------------------------------------- Ahu Demir, NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst [23] -------------------------------------------------------------------------------- So my second question will be about the partnership that was mentioned in the previous quarter earnings calls. So are you still seeking for additional assets? And have you made any -- develop any additional progress in that? And if so, when should we expect any new [bonus] or partnership? . -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [24] -------------------------------------------------------------------------------- Thank you, Ahu. Avi, would you like to handle that? -------------------------------------------------------------------------------- Abraham N. Oler, Onconova Therapeutics, Inc. - Senior VP of Corporate Development & General Counsel [25] -------------------------------------------------------------------------------- Sure. Thanks, Ahu. And thanks, Steve. I joined Onconova because Steve and Rick have a tremendous track record of developing oncology drugs, and we're very excited about ON 123300 in oral rigo as well. We are actively looking for opportunities to enhance our portfolio. And when there are future developments, we will certainly report them. We are actively looking. -------------------------------------------------------------------------------- Operator [26] -------------------------------------------------------------------------------- And our next question comes from Yale Jen from Laidlaw & Company. -------------------------------------------------------------------------------- I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [27] -------------------------------------------------------------------------------- The first question is that I just wanted to be clarified that for the 123300, when you get into expansion stage, you mentioned 36 patients. Are those only for the breast cancer or the breast cancer and initial combined? -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [28] -------------------------------------------------------------------------------- Rick, what are the plans once you get the maximally tolerated dose? -------------------------------------------------------------------------------- Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [29] -------------------------------------------------------------------------------- Right. So I think that's for both diseases. And so I don't know how they would be evenly distributed in terms of enrollment. There's also going to be, in the HanX study, an enrichment in their expansion phase for patients with breast cancer. So the advantages of this study are the simultaneous conduct of 2 Phase I studies in advanced cancer with the same agent. And I think that the data is likely to be very complementary, but also we'll have more data than we might typically see develop in the same time frame with most agents. So we're very excited about this opportunity of 2 simultaneous Phase I studies. -------------------------------------------------------------------------------- I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [30] -------------------------------------------------------------------------------- Okay. Great. That's helpful. And maybe just to add on that a little bit, which is that for the Phase I dose-finding study in the United States, the patient of metastatic breast cancer patients, but not necessarily all patients are current CDK4/6-resistant patients, at least on the dose-finding part. Is that correct? -------------------------------------------------------------------------------- Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [31] -------------------------------------------------------------------------------- Yes. I mean, the patients with advanced phase disease that are hormone receptor positive HER2-, standard of care is generally that these patients will have received a CDK4/6. It's possible they might come into our study after third line therapy, with some form of chemotherapy as well as part of their prior treatment. And certainly, those patients would be eligible. And so I'm a little hesitant to say that they would only be following CDK4/6. They might have also had other therapies. . And I think it's importantly emphasizing that the commercially available CDK4/6 inhibitors are not curative. And so the need -- there's a high need for these patients continuing despite the advances in the standard of care that they have made. -------------------------------------------------------------------------------- I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [32] -------------------------------------------------------------------------------- Okay. That's very helpful. And actually, to second, your answer here, maybe just the final question here is that you mentioned that 123300 is cytotoxic whereas the others marketed now is cytostatic. Could you explain the reason in terms of mechanism of actions why? Is that just because you target 1 more molecular target to cause that? Or any other comments on that? -------------------------------------------------------------------------------- Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [33] -------------------------------------------------------------------------------- Well, I think my comment is the cytotoxicity is due to the ARK5 inhibition that occurs with CD -- with ON 123300. Remember that this is a dual inhibitor in contrast to the other CDK inhibitors. And it is the ARK5 inhibition, sorry, inhibition of ARK5 that disrupts cellular energy metabolism in the cancer cell. And that's what causes the cytotoxicity. And this is what we think is also a particularly advantageous aspect of this drug in these patients. . -------------------------------------------------------------------------------- I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [34] -------------------------------------------------------------------------------- Okay. Great. That's very illuminating, and congrats on the progress on this program. -------------------------------------------------------------------------------- Operator [35] -------------------------------------------------------------------------------- Thank you. And I'm showing no further questions at this time. I'd like to turn the call back over to the speakers for any closing remarks. -------------------------------------------------------------------------------- Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [36] -------------------------------------------------------------------------------- Thank you all for participating in today's update call. We greatly appreciate it. We're very excited at Onconova to pivot to the development of a new lead product, ON 123300, and look forward to upcoming important milestones in the near future as follows: one, we plan to file the U.S. IND for ON 123300 in the coming weeks, followed by a clinical trial initiation, with patient enrollment expected to begin in the first half of 2021; two, the pipeline of investigator-sponsored studies with oral rigosertib is advancing, and further progress is anticipated in 2021, including establishing a dose for further study of the combination of oral rigosertib and nivolumab in KRAS-mutated non-small cell lung cancer that will establish the dose of the combination in other solid tumor RAS-driven cancers; and three, we are actively evaluating strategic opportunities to enhance our product portfolio. We truly appreciate your continued interest in the programs of Onconova. Should you have any additional questions, please feel free to contact any of us. Thank you, and have a nice and enjoyable evening. -------------------------------------------------------------------------------- Operator [37] -------------------------------------------------------------------------------- Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and you may now disconnect. Everyone, have a wonderful day.