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spk06: Ladies and gentlemen, thank you for standing by. Welcome to the Antenova Therapeutics third quarter 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. And please press star followed by one on your touchtone phone. If anyone has difficulty hearing the conference, Please press star zero for operator, press star zero for operator assistance. As a reminder, this call is being recorded today, November 12th, 2020. At this time, I would like to turn the call over to Avi Oller, Senior Vice President of Corporate Development and General Counsel.
spk11: Thank you, operator. Good afternoon, everyone, and welcome to Ancanova'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.ancanova.com. On today's call, Dr. Steve Fruchman, 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. Ankanova 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 is my pleasure now to turn the call over to Steve.
spk02: 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 Ankenova, 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 regocertib in patients with COVID-19 disease. However, cancer and the development of effective new anti-cancer therapies remains a significant health issue and is our corporate focus. We believe Ankenova 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 ON123300 entering the clinic. In a phase one study in China, an oral regocertib 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 at Ankenova brings substantial drug development expertise and a previously of successes in anti-cancer drug development to our company, Akanova. 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 ON123300, which is a proprietary first-in-class multi-kinase inhibitor targeting CDK4-6 and ARK5. ON123300 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 merely 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, ON123300 represents an innovative potential approach for treating solid tumorous and hematologic malignancies that are refractory or have become resistant to the commercially available CDK4-6 inhibitors. Based on preclinical models, ON123300 may have utility for patients with certain types of breast cancer and non-Hodgkin's lymphoma. And based on these preclinical models, ON123300 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 ON123300 can cross the blood-brain barrier. We are particularly pleased that during the third quarter, ON123300 entered the clinic in China with our partner, Honex Biopharmaceuticals. The Honex Phase I Dose Escalation Study began in September. As of today, the first cohort of three patients, each who has breast cancer, has been enrolled. The phase one study in China is a standard three by three dose escalation study with each cohort requiring three or six patients depending on the number of dose-limiting toxicities observed, if any are observed. This phase one study is expected to enroll patients with advanced relapsed refractory cancer at two sites in China, and together with our planned phase one study in the U.S. will inform the future development of O.N. 1, 2, 3, 300. 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 1 dose escalation and dose expansion study will differ from the Honex study in both dosages and treatment cycles, but believe the data from these two studies will generate important information to inform anticipated later stage studies. Our current plan is for the phase one trial in the U.S. to assess safety, tolerability, and pharmacokinetics of ON123300 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 negative metastatic breast cancer with clinical resistance to the approved second generation CDK4-6 inhibitors. Once the recommended phase two dose is established, our plan is to enroll at least 36 hormone receptor positive HER2 negative 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 Hanex will dose patients daily for 21 days. And in the US, we will study continuously daily dosing for a 28-day cycle. Notably, of the three currently approved CDK4-6 inhibitors, two were tested and used for dosing in 21-day cycles, and one was tested in a 28-day cycle. All three are blockbuster drugs marketed by well-known pharmaceutical companies. We expect these two phase one studies, the one in China and the one in the US, to collectively increase the number of patients studied and thus to augment our understanding of the safety profile of ON123300. Although designed as a classical phase one study, to establish safety, these studies may also provide preliminary important efficacy signals. We believe the results of two simultaneous phase one 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 regocertib, which is directed to patients with cancer who may carry a KRAS mutation. Following the negative overall survival data readout of our Phase III-inspired trial testing intravenous regocertib, in higher risk myodysplastic syndromes, we are encouraged by investigator-initiated studies aimed at alternative diseases characterized by KRAS mutations that are underway or proposed with oral regocertib. On our last call, we shared with you that during the third quarter, a phase one dose escalation study had been already initiated at a leading medical center in New York City, exploring the use of oral regocertib 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 Abdevo. As of today, this study has enrolled five patients. It is designed to identify the recommended phase two dose, to further study the combination in future studies, and to characterize the safety profile of the combination treatment. Dosing results of this phase one trial are expected in 2021. Note that the most recent dosing cohort has already received the 560 milligram twice daily dose of oral RegoCertib, 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 two testing. However, if no additional dose-limiting toxicities are observed with additional patients entered into the current trial, then further dose increases of regocertib 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 Rigocertum 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've progressed on first-line therapy with a potential efficacious second-line approach. In addition, a multi-site an investigator-initiated Phase 1b-2 study with regocertum monotherapy has opened. This is studying patients with advanced squamous cell carcinoma associated with recessive, dystrophic epidermolysis bullosa and an extremely rare genetic mutation of RAS, an area associated of high unmet medical need. The first patient is expected to be enrolled in 2021. Additional investigator-initiated preclinical studies with oral regocertib 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 Ancanova is on advancing our cancer therapeutic pipeline to help patients. Based on robust preclinical data, we are keen to investigate the potential of ON123300 in the clinic and to further the promise of oral rego-certificate 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.
spk05: Mark Guerin 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 ON123300, partially offset by lower expenses for the oral-reg assertive combination program and the Phase III INSPIRE study. We announced the Phase III INSPIRE results on August 24th. 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 pre-commercialization, 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.
spk02: 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.
spk06: Ladies and gentlemen, if you wish to register for a question for today's question and answer session, you will need to press star, then the number one on your telephone. If your question has been answered or you wish to withdraw your request, you may do so by pressing the pound key. If you are using a speakerphone, please pick up your handset before entering your request. One moment for the first question. Our first question comes from Joe Pantinis of HC Wainwright. Your line is open.
spk01: Hey, guys. Good afternoon. Thanks for taking the question and hope you're all doing well. So a couple 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 five 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, you know, ASCO or other conferences roll around, would we be targeting those types of releases or is this really up to the investigator?
spk02: Joe, thank you for that question, and I'll ask Rick to take it. Please, Rick.
spk10: 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 email today, announced that abstract deadline is February 17th. And so to have an abstract submitted for what I assume will be a virtual meeting next May, June timeframe, that's the timeline 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 two 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 17th 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 timeframe 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.
spk01: Great. Thanks for that, Rick. And then going backwards, so it's very intriguing, this new investigator study in squamous cell carcinoma for R-deb 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 regocertib to date because the patients with R-deb 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.
spk02: 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?
spk10: 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.
spk09: No, a month, unless I misstated. A month.
spk10: Oh, sorry. Thank you. I think, first of all, let me clarify. This phase one study we're doing is in adults age 18 and over. At this point in time, it's... 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 there 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.
spk01: Got it. Very helpful, again. And then I guess More quickly, because you really did, Steve, delineate, you know, the types of dosing differences you're going to be looking at for 1, 2, 3, 300 is, you know, I guess based on, let's 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? Yeah.
spk02: Yeah, 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 can 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 the 21-day regimen or the 28-day regimen? And until we have the data, we can't answer your question, Joe.
spk01: But thank you. Understood. Thanks for the added details, guys.
spk03: Thank you. Our next question comes from Jason McCarthy from Maxim Group. Your line is open.
spk07: Hi, everyone. It's Dave on the line for Jason. Thanks for taking my question. So when can we expect a data react from the phase one Chinese trial? And do you guys plan on exploring any potential combination trials with OAM 1, 2, 3, 300?
spk02: Thank you for that. Rick, would you like to handle that?
spk10: 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, you know, 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 two dose, as well as a safety profile in the monotherapy setting. I think 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 on 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, both studies are phase one. Obviously, reading efficacy signals with these studies can be challenging, and that's certainly not the primary objectives of this study.
spk02: If I could expand on Rick's comments regarding The combination approach is the 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 08123300 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 inhibitor or some other compound, will have even greater efficacy. Clearly, those studies will have to be conducted after Rick's team determines what the maximally tolerated dose for the phase two shall be.
spk10: I would just add it also depends what disease we see a response in. You know, what Steve's described is for metastatic breast cancer. But if we had a response in another tumor type, which there may be because of the ARC5, 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.
spk07: Great. Thanks for the additional color, guys. Appreciate it.
spk03: Thank you. Our next question comes from Ahu Demir from Noble Capital Markets. Your line is open. Good afternoon, Tim.
spk04: Thanks for taking my question. I want to follow up on the CDK46 and ARC5 targeting. So I am really curious, is ARC5 amplified in any other cancers? Do you believe one of the cancers will respond better as Rick comments? 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?
spk02: Thank you, Ahu. And Rick, would you like to take that, please?
spk10: 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 upregulation of the target. And so we'll be of interest as we move through the clinical studies to see what kind of safety and efficacy we observe in those diseases.
spk02: And in addition, unfortunately, women with metastatic breast cancer frequently have metastatic disease to their brain. We hope, based on what Rick said in our evidence of efficacy targeting ARK5 and thus crossing also the blood-brain barrier, that that could be a great benefit to women with metastatic breast cancer who are at risk for CNS disease. Thank you very much for the question. Yes, we're very excited about the future development of ON123300.
spk04: So are we, Steve. So my second question will be about the partnership that was mentioned in the previous quarter earnings call. So are you still seeking for additional assets and have you made any, developed any additional progress in that? And if so, when should we expect any news on the partnership?
spk11: Thank you, Ahu.
spk02: Avi, would you like to handle that?
spk11: Sure. Thanks, Ahu. And thanks, Steve. I joined Onconova because Steve and Rick have a tremendous track record developing oncology drugs, and we're very excited about ON123300 and Oral Rego 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.
spk04: Okay. Thank you very much for taking my questions.
spk02: Thank you, Ahud.
spk03: Thank you. And our next question comes from Yale Jen from Laidlaw and Company. Your line is open.
spk08: Good afternoon, and thanks for taking my question. The first question is that I just want to be clarified that for the 1, 2, 3, 300, when you get into the expansion stage, you mentioned 36 patients. Are those only for the breast cancer or the breast cancer and the NHL combined?
spk02: Rick, what are the plans once we get the maximally tolerated dose?
spk10: 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 two phase one studies in advanced cancer with the same agent. And I think that the data is likely to be very complimentary, but also we'll have more data than we might typically see developed in the same timeframe with most agents. So we're very excited about this opportunity of two simultaneous phase one studies.
spk08: Okay, great. That's helpful. And maybe just tag on that a little bit, which is that for the phase one dose finding study in the United States, the patient are 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?
spk10: Yes. I mean, the patients with advanced phase disease that are hormone receptor positive, HER2 negative, 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 important to emphasizing that, you know, the commercially available CDK4-6 inhibitors are not curative. And so there's a high need for these patients continuing, despite the advances in the standard of care that they have made.
spk08: Okay, that's very helpful. And actually, just back on your answer here, maybe just the final question here is that you mentioned that 1, 2, 3, 300 is cytotoxic, whereas the others, the marketed drug is cytostatic. Could you explain the reason in terms of mechanism of action? Why? Is that just because you target one more molecular target to cause that, or Any other comments on that?
spk10: Well, I think my comment is the cytotoxicity is due to the ARK5 inhibition that occurs with ON123300. Remember that this is a dual inhibitor in contrast to the other CDK inhibitors, and it is the ARK5 inhibitor 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.
spk08: Okay, great. That's very illuminating. And congrats on the progress on this program.
spk02: Thank you. Thank you, Yael.
spk03: Thank you. And I am showing no further questions at this time. I'd like to turn the call back over to the speakers for any closing remarks.
spk02: Thank you all for participating in today's update call. We greatly appreciate it. We're very excited at Ankenova to pivot to the development of a new lead product, ON123300. and look forward to upcoming important milestones in the near future as follows. One, we plan to file the US IMD for ON123300 in the coming weeks, followed by clinical trial initiation with patient enrollment expected to begin in the first half of 2021. Two, the pipeline of investigative-sponsored studies with oral regocertib is advancing, and further progress is anticipated in 2021, including establishing a dose for further study of the combination of oral regocertib and nivolumab in KRAS mutated non-small cell lung cancer and 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 Ancanova. Should you have any additional questions, please feel free to contact any of us. Thank you, and have a nice and enjoyable evening.
spk03: Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and you may now disconnect. Everyone, have a wonderful day.
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