Traws Pharma Inc (TRAW) 2020 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standby, and welcome to the Onconova Therapeutics First Quarter 2020 Earnings and Corporate Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded.

I would now like to turn the conference over to your host, Mr. Avi Oler, Senior Vice President, Corporate Development and General Counsel. Thank you, sir. Please go ahead.

Thank you, operator. Good afternoon and welcome to Onconova's First Quarter 2020 Corporate Update and Financial Results Conference Call. Earlier this afternoon, we issued a press release outlining our financial results and business progress during the quarter. If you have not seen this press release, it is available on the Investor Relations page of our website at www.onconova.com.

On today's call, Dr. Steve Fruchtman, President and CEO, will discuss the company's recent highlights and anticipated clinical and business milestones. After Steve completes his opening remarks, Mark Guerin, our Chief Financial Officer, will review first quarter financial results. Following Mark's report, we will move to the Q&A portion of the call, which will be joined by Dr. Rick Woodman, our Chief Medical Officer. Lastly, Steve will come back with some final comments and a review of our upcoming milestones.

Before we begin, I remind everyone that statements made today 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. 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 to now turn the call over to Steve.

Thank you, Avi. Good afternoon, everyone, and thank you for joining today's call. First, our hearts go out to the many individuals and families impacted by the devastating COVID-19 pandemic. The world has truly changed, and we hope that brilliant scientists from around the world can bring new therapies and preventions to this devastating plague.

Onconova demonstrated significant progress during the first quarter of 2020, highlighted by the completion of enrollment of our pivotal Phase III INSPIRE trial in higher-risk myelodysplastic syndromes. We are fortunate to have achieved full enrollment prior to the profound impact of the worldwide COVID-19 pandemic, which has forced disruptions to research studies at many hospitals and cancer centers across our globe.

With enrollment now completed, Onconova's pivotal Phase III INSPIRE trial is advancing to the next pivotal catalyst. Based on historical survival trends in the INSPIRE trial, we continue to anticipate reporting top line survival data in the second half of 2020. And we expect to present the results of the INSPIRE trial at a major medical meeting later this year. With INSPIRE enrollment now complete, we are preparing for when we reach 288 survival events before analyzing and releasing top line survival data.

To shorten time lines for our anticipated NDA submission to the FDA, we have already begun NDA work prior to data readout. We are working with regulatory consultancy experts on our NDA document for the U.S. FDA as well as on the MAA document for the EMA to be in position to expedite our health authority applications when data becomes available.

We are also advancing our plans to be ready for commercialization. And to develop internal Onconova expertise, we have nominated a commercial expert, Ms. Terri Shoemaker, to our Board, who was instrumental in the commercialization of azacitidine, the most frequently prescribed pharmaceutical agent in higher-risk MDS.

As you recall, INSPIRE is an open-label, randomized, controlled, international study designed to determine the efficacy, safety and tolerability of single-agent intravenous rigosertib in the treatment of patients with second-line, high-risk MDS. Patients in this study are less than 82 years of age and have progressed on, relapsed or failed to respond to previous treatment with the standard of care hypomethylating agent therapy. The study randomized patients to receive either intravenous rigosertib with best support of care or the physician's choice of therapy with best support of care.

The primary end point of this study is overall survival of all randomized patients in the intent-to-treat population. There is also a second opportunity for an FDA approval, which is the sequential analysis of the overall survival of the very high-risk subgroup as defined by the revised International Prognostic Scoring System. Should rigosertib prolong survival in the INSPIRE trial in a statistically significant manner, we believe rigosertib could be the first new treatment for higher-risk MDS in more than 15 years.

Today, we disclosed that at the European Hematologic Association's upcoming virtual congress, Onconova and our collaborators at MD Anderson Cancer Center and the centers participating on the INSPIRE trial have an accepted presentation. The presentation, which was just posted to the European Hematology Association's website, detail the impact of the RAS pathway mutations on patients failing azacitidine and is entitled, Mutations in RAS Pathway Genes Correlates with Type of Failure to Azacitidine: Genomic Analysis at Randomization onto the INSPIRE Trial.

As you know, advances in the understanding of genomics have revolutionized cancer care. Participants on the INSPIRE trial received deep genomic sequencing of their blood or bone marrow at randomization and at multiple time points in their treatment during the study. The genomic data from the INSPIRE trial identifies the most common mutations in high-risk MDS following azacitidine failure, including those of the RAS pathway that may be targeted by rigosertib. We believe this data presentation will further advance the learnings about MDS, the important role of genomics and the possible place of rigosertib treatment for MDS and other RAS-driven cancers.

We have made important progress with our additional pipeline programs as well. In addition to the INSPIRE trial, we are advancing plans for a pivotal Phase II/III combination trial of oral rigosertib and azacitidine in adult patients with HMA-naive, higher-risk MDS. We received feedback from the FDA in 2019 and are preparing a Phase II/III protocol for submission based on their guidance. We anticipate meeting with the FDA in the third quarter of this year after submitting a Type C meeting request to consult with FDA. We anticipate this new registration trial will begin later this year following the FDA feedback and following the survival pivotal data readout from our INSPIRE study.

We have also received notification that the Phase I trial, which forms the basis for this new pivotal trial with oral rigosertib combined with azacitidine in HMA-naive, high-risk MDS patients, has been accepted for publication in Leukemia Research and anticipate its publication in the upcoming months.

In addition to studying rigosertib in MDS, we are primed for additional rigosertib development progress, including the to be initiated Phase I/IIa study of rigosertib plus nivolumab in Stage 4 KRAS-mutated lung adenocarcinomas following the reopening of clinical cancer research programs post the COVID-mandated stoppage as well as additional planned indications for rigosertib in other KRAS-mutated cancers and our pipeline programs. The study in KRAS-mutated lung adenocarcinoma will be an investigator-sponsored trial, and we anticipate the first patient will be enrolled following the mitigation of the burden of the COVID pandemic that has been placed on our academic medical centers.

While checkpoint inhibitors represent a significant advancement in the standard of care in treating lung cancer and have achieved blockbuster status many times over, tremendous unmet medical need continues to exist following disease progression. In our view, this makes our novel combination approach with rigosertib a very attractive option to pursue in lung cancer and potentially beyond.

And beyond rigosertib, ON123300 is our investigational first-in-class dual inhibitor of CDK4/6 and ARK5. We believe ON123300 has the potential to treat numerous cancers, including refractory metastatic breast cancer, with CDK4/6 inhibitors already commercially available. For those who are not familiar with this field, CDK inhibitors have emerged as promising compounds targeting very large cancer indications such as hormone receptor-positive metastatic breast cancer. Due to its unique targeting of ARK5 as well as CDK4 and 6, we believe ON123300 has the potential to overcome many of the existing agents' limitations, making it potentially suitable for certain cancers that may not be responsive to the current generation of commercially available CDK4/6 inhibitors. If successful, we believe ON123300 could address this very large market opportunity.

We maintain global rights of ON123300 outside of China. Our partner in China for this compound is HanX Biopharmaceuticals, who funded the Chinese IND-enabling studies. The Chinese IND was approved in January of 2020 by the Chinese health authority. We anticipate a Phase I study may begin in China in the second half of 2020. We also intend for the Chinese IND-enabling studies to comply with our FDA standards. To the U.S. and the rest of the world outside of China, our manufacturer for ON123300 is now qualified. We plan to file a U.S. IND in the fourth quarter of 2020 after obtaining the required manufacturing data.

With regard to business development. During the first quarter, we reacquired rigosertib rights in Greater China. As a result, Onconova controls the rights for rigosertib in the U.S., Europe and China, which are among the largest pharmaceutical markets in the world. Last year, we announced plans to launch an early access program with Inceptua Medicines Group. We anticipate launching this program in select countries in the second half of this year. We expect to continue to evaluate opportunities as we progress from one milestone to the next milestone.

As a reminder, our upcoming Annual General Meeting of Stockholders is coming up on May 27. I encourage stockholders to vote at our upcoming Annual General Meeting. Our proxy materials are available on our website. I am very excited that Onconova's Board of Directors has nominated life science industry veteran, Terri Shoemaker, to join the Board at this time. As mentioned, Terri has highly relevant experience in the MDS space. Terri was a key executive in the launch of azacitidine in MDS and will be a very valuable addition to our Board of Directors. We believe her experience in developing and managing commercial organizations in the life science industry will be instrumental in our efforts moving forward as we prepare for potential commercialization of rigosertib.

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 first quarter 2020. Mark?

Thanks, Steve, and good afternoon, everyone. Cash and cash equivalents as of March 31, 2020, totaled $31 million compared to $22.7 million as of December 31, 2019. As previously noted, common stock warrant exercises since our financing transaction in November 2019 have added $10.6 million of cash to our balance sheet. Also, of the almost 29 million stock warrants outstanding as of March 31, 2020, over 80% of them were in-the-money as of May 13. Based on our current projections, we expect that our cash and cash equivalents will be sufficient to fund our ongoing trials and operations into the third quarter of 2021.

Our net loss was $5.1 million for the quarter ended March 31, 2020, compared to $7.6 million for the comparable period in 2019. Research and development expenses were $3.4 million for the quarter ended March 31, 2020, and $4.1 million for the comparable period in 2019. General and administrative expenses were $1.8 million for the quarter ended March 31, 2020, and $3.2 million for the comparable period in 2019.

This completes my financial review. I'll now turn the call back to Steve.

Thank you so much, Mark. With that, we'd like to open the call for questions. After the Q&A, I'll finish with some final closing remarks. Operator, please open the call to Q&A session, and thank you.

(Operator Instructions) Our first question comes from the line of Joe Pantginis with H.C. Wainwright.

Glad you're all doing well. So I have 3 questions, 2 of which, I think, are pretty much logistical. The first one is with regard to INSPIRE, it's great that you enrolled everyone right now and things are progressing and the time lines are still on track. So I was just curious, as part of your -- I guess, call it, your statistical assumptions now with COVID, is there a potential for any loss to follow up for any of these patients that you might not hear about some of these events? Or is it not a concern?

I'll ask Rick to take that question, and thank you, Joe.

Yes, Joe. Thank you. The main challenge with the COVID pandemic for our global study has been monitoring of the sites. Fortunately, the number of patients in which we are not able to confirm survival events is extremely small. And we anticipate that continuing in part due to the efforts of our CRO and the clinical research assistance in the field and the team in Onconova as well as some good luck. And I think that we anticipate for the remainder of the collection of survival events that we will be able to continue doing that monitoring. But it is a challenge, and the monitors and the team have -- had to develop unique ways in which to interact with the sites because of the pandemic.

Got it, Rick. And then my second logistical question, if you will. I know we discussed this in the past, but some time has elapsed, and I just want to make sure if your thinking is still the same with regard to the communication strategy around putting out the data for INSPIRE. So since you're looking to present them at a major medical meeting in the second half, I'll just say presumably ASH, would you look to then have one of those typical top line press releases to say, okay, it hit, and we'll give the further data at an upcoming conference? Or not hit as...

Avi, why don't -- I'll ask Avi to take that one, if I may. Go ahead, Avi.

Sure. Sure thing. In terms of communication, Joe, thanks for the question, but you're exactly right that we would anticipate announcing the data when it is ready at a top line level and presenting full data at an upcoming major medical meeting such as ASH or another major medical meeting.

Got it. And then my question is -- or my third and last question. With regard to the upcoming Type C meeting, obviously, you've already had a lot of productive discussions with the FDA around the study design. So I guess I would ask it 2 ways. What's your wish list of what you want to get out of there? And what are the key outstanding things that you need to get solidified?

Rick?

Yes, Joe. So I think the first part to your question is that we want to get agreement from the FDA on a novel, unique, adaptive design, a combination of a Phase II/III. And this adaptive design we presented at ASH and some of the unique features. We feel this design is particularly advantageous for us in a variety of ways as well as the medical community and the health authorities. And I think it is the additional challenge that we have is developing, particularly, as we indicated in the abstract at ASH, a very rigorous and robust interim analysis that allows us to move forward into the Phase III part of the study.

Your next question comes from the line of Naureen Quibria with Maxim Group.

So first, I guess, starting first with INSPIRE. Can you remind us or are you able to disclose what the current event rate is right now? And is there an average number of events that you're seeing per month? Are you able to discuss that in any detail?

I think I'll try my hand at that, and thank you very much. We did reveal, I believe mid-March, that we have over 85% of our survival events that we require of the 288. And the reality is it's quite variable. We do monitor by month every -- the survival events that we see, it is variable. But based on what we are observing, we anticipate reaching pivotal data the second half of 2020. So before the end of the year. It's harder -- it's very hard to make a more accurate prediction than that.

Got it. That makes sense. And so I have a really broad sort of theoretical question, my next one. And that's regarding your second study with rigosertib. The treatment regimen in MDS, high-risk MDS landscape, seems to parallel that of AML. And in AML, the combination with venetoclax and a hypomethylating agent is part of the treatment paradigm and at least as a treatment of choice for a select group of patients. Now if we were looking at the data at ASH last year, there was a study that posted positive response rates in high-risk MDS with venetoclax and azacitidine. But rigosertib with aza actually posted numerical higher response rates in the same patient type, if I recall correctly, and that was also at ASH. Since doctors are familiar with venetoclax and since that data was positive, what are your thoughts about where you think rigosertib may be placed in this patient type? And in terms of strategy, if, say, venetoclax gains approval well in advance, would that alter your current strategy?

Rick?

Well, thank you for your question. I think that there's a couple of aspects to that question, and I'll deal with each of them individually. First and foremost is that the venetoclax is ineffective as a single agent in AML or MDS. And so venetoclax needs a partner compound. I think it's clear the field is looking for doublet therapy. And to really effectively achieve that, they need agents that have differing mechanisms of action and, in fact, can be administered easily for patients. So we are looking at the potential and I think the field would look at the potential for any agents that can be combined orally. And this is why our Phase II data with oral rigosertib is so important because it satisfies at least many of the features you would look for in a doublet combination: novel mechanism of action, oral formulation and nonoverlapping toxicity.

And so I think the field is advancing. I think both venetoclax and rigosertib will offer new therapeutic options for patients, and I think this is the real highlight of both venetoclax and rigosertib in the area of MDS. I think that in terms of the future, I think that it's unlikely that venetoclax will precede rigosertib. I think that they have yet to demonstrate any randomized data. And I think that, that clearly needs to be demonstrated for the scientific community to evaluate venetoclax appropriately. So I anticipate that these agents potentially would be -- their timing would be such that they could be combined together in and around the same time and they would offer the advantages I mentioned a moment ago.

Got it. That's really, really helpful. And just one last question. With regard to the planned study with the CDK4/6 in the U.S., you mentioned that the IND will be filed or submitted in the fourth quarter. I was just curious, has the study design been formalized? Will you start with the monotherapy and then a combination with, say, letrozole? Can you discuss a bit more about that program?

Rick?

Yes. So I think, first of all, we anticipate that ON123300 will potentially has the mechanism of action that could be effective in multiple tumors. It may be effective in the current conventional CDK4/6 inhibitors, patients that are resistant to those agents. It will most likely need to be combined with some sort of hormonal therapy as is currently given, particularly if it were to be moved to earlier lines of therapy.

Your next question comes from the line of Ahu Demir with NOBLE Capital.

My first question will be on commercialization of rigosertib efforts. What do you plan to do? When do you plan to initiate? And what do you think the financial impact would be on that front?

Mark, I heard the word financials. Would you like to take that?

Yes, Steve. Thanks. I'll be happy to. And Ahu, thanks for the question. While we're not able to provide any specific information about what we have spent so far or precisely what we plan to spend between now and top line data and then afterwards, I can tell you that we started our pre-commercialization readiness activities earlier this year. And as you might expect, our initial focus was on the longer time line pre-commercial activities. So once we got to full enrollment, we undertook that initiative with a focus on the long time line things. I hope that, that answers your question. If it doesn't, please feel free to follow up, and I can try to answer a follow-up question.

Sure. That's helped, Mark. My other question would be on the RAS program, Steve, [of full ranging all] clinical trials, say, do you imagine the RAS lung cancer trial will initiate right away? Or are there any other things that you need to accomplish prior to starting it?

Ahu, thank you for that. The site is ready to go, meaning this trial is IRB approved, and we -- and the site is ready to put patients on to this Phase I, but all new clinical research is on hold as the pandemic impact on academic medical centers, hopefully, is reduced or mitigated. We hope that cancer research -- clinical cancer research will be restarted. And once that happens, we anticipate the patients who are already being screened for this study will be put on to this new study.

That's great. And one last question -- Steve, do you have something to say, Steve?

No. I was just saying we're obviously very eager to get it started. So I think it's all ready to go.

All right. That's great. My last question on the CDK program. So considering you expect to do the submission in the fourth quarter, do you expect any delays driven by COVID and manufacturing issues or any other delays we expect? Or is this still on track to be on Q4 2020?

So I'll take that. We don't expect any -- we have a manufacturer identified. They have to do validation of the manufacturing processes. We don't expect any delays regarding that from the COVID pandemic. We already have a Phase I site identified. Again, that's a bit of an unknown because we don't know what's going to happen to the hospital system and the restarting of clinical cancer research. We hope and pray by the end of this year when we anticipate possibly the Phase I trial with ON123300 being started that clinical cancer research will be open again, and then our trial will be one of the studies across the U.S. that gets restarted.

Your next question comes from the line of I-Eh Jen with Laidlaw & Company.

My first question is regarding the COVID-19 impact. First of all, does that have any impact for the INSPIRE study in terms of patient receiving treatments? Any interruption or any impact on that even though they all have been enrolled?

Rick?

Thank you for your questions. So first and foremost that we do not anticipate any differences in the impact of COVID-related illness on the investigational arm, patients treated with rigosertib, versus the physician's choice arm. At the present time, and we've been monitoring very carefully the COVID impact on our global sites and centers, and to date, we've not seen any real dramatic impact on anything other than collection of data and monitoring.

And that's more due to the impact of COVID on the care that's happening at the various sites, site staff. In some places, site staff who are involved in studies do not have access to the hospital, and this obviously impacts our ability to work with them in collecting data. We are finding novel ways as permitted by local health authorities to do that. And to date, we've been very successful in doing that. And as Steve mentioned in his outset, we achieved enrollment of the 360th patient in our target enrollment on March 17. So everyone is enrolled. It's now a matter of following all of these patients.

Okay. Great. That's very helpful. And that's very good for the execution. The next question I have probably is a little bit sort of unfortunate situations. Just curious, given that most of the patients are [LV] and you say the average age -- median age is 82, do you anticipate or speculate, I should say, that the morbidity -- the co-morbidity will play into this and the time line, unfortunately, or fortunately, in this case, might be shortened for you guys to get to the 388 number?

So I'll take that one. So I just want to correct, I-Eh, the eligibility criteria is under the age of 82. It's not a median age of 82. The median age of MDS is in the late 60s. So with that said, we don't anticipate any impact of COVID-19 because it's a well-powered trial. And we are also at the major medical centers across the globe. And MDS patients obviously do develop pneumonia, but Rick and his team are monitoring and the centers are checking if a patient with MDS on INSPIRE has a pneumonia, they are checking for the evidence of COVID-19. So that is continuing. And in a well-powered trial, since COVID-19 may impact on both arms, we don't believe that it should impact on the final outcome of the trial.

Of interest, and I can't say I understand it, ASH just published their survey of 111 patients with hematological malignancies who had COVID-19 that caused their death. And despite all of the patients, 111, having a hematological malignancy, there is no MDS patients identified in that cohort. I can't say I understand that data, but that's the data from ASH. And we don't anticipate to summarize that COVID-19 should impact on the pivotal data that we anticipate from the INSPIRE trial in the second half of 2020.

Okay. Great. That -- I appreciate the explanation. And maybe the last one is that given -- I mean -- should the data be positive and -- first of all, I didn't get what time you might be able to file that. Would that be in 2021 or even late or maybe second half of 2021? Secondly is that in terms of manufacturing, particularly, CMC, all these aspects, how does the company intend to manage that at this moment?

Regarding -- I think, I-Eh, what you're asking is about the time lines for our NDA application. So we anticipate once we flip the card and hopefully have positive data, we anticipate it will take us -- because we already mentioned that we're doing a pre-NDA work already, we're not waiting to flip the card. A lot of CMC materials, toxicology materials can all be ready start to be written. But once we flip the card and have hopefully positive data, we anticipate a time line of 7 to 9 months to submit our NDA application for IV rigosertib.

And the CMC part of -- you mentioned that it's already in the process of checking them and making repeated batches or intend to make repeated batches to confirm the uniformity of the product.

That is correct. We have, just in case you didn't know, a full-time CMC expert on our staff at Onconova, who is leading those efforts to make sure that our CMC meets all regulatory requirements and is looking into initiating the writing of that part of the NDA. There's no reason to wait for the pivotal data to be read out. We can start that work already, and we have.

That concludes our Q&A session for today. I will now turn the call over back to Mr. Steven Fruchtman for closing remarks.

Thank you so much. And thanks to all of you for participating on today's update call. We're obviously very excited about the progress we have made with IV rigosertib and our pipeline programs overall. I hope you feel and share our enthusiasm.

Important milestones we look for in the near and medium term include, and this listing is in no particular order: first, our EHA presentation based on the genomics data from the INSPIRE trial; second, initiating enrollment of the Phase I/IIa trial of rigosertib plus nivolumab in KRAS-mutated advanced non-small cell lung cancer as an investigator-initiated study; third, beginning a Phase II/III combination study of oral rigosertib plus azacitidine in HMA-naive, higher-risk MDS patients following the INSPIRE data readout; fourth, U.S.A. IND submission of ON123300 during the fourth quarter of '20 followed by a clinical trial initiation; and number five, and most importantly, which gives us great enthusiasm, during the second half of this year, the release of top line survival data from the INSPIRE trial after reaching 288 survival events.

In closing, I encourage all of our stockholders to attend our upcoming Annual General Meeting of Stockholders later this month on May 27. We truly appreciate your continued interest in all of our programs at Onconova. Should you have any additional questions, please feel free to contact us. Please stay safe, and thank you all for your participation. Operator, you may now end the call.

Ladies and gentlemen, this concludes our conference for today. Thank you for participating. You may now disconnect.