Onconova Therapeutics, Inc.
Q3 2018 Earnings Call Transcript

Published: 13 Nov 2018

[Operator:]

Good day, ladies and gentlemen. And welcome to Onconova Therapeutics Third Quarter 2018 Earnings Conference Call. At this time, all participants are in a listen-only mode. [Operator Instructions] Later we will conduct question-and-answer session, and instructions will follow at that time. As a reminder, today’s conference maybe recorded. I’d now like to introduce your host for today’s conference, Dr. Ramesh Kumar, CEO. Sir, please go ahead.

[Dr. Ramesh Kumar:]

Thank you, Liz. Good morning, everyone, and welcome to our third quarter 2018 results call. Joining me from our management team are Dr. Steven Fruchtman, our President; Mark Guerin, CFO; and Dr. Richard Woodman, who recently joined the company as Chief Medical Officer. The third quarter was marked by the achievement of many important objectives, enabling us to advance our programs towards value inflection milestones in 2018 and 2019. These include enhancement of intellectual property position for the Rigosertib by expanding the geographical coverage of our patents and extending patent protection in the USA to 2037. Acceptance of four abstracts for presentations relating to Rigosertib at the 60th American Society of Hematology Annual Meeting and Expo in San Diego, California taking place from December 1 through 4, 2018. Our novel CDK4/6+ARK5 inhibitor ON 123300 is at advanced pre-IND stage and moving towards an IND in 2019. This program is being developed with HanX Biopharmaceuticals our partner in China. We are pleased to further strengthen our senior leadership team with the appointment of Dr. Rick Woodman as CMO. Rick was most recently with Novartis, where he served as Senior Vice President and Head of U.S. Oncology Clinical Development and Medical Affairs. We are pleased that Rick has joined Onconova and we look forward to his valuable contributions toward the continued development of Rigosertib. Together with our strength balance sheet these recent developments position our programs to many near-term value inflection points and business development. And now I will turn the call over to Steve for a further discussion of the excellent progress we’re making in our clinical development program. Steve?

[Dr. Steven Fruchtman:]

Thank you very much, Ramesh. At Onconova, we continue to be very excited about our differentiated pipeline and the strong progress we’re making in our ongoing clinical trial programs that are advancing very nicely towards important inflection points. These programs include our lead clinical program the Phase 3 INSPIRE pivotal trial with intravenous Rigosertib for high risk second-line patients with myelodysplastic syndromes also known as MDS who have failed to respond to progressed while on hypomethylating agents such as a Azacitidine or Decitabine. In January of 2018, we announced a completion of a preplanned interim safety and efficacy analysis leading to an increase in the sample size for the ongoing pivotal Phase 3 INSPIRE trial. We expect to complete full approval to this trial and provide topline data in the second half of 2019. We have two Rigosertib clinical programs, one, with intravenous Rigosertib, and the second, with oral Rigosertib to address the unmet medical needs of high-risk MDS patients. The INSPIRE trial with intravenous Rigosertib is ongoing and the Phase 2 combination trial of oral Rigosertib with injectable Azacitidine will be presented at the upcoming American Society of Hematology Meeting, which is also referred to as ASH. The combination trial is in patients with high-risk MDS and includes both HMA naïve, as well as patients who are refractory to HMA or Azacitidine therapy. The synopsis for this proposed pivotal Phase 3 trial to follow the combination Phase 2 trial to be presented at ASH will be in high risk patients with MDS and has been reviewed with the U.S. and ex-U.S. health authorities, and we have agreed on the trial design and a composite response endpoint. We plan to conduct this pivotal Phase 3 trial under a Special Protocol Assessment or SPA to be filed by the end of this year 2018. This filing will be followed by a similar submission in Europe and Japan, the latter by our partner in Japan and Korea SymBio. After the SPA negotiation process is completed, the pivotal Phase 3 trial for the combination product for front-line HMA naïve high-risk MDS patients may be initiated pending financing or business development activities. As a reminder, and for those who may be new to the Onconova story, MDS is a very complex disease of bone marrow failure syndromes associated, with the infiltration of the bone marrow with leukemia cells and is most often seen in elderly patients. Up to 30% of patients with high-risk MDS may advance to acute leukemia, typically AML, which is why and the reason they are designated as high-risk MDS patients. The patients who transform to AML are refractory to hypomethylating agents, as well as standard induction chemotherapy and typically unfortunately succumb to their underlying disease. There are no approved products in the world for high-risk MDS patients who fail hypomethylating agent, which is the current standard-of-care for high-risk MDS. Thus Rigosertib has the potential to address this critical unmet medical need. We have also conducted a Phase 2 trial with oral Rigosertib in low-risk MDS patients. The data was most recently presented at the 2017 ASH meeting. This trial focused on low-risk MDS patients who are red cell transfusion dependant. Similar to high-risk MDS patients, low-risk MDS patients also suffer from inadequate bone marrow function and are typically unfortunately unable to produce adequate numbers of circulating blood. But they have a low-risk of transforming to acute leukemia than those with high-risk disease and thus the low-risk MDS designation. There are more than 10,000 low risk MDS patients in the U.S. and these patients also have a tremendous unmet medical need due to their need for transfusional support and we hope to address this need. Our therapeutic goal is improving their bone marrow function and ideally making these patients either red cell transfusion independent or reduce their need for transfusional support. We have continued to actively participate in and present at major MDS conferences across the globe on our ongoing trials. Following the interim analysis of the pivotal INSPIRE Phase 3 trial, we reported results across our MDS pipeline. We presented initial Phase 2 safety data from the expansion study of oral higher dose Rigosertib in combination with Azacitidine in patients with MDS at the recent 6th International Bone Marrow Failure Disease Symposium in March of 2018. We previously presented efficacy data at ASH with this combination and the data demonstrated an encouraging overall response rate of 76%, 62% in patients following HMA failure, and 85% response in HMA naïve patients. As Ramesh already mentioned, we were pleased to have four abstracts related to Rigosertib accepted for presentation at the upcoming 60th American society of Hematology Meeting. Dr. Shyamala Navada of the Icahn School of Medicine at Mount Sinai Hospital in New York on behalf of all of our co-investigators, will present updated efficacy and safety data from the Phase 2 combination trial of oral Rigosertib plus azacitidine. Additional presentations at ASH will highlight the PK/PD and safety clinical data from patients treated with this combination, as well as a punitive biomarker to predict responses to Rigosertib will also be presented. As we make progress with our key Rigosertib trials in adult MDS, and as I mentioned, we await the results from our funded collaboration under a CRADA with the National Cancer Institute or NCI in pediatric cancer associated RASopathies in children born with the RAS mutation. The NCI is conducting PK/PD and dose escalation studies in preclinical models to prepare for dosing of pediatric patients with single-agent Rigosertib. A clinical trial protocol concept has been developed and is under review at the NCI. Based on NCI guidance, we expect the first pediatric patients to be put on study in the first half of 2019. Regarding one of the RASopathies , juvenile myelomonocytic leukemia or JMML, also referred to as pediatric MDS, the National Cancer Institute intends to conduct a Phase 1 trial with Rigosertib as part of a collaborative initiative with Onconova for the treatment of JMML and although oncological RAS driven genomic pathway diseases. As I mentioned, we have a cooperative research and development agreement or CRADA with the NCI and clinical protocols under their review. We anticipate this trial will start in the first half of 2019. In addition, preclinical models of JMML are being studied at the University of California at San Francisco, an expert center in the studies of JMML and is being funded by the leukemia and lymphoma society. We also have a number of investigator initiated studies. A study for patients with myeloproliferative neoplasms or MPNs where the bone marrow makes too many circulating blood cells is being conducted at MDS and Cancer Center. And the second study on RAS driven rare squamous cell carcinoma of the skin is being run at centers of excellence in Europe with expertise in this disease -- in this rare condition. Additional combination studies with Rigosertib in solid tumors are under consideration. In summary, there are many important ongoing activities related to the advancement of both intravenous and oral Rigosertib programs in MDS, which are moving forward toward impactful milestones for Onconova in the near-term. We will remain focused on these programs, while also looking to enhance the potential of Rigosertib in additional indications and collaborate -- and combinations through collaborations and partnerships. With that, I thank you and I will turn the call over to Mark Guerin, our Chief Financial Officer, for a discussion of our financial results for the quarter. Mark?

[Mark Guerin:]

Thanks, Steve, and good morning, everyone. Net loss was $5.3 million for the third quarter ended September 30, 2018, compared to a net loss of $7 million for the third quarter ended September 30, ‘17. Our research and development expenses were $4 million for the third quarter of ‘18, compared to $5.1 million for the 2017 period. General and administrative expenses were $1.7 million for the third quarter of ‘18 and for the third quarter of ‘17. Our net loss was $14.8 million for the nine months ended September 30, 2018, compared to a net loss of $17.9 million for the comparable 2017 period. At the end of the quarter cash and cash equivalents totaled $22.4 million, compared to $4 million at December 31, 2017. We believe that our cash and cash equivalents of $22.4 million at the end of September will take us into the fourth quarter of 2019 based on our current plans and projections. That completes my financial review. I will now hand the call back to Ramesh for his closing remarks. Ramesh?

[Dr. Ramesh Kumar:]

Thanks, Mark and Steve, and welcome Rick to Onconova. As you can see, we have many rapidly advancing programs and we expect to report incremental data in 2018 and 2019, and pivotal Phase 3 data in 2019. Our near-term pipeline program objectives include finalizing the Phase 3 protocol under SPA for oral Rigosertib in combination with the Azacitidine in first-line high-risk MDS, starting the RASopathy clinical trial and advancing our novel CDK directed compound to the clinic in partnership with HanX. Our most important objective remains completion of the INSPIRE trial and the expected data read out in the second half of 2019. Key to our strategy is initiating additional collaborations and geographic licensing agreements for our entire pipeline, bringing resources and new opportunities for regaining value. We hope to report on the results of these efforts in the coming months. We also look forward to continuing our track record of quality publications and scientific presentations to announce results of our ongoing and completed studies. With our cash on hand regained NASDAQ compliance and multiple late-stage clinical stage programs, we remain confident we will reach key clinical milestones in advance business opportunities for our entire pipeline over the next 12 months to 18 months. Steve, Mark and Rick and I look forward to keeping you apprised of key developments. With that, I would like to open the call for questions. Liz?

[Operator:]

[Operator Instructions] Our first question comes from line of Jason McCarthy with Maxim Group. Your line is now open.

[Jason McCarthy:]

Hi. Thanks for taking my question. So related to the INSPIRE study, without giving too much away, could you go into a little bit more detail on the trial progress in terms of enrollment and the number of events that have occurred thus far?

[Dr. Ramesh Kumar:]

Thanks, Jason. Steve, will address that.

[Dr. Steven Fruchtman:]

Thanks Jason. So based on our monthly accrual which has been quite consistent and we’re very pleased with it. We anticipate full accrual of the INSPIRE trial second half of 2019 and we also anticipate of the unfortunate short life expectancies of these patients that pivotal data which is going to be based on survival as you may recall 288 death events. We anticipate full accrual and overall survival to be quite linked, so we anticipate pivotal data towards the second half, perhaps, the latter half of 2019.

[Jason McCarthy:]

Okay. Thank you. And -- as a follow-up as we approach that pivotal data, could you talk about how many of the major centers are involved with the INSPIRE study or other Rigosertib programs?

[Dr. Steven Fruchtman:]

So regarding the INSPIRE trial, we have is a global trial, as you know, and we have over 150 clinical sites and centers of excellence across the globe. The major MDS centers of excellence in the U.S., Europe, Australia, Israel. So it’s a global trial with many sites continuing to accrue. Regarding the combination Phase 2 trial, Jason, although, that trial is rapidly accrued, we were able to have full accrual just in the U.S. and again at centers of excellence in the U.S. as well. In addition, of course, the INSPIRE trial is being done with our corporate partner in Japan through SymBio.

[Jason McCarthy:]

All right. Thank you. And then just as we approach the IND and this one last quick one, could just talk a little bit more about the opportunity presented with CDK program?

[Dr. Ramesh Kumar:]

Yes. Good question. As you know, CDK is probably one of the most exciting new target to emerge in last five years or so. And we all know that very big companies, including Pfizer, Novartis and Lily have compounds in the market, once since three years, the others for about a year or so. And everyone believes that this will address many, many solid tumors. Our data suggests that our molecule may go beyond solid tumors into multiple myeloma and other T and B cell, the malignancy certain gastric cancers and that belief is based on data suggesting that the inhibition of ARK5 opens the door to many other targeted mechanism driven, biomarker driven investigations. So in short this program is moving forward towards an IND and we expect in collaboration with HanX, our partner in China to file IND, we will file in the U.S. and Europe, and they will file in China and we will do a pretty expansive Phase 1 study, including a diversity of patient types and we hope to give you updates on the progress of the IND, as well as the further details of the Phase 1 early next year.

[Jason McCarthy:]

Okay. Thank you very much for taking my questions.

[Operator:]

Our next question comes from Joe Pantginis with H.C. Wainwright. Your line is now open.

[Joseph Pantginis:]

Hey, guys. Good morning. A couple questions if you don’t mind, so I know you, probably, can’t say too much about the design of the upcoming Phase 2, I am sorry, Phase 3 oral study, because you’re in the iterative process with the FDA regarding the SPA, but was just curious if you have any broad strokes with regard to the potential size and if there’s any potential adaptive design to the study?

[Dr. Steven Fruchtman:]

So we have discussed based on the preliminary data, Joe, which again will be updated at the upcoming ASH meeting, but we have already interacted with the FDA and EMA based on the preliminary data of the combination trial. We have an agreement what that trial will look like. It’s going to be for patients who are treatment and HMA naïve with high-risk MDS. The trial will consist of a placebo controlled blinded trial of oral Rigosertib plus Azacitidine versus oral placebo plus Azacitidine. And the endpoint will be a composite response endpoint based on the most recent discussions with the agencies of complete response and partial response based on IWG. The size of the trial will have to continue to be discussed with the agency based on the clinical benefit, but that will be part of the SPA negotiation.

[Joseph Pantginis:]

No. That’s helpful. Thanks, Steve. And then, just curious, because obviously, it’s an early-stage program, but very promising with regard to the potential patient benefit in these pediatric for the RASopathy. And I know this is a very broad stroke type of question and looking deep into the future, but what a potential regulatory path might look like in these pediatric ultra orphans?

[Dr. Steven Fruchtman:]

Joe, that’s great question. So these children are unfortunately desperately ill, none of the typical standard therapy work. They also try like adult Azacitidine and hydroxyurea, and these children need to have an allogenic stem cell transplant, but as you know that can be difficult to identify. So we like Rigosertib to be study again in collaboration with the NCI for JMML. Some of the endpoint will be control of the hyperleukocytosis these patients have, a high white count. They have enormous livers and spleens. And if you look at how Jakafi was approved in myeloproliferative neoplasms it was basically symptomatic improvement and reduction in the size of the spleens. So one of the endpoints to be discussed with the health authorities would be symptomatic approve -- improvement, control of the blood count, control of the enormous livers and spleens, and also as a bridge to transplant. For patients and children who have already been transplanted, unfortunately the relapse rate is very high. So the other approach will be post-transplant to explore the possibility of Rigosertib for clinical benefit for these children. But obviously we need to first conduct a trial at the NCI and then interact with the health authorities to get an approval pathway. But those are some of the possible ways of approaching the answer to your questions, Joe.

[Joseph Pantginis:]

Got it. Thanks for the added color, Steve.

[Operator:]

[Operator Instructions] Our next question comes from Yale Jen with Laidlaw. Your line is now open.

[Yale Jen:]

Good morning and thanks for taking the questions. Just a little bit follow-up with what Joe just asked and maybe just expand a little bit. You mentioned that composite -- it is a composite endpoint for the proposed Phase 3 study you also mentioned that CR and PR, which is sort of fall into the OR endpoints. So is there any other sort of general aspect will be incorporated into these composite endpoints?

[Dr. Steven Fruchtman:]

Well, there will or there is always secondary endpoints as well, but the primary endpoint we anticipate will be CR plus PR, but as per the international working group criteria for response. But there are other endpoints in that IWG, including marrow CR, including hematological improvement, the platelets, red cells and white cells of marrow function improvement will be a secondary endpoint, time to leukemic transformation, because again these are all high-risk MDS patients and there will be a significant rate of leukemic transformation and thus that will be a secondary endpoint as well and typically a secondary endpoint will most likely also be survival. So those are the multitude of endpoints we anticipate the agency will want us to look at in that pivotal Phase 3 trial.

[Yale Jen:]

And based on the timeline do you have some projection as when the SPA might be sort of granted?

[Dr. Steven Fruchtman:]

Well, we -- our plan is to submit the full protocol and the SPA by the end of December, at the end of 2018. And typically it takes about 90 days, three months for those interactions with the agency to be finalized. So some time first quarter of 2019 we anticipate that based on funding we’ll be able to initiate the trial.

[Yale Jen:]

And then maybe just one more question here, which is for the 123300, and that is actually come from investor who ask us regarding. Could you give us a little bit more detail in terms of the compound itself regarding, for example, PK, half-life and some other aspects, So to get a better thoughts or handy for cap of the future development of compound?

[Dr. Ramesh Kumar:]

Yale, up to the point we did our agreement with HanX. The compound has been internally developed through collaborations and there about 15 publications regarding every aspect, chemistry, all the way to be PK/PD available and we can share some of those with you or they may be available on our website. So very briefly this is a small molecule drug, oral delivery, obviously, we’re hoping that it is once a day, but that remains to be established in Phase 1 studies. The drug is of the same potency as Palbociclib or Kisqali or Verzenio as far as CDK4 and CDK6 are concerned. But when you look at the new target, we have defined ARK5, all these other compounds don’t hit that target and we are nanomolar portent against ARK5. So our compound is distinguished by three properties. One, the ARK5 angle, number two, single agent activity, and number three, activity in preclinical model seen in Rb negative situations. You know, Yale, that Rb negative is not compatible with the first generation CDK4 compounds. As a matter of fact, Palbociclib resistance has been linked to Rb negative. So we are hopeful that are drug has enough differentiation, enough superior activity, which can be established in Phase 1 studies. Hope that answers your question.

[Yale Jen:]

Absolutely. That’s a lot of detail and I am really appreciated. So, again, congrats on the progress and look forward -- to updates coming forward.

[Dr. Ramesh Kumar:]

Thank you.

[Operator:]

[Operator Instructions] I am showing no further -- we do have a question from the line of Howard Grant [ph]. Your line is now open.

[Unidentified Analyst:]

Yes. Hello. Thank you for taking question. This is regarding the poster for the oral combo Phase 2 upcoming at ASH. And I was wondering if you could comment and provide, perhaps, a little color on what appeared to be a high discontinuation rates?

[Dr. Ramesh Kumar:]

Could you repeat what -- where is the data coming from and what particular study you’re referring to?

[Unidentified Analyst:]

Yes. Yes. On the upcoming poster that you will be presenting at ASH for the oral combo Phase 2, the expanded data, it appeared to have a somewhat high discontinuation rates and I was wondering if you could comment on this

[Dr. Ramesh Kumar:]

It’s probably not appropriate. As you know, ASH imposes an embargo and reading an abstract is usually not getting complete information. I recommend you attend the oral session if you are San Diego on December 1 or we will do a press release with more details following that presentation. So because of the embargo rules, we are not able to give you more data or discuss the data in the abstract today.

[Unidentified Analyst:]

Okay. Thank you.

[Operator:]

I’m showing no further questions in queue at this time. I’d like to turn the call back to management for closing remarks.

[Dr. Ramesh Kumar:]

Thank you, Liz. I thank all the attendees today and my colleagues, Steve, Mark, and Rick, for participating in this update, and we are available for the analyst who do follow-ups throughout the day and tomorrow. Thank you again and have a great day.

[Operator:]

Ladies and gentlemen, thank you for your participation in today’s conference. This concludes the program and you may now disconnect. Everyone have a great day.