Onconova Therapeutics, Inc.
Q3 2017 Earnings Call Transcript

Published: 9 Nov 2017

[Operator:]

Good morning, and welcome to Onconova’s Third Quarter 2017 Earnings Call and Webcast. At this time, all participants have been placed on listen-only mode. At the end of the prepared statements, participants will have the opportunity to ask questions. [Operator instructions] Please note that the remarks today will include forward-looking statements and that actual results could differ materially from those projected or implied in our forward-looking statements. For a description of important factors that could cause actual results to differ, we refer you to the forward-looking statements in today’s press release and the note on forward-looking statements in the Company’s SEC filings. It is now my pleasure to turn the call over to Onconova’s CEO and President, Dr. Ramesh Kumar. Dr. Kumar, please proceed.

[Ramesh Kumar:]

Thank you, Caja. Good morning, and welcome to our third quarter 2017 result call. Joining me from Onconova’s management team is our CFO, Mark Guerin. This quarter, we have made a lot of progress and now we're approaching key milestones for our lead clinical programs addressing the needs of patients with myelodysplastic syndromes or MDS. A preplanned interim analysis of the adaptive designed inspired trial for IV rigosertib and patients with high risk MDS is anticipated in the coming months. We're also encouraged by the recent increase in enrollment for this global trial, this suggestfull enrollment can be achieved in the first half of 2018. We're also making solid headway in our rigosertib azacitidine combination program and now are in position to initiate a special protocol assessment process for a Phase III trial early next year. Our preclinical RASopathies program is advancing as planned and last month we held a key opinion leader breakfast in New York to discuss new developments for pediatric patients for RASopathies. Looking ahead, we have two poster presentation at the 2017 ASH meeting, demonstrating long-term transfusion independence in low-risk MDS going out multiple years. All in all, I'm very pleased with the progress in the third quarter and outlook. In addition, we continue to focus on multiple business development initiatives trying to partner both rigosertib geographically in our earlier stage pipeline products. I will no discuss in more detail recent progress in our Phase III inspired trial. Where we are testing the potential of IV rigosertib as an effective life extending second line therapy for MDS patients for whom hypomethylating agents or HME have failed. This is our main focus in our most advanced program. I'm pleased to report that the statistical analysis plan or SAP for both the interim and topline analysis has been reviewed by the FDA and the European Medicines Agency. And based on their guidance, we have now finalized the SAP. In this trial of 225 patients, the interim analysis will be triggered by the ADA-ed deaths event. Based on our modeling, this could take place as early as by the end of year or very early next year. Since the date of interim analysis is tied to reaching a preidentified number of death events, it is not possible to accurately forecast a precise time of completing the interim analysis. Based on the various procedures we have created for the IAA under the SAP, we anticipate that the interim analysis process will be complete within a couple of weeks of reaching the planned number of events. As we have discussed previously, inspired trial design is adaptive and permits choice of options, including a futility analysis and trial expansion using preplanned statistical criteria. The SAP permits two analysis; overall survival and the intent to treat ITT population and in the subgroup of patients classified as having very high risk or VHR MDS as defined by the IPSS-R scoring system for risk. The statistical parameters were success under these scenarios are predefined in the SAP. As a reminder, the inspired trial is being conducted in a targeted population of second line patients and is designed based on learnings from our Phase III on time trial. This study help define subgroups of patients who appeared to experience improvement in the primary endpoint of overall survival. We believe that identification of the patient population most likely to respond helps increase the likelihood of a favorable outcome of the study. As of October 31, the global inspired study had patients enrolled in 22 countries across four continents, North America, Europe, Asia and Australia. They had 170 sites. Only five more sites remain to be open and we expect that this will occur this month. Since we experience a slowdown in enrollment mid-year, we undertook measures just for enrollment including the addition of trial sites in three new countries and changes within the CRO group. These efforts are now paying off. I'm pleased to report that these actions led to a recent increase in the enrollment rate for this trial. As the result, we expect full enrollment to be achieved in the first half of 2018, followed by topline analysis after 176 events in the second half of 2018. Our second advance program is in oral rigosertib plus azacitidine combination as a potential first inline therapy for patients with high risk MDS. After completion of the Phase II study in 2016, we obtained regulatory guidance from the FDA and EMA and then started an expansion phase of the trial. We are now awaiting the results of this expansion trial. Once the expansion trial is complete, expected by year-end, we plan to design and submit the pivotal Phase III protocol to the FDA in the first half of 2018 under the SPA process. The expansion trial is designed to enroll up to approximately 40 patients, more than half of the trial has been accrued in multiple sites in the USA. Based on this encouraging progress, we have decided to limit the trial to U.S. sites only. The Phase III trial design is a one-to-one randomized control trial of oral rigosertib plus azacitidine compared with azacitidine plus placebo in first line patients with high risk MDS. Initiation of the Phase III trial which is planned to be conducted globally requires additional financing or business development transactions or a combination of both. We plan to present initial data from this expanded study at a scientific conference in early 2018 highlighting the results of those selection and optimization of the combination regimen. Previously presented data demonstrates that the combination therapy may overcome hypomethylating agent resistance and also indicates that further study of rigosertib and Acute Myeloid Leukemia [AML] is warranted. Given that as many as 30% of MDS patients go on to develop AML, it is also intention to study AML in the future. The advancement of our two lead programs during this quarter is complemented by recent advances in our collaborative RASopathies or front row program. We have initiated a multi-institutional collaboration to evaluate rigosertib in pediatric RASopathies which may provide additional potential markets for rigosertib. The collaborators include major national institutes such as the NCI, academic institutes and nonprofits. RASopathies or related genetic syndromes usually caused by mutations that all to the RASo family and mitogen activated protein or MAP kinases that control signal transduction. In mid-October, we hosted a key opinion leader meeting in New York to discuss novel approaches to RASopathies. The meeting featured presentations by Dr. Bruce Gelb of Mount Sinai and Dr. Elliot Stieglitz of the University of California, San Francisco. They discussed new developments for pediatric patients with RASopathies. I'm also pleased to report that we have completed and expect to sign a CREDA, Collaborative Research and Development Agreement with the U.S. National Institutes of Health to advance rigosertib in pediatric clinical trials at the NCI. This trial is expected to start next year and will be funded by the NIH. Also, in the third quarter, we entered into strategic collaboration with Cellectar Biosciences to develop new phospholipid drug conjugates combining select proprietary compounds or payloads from our early stage product pipeline to select our patented phospholipid ether delivery platform. We are encouraged by the progress in our late stage programs in the exciting developments underway in our earlier stage programs and collaborations. I will now turn the call over to Mark Guerin, Onconova's Chief Financial Officer for a discussion of our financial results in the quarter.

[Mark Guerin:]

Thanks, Ramesh. At the end of the third quarter, our cash and cash equivalents totaled $7.6 million compared to $21.4 million as of December 31st 2016. Our total net revenue was $0.1 million for the third quarter and $0.6 million for the nine months ended September 30th, compared to $1.7 million and $5.4 million respectively for the comparable periods last year. Research and development expenses were a $5.1 million for the quarter and $14.6 million for the nine month period compared to $4 million and $15.4 million respectively for the year ago periods. General and administrative expenses amounted to $1.7 million for the third quarter and $5.6 million for the nine months ended September 30th, 2017 compared to $2 million and $7.2 million respectively for the same period in 2016. I'll now hand the call back to Ramesh for his closing remarks.

[Ramesh Kumar:]

Thanks, Mark. Looking ahead to December, we plan to present data relating to rigosertib at the ASH annual meeting in Atlanta, Georgia. Our first poster presentation will be a long term follow-up of patients in a Phase II clinical trial, a single agent oral rigosertib in low risk transfusion dependent MDS. And our second presentation will detail studies on the mechanism or action of rigosertib azacitidine combination therapy for MDS. These studies will highlight the potential use of oral rigosertib beyond the second line indications targeted under the inspired trial. We're also presenting results from three studies relating to rigosertib and ON 123300 and orally administered novel CDK4/6 + ARK5 inhibitor at the American Association of Pharmaceutical Scientists, AAPS conference in San Diego next week. I'm gratified by the rapid progress in our late stage trials which are setting the stage for multiple key catalyst in 2018. We expect interim analysis of the inspired trials soon and believe full enrollment can be achieved in the first half of 2018. We're advancing the oral rigosertib combination program towards an SPA for a pivotal Phase III trial early next year. These programs and collaborations demonstrate the death of our pipeline and the many opportunities that lie ahead. We are proud to be making advances in the treatment landscape and look forward to updating you on our near-term milestones. I would now like to open the call to discussions. Caja?

[Operator:]

Thank you. [Operator Instructions] And our first question comes from Jason McCarthy from Maxim Group. Your line is open.

[Jason McCarthy:]

Hi guys, thanks for taking the questions. First question is on the inspired interim analysis. Ramesh, to your point it is an adaptive trial design. Yes, can you walk us thorough what the possible outcomes are whether there are opportunities to skew the patient population to the very high risk patients where we saw a great data that most benefit in the ONTIME trial? Can you just walk us thorough what we could possibly expect?

[Ramesh Kumar:]

Thank you much, Jason. As you know FDA, the new FDA is very supportive of effective design trials. Because they want the development to be accelerated. So, when we design inspired in early 2015, based on as you pointed out, the very strong findings which we publish in Lancet Oncology showing that certain subgroups which are high risk subgroups either by defined by the karyotype such as monosomy 7 or trisomy 8 or defined by the IPSS-R risk core. So, the higher risk core indicated a greater benefit. And this could be rationalized based on the biological rationale, the mechanism or action of the drug. So, keeping these two factors in mind, 1) that the drug had activity in subgroups and 2) that the activity correlated with the risks or higher the risk or the better the activity. We decided to make this a trial where there is a demarcation within the ITT subgroup. ITT is all the patients which were carefully selected to be in the inspired trial. Then we took another cart which was very high risk as defined by the IPSS system, which is roughly IPSS risk core of 6.5 or higher, very objective criteria, a composite scoring system which allows us to define the right patients. And our prediction was that compared to the previous trial, the new trial which is designed for higher risk patients, the very high risk group would be larger. And I can tell you that that's exactly what we are finding out that in the new ITT population, the very high risk group continues to be the majority of the patients, a significant majority of the patients. So, adaptive design will allow us to make a decision either at interim end point or at the topline analysis to focus only on the very high risk program. So, in summary, at the interim analysis we face several forks in the road not just one fork in the road. One is to continue as planned, the second one is to refine the trial by adding more patients which is a standard definition of adaptive design. And the third, which is a creative design element that our CMO introduced, which is to continue to focus only on the very high risk patients in the trial. I hope I addressed the question adequately.

[Jason McCarthy:]

It had, thank you. And just one more question. It's related to your KOL and R&D event. A lot of work has gone into targeting RAS over the decades and rigosertib is just seen is the first real candidate. That seems they really disrupt multiple RAS signaling pathways and at that event, there was some discussion of moving a drug like rigosertib to other indications like JMML or cardiac myopathies where I don’t think it's as well known that RAS plays a significant role there. Can you discuss what the plans are, there is some mention of National Cancer Institute getting involved and maybe some investigator sponsored studies that could start to initiate in 2018?

[Ramesh Kumar:]

Thank you. When we started looking at the RASopathies field, we were very surprised. There is a very strong patient advocacy in these diseases, mostly coming from families because this disease affects young children and it's fatal for almost all of the cases and there is no cure, no treatment today available. And then the second push comes from the experts, the investigators like Dr. Gelb, Dr. Stieglitz, Dr. Menlo at UCSF and Charlotte Niemeyer in Germany. So, these experts have dedicated their entire career to study RASopathies. And when we added up the entire RASopathies universe and we found out that it's not that rare, there's a lot of patients every year, a lot of young children, some diagnosed within weeks of their birth which are affected by this anomaly. And you pointed out that RAS is a key and therefore we define the disease as RASopathies. And as you pointed out RAS is not a single entity or a single network or a single pathway, RAS actually is a very big control point around which revolve as many as 15 different pathways. And as we published in 2016 in the journal cell, rigosertib is able to really attack many nodes of this pathway by its RAS binding domain mechanism. So, there was a complete harmony between the need and the available drug and when our CMO, Dr. Steve Fruchtman made the trips to visit with the families at the RASopathies Congress to the UCSF and to the NCI to present our story, there was a very good resonance, they all wanted to help. And then we talked to other patient advocacy organizations like Leukemia Lymphoma Society which as many of you will remember gave us a $10 million grant to do our ONTIME study in MDS. So, they have a great deal of affinity for MDS in children which is also known as JMML. So, a perfect storm came together and sometimes in the second half of this year and culminating in this last quarter, we were able to pull together a multi-institution, multi-investigator study which is both preclinical fork for JMML as well as clinical in a Phase I all-comers trial to be funded by the NCI, the protocol for which has being reviewed and approved as we speak.

[Jason McCarthy:]

Great, thank you for taking the questions, Ramesh.

[Ramesh Kumar:]

Thank you, Jason.

[Operator:]

Thank you. Our next question comes from Joe Pantginis from H.C. Wainwright. Your line is open.

[Joe Pantginis:]

Hi guys, good morning, thanks for taking the question. Ramesh, my first question I'd like to talk about the SAP you just finalized and a little bit of the extended time that it took to get to this point. And I just wondering can you describe I guess some of the ice you needed to dot and the tea is crossed especially since you had to finalize this in two different regulatory agencies both the FDA and the EMA?

[Ramesh Kumar:]

Joe, thank you. Actually, when we started the trial which was February of 2015, we had the overall structure in our mind, in our statistician and our clinicians put together a very good proposal which FDA reviewed as part of the approval of our CTA Clinical Trial Application in August of 2015. So, from our point-of-view, everything was pretty much set up to go and we had actually oral in our meeting and then subsequently written concurrence from the agency. But as you know this is a global trial, we are not just in U.S. and Europe, we're also in Japan. Our partner SymBio is enrolling 10% to 15% of the inspired trial at their cost in Japan. So, they have gone to the PMDA which is the Japanese FDA. So, really the complication was A) the European process is designed differently than the FDA process. European process typically is slower. So, we first went back to the FDA, got their concurrence with what we had agreed in 2015. Then we went to the EMA initiated scientific advice process, then we had to reconcile everything. So, we had to go back to the FDA. And since this is an adaptive design, this is not a vanilla SAP, FDA asked us to make sure that there are firewalls, there are three different groups, the statisticians, the executive committee, the company, and there is a mechanism prespecified mechanism for correcting alpha providing appropriate adjustments to Alpha because of the inspire interim analysis. So, all of this seems boring and for most people it is boring but statisticians get into this and I think we have created a SAP and an adaptive design which hopefully when we publish people will say that this is really innovative and really helps the trial and helps the patients in the trial. I hope I address that question.

[Joe Pantginis:]

No, absolutely, Ramesh. Thanks, I mean being able to address all these things behind the scenes ahead of time hopefully gives inspire its best shot possible. It sounds like it does. With regard to the, I think I heard you say early 2018 for the expansion phase with regard to the oral rigosertib and its azacitidine combo, I know you can't talk about the date of it maybe a little bit about around the expectations about what we would see in this dataset. Would it be the full 40 patients and what would you consider our benchmarks for success that we could look towards?

[Ramesh Kumar:]

Thank you. As we announced before, the Phase II data was quite impressive. We had 80+ percent overall response rate of the combination in the frontline setting including 35% of the patients achieved complete remission. This kind of data has not been seen before. So, we felt that since we were going to focus on and inspired for 2017, it made a lot of sense for us to continue to explore that exciting data both in terms of the efficacy that was noted before and also focusing on the safety tolerability of that. So as we have forecast, we expect to see all 40 patients in the trial this year in about 10 different sites in the U.S. alone. So since the trial was enrolling so quickly, we decided not to go to Europe because that takes additional time. So we will have 40 patients enrolled and the good news here is that the assessment of success of the treatment is response based and can be had as little as 2 to 3 months after the patient get on the drug. So we expect to provide you a lot of efficacy and tolerability data and since the first patient in the expansion was started early this year, you will have long-term use of the drug effect on various parameters including complete remission, transfusion independence. So we expect and for this reason because we wanted to present a full picture, we decided to withhold partial presentation at ASH or some of the early meetings that are available. So we will select a meeting where we will have the right experts and we will present it as early as possible in 2018 and again the focus here is to advance what we knew from our original phase 2 data and then focus on what we have learned by this dose optimization, by taking care of patient reported events. So in this expansion phase we have given a diary to each patient so they can take note of the tolerability issues. So I think we are making announcement on what conference we will be presenting and hopefully in the very early part of 2018.

[Joe Pantginis:]

That's great, thanks for the additional details Ramesh.

[Ramesh Kumar:]

Thank you, Joe.

[Operator:]

Thank you. Our next question comes from Yale Jen from Laidlaw & Company. Your line is open.

[Unidentified Analyst:]

Hi Ramesh, it's actually Pat Gallagher, Yale just stepped out but he should be back in momentarily. I think the number of his questions have been answered but perhaps you can, if possible talk a little bit about the Cellectar collaboration and how you anticipate that complementing your current development programs and also how it might expand the pipeline moving forward, I know it's early days but any color on that would be very helpful?

[Ramesh Kumar:]

Thank you, Patrick. As many people know especially the covering analyst that the company is founded on proprietary chemistry platform and proprietary drug discovery platform and over the years we have been able to identify very, very promising candidates. But since 2015, since our focus was narrow and laser focus on getting rigosertib to the market, we de-prioritized many of these early-stage programs. So in addition to the molecules that we have partnered with Cellectar which relate to our Briciclib compound for which we have phase 1 data already in hand, we are also putting a lot of emphasis on the CDK 4/6 +ARK5 compound because we are finding out that there is a great need from both small and large companies for both U.S. and ex-U.S. companies to acquire or to partner these compound. So you’re going to be hopefully hearing a lot more about these collaborations in 2018, particularly how a collaboration can take additional compounds into the clinic while we remain focused on the multiple opportunities, multiple shots and goal we have on rigosertib.

[Unidentified Analyst:]

That's very helpful. Thank you.

[Operator:]

Thank you. [Operator Instruction] And I am showing no further questions from the phone lines. I will now like to turn the conference back over to [indiscernible] for any closing remarks.

[Unidentified Company Representative:]

Thank you for your questions and your attention today and we look forward to speaking with you again next quarter. In the interim management remains available to meet with you and answer any questions that you may have. Thank you and enjoy the rest of your day.