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Edited Transcript of ONTX earnings conference call or presentation 14-Aug-19 1:00pm GMT

Q2 2019 Onconova Therapeutics Inc Earnings Call

Newtown Aug 23, 2019 (Thomson StreetEvents) -- Edited Transcript of Onconova Therapeutics Inc earnings conference call or presentation Wednesday, August 14, 2019 at 1:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Abraham N. Oler

Onconova Therapeutics, Inc. - VP of Corporate Development & General Counsel

* Mark Patrick Guerin

Onconova Therapeutics, Inc. - CFO

* Richard Charles Woodman

Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development

* Steven M. Fruchtman

Onconova Therapeutics, Inc. - CEO, President & Director

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Conference Call Participants

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* Ahu Demir

NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst

* I-Eh Jen

Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst

* Joseph Pantginis

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

* Naureen Quibria

Maxim Group, LLC - Senior Equity Research Associate

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Presentation

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Operator [1]

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Good morning and welcome to Onconova Therapeutics Corporate Update and Second Quarter 2019 Financial Results Conference Call. At this time, I would like to turn the call over to Avi Oler, Vice President of Corporate Development and General Counsel.

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Abraham N. Oler, Onconova Therapeutics, Inc. - VP of Corporate Development & General Counsel [2]

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Thank you, operator. Good morning, everybody, and welcome to Onconova's Second Quarter 2019 Corporate Update and Financial Results Conference Call. Earlier this morning, we issued a press release with second quarter 2019 financial results and business updates. If you have not seen this morning's press release, it is available on the Investor Relations page of our website at www.onconova.com.

On today's call, Dr. Steven Fruchtman, President and CEO, will discuss the company's recent highlights and anticipated clinical and business progress. After Steve completed his opening remarks, Mark Guerin, our Chief Financial Officer, will review second quarter 2019 financial results. Following Mark's report, we will move to the Q&A portion of the call. Dr. Rick Woodman, our Chief Medical Officer, will also be available to respond to questions. Lastly, Steve will come back with some final brief remarks and a review of upcoming milestones.

Before we begin, I would like to remind everyone that statements made 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 morning and the risk factors in the company's current and future filings with the SEC.

With that, I'll turn the call over to Steve.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [3]

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Thank you so much, Avi. Good morning, everybody, and thank you for joining today's call. The first half of 2019 was a strong period for Onconova, highlighted by our continued progress towards completing enrollment of our global pivotal Phase III INSPIRE trial. Upon completion of enrollment and 288 death events, we look forward with great anticipation to reporting top line data in the first half of 2020.

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

The primary endpoint of this study is overall survival of all randomized patients in the intent to treat population. There's 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.

In terms of enrollment on the trial, more than 140 trial sites in 24 countries across 4 continents are open, including 21 sites in Japan. The company opened new clinical trial sites in countries already participating on the INSPIRE trial. Additional geographies, most importantly Brazil, because of its huge population and thus anticipated high number of patients with MDS, are being opened during the coming months with a goal of adding approximately 25 more sites there. This strategy is designed to support the goal of achieving full accrual to the INSPIRE trial by the end of 2019. Should rigosertib significantly prolong survival on the INSPIRE study, we believe rigosertib will be the first new treatment for higher-risk MDS in more than 15 years.

In addition to the INSPIRE trial, we are advancing toward the start of a new pivotal Phase III combination trial of oral rigosertib and azacitidine for the treatment of adult patients with first-line higher-risk MDS. In December of 2018, we applied to the U.S. Food and Drug Administration for a Special Protocol Assessment, also known as a SPA, for this trial. We anticipate completion of the SPA process and the initiation of the pivotal Phase III trial toward the end of 2019.

A number of important abstracts that present progress on the INSPIRE trial and the combination trial of azacitidine with oral rigosertib have already been submitted to the American Society of Hematology Annual Meeting, which is scheduled for December 2019 in Orlando, Florida. While our focus remains on MDS and completing enrollment in the INSPIRE trial, we have made important progress with our pipeline program, ON 123300, our investigational, first-in-class, dual inhibitor of CDK4 and 6 and also ARK5, which we believe has the potential to treat numerous cancers, including refractory metastatic breast cancer.

As a reminder, we entered into a license agreement with HanX Pharmaceuticals for ON 123300 in December of 2017, under which HanX will provide all funding required for Chinese IND-enabling studies performed for Chinese food and drug IND approval. The companies also intend for these studies to be fully compliant with U.S. Food and Drug Administration standards. Onconova and HanX completed a pre-IND consultation with the U.S. FDA, and we have received the FDA's guidance for the manufacture of ON 123300 and preclinical development plan.

For those of you who are not familiar with the field, CDK inhibitors have emerged as promising compounds targeting very large cancer indications, such as hormone receptor positive metastatic breast cancer. The current generation of CDK inhibitors have their limitations. Due to its unique targeting of ARK5 as well as CDK4/6, we believe ON 123300 has the potential to overcome many of these limitations, making our drug candidate potentially suitable for certain cancers that may not be responsive to the current generation of CDK4/6 inhibitors. If successful, we believe ON 123300 could address this very large market opportunity with a potentially better therapeutic.

In addition to the INSPIRE trial with IV rigosertib and the planned Phase III trial of oral rigosertib in combination with azacitidine in first-line MDS, we are also developing rigosertib for the treatment of pediatric RASopathies, a group of rare syndromes that together are the most common genetic conditions globally. These includes juvenile myelomonocytic leukemia, also known as JMML, a rare and aggressive childhood leukemia caused by excessive proliferation of monocytic and granulocytic cells that unfortunately infiltrate various organs.

The prognosis for children with JMML is very poor, it's invariably lethal and the only curative therapy is a hematopoietic stem cell transplant. Thus, there is a significant unmet medical need.

The JMML program may advance into clinical trials this year, and we are excited about the potential of rigosertib due to its unique mechanism of action in the treatment of these devastating childhood illnesses. The NCI Pediatric Oncology branch has also studied patient-derived xenograft models from their patients with RAS-mutated cancers.

In addition to these programs, we have plans to pursue solid tumor cancers driven by mutated RAS genes or the RAS pathway, which together represent 1/3 of all human cancers. This plan includes investor -- investigator-initiated Phase I study of rigosertib in combination with a commercially available PD-1 inhibitor to be supplied to patients with progressive KRAS-mutated non-small cell lung cancer.

SymBio Pharmaceuticals, our collaborator for development and commercialization of rigosertib in Japan and Korea, is planning to conduct a similar study along with us. Under the terms of the agreement signed in 2011, SymBio has an exclusive license for Japan and Korea and will develop and commercialize rigosertib in these countries. Onconova received an upfront payment and will receive milestone payments tied to the progress of rigosertib development as well as sales milestone payments plus royalties on net sales. Onconova supplies drug product for clinical trials conducted by SymBio in Japan. Our partner continues to work with us to conduct a KRAS-mutated non-small cell lung cancer trial in Japan, and we expect the trial will start this year.

With respect to business development, we recently announced a collaboration with Mission Bio, a San Francisco-based company that studies single cell populations to uncover mutations with their unique Tapestri platform. The Tapestri platform is the industry's first single cell DNA sequencing platform, enabling detection of possible genetic heterogeneity in disease progression and treatment response. Mission Bio and Onconova will utilize the Tapestri platform to study rigosertib as part of planned clinical trials. We believe single-cell genomics may identify mutations with better resolution than that of traditional sequencing genomic methods, allowing a view into each patient's disease at the cellular level.

In addition, the Tapestri platform, through our research and development program, by that addition, we are including the opportunity to study single-cell clones in MDS and determine the sequence of acquired genetic abnormalities and the influence of rigosertib regarding clinical outcomes. These studies have the potential to make a meaningful difference in the lives of patients with MDS and greater understanding in the pathophysiology of MDS and how rigosertib influences that pathophysiology.

We also recently entered into an additional license agreement with our partner HanX, focused on the development, registration and commercialization of rigosertib, along with other novel oncology products in China. We see this second license agreement with HanX as important to the advancement of this study of rigosertib in high-risk MDS and solid tumor indications in the future.

Under the agreement, Onconova granted to HanX, an exclusive license to develop and commercialize rigosertib in Greater China, and a nonexclusive license to manufacture rigosertib in Greater China as well. In exchange for these rights, HanX committed to upfront payments totaling $4 million. This includes a $2 million fee for an investment totaling $2 million in Onconova common stock purchased at a premium to market.

In addition, HanX agreed to place $2 million in escrow in local currency to cover rigosertib clinical development expenses in Greater China.

HanX also plans to participate in our INSPIRE trial, depending on their regulatory approval and their timelines. Onconova could receive up to $45.5 million in regulatory development and sales-based milestone payments, plus tiered royalties up to double digits on net sales in Greater China. We will supply the finished product for sale in the licensed territories, and HanX will also support our clinical trial initiatives in Greater China.

Now I'd like to turn the call over to Mark Guerin, our Chief Financial Officer, for a discussion of our financial results for second quarter '19. Mark?

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Mark Patrick Guerin, Onconova Therapeutics, Inc. - CFO [4]

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Thanks, Steve, and good morning, everyone. Cash and cash equivalents as of June 30, 2019, totaled $5.9 million compared to $17 million as of December 31, 2018. Based on our current projections and receipt of funds due from HanX, we believe that our cash will be sufficient to fund ongoing trials and operations late into the fourth quarter of 2019.

The company was notified by NASDAQ on July 26 that NASDAQ had accepted the company's plans to regain compliance with the stockholders equity listing requirement by November 18, 2019.

Net loss was $3.6 million for the second quarter ended June 30, 2019, compared to $4.3 million for the comparable 2018 quarter. Research and development expenses were $3.9 million for the second quarter ended June 30, 2019, and $4.1 million for the comparable period in 2018. General and administrative expenses were $1.8 million for the second quarter ended June 30, '19, and $2.1 million for the comparable period in 2018. We continue to manage our resources carefully while maintaining a primary focus on completing the INSPIRE trial.

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

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [5]

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Thank you so much, Mark. With that, we'd like to open the call for questions. After the question-and-answer period, I'll finish with some closing remarks. Operator, please go ahead with questions, and thank you.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from Dr. Joseph Pantginis with HC Wainwright.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [2]

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Guys, my questions are a little bit nuanced, so hopefully you can bear with me. With regard to INSPIRE, obviously this is a fluid -- the ongoing enrollment and time lines are very fluid, so I'm just curious if you could discuss your prior guidance saying that the top line data might occur at the same time as enrollment and how we might be able to read into the additional sites coming from Brazil and other sites as well, while events continue to occur with patients that have been on study for quite some time now.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [3]

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So thank you, Joe. I'll ask Rick to address your question.

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [4]

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Thank you, Steve. There are several components to your question, Joe, and I'll try to address each of them. First of all, as I think many of you may know, in March, we announced that we achieved a critical milestone enrollment of 75%. We are certainly well above that. Enrollment continues to proceed as planned. We still plan to complete enrollment by the end of 2019. We look forward very much to the Brazilian contribution. In my own personal experience with numerous global studies, Brazil has always been a strong contributor to hematology studies, not only because of their population but their hematologic expertise and network of hematology centers. So I think that will certainly allow us every opportunity to complete enrollment this year.

The change in VHR, the worst prognostic group in the study, varies over the course of the study. Currently, it's running around approximately 70%. And this is particularly important for your question about enrollment and survival events. Obviously, this population when untreated has the worst prognosis; median overall survival is generally well below 4 months. Because this population is the largest subgroup in the study, it has 2 particular implications. It is possible that there will be a close relationship between enrollment of 360 patients and the required number of survival events per protocol, which is 288 events. The greater the proportion of VHR, the more likely the median overall survival in the control arm will be reduced, and this is certainly something we're anticipating and tracking carefully. One of the things that I think is particularly fortunate is that the number of patients who are lost to follow-up in the study is very small. And so we will continue to track both recruitment and survival events closely. I think it also, as Steve pointed out, there is a primary endpoint for the VHR subset. And this may be particularly important when we go to the primary endpoint analysis. With that, I hope I have addressed each of your questions, Joe, and thank you for them.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [5]

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You certainly have, Rick. And then the next question is sort of shifting over to oral rigosertib and the SPA. My assumption is you guys are in hot and heavy discussions with the FDA with regard to getting to the finalization of the SPA. Just curious, at this point, as things continue to progress, what the gating factors are. I know previously, you're talking about maybe the statistical analysis plan. But I was also curious, does INSPIRE impact your discussions at all, and would the FDA be waiting on anything from INSPIRE?

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [6]

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Thank you again for that question. There's multiple parts to it. First, let me clarify. I don't think we're in any hot and heavy discussions with the FDA. We're in discussions and communication with the FDA. We are at the point where we finalized our responses to their initial review of the protocol, many of which we agreed with the requested changes. Much of the study design is agreed upon. There are 1 or 2 final remaining points that we need clarification on. I think that the Phase II study of oral rigosertib/azacitidine has become particularly valuable and informative for both us and the FDA. And certainly, that is a very positive thing when you go to develop a registrational Phase III and you have a informative Phase II. I think in terms of INSPIRE, there's really -- there's been no linkage with INSPIRE and this Phase III study of oral rigosertib combination. The only thing that might have an impact is if we were to have a positive survival endpoint with INSPIRE. The impact that would have on the future regulatory discussions could be important.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [7]

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And Joe, just to add what Rick just said, we don't really know FDA thinking. As you know, it is unusual in oncology to have receptor response trial. So in fact, the new Phase III doubling trial, we understand, through our communication with the FDA, that it will be a response trial. And perhaps, that is because INSPIRE is a survival trial. So the FDA views this as we will have 2 trials. One, a survival trial to be completed with the data expected in the first half 2020, and therefore, the second -- in a way, a confirmatory trial in first-line, they've accepted to be a response trial with a composite response of complete response and partial response, both implying the peripheral blood count has normalized.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [8]

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Got it. No, that's very helpful also. And if you indulge me one other question, please. Maybe for Mark and towards your current cash resources. You mentioned that also includes anticipated milestones from HanX. Was curious, if you do anticipate milestones, which I'm sure you do, based on your current collaborations and partnerships. But that you're not including just based on the timing of these milestones and I'll sort of link that to a leading question of how your potential partnering discussions are going that could lead to a significant nondilutive inflow of cash.

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Mark Patrick Guerin, Onconova Therapeutics, Inc. - CFO [9]

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Thanks, Joe. If I understood your question, we -- our cash runway that I mentioned in the earlier part of the call, assumes the upfront money from HanX. It does not assume any milestones. The milestones are a little bit further out. And so I think you're asking about milestones, it's not actually milestones, it's just the upfronts.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [10]

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No, understood. I'm just saying like maybe there were milestone payments or collaborative payments that you might be expecting but the timing is a little more unsure in the relative nearer term, say, as will slip into 2020, but you're not ready to put that into your current cash guidance.

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Mark Patrick Guerin, Onconova Therapeutics, Inc. - CFO [11]

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That's correct, Joe. Well put, that's right.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [12]

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And then the just how this might link to how your ongoing partnering discussions are going.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [13]

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Avi will take that, Joe.

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Abraham N. Oler, Onconova Therapeutics, Inc. - VP of Corporate Development & General Counsel [14]

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In terms of your question, and thank you for it, Rick and Steve are mentioning how our anticipated timing for top line data is first half of 2020, and this relates very much towards this development discussions as we near that catalyst and that event for the company, there are ongoing processes. There's nothing to announce at this time. But we are seeing interest in those will heat up as we approach those events.

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Operator [15]

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And our next question comes from Dr. Jason McCarthy with Maxim Group.

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Naureen Quibria, Maxim Group, LLC - Senior Equity Research Associate [16]

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This is Naureen for Jason. So I sort of have a broad question within -- and this is regards to the RAS base, it's been hitting up quite a bit, particularly with regard to KRAS and some of the positive data that's been reported at ASCO by Amgen. And in that context, which where you have Onconova, which has the most advanced RAS program, but it's been sort of flying under the radar. Could you perhaps put into perspective [how we view] Onconova as an oncology company and not just as a player in the MDS base but where rigosertib may also fit in the space?

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [17]

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Thank you, Naureen, for that insightful question. So we actually think the data presented by Amgen has reinvigorated the RAS space. As you know, there's been a -- there's been an important question for decades, is RAS targetable? We believe, based on the paper published by Dr. Prem Reddy in Cell 2016, that the mechanism of action of rigosertib, which is unique, targets the RAS pathway and RAS proteins that interact with RAS. And thus, the RAS pathway is modulated. Amgen has presented data I believe in only 10 patients. We've treated over 1,000 patients with rigosertib. The Amgen mechanism of action is somewhat different, it targets a specific mutation. Rigosertib, theoretically, should modulate any gene abnormality involving the RAS pathway, so it's a broader mechanism of action. But we actually thank Amgen for reinvigorating this space and to show the research scientists to confirm our data that RAS is targetable. And to add to that, there is, I believe for the first time, a RAS-based conference in Boston at some time in September of 2019, and Onconova, along with Amgen and a number of other companies, will be presenting our research and clinical data on targeting RAS and clinical implications for patients with cancer.

And I mentioned the word cancer to answer the second part of your question. We are focused on MDS and we have been focused on MDS since I came to Onconova and Rick joined me to develop the clinical pathway. But we believe rigosertib has the potential to target other diseases, and thus, we are moving, as we mentioned in the earlier part of the call, into a very important space, and that is KRAS-mutated non-small cell lung cancer. All patients with lung cancer these days should have genetic -- full genetic genotyping, which is done. 30% of the patients are -- have a mutation of KRAS. The first line therapy typically involves an immuno-oncology approach, which has changed the standard of care, but all of these patients will progress. So we believe there will be a role for targeting KRAS with rigosertib using an alternative I/O approach, and thus, we will open as part of an investigator-initiated trial as a part of a Phase I to determine the dose of an alternative immuno-oncology agent provided commercially to the site plus oral rigosertib for patients with KRAS-mutated non-small cell lung cancer. So I hope that answers your question, Naureen.

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Naureen Quibria, Maxim Group, LLC - Senior Equity Research Associate [18]

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It does. And actually leading into my second set of questions with regard to the KRAS studies that you're going to have. You mentioned that it will be all the KRAS mutations, correct? So in terms of the IST as well as the SymBio, I believe the IST, you'll have a combination with the PD-1. Is the SymBio going to be a monotherapy study or will it be in combination as well?

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [19]

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No, you're right. We will target all -- so patients with all KRAS-mutated non-small cell lung cancer will be eligible for the trial, and a trial in the U.S. and the trial in Japan is going to be a combination trial with an immuno-oncology agent.

By the way -- I'm sorry, Naureen, provided for free -- the immuno-oncology agent will be provided for free for patients participating on the trial.

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Naureen Quibria, Maxim Group, LLC - Senior Equity Research Associate [20]

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Great. And last thing, so these are both going to be -- if you can frame our expectations with regard to the timing and potential, I know it's a bit far away, initial data readout for INDs, do you have any idea?

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [21]

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No, the reality -- no. We anticipate the trial to be opening in the U.S. by the end of the year. It's a Phase I, we hope the first number of patients to be entered onto the trial in 2019, and depending on when we see the MTD, we'll determine how long the trial will take. But we estimate maybe 20 to 30 patients, but that's really not known. So it's a little bit unknown when we'll have the data, but we hope and to begin the trial, initiate the trial this year.

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Operator [22]

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And our next question comes from Dr. Ahu Demir with NOBLE Capital Market.

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Ahu Demir, NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst [23]

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My first question will be the recently published partnership with Mission Bio. I was wondering how this precision medicine network will be added to your clinical trials, which clinical trial will be included for (inaudible) high-risk MDS, CDK program? Also I was curious how patient samples are collected, is it genome sequencing? And potentially the time line when this approach will be implemented in the trials? And when should we expect results from that?

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [24]

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Well, thank you for your questions. I think that the clear primary focus with the Mission Bio Tapestri platform is MDS. This is certainly a disease that, for many reasons, makes this platform of single-cell genomic analysis particularly valuable, especially in patients who have failed HMAs. It's estimated that 80% of patients in that setting have a mutation. The vast majority have more than 1 mutation, and the significance of each mutation is not entirely known or appreciated, particularly when it comes either to progression or in terms of response. And so this is particularly valuable in our understanding of the value and mechanism of action of rigosertib in these patients. We look forward to seeing this analysis. It does require somewhat of a different collection than the standard conventional novel gene sequencing approach, which requires DNA. Mission Bio's platform requires cells -- live cells collected from the aspirate. So this will require some different logistical aspects in the study.

Certainly, I think that we would look at both INSPIRE, even with the limited number of patients that are required to complete enrollment, as well as interest in the upfront Phase III study with the combination of oral rigosertib and azacitidine. I think this cutting-edge science is anticipated to be particularly valuable. I think as we gain more experience, we'll move into other therapeutic areas. It always becomes a little more of a negotiation when you are discussing investigator-sponsored trials. But certainly, I think the value of this platform is appreciated by everyone, and those in the field are extremely interested in us incorporating this. I will make mention that one of the ASH abstracts that's submitted is looking at genomics in patients who have HMA failure, and that's one of the abstracts we did submit to ASH and it indicates our interest in understanding genomics and rigosertib therapy and effectiveness. Thank you for your question. I hope I've covered all of your interest.

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Ahu Demir, NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst [25]

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My next question will be on the CDK program. Our -- so the main catalyst is of course, the IND, however I was curious if you plan to publish any additional data for differentiating factors of ON 123300, similar to your previous presentations that you actually show favorable reduced neutropenia compared to other CDK programs. So do we have any results that we should keep an eye on?

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [26]

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Well, thank you for the interest in ON 123300. Abbreviated, ON 123, so...

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Ahu Demir, NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst [27]

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That's a mouthful, Avi.

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [28]

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This is Rick Woodman speaking.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [29]

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I think we're better off with Rick. But thank you, Avi.

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [30]

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So you have to keep in mind that we have no clinical human data on ON123. What we do have is preclinical animal model data. And in that setting, we see very similar safety profile to what has been published with the other CDK 4/6 inhibitors, mainly the occurrence of underlying gastrointestinal effects. But having said that, the other organ systems are relatively spared, which makes our hope that when we get into the first-in-human study, that we will continue to see a promising safety profile. But at this time, that remains unknown. The one thing that I can say in the animal models with ON 123, the effects on the bone marrow are limited and reversible.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [31]

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And I would add to Rick's comments that in breast cancer cell lines that are refractory to the standard CDK4/6 inhibitors, they -- these refractory breast cancer cell lines will respond to ON 123, and that's why we're excited about our compound and look forward in the Phase I to entering unfortunate women with hormone receptor-positive metastatic breast cancer who progressed on commercially available CDK4/6 inhibitors, to see if there will be response to ON 123. Obviously, we're hoping to see that.

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Ahu Demir, NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst [32]

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I have 2 additional question, if I'm not taking too much of your time. Regarding the RAS conference in Boston end of September, you mentioned you will be presenting clinical data, will it be MDS or do you plan to present data in lung cancer or any other indications?

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [33]

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That's a great question. Haven't put a slide deck together yet, Ahu. But clearly, we'll be focusing on the mechanism of action of rigosertib, emphasizing the studies that prove and ensure that it was a RAS inhibitor, explaining that to the audience. We will present clinical data as well based on, both the INSPIRE trial and the doublet trial with oral rigosertib. Since you asked the question and we're thinking about it, we probably will and should show our data in patient-derived xenograft models with KRAS-mutated non-small cell lung cancer. So we probably and should show that data as well, and thank you for that question because it helps us think about what we should show at that upcoming conference.

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Ahu Demir, NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst [34]

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Sure. My last question will be to Mark, so I cover the whole team. So Mark, I noted R&D expenses was reduced in this quarter. What was the driver for that?

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Mark Patrick Guerin, Onconova Therapeutics, Inc. - CFO [35]

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Well, I think it was in part because of lower expenses on the combination program in 2019 as compared to 2018 because -- but that was partially offset by slightly higher spending in the 2019 period on INSPIRE when compared to 2018. So really, that's mostly it on the development cost side. Personnel costs are a little bit lower, but the big driver was lower spend in clinic driven, mostly by less spend on combination.

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Operator [36]

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And our next question comes from Dr. Yale Jen with Laidlaw & Company.

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I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [37]

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Many have been answered, so I have 2 here. The first one is, correct me if I'm wrong, that what I heard is that you might start the oral rigosertib trial, Phase III trial toward the end of the year. Is that correct? If so, could you give a little bit more color of that development?

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [38]

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Sure. This is Steve, and thank you Jen. We very much want to open up the doublet 0915 trial in a small number of select sites. It depends on our ability to have financing to support that because our goal is to (inaudible) our resources for INSPIRE. But our other goal would be to open a number of sites, let's say 2 in the U.S. and now with our collaboration with HanX, perhaps open a site in China as well and a site in Japan because both China and Japan, as well as internationally, are all eager to begin the doublet trial. So we'd like to start small in 2019. And then after additional financing is obtained, to be able to open up a global trial. We have the sites required for that trial but will be premature to do at this point due to financing. We believe it was beneficial to these patients as the development of rigosertib to open the doublet trial in small number of sites in the U.S. a site in China, a site in Japan and then grow from there.

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I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [39]

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And would that be depending on the getting of a SPA designation or that's just the 2 separate situations -- events?

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [40]

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In reality, as you know, we don't need the SPA to open the sites. But we will prefer, since we're going through efforts of obtaining it, we've already received from the FDA, the key feedback, what is that? That they've accepted a response trial. We also understand from the FDA what the delta is anticipated for approval compared to the control arm, and those are the key, 2 key principles of the protocol. So the remaining discussions with the FDA, I recall something -- some technical factors about protocol. So the answer to your question is we anticipate and are working with the FDA, anticipate receiving the SPA, we'd probably wait for that to happen, but it's not required. We don't need necessarily to have a SPA to open up a pivotal Phase III -- new pivotal Phase III trial.

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I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [41]

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Understood and appreciate that. Maybe one more question here, which is the collaboration with the Mission -- with the Tapestri. You mentioned earlier that you were, I guess, apprised also to the INSPIRE -- patient still in the INSPIRE study. First of all, would you give us some sense that would that be all the patient still alive today? And second or when you can actually conduct the study, the testing? And secondly, it is a little bit more detail in terms of what aspect to be measured to track the treatment efficiency or response.

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [42]

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Thank you for the question. I think that the patients on study will be of limited value for the Tapestri single-cell genomics analysis in of the fact that we don't have baseline by which to understand the changes in the dynamics of the mutational profile. I think it's potentially possible that for patients who -- coming into the study, it may be possible to collect samples. However, keep in mind that this is not DNA, which can be obtained and stored and shipped anywhere in the world. These are single cells that are required. And when in discussions with Mission Bio, they told us that there is a limitation on what sites around the world we can get samples from in time to do the appropriate analysis. So I think that it -- the logistical challenges are greater with INSPIRE. It would obviously be easier to include genomic analysis in the upcoming new Phase III study, and we certainly have included that in the protocol, exploratory endpoint with some form of genomic analysis. So I think right now, a lot will be influenced by logistics.

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Operator [43]

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And I'm not showing any further questions at this time. I would now like to turn the call back over to Steve Fruchtman for any further remarks.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [44]

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Well, thank you all for participating on today's update call and your excellent questions, which we hope we've addressed. We're very excited about the progress we're making in the INSPIRE trial and other pipeline programs. And I hope you share our enthusiasm. In addition to executing our NASDAQ-approved plan to regain our compliance with listing standards, important milestones we look forward in near and medium term will include: one, complete enrollment of the required 360 patients in the Phase III INSPIRE trial by the end of the year; two, finalization of the special protocol assessment agreement with the FDA for a pivotal Phase III combination trial of oral rigosertib and azacitidine in the first line high-risk MDS patients this year; three, initiation of a Phase I study with rigosertib in refractory KRAS-mutated non-small cell lung cancer; four, submission of an IND filing for ON 123300; and five, and most importantly, the release of top line data from the INSPIRE trial in the first half of 2020 following approval of 360 patients and 288 death events.

This concludes my closing remarks. As always, we appreciate your continued support. We have some very important milestones coming up, continue to follow us. And if you have any questions, please feel free to reach out and contact us, and thank you again. Operator?

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Operator [45]

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Ladies and gentlemen, thank you for participating in today's conference call. This concludes today's event. You may now disconnect.