Traws Pharma Inc (TRAW) 2014 Q1 法說會逐字稿

Good afternoon. We will begin the conference call in just a moment. Initially, all participants will be in a listen-only mode. There will be a question-and-answer session following the conclusion of the prepared remarks.

At this point, I will turn the call over to Benjamin Hoffman, Director of Public and Investor Relations at Onconova.

Good afternoon and welcome to our first-quarter 2014 earnings call. Earlier this afternoon, we issued a press release providing an operational and financial update. The press release is available under the Investors and Media tab on our website. A replay of this call can also be accessed on our website approximately two hours after its conclusion.

Joining me on today's call are Onconova's President and Chief Executive Officer, Dr. Ramesh Kumar, and our Chief Financial Officer, Ajay Bansal.

During this call, we will be making statements about the Company's future expectations, plans and prospects that constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements. Additional information on factors that could cause results to differ is available in our most recent SEC filings.

In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change.

Now, I would like to turn the call over to Onconova's President and CEO, Dr. Ramesh Kumar, for his introductory remarks.

Good afternoon and thank you for joining us. At Onconova, we are focused on the development of rigosertib, and to bringing this novel therapy to cancer patients in need. In February, we announced topline results of the Phase III ONTIME trial for intravenous or IV rigosertib in higher risk myelodysplastic syndrome, or MDS. As previously disclosed, the study did not meet its primary endpoint in the intent to treat population. However, we have noted encouraging survival benefit in subsequent analysis. Currently, we are preparing to discuss these results with the regulatory authorities in the US and Europe.

We also continue to evaluate rigosertib in additional clinical trials with patients with MDS and solid tumors.

Now let me turn to our CFO, Ajay Bansal, for an overview of our first-quarter financials. Ajay?

Thank you, Ramesh, and good afternoon everyone. Our financial results were included in this afternoon's press release and will also be available with additional detail in our 10-Q.

Our research and development expenses were $14.2 million for the first quarter of 2014 and our G&A expenses were $4.9 million.

In terms of our cash position, we ended the first quarter with approximately $84.6 million in cash and cash equivalents. Our cash used in operating activities in the first quarter was approximately $15.4 million. This compares to $16.6 million for the fourth quarter of 2013. We continue to manage our resources in sync with our development effort and at the current bond rate, we have enough cash on hand through the middle of next year.

At this point, let me turn the call back to Ramesh for a more detailed discussion of our development programs in MDS and solid tumors and our upcoming milestones.

Thank you, Ajay. First, higher risk MDS. As you likely know, currently there are no approved therapies for higher risk MDS patients after they fail or stop responding to hypomethylating agents, or HMAs. These agents are effective only for a fraction of treated patients and are not curative. The general outcome for the majority of HMA treated MDS patients include either progression of disease while receiving their initial course of HMA, or failure to respond to a full course of HMA treatment. Collectively, these two groups are referred to as patients with primary HMA failure, or patients who relapse following an initial response to HMA therapy, these patients are referred to as patients with secondary HMA failure.

In February, we announced results on topline analysis of the Phase III ONTIME trial of IV rigosertib in higher risk MDS patients previously treated with HMA's. Based on ITT analysis, the trial did not meet its primary endpoint of a statistically significant improvement in median overall survival in the IV rigosertib plus best supportive care arm. However, the preplanned analysis demonstrated an increase in median over survival of 3.9 months as a ratio of 0.66, P value of 0.017 in the subset of patients with primary HMA failure. This subgroup comprised 62% of the patients in all of the ONTIME trial and had a median overall survival of 8.5 months in the rigosertib plus the rigosertib arm versus 4.6 months in the best supportive care arm. Thus the substantial portion of the total patient population with a short life expectancy and no approved therapies appear to have benefited in this first ever randomized trial in post-HMA MDS patients.

The ONTIME trial was conducted in the US and five European countries, and we are now in the process of initiating discussions of the medical need and the significance of our data with regulators from both continents. Regulatory feedback expected in the coming months will determine the next steps for rigosertib in this patient population.

We previously announced the initiation of the Phase IIIb trial referred to as 300424, a single arm-based IIIb trial intended to provide additional tolerability and activity data for IV rigosertib in post-HMA MDS patients. The trial is designed to enroll 90 patients and is now open in two dozen US and European sites with a third of the patients already enrolled. And based upon encouraging nonclinical data, we are advancing an oral dosage form of rigosertib in combination with azacitidine or Vidaza front line higher risk MDS patients.

The Phase I/II study of oral rigosertib plus azacitidine has completed the first two dosing cohorts in the dose escalation stage. Once the final dose is selected, Phase II will initiate at multiple sites in the US and Europe. We expect additional data will be available in the second half of 2014.

Now, lower risk MDS. Patients with lower risk MDS are cytopenic and suffer the burden of frequent transfusions. For transfusion independent lower risk MDS patients, treatment options are limited to Revlimid, which is indicated only for delphi few patients, ESA's or erythrocyte stimulating agents, and transfusions and supportive care. Based on encouraging data we presented at the 2014 ASH meeting and regulatory feedback from the FDA, we are advancing oral rigosertib as transfusion sparing therapy for unmet needs of patients with lower risk MDS.

We are continuing our regulatory dialogue with agencies in Europe aimed at establishing the parameters for a pivotal trial, based on the genomic methylation analysis presented at the 2013 ASH meeting, we are enrolling cohort of 20 additional patients to further explore this potential diagnostic marker for preselection of patients who are likely to respond to rigosertib treatment.

The additional supporting data will also be available from an ongoing multisite Phase II study referred to as the 0908 study.

Solid tumor programs. We are also studying rigosertib in solid tumors and recently initiated a Phase I trial to evaluate the combination of oral rigosertib plus cisplatin in radiotherapy, or chemoradiotherapy, or CRT, in patients with head and neck cancer. Published non-clinical studies provide support for a potential synergistic or super additive benefit of combining rigosertib with CRT. This multicenter trial will determine the maximum tolerated dose of rigosertib while also assessing the safety, tolerability, and equinity of this combination.

In other news, an illustration of the breadth and depth of our proprietary pipeline of novel targeted agents is the [Rasturib] presentation from the AACR annual meeting and April. At AACR, we presented seven scientific posters highlighting data relating to the molecular mechanism of action of rigosertib, and two new development programs targeting PLK2 or polo-like kinase-2, and CDK-4 ARK-5 kinases, slightly independent kinase-4 and bank regulated kinase-5.

In summary, rigosertib is the primary focus of our research and development efforts and we remain dedicated to serving the unmet needs of patients with MDS. Our key upcoming milestones include: one, discussions with US and European regulatory authorities regarding development of rigosertib in higher risk MDS during the second and third quarters of 2014; two, clarity on the utility of the prognostic genomic methylation marker for transfusion dependent lower risk MDS patients in the second half of 2014. This could drive the design initiation of the later stage oral rigosertib trial in lower risk MDS. Three, started the Phase II stage of the combination trial of oral rigosertib and azacitidine in first-line MDS in the second half of 2014. Plus, we have key milestones coming up in the remainder of the year.

This concludes our prepared remarks and we will be open -- will open the call for your questions. Operator?

(Operator Instructions). Kim Lee, Janney Capital.

(Operator Instructions). Howard Liang, Leerink Partners.

This is Rich [Gauze] calling in for Howard. Thanks for taking my questions. I was wondering if you could give any more detail regarding the timing of the lower risk Phase III initiation.

Thank you for your question. We have guided second half of the year for potential start, and since we are coordinating the efforts in US and Europe, it's very difficult to really narrow it down.

So really, as I explained, there are three factors. One of course is the methylation signature and how best we can incorporate it. Second, guidance, on top of the FDA guidance, guidance from European regulators. So these factors are going to probably make it difficult to define it any further than H2 2014 at this point.

Okay, thanks. And also regarding the milestone payment relating to the decision to proceed in lower risk, do you receive that when the trial is initiated?

It's difficult to qualify that. At this point, really we can't make a specific statement to that effect without consulting with our partner. So that's the best I can say at this point. Do you want to add to that?

No. I think, as we have disclosed in our filings, we sort of feel that the (inaudible) deal from joint decision by the parties to proceed with the development of rigosertib in lower risk MDS. So whenever we jointly decide, that's when the payment becomes due.

Okay, great. Thank you.

Jonathan Eckard, Citigroup.

This is [Elone] in for Jonathan Eckhard. And I just wanted to gain a little bit more color surrounding the combination therapy in front line MDS. So, could you just give us a little bit of a better idea in terms of the primary hurdle? Is it duration of response? Is it overall response, just to give a little more color on that, and when we could see an update on the Phase II started there.

Certainly. Thank you. As most of you know, azacitidine, or Vidaza, is the dominant HMA because it's approved both in US and Europe. Azacitidine is primarily used in the US at this point for MDS. And as I mentioned earlier, a lot of patients don't respond to either Vidaza or decitabine. So, there is an open window for new approaches, including combination therapy approaches in front line MDS.

Number two, what we have shown, and it's the subject of an issued US patent, is that rigosertib can synergize with azacitidine. So, rigosertib plus azacitidine appeared to be synergistic in these model systems. So, based on these studies, we started a Phase I/II development program which is now running at two sites in the US. And in this program, first we determine the appropriate dose of rigosertib to use with the standard label dose of azacitidine. So we are doing it in steps and we disclosed this earlier, is that we are going to go from one dose to a second dose to a third dose, and then find out whether we can use a full dose of rigosertib as defined by Phase II studies in lower risk MDS patients, full dose of azacitidine as indicated in the label of azacitidine. And once we reach that, we will expand the study to include more patients. That's the second half of the trial or Phase II portion of the trial. So having completed the first two dose cohorts successfully and advanced to the third cohort, we feel that it's highly likely that we will be able to start the second part of the trial in the third quarter of this year. So, we are also hopeful that later this year we will be able share safety tolerability and preliminary efficacy data for the whole program.

Thank you.

(Operator Instructions). Kim Lee, Janney Capital.

Good afternoon. Sorry about that earlier, guys. Just a quick question on the utility of your prognostic methylation marker. Can you tell us your plans going forward for this? Is this something that you'll kind of use in your Phase III studies? Just a little more clarity on that would be great. Thanks.

Kim, thank you. As you know we disclosed at ASH that here is the genomic methylation signature that helps distinguish responders from nonresponders. In other words, using bone marrow biopsy samples from patients prior to treatment and using methylation as a marker, the investigators were able to cull the responders from nonresponders. So potentially a very, very useful tool going forward.

So in our discussions to the first quarter with the FDA, we had a good discussion on this thing. And although we are certain that we are going to use this marker in our next stage trials, the question really is are we going to preselect the patients for the trial, or are we going to use the trial to provide additional stratification or subset information?

And to get a really good handle on the question, we feel that having another 20 patients worth of data will be highly useful. So, accordingly, we started an additional cohort of 20 patients in which the DNA analysis will occur upfront and in the treatment and then we will reconcile treatment effect with the genomic results.

So, the result which we have in hand are very promising. The validation cohort will direct us more appropriately either to a stratified trial or a selective trial. So, those are the two things which will become clearer after we have the validation work completed.

Okay. And just a follow-up question. How did you determine that expansion to 20 patients would be enough data?

It was just we looked at what we had, and it looked like in a 60 patient study that we presented at ASH, roughly a third of the patients had that data available. And in discussion with the regulators, it became clear that having twice as many samples, we ended up with about 40, would give people a lot of comfort. Because if you recall, about a dozen of those patients were methylation type that were responders. So having another -- doubling that number of patient samples would give us more comfort on the value of the potential marker.

Great, thanks.

We are now out of time for questions, and I would like to turn the conference back to leadership for any further remarks. Thank you.

We thank the participants and we look forward to seeing many of you at ASCO or other conferences and in our next call. Thank you.

Ladies and gentlemen, thank you for participating in today's meeting. This does conclude the program, and you may all disconnect. Everyone have a good day.