Traws Pharma Inc (TRAW) 2014 Q2 法說會逐字稿

Good afternoon, we will begin the conference call in just a moment.

(Operator Instructions)

At this point, I'll turn the call over to Mr. Ajay Bansal, Chief Financial Officer at Onconova. Please go ahead.

Thank you, Karen.

Good afternoon and welcome to our second-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 President of Research and Development, Dr. Tom McKearn.

During this call we will be making statements about 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 turn the call over to Ramesh for his introductory remarks.

Good afternoon and thank you for joining us.

At Onconova we are focused on the rapid and efficient development of rigosertib for patients with myelodysplastic syndromes, or MDS. We have made significant progress on our quests. As previously disclosed, the Phase 3 ONTIME trial testing rigosertib in higher risk MDS who had previously failed HMA or hypomethylating agent therapy did not meet its primary endpoint and the intent to treat ITT population.

However, these results suggested a treatment benefit is an important subset of patients referred to as Primary HMA Failures. The past few months we have had discussions with key opinion leaders and regulatory authorities in order to define fast forward for rigosertib in Primary HMA Failure MDS patients.

Based on a meeting with the FDA, we understand that an indication could be sought specifically for primary HMA failure patient population. We are now designing an approval-track pivotal trial in this patient population. We expect to provide an update on our clinical development plan in this indication in the fourth quarter of this year. In addition to developing rigosertib IV in higher risk MDS, we continue to advance rigosertib oral for patients with lower risk MDS and for all MDS patients as a combination therapy with azacitidine.

Consistent with our focus on efficient development of rigosertib, we have undertaken measures towards reducing our burn rate. We are reducing our workforce by approximately 15%, and are making appropriate adjustment to overall expenditures. These cost reductions are primarily related to clinical programs beyond our current focused area of MDS and AML, additional CMC activities, non clinical development and some earlier stage pipeline.

At this point, I'll turn the call to Tom McKearn, our President of R&D, for a more detailed discussion of our rigosertib development programs. Tom?

Thank you, Ramesh, and good afternoon, everyone.

As you are aware, higher risk MDS is a serious disease with limited treatment options. Currently non del q5, higher risk MDS patients are largely treated with hypomethylating agents, or HMAs. About 40% of such higher risk MDS patients initially respond but then relapse following HMA therapy. Therefore, the majority of treated patients derive no clinical benefit from these HMAs.

The HMA patients are referred to as Primary HMA Failures. Primary HMA Failure represents a significant unmet medical need with a dismal prognosis characterized by short life expectancy. Our ONTIME trial was the first ever randomized trial in post-HMA higher risk MDS patients. This trial included both Primary HMA Failure patients and those who progressed after initially responding to HMA therapy.

As announced in February, and as Ramesh previously described, the ONTIME trial failed to demonstrate a statistically significant difference in overall survival in the intent to treat population. However, the top line results suggested a treatment benefit of rigosertib therapy in the Primary HMA Failure patients.

In our second quarter, we met with the FDA to discuss the results from the ONTIME trial and to seek guidance for development of rigosertib IV in higher risk MDS patients. Based on our meeting with the FDA, we understand that an indication could be sought specifically for the patients who had Primary HMA Failure. Following these discussions, we are now designing an approval-track pivotal trial in this patient population. We expect to provide an update regarding this trial in the next quarter.

In addition to our discussions with US regulators, together with our European partner, Baxter, we have also had meetings with several European national regulatory agencies. These discussions have also affirmed the unmet medical need in Primary HMA Failure patients.

So let me now provide an update on our clinical development programs with rigosertib oral. Our first program with rigosertib oral is in patients with lower risk MDS. These patients are cytopenic and suffer the burden of frequent transfusions. For transfusion-dependent lower risk patient, treatment options are limited to Revlimid which is indicated only for the del 5q patients to erythropoiesis-stimulating agents, or ESAs, and to transfusion as supportive care. We are developing rigosertib oral as a transfusion-sparing therapy a lower risk MDS patients.

In December last year, we presented encouraging data from our 09-05 Phase 2 trial presenting these at the annual ASH meeting. The data revealed that the transfusion sparing activity of single agent oral rigosertib was found in transfusion dependent lower risk MDS patients. We also described the potential of a prognostic genomic methylation assay in selecting patients for future trials. To this end we are enrolling a [quote] cohort of 20 lower risk MDS patients to expand our data on the utility of a prognostic genomic methylation marker.

Recruitment is also continuing in a second Phase 2 trial 09-07, to explore dose and schedule optimization and to compare continuous dosing with interrupted, that is dosing two out of three weeks in a three-week treatment cycle. Based on the anticipated timing of genomic methylation signature and dosing optimization data, we now believe that a pivotal trial of oral rigosertib in lower risk MDS would not commence before the first half of 2015.

In our second program with oral rigosertib, we are advancing rigosertib in combination with azacitidine as a treatment for all MDS patients. We have successfully completed the Phase 1 portion of a Phase 1/ 2 clinical trial and are now enrolling patients in the Phase 2 portion at multiple sites in the United States and Europe. In the Phase 1 portion of that trial, the combination therapy was well tolerated in the study population.

The combination dosing schedule of oral rigosertib in the final cohort given as of 560 milligrams in the AM and 280 milligrams in the PM with a indicated dose of azacitidine has been selected for the Phase 2 portion of the trial. We expect to present results of the Phase 1 portion of this combination at upcoming scientific meetings. I would like now to turn the call back over to Ramesh for his concluding remarks.

Thank you, Tom. Rigosertib remains the primary focus of our R&D efforts and we are dedicated to rapid and efficient development of rigosertib for patients with MDS. We're encouraged by the feedback we have received from key opinion leaders globally and the discussions we have had with regulatory agencies.

The next quarter following further discussions with the FDA, we expect to provide you with an update on our approval-track pivotal trial for rigosertib IV in Primary HMA Failure patients. Another encouraging aspect of our program is the IP coverage, our intellectual property coverage for rigosertib, which currently extends to 2026 with composition (inaudible). We continue to work and expand and broaden this coverage.

Looking forward, we expect to have a strong presence at the ASH Annual Meeting in December. We have submitted a number of abstracts and hope to present data on all three of our MDS programs. If these abstracts are accepted for presentation, we expect to provide number one, detailed results from the ONPLAN trial in higher risk MDS including additional analysis in Primary HMA Failure patients. Tom mentioned that this was the first randomized trial in this patient population.

Number two, data from genomic signature and dose optimization studies in low risk MDS patients. Number three, results from the Phase 1 portion of the rigosertib azacitidine combination study in front line MDS. And four, further clarification of rigosertib mechanism reaction and biological plausibility in its action in MDS. And finally, we also expect to talk about other relevant areas in MDS and rigosertib.

This concludes our prepared remarks and we are now open the call for your questions. Operator?

(Operator Instructions)

Kim Lee, Janney Capital.

First off, can you give us some clarity on your discussions with the FDA as to what did they say and what kind of guidance did they provide to you to indicate that the subset population is a way to get your drug approved? And also, can you go into a little more detail also on your discussions with the EMA and where things stand -- what kind of trials will be needed for European approval? And then I have some follow-up questions. Thanks.

Thank you, Kim. The discussions are continuing. As you know it's a pretty complicated process. We've had very good meetings, as I mentioned, both with the FDA and in Europe; but this is a dialogue that continues. So at this time we feel comfortable about making two disclosures. Number one, agencies have recognized that post-HMA, the Primary HMA Failure indication is a very important unmet need. And secondly, that this is specific indication that could be pursued for regulatory approval of rigosertib.

So beyond that, because of the nature of the discussions and the continuity of this dialogue, we are not prepared to say more at this point.

Okay. And also in Europe -- what kind of trials would you need in Europe?

Again, beyond the two points I made, which are consistent in our feedback both in US and Europe, we are not at this time in a position to give more specific details for the trial either from the US or the Europe perspective. As you know, we are committed to developing this program globally. So in addition to Europe, our trials are ongoing in Japan as well. So it will be a concerted, coordinated global effort; and we expect to provide more color to that in the fourth quarter.

And what could your Phase 3 study design look like for US approval? And when do you expect to start that study?

The trial design has been made a topic of ongoing discussion, so at this point probably not a good idea to give more clarity on that. But suffice it to say that we want to find the most efficient and most coordinated way to seek approval for rigosertib for MDS patients in US, Europe and eventually, Japan. And we are pursuing every option possible in terms of trial design, in terms of the size and scope of the trial, and various regulatory mechanisms that are available. But at this point we have to defer further details till our next communication.

Okay and one final question before I jump back into the queue. As far as the lower-risk MDS program goes, do you still anticipate data from your Phase 2 portion of the study to be available second half of this year?

As you know, Kim, we announced pretty much the entire Phase 2 results last year, but two ongoing aspects of that trial. One to do with genomic methylation we expect to talk more about it. And the other one is the dose optimization to get the maximal benefit without any noticeable adverse events. Those two aspects are ongoing and we expect to present data, maybe even publish data, in the coming quarter.

Okay, great. And do you expect to use those genomic methylation marker to preselect patients for a Phase 3 study? Or how do you intend to use this marker?

As you may recall, we presented some preliminary information at the ASH meeting last year, so that for those who may not remember that, this is an assay performed on bone marrow samples obtained at baseline. And the data suggest that patients who ultimately respond to the oral rigosertib therapy have a unique signature upon assessment using a particular panel of genetic probes and then an identification methodology. So we have expanded that somewhat further and will be reporting that update in the near future. But we are encouraged by that finding, and it would serve, if confirmed, as the basis for identifying responders prior to initiation of therapy.

Just to add to that, I think it's extremely highly desirable to select patients, as our experience with high-risk MDS shows; and if you have a tool such as a genomic methylation signature, that will be really wonderful for the patients and for the trial. So we're committed to exploring that and we expect to show more results very shortly.

Jason Zhang, Edison Investment.

Ramesh and Tom, I didn't hear you talking about the rules of ONTIME data and also the ongoing Phase 2 trial, the single arm study trial data will play in the future of regulatory approval of rigosertib in high-risk MDS. Could you elaborate a little more on that?

Jason, first of all, we haven't said anything about the nature or the specific type of the trial. But certainly Tom will address the value of the randomized results that we already have.

Tom?

The randomized studies that we've done -- you're referring to the ONTIME trial -- represent the first study done in this patient population. And it appears that there's a clear distinction between two populations of patients which heretofore had been identified in a couple of discrete publications, but never with the implication that they might respond quite differently to second-blind therapeutic intervention.

So this is a really very important finding and it seems at first blush that it's quite clear cut in terms of the degree of differentiation of the two populations of so-called Primary HMA Failure patients and the so-called Secondary HMA Failure patients. So this is part of the information that was discussed at some length with the regulatory authorities and was part of their agreement with us that the path forward seems very much to be centered on identifying the Primary HMA Failure patients as the much more logical and responsive patient population to therapy with the IV rigosertib agent.

Thanks.

Okay, that was very helpful. But again, I don't know how much you can tell us about your plan before you actually [reveal that]. Can I assume that you maybe in the future can still use the data to some degree in the overall approval strategy?

Well, we must. It was a registrational trial and it certainly will be part of the dossier that's submitted. And from a safety point of view, of course, it is critical that all of that information be reviewed, looked at carefully. We're happy to do that. It was a very well-tolerated agent in this trial; and it's the first controlled trial. So it's relative to a treatment arm for the first time, of any size whatsoever. And that comes out very favorably, we believe, in terms of showing a continued very well-tolerated response to the rigosertib therapy.

Jason, in addition to the regulatory aspect, an important aspect is the publication of the data. So we look forward to presenting the full data, which is quite complex and eagerly awaited by the community at conferences and in journals, to show exactly, as Tom pointed out, the activity and the tolerability safety data from this trial, which was a global trial.

May also update us about the status of the Phase 2 trial? Because sometimes you refer to -- well, I think it was quarter Phase 2 trial, the patient to have come off the ONTIME study that received rigosertib IV formulation.

Jason, you're referring to the 04-24 trial, which is a IV rigosertib trial in high-risk MDS patients. Tom will give you an update on that.

So that trial was designed and opened after the accrual to the pivotal trial was complete. And it is meant to enroll those patients who progressed and failed on the hypomethylating agent. So it's a similar and overlapping, but not quite identical, population of patients to the one that we've described for you a moment ago -- that subgroup of patients with the Primary HMA Failure. The trials opened in both US and European sites, and we will be providing more information on this trial as we discuss the import of this and continue to have these discussions with the regulatory bodies in both the US and in Europe.

And to clarify this trial, 04-24 trial was tabbed as a Phase 3b trial, not a Phase 2 trial.

Okay. Maybe one more before I get back.

So this is the first time we actually heard of the Primary HMA Failure definition. Between you and FDA, is it a very clear definition of this? And could you share that with us if it is well-defined?

Tom will start and I may add something. Tom, go ahead.

So this population has been identified in a couple of different review articles. They look at the outcome of the current therapy that's available for patients with a higher-risk MDS. And so we in fact did not invent or come up with this independently. The papers were authored by both European and US investigators.

So it's, I believe, one of the levels of heterogeneity that has been documented within the population of MDS patients as they progressed through the various stages of their disease process. Ours now is the first second-line intervention, and in fact one of the novel findings from the 04-21 study is this apparent clear-cut difference in the response of Primary HMA Failure patients as compared to Secondary HMA Failure patients.

So as Tom said, the concept of Primary HMA Failure did exist in the literature and among the specialists, but this was really the first time where a therapeutic agent was able to basically see that difference in a trial setting. And the question really is that what is fundamentally different, what makes a patient with Primary Failure different than one who actually succeeds with HMA treatment? And this is a so-called concept of plausibility, biological [MOA] relationship, and we are looking forward to talking more about it in future conferences and publications.

So the Primary HMA Failure is significant part of the whole MDS problem. The majority of the patients don't benefit from HMA and therefore they are looking for the treatment directed to them. And it looks like, from our discussions and from our data, that rigosertib is in a position to serve these patients. And that's really our focus of development.

Desh Govender, Cedar Lane.

I had a couple follow-ups on rigo and high-risk and your discussions ongoing in respect to the ongoing nature of those discussions. But, Ramesh, maybe you can give a little clarity as to when those discussions will become more clearly defined, as well as -- I am assuming that everything is on the table, given the risk-benefit profile of the drug, that even an accelerated basis would be at some point discussed and warranted, given as the data or the publication come to the community?

And I had a -- second question was on Baxter; where do they stand and what's the next trigger for them? And also what trial specifically are they going to be funding? And then I had one follow up, but I'm more interested the optionality you have with the agency on both sides of the -- on the Europe as well as the FDA.

Thank you, Desh.

For your first question, I think fourth quarter will provide really potentially two sets of opportunities to provide more clarity, more updated information, both from a regulatory point of view and from the science point of view; because we are hoping to present the data that clarifies what level of activity and the nature of the data and the nature of the safety profile. So all of that will give the expert (inaudible) investors a much clearer view of where rigosertib stands in terms of activity and tolerability.

Secondly, the regulatory dialogue, as you know, is a continuum; but we expect that in fourth quarter we'll have a significant information to add to what we said today about the development pathway. So clearly the coming months will be as important as the preceding months were in terms of seeking and consolidating the feedback into a more concrete next step and the nature of the next step. And we feel that, that information will provide a lot of what you're asking for.

And I'm going to turn over to my colleague, Ajay, for your second question.

Yes, Desh, with respect to Baxter, of course we are working very closely together. They have been enrolled in a number of the European discussions that we have had with the regulatory agencies. Our collaboration with them is very strong, very collaborative relationship. And as I said, we are working really closely to advance rigosertib in both higher- and lower-risk MDS.

And so then the next milestone payment? And when can we expect more clarity on that?

Yes, so the milestone payments, as we have disclosed in the Q and in previous occasions as well, the milestone payments that could come in the coming months. One was, we talked about one we decide together to advance the lower-risk program to the next stage, there will be a milestone payment of $25 million when together we make that decision. Then there was a possibility of a $15 million milestone payment upon agreement to file in Europe with the higher-risk; and I think that milestone payment of course gets pushed off now for the time being. So I think the most immediate one would be the $25 million payment when together we decide to advance lower-risk in further development.

Okay. And then one final on -- can you get us an update on head and neck, please?

Tom, please.

So we have two developments in the area of head and neck. We've now had the chance to review the findings from the Phase 2 trial that was a monotherapy trial in head and neck in second- and third-line refractory patients. And the response rate there was not sufficient to warrant continuation of the trial in that patient population.

We have, however, already initiated additional activities in head and neck cancer patients who are undergoing or being evaluated for chemoradiation therapy. And we are adding rigosertib to the platinum-based chemoradiation therapy regimen, based on studies that our group has done showing a synergy in activity between the platinum-based radiosensitizers and rigosertib.

So we do remain, therefore, involved and active in the field of head and neck cancer, but now moving actually closer to front line in terms of doing this with chemoradiation therapy protocols.

Thank you.

(Operator Instructions)

Kim Lee, Janney Capital.

(Operator Instructions)

And as I see no further questions in the queue at this time. I would like to turn the conference back to Mr. Kumar for any closing comments.

Thank you very much for joining us today. Please note that this will be our last quarterly earnings call for the foreseeable future. We'll continue to communicate frequently with you, as I mentioned, if in disclosures and progress warrant it. And what we decided really is that in the middle of earnings season with everybody so busy, it doesn't really make sense to just have a call for the sake of it. So instead, as and when we have news we'll present full update to you and to the investors, and I hope that we'll start by doing something in the fourth quarter, as we previously discussed.

So thank you again and have a nice evening.

Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program and you may now disconnect. Everyone have a good day.