Written Transcription of Ray's Prepared Statement from Conference Call
Took me two hours...I'll tried to do the Q & A later...that had good partnership information in there. FYI doing this has allowed me to learn that there is no conference call on august 26th. enjoy this, its great when you can read it, and i know 90%+ of you didn't listen to the call. This was transcribed to the best of my, ryjo8831's, ability and is obviously unofficial.
At 5 minutes and 27 seconds into the conference call, CEO Dr. Raymond Warrell speaks:
Thanks, Gary. I’m going to focus my remarks primarily on clinical developments, and then provide some comments on our financial status.
As most of you know we completed enrollment into our Phase III trial of Genasense in patients with advanced melanoma known as AGENDA. A total of 315 patients were ultimately accrued in this trial, these patients derived from sites in the U.S., Western Europe, Canada, and Australia. The goal of this study was to replicate findings observed in our previous trial, using a biomarker to define a potentially chemotherapy sensitive population. Our prior trial, known as GM301, achieved all of its secondary endpoints, including Overall Response and Progression Free Survival (PFS), and it narrowly missed its primary endpoint of Overall Survival, which was numerically superior, but with a p-value of 0.077 for the entire population. Our subsequent analyses show that low LDH, a readily available blood test that we used for stratification in the last study, was significantly associated with improved survival. Moreover, this outcome was observed in a population comprised of more than 500 individual patients. The importance of LDH as a powerful prognostic factor had already been well established.
This past quarter the EORTC, which is Europe’s largest oncology cooperative group, published their findings that validated the impact of low LDH in a completely independent group of study patients who had received completely different types of chemotherapy. Thus, all of these factors and the robust sizes of the populations on which these observations were based combined to increase both the importance of our findings, and also to make it unlikely that our observations were due to chance or to post hoc analyses of patient subsets. It is these analyses that form the basis of the projections that were developed for the AGENDA trial. AGENDA was double blind, and entry was restricted to patients whose baseline LDH did not exceed 80% of the upper limit of normal. This latter change in particular represents our major effort to hyper-enrich the study for patients who are maximally likely to benefit. With closure of enrollment, our blinded and blended update indicates that patients accrued into AGENDA were very similar to patients with low-normal LDH in the preceding study. Moreover, during the past quarter, the independent Data Monitoring Board for this trial conducted an important post-accrual analysis for safety and futility. Those of you who follow recent developments in melanoma will recall that during 2009 two similar futility reviews sunk the most recent Phase III drugs in melanoma, namely Elesclomol from Synta, and Nexavar from Onyx and Bayer. Thus we were very pleased that the Genasense analysis passed this key review point, and that the committee recommended that the trial continue to completion. Parenthetically, it has hardly escaped our notice that during the past quarter, Bristol Myers has paid $2.1 billion dollars for the HALF, that would be HALF, of the melanoma drug from Medarax that they did not already own, a drug known as Ipilimumab, also a compound that is pre-data.
I want to provide our expected timeline of events. AGENDA has co-primary endpoints that are hierarchically ranked. The first is Progression Free Survival, or PFS. The second is Overall Survival. We currently expect to conduct the PFS analysis approximately six months after the last patient was enrolled. We are completely on track to have a sufficient number of progression events that will generate this primary analysis, and we will not be conducting any interim analysis for PFS. We expect to release the top line PFS data in the early Fall, along with complete and quantitative data at a subsequent scientific meeting. Assuming the PFS result is significant, we plan to file for approval of Genasense in patients with advanced melanoma, on the basis of PFS, combined with various secondary endpoints, and of course, safety. We believe that the demonstration of increased Progression Free Survival not in one, but now two randomized control trials will suffice for worldwide regulatory approval. Our preliminary consultations with regulators in the major European countries have affirmed this strategy. We have formally submitted our intent-to-file notice for the marketing authorization application, or MAA, in Europe, and at their meeting in June the EMEA assigned Spain and France as Rapporteur, co-Rapporteur countries respectively. We note that these were both Rapporteur countries for our prior application, so those reviewers should be very familiar with melanoma as a disease, and our findings in particular. We will undertake similar discussions with the FDA after our primary data become available. We’ve also reported positive news using Genasense combined with an entirely different chemotherapy program. While our Phase III studies have all used Dacarbazine chemotherapy, investigators at NYU have been studying Genasense in combination with temozolomide, which is a derivative of DTIC, or Dacarbazine, and Abraxane for treatment of certain patients with advanced melanoma. At ASCO this past June they reported that this combination was also associated with both high response rates as well as potentially increased survival when compared with the Genasense Dacarbazine program. Thus, as we have anticipated, it appears that Genasense can be successfully combined with and can enhance the activity of a number of other chemotherapy drugs. We have also sought to develop treatment regimens that are easier for physicians and patients, and toward that end we have completed early studies using high dose Genasense given as a one hour IV infusion twice per week. I am pleased to note that this new infusion program is now open to patients with melanoma and we anticipate preliminary efficacy {transcriber note: recording cut out – maybe he said “data to be released”?} in the fall of this year as well.
Tesetaxel
For the other products in our portfolio, we will complete all enrollment later this quarter in the dose ranging study of Tesetaxel given once every three weeks. Tesetaxel is an oral form of the taxane drug class, which is the most widely used class in cancer medicine, including such drugs and well known brands Taxol, Taxotere, and Abraxane. All of these prototype agents are given IV, and most are associated with quite severe side effects including nerve damage if given for prolonged periods. We believe Tesetaxel may avoid many of these serious side effects while retaining high anticancer activity. From a development standpoint, Tesetaxel has now opened a substantial lead over all other competitors. As a consequence we believe that Tesetaxel can be the first oral taxane that receives regulatory approval. The drug has now completed three Phase I and five Phase II studies in more than 275 patients. Distinct anticancer activity has been shown in the Phase II studies of gastric cancer and breast cancer. In our ongoing dose ranging study we ourselves have observed objective responses in patients with nasopharyngeal cancer, GI Stromal Tumors or GISTs, and colorectal cancer. In the final phase of the current study we have converted all final patients to a so-called “flat dose”, specifically to a prescribed single dose of 50mg rather than a weight-based dose, that will also improve patient convenience. We are keenly interested in evaluating at least one alternative schedule for Tesetaxel, in particular the schedule that is once weekly for three weeks. For Taxol, but not for Taxotere, this schedule has proved significantly superior in patients with breast cancer to the once every three week schedule that we have tested to date. Therefore before we begin the expensive and extended studies for registration, we believe its excentral to evaluate this alternative schedule and to prospectively evaluate which of these schedules is going to be therapeutically superior.
Finances
Let me now turn and discuss our current and projected financial circumstances. The last few quarters have proved exceptionally challenging to many small companies. Those that have not been able to secure financing have not survived. In April as Gary pointed out, Genta {transcriber note: taping cut out…} convertible debt transaction, we followed that up in July by closing on the first $3 million dollars of a combined debt and equity raise. As Gary noted we have negotiated with the investors in that round, to increase the size of that round, from $10 million dollars to a total of $13 million dollars. For this improved and additional $10 million dollars in capital, and with that increase, we should have sufficient cash to get into December, and certainly sufficient cash to get the data in our Phase III AGENDA trial. Fundraising this environment has been exceptionally difficult, but we are fortunate in having some exceptional late stage products, whose near term value has been recognized. After a searing string of failures from melanoma patients, we are the next company to report data, and with positive results this fall, Genta stands as the company that may have the first new drug approved for melanoma in more than 40 years. The Genta management team is highly experienced, and has successfully registered a number of oncology products. If our pending trial is positive, we can submit our regulatory applications in less than 9 months. We look forward to seeing you at the upcoming stockholders meeting on August 26, but our next scheduled call with shareholders will be to discuss the AGENDA results with you. We hope you will be all tuning in for what we hope will be very positive news. That concludes my prepared remarks and I’ll be pleased to take any of your questions.
