Molecular Templates Inc (MTEM)

[trop]

"The Life Sciences Report: Do you have another name with a similar trial-failure theme?

George Zavoico: I'd like to mention Threshold Pharmaceuticals Inc. (THLD:NASDAQ). Its drug, evofosfamide (TH-302), a hypoxia-activated chemotherapy prodrug, failed as frontline therapy in soft tissue sarcoma and in pancreatic cancer when combined with doxorubicin and gemcitabine, respectively. Threshold was in a partnership with Merck KGaA (MKGAY:OTCPK) on this. But, in looking at the pancreatic cancer data, there was a substantial and significant—almost 50%—improvement in the overall survival in Japanese and South Korean patients in the trial. It just barely missed in the U.S. with a p-value of 0.058, and in the rest of the world in the intent-to-treat population. Looking at the data closer, Threshold found that overall survival, progression-free survival and the overall response rate for the intent-to-treat population was very similar to that of low-dose evofosfamide in the Phase 2 trial. Since the improvement in these efficacy parameters was much more impressive with a higher dose in the Phase 2 trial, Threshold went with high dose in the Phase 3 trial. But the finding that the efficacy parameters looked like what was seen in Phase 2 suggests that a substantial number of patients may not have gotten the high dose. How can this happen? Perhaps patients weren't as well monitored as they were in the Phase 2 trial. Perhaps when some of these patients began getting a rash, mucositis or gastrointestinal disturbances, they were taken off the drug or the dose was reduced, whereas in the Phase 2 trial, with better monitoring, they may have been treated for those symptoms, and therefore they were able to stay on the higher dose and experience the efficacy. Since patients treated in Japan and South Korea did better, it also suggests that patients were monitored better there. Moreover, there may have been an incentive to get patients off this trial when adverse events emerged in order to switch them to the combination of gemcitabine and Abraxane, which was approved midway through Threshold's trial in the U.S., but not in Japan.

The Life Sciences Report: Was there an assumption that evofosfamide was a dud? Is this a case of shoot first and ask questions later?

George Zavoico: That's how investors saw it—just looking at the top line of the Phase 3. I'm confident that evofosfamide is an active drug, and the company confirmed publicly on March 10, with its Q4/15 financials, that it will continue to develop the drug in Japan. Threshold is also continuing development of evofosfamide for other indications where it has seen some promising preclinical results. It is about to begin studies of evofosfamide in combination with immuno-oncology agents, which target the immune system and not the tumor cells. Effector T-cells need a lot of oxygen to kill tumor cells, and when they encounter a hypoxic region, they just cannot do their job and spare those tumors a certain death. If you administer a drug that is activated by a low-oxygen environment and disrupt the hypoxic regions in tumors, then effector T-cells may be able to go into those regions and attack tumor cells that are otherwise hidden from the immune system. I think it's worth watching Threshold Pharmaceuticals carefully.

The Life Sciences Report: Thank you so much, George."


https://www.thelifesciencesreport.com/pub/na/how-three-companies-have-been-resurrected-from-failed-clinical-trials-george-zavoico-of-jonestrading

Dr. George Zavoico, senior equity analyst at JonesTrading Institutional Services LLC, has more than 10 years of experience as a life sciences equity analyst writing research on publicly traded equities. His principal focus is on biotechnology, biopharmaceutical, specialty pharmaceutical, and molecular diagnostics companies. Previously, Zavoico was a senior equity research analyst in the healthcare sector at MLV & Co., and an equity analyst at Cantor Fitzgerald and Westport Capital Markets. Prior to becoming an equity analyst, Zavoico established his own consulting company serving the biotech and pharmaceutical industries, providing competitive intelligence and marketing research, due diligence services and guidance in regulatory affairs. Zavoico began his career as a senior research scientist at Bristol-Myers Squibb Co., moving on to management positions at Alexion Pharmaceuticals Inc. and T Cell Sciences Inc. (now Celldex Therapeutics Inc.). Zavoico has a bachelor's degree in biology from St. Lawrence University and a Ph.D. in physiology from the University of Virginia. He held post-doctoral fellowships at the University of Connecticut School of Medicine and Harvard Medical School/Brigham & Women's Hospital. He has published more than 30 papers in peer-reviewed journals and has coauthored four book chapters. He received The Financial Times/Starmine Award two years in a row for being among the top-ranked earnings estimators in the biotechnology sector.


DISCLOSURE:
1) Dr. George S. Mack conducted this interview for Streetwise Reports LLC, publisher of The Gold Report, The Energy Report and The Life Sciences Report, and provides services to Streetwise Reports as an independent contractor. He owns, or his family owns, shares of the following companies mentioned in this interview: None.
2) The following companies mentioned in the interview are sponsors of Streetwise Reports: Resverlogix Corp., Sunesis Pharmaceuticals Inc. The companies mentioned in this interview were not involved in any aspect of the interview preparation or post-interview editing so the expert could speak independently about the sector. Streetwise Reports does not accept stock in exchange for its services.
3) George Zavoico: I own, or my family owns, shares of the following companies mentioned in this interview: None. I personally am, or my family is, paid by the following companies mentioned in this interview: None. My company has a financial relationship with the following companies mentioned in this interview: None. I was not paid by Streetwise Reports for participating in this interview. Comments and opinions expressed are my own comments and opinions. I determined and had final say over which companies would be included in the interview based on my research, understanding of the sector and interview theme. I had the opportunity to review the interview for accuracy as of the date of the interview and am responsible for the content of the interview.
4) Interviews are edited for clarity. Streetwise Reports does not make editorial comments or change experts' statements without their consent.
5) The interview does not constitute investment advice. Each reader is encouraged to consult with his or her individual financial professional and any action a reader takes as a result of information presented here is his or her own responsibility. By opening this page, each reader accepts and agrees to Streetwise Reports' terms of use and full legal disclaimer.
6) From time to time, Streetwise Reports LLC and its directors, officers, employees or members of their families, as well as persons interviewed for articles and interviews on the site, may have a long or short position in securities mentioned. Directors, officers, employees or members of their families are prohibited from making purchases and/or sales of those securities in the open market or otherwise during the up-to-four-week interval from the time of the interview until after it publishes.