The special New York Academy of Sciences meeting entitled "Therapeutic and Diagnostic Modalities Targeting Hypoxia in Cancer" took place Wed. March 14th in the brand new headquarters of the Academy on the 40th Floor of the new 7 World Trade Center building. The old 7 World Trade Center building had been damaged so badly on 9/11 that it had to be taken down completely and rebuilt from scratch. The view of Lower Manhattan from this conference room was absolutely spectacular. This part of New York City is going through an exciting rebirth. From the conference room windows, one could not only see all of Lower Manhattan but also look down on some 3,000 construction workers who are currently rebuilding the entire Ground Zero site (Freedom Tower, Two World Trade Center, etc). About a thousand tourists per day also visit the 9/11 Memorial, which has restricted access and requires a special pass.
The first thing I noticed when I arrived at 7 World Trade Center was that there were a lot of German-speaking people entering there (all scientists/executives from Merck KGaA). They seemed proud and excited to be there. I congratulated some of them on their collaboration and development program with Threshold. I understood that they are holding additional meetings with Threshold, Siemens, and perhaps scientists from another pharmaceutical company as well, in NYC tomorow. It seemed that the Threshold people and the Merck KGaA people all get along very well, so I don't think that we have to worry about the sort of nightmare scenario of dysfunctional human relationships that plagued Chrysler and Daimler-Benz when those two companies merged and tried to work together.
No OS will be give at AACR? Sorry to hear that. Could be good news as the trial enrollment ended early and failing patients of crossover were allowed to crossover. Wild guessing tells me that for for tells good news about OS.
I'm sure the whole medical community is anxious to see TH-302 on the market and available for off label use. Pancreatic cancer may be the best cancer indication to attack to get early approval.
PFS coming is great. Now we all have to look forward to hints about when we can expect hear a guesstimate about the date to expect OS numbers. No doubt the longer we wait the better for the patients involved. Hope to hear good news about the crossover patients also.
GLTA, many more cancers and drug cocktails ahead before we know the true and final value of TH-302
Yes, my friend is still alive and working full time after 1 year with Stage IV pancreatic cancer. He spent 10.5 months in the trial, went off of it in Jan. due to neutropenia. Tredleon is sure that this was caused by the gemcitabine and not the TH-302. Indeed, earlier Phase I trials of TH-302 as a monotherapy demonstrate an excellent safety profile, and gemcitabine does indeed cause neutropenia on its own.
Triad, your analysis of the presentation is absolutely superior! Exciting to see I am adding to a long list of grateful hearts expressing our gratitude for your attendance and willingness to share your thoughts and breakdown of the meeting. Outstanding synopsis!
I spent a few hours reviewing the slides posted last evening. The possibilities and potential of this drug are almost inconceivable, just staggering and mind blowing! Impressive the credentials of the medical professionals and facilities involved in the research. To your knowledge, are there any papers, related case studies published in any journals that I could further read to get a better understanding from a medical standpoint that you are aware of or that may have been mentioned? I plan to do some research, you have provided names, I should be able to locate information on my own.
Thank you for the update triad. Appreciate you going to the meeting and reporting back. Good stuff. Seems positive. AACR should be interesting as they present the details of the data. Also looking forward to the OS coming out in the summer or fall.
Yep, sounds good moving forward. It's very helpful to have a "board member" actually at the conference. That's a lot of great color commentary you don't get from slides Thanks Triad!
Dr. Charles Hart of Threshold gave the last talk of the day. As expected, his talk was an overview of what Threshold has accomplished with hypoxia-targeted small molecules. He outlined how THLD scientists made TH-302 (through combinatorial synthesis). He also presented the Phase 1/2 and the Phase 2b pancreatic cancer data and confirmed later during questions that the dosage-dependent data for the Phase 2b would be broken out at the AACR. He was upbeat but also seemed nervous, in an excited sort of way. One area of tremendous potential appears to lie with prospects of using TH-302 together with angiogenesis inhibitors like Avastin or Sutininib. It has been found that when these anti-angiogenic drugs cut off the blood supply to the tumors they make the tumors more hypoxic, and that is bad. There is huge potential for TH-302 here, because Avastin needs a resurrection. The hypoxia that results from Avastin treatment leads to no overall increased survival, but TH-302 could solve this problem.
Dr. Hart said that Threshold had to do extra preclinical work to prove that the drug was not toxic to the retina or the thymus (normally the only two hypoxic portions of the body). It passed these additional studies with flying colors, unlike just about any other prior drug in this class. So this was really good news.
Dr. Hart also did say that the data is fully consistent between the different dosage arms of the Phase 1/2 and the Phase 2b trials, but he did not go into any details there (AACR data embargo prohibits that). He also said that no OS data would be presented at the AACR but during questions he reiterated that the OS data is still maturing and could in fact warrant a request to the FDA to approve the drug early (without Phase 3 data). He said as of now, this is unknown but still possible.
This is a great report. For those of us, who did our research and bought the stock, this gave us all the info. we wanted to know at this stage, and it was positive news. Ofcourse, we knew that the pumpers and dumpers were using this meeting as an opportunity to trade this stock. We knew that as they pumped up the price, it would fall on the eve of the meeting, and day after. So, there is no angst regarding today's price drop. What we do know is, that it is never going back to a $2 or $4 stock, even if MMs try. Only scientific data and FDA reports will determine that, and so far the news has been positive. We also love that there is renewed hope for future Cancer patients, which would no doubt include some of those shorting the stock, and posting on this board every other minute. Scientific progress helps even the Naysayers.
Thank you Triad for your work and posts. You have gone Above and Beyond the Call of Duty for this mesaage board. As many do, I enjoy your posts and insightfulness on Threshold and its research.
Sounds like the symposium played out very much as I posted it would. Plenty of data confirmation, and a prestigous honor, but not really any new news that would move the stock. Dr. Selick will make these presentations.
A couple of questions for you though, that might give everyone a better sense of Threshold's importance in their research and stock investment.
1) How much time was allocated for Dr. Harts presentation versus everyone elses?
2) What was your sense on how advanced Threshold is in their research and in moving towards getting TH-302 to patients and to market versus other competitors?
3)Were you able to identify any equity analyst or business news people in attendance?
Thanks Traid, I appreciate you taking the time to post your observations on the meeting. I have always appreciated your insight into Threshold and you are probably one of the reasons I have hung in so long on this, and now reaping the benefits of being a long time investor in THLD.
Thanks Triad! Very good report! I sense that the company is moving forward steadily and confidently. This is a good sign. The last comment is telling in that the OS data appears to be very good thus far.
Now for the NYAS meeting itself. It began with George Zavoica of MLV giving a brief introduction about hypoxia in general as it relates to physiology and cancer. in particular. I was impressed with George and how he put this whole conference together with Jennifer Henry of the NYAS. George has a Ph.D. in physiology from the Univ. of Virginia, and he did postdoctoral work at UConn and Harvard. He has made a gradual transition from bench scientist to biotech analyst, to entrepreneur, and is now trending toward venture capitalist. George introduced the first speaker, Professor Mark Dewhirst from Duke University. Dr. Dewhirst has been working on tumor hypoxia since before anyone even knew what that was, and has had over 30 years of uninterrupted NIH funding on this work. He is truly a pioneer in this field and perhaps even a future Nobel Laureate.
A recurrent theme in the conference was the importance of developing better imaging methods as a diagnostic tool for hypoxic cancer patients and to ascertain whether a particular treatment is truly working on the hypoxic tissue. THLD is collaborating with Siemens in this area. Hartmuth Kolb of Siemens USA gave a talk about a new imaging agent he developed, and he is using this in the collaboration with Threshold. The 2-nitroimidzole motif was featured again and again today, both in drugs like TH-302 and in several hypoxia-activated imaging agents.
Dr. Barry Selick (CEO of Threshold) did not speak at he meeting but he did get up and ask Dr. Giovanni Melillo (from Bristol Myers Squibb) some questions about whether in principle HIF-1 (hypoxia inducible factor-1) itself is a feasible drug target. The verdict was "perhaps someday but not now". The problem with direct HIF inhibitors is that currently, you still cannot tell whether you are inhibiting the HIF protein directly or whether you are inhibiting HIF gene expression. This matters a lot, and Dr. Melillo's answer seemed to please Dr. Selick (since TH-302 does not work through that mechanism but rather it selectively cross-links DNA in hypoxic cells).
Dr. Maria Papadopoulou from the Univ. of Chicago North Shore Medical Center spoke about NLCQ-1 a compound that is less potent than TH-302 but may diffuse further into the tumor. It seems promising, but her data is all preclinical at this stage.
One of the most telling moments actually occurred early-on was when Dr. Zavoica was introducing Dr. Derwhirst. He said that Dr. Derwhirst has been working in this field for so many years and that "all of his tremendous efforts are going to pay off soon". Then he paused and said, "well of course his efforts are already paying off". This may have been bit of a slip (after all Professor Derwith is one of the preeminent scientists in the world on tumor hypoxia. He has had successes but he has also seen failure several years ago with tirapazamine (TPZ), which failed to meet its primary endpoint in a clinical trial. Threshold investors should probably be pleased by the positive, though vague, foreshadowing exhibited here. I certainly learned a lot today, and I met a several interesting people during the coffee break and social mixer following the talk. There were also a lot of graduate students there from NYU and Columbia, as well as several scientists from Sloan Kettering.
A lot more scientific information about the dynamic and fluxional nature of tumor hypoxia was presented at today's conference, and also a lot more about tumor imaging but I think that I have touched on the big picture here. Good Luck Everyone.
Thanks Triad great report. It just galvanizes my thoughts on this company that much more! When I bought this several months ago I felt really good about it. I greatly appreciate your work on this. I'm sure all others feel the same way. I think we are on to something huge here. IMO we will go much higher in the near future.