SPCEO1 wrote: Your last paragraph is so correct and it ends with "If they can get there" on efficacy. In two days we will be six months into the phase 1b portion of the trial with no factual updates. We had a string of optimistic management presentations ("a few, several maybe many" updates between mid August and Christmas and "we think we have the key to unlock cancer cells" in mid September) and then a non-cancer focused Q3 earnings call, no more presentations and no press releases on cancer. Similiar things happened last year when TH went silent for many months starting in Fall. Could some issue have arisen in the phase 1b that has led to internal optimism to wane just as the safety issues at the 420mg dosage level did in the phase 1a? That certainly is something worthy of our consideration. Also, we have not seen anything suggesting that any new testing sites have openede as planned. The fact they were looking to open new testing sites suggested there were no problems in the phase 1b other than a difficulty in attracting enough patients, which was a positive in regard to any safety concerns arising that may not have yet been announced. Safety issues would not be good, enrollment issues can be solved - it just involves more time. And timelines were extended on the Q3 call so that suggests the issue is with the number of patients, not safety.
Still, as I have said before, the theory behind TH-1902 and its preclinical success leads this amateur scientist to think we should have seen some reportable efficacy results even if only 20-25 targetted patients have been recruited by now. I know I may be expecting too much too soon but our CEO did say in mid August that something positive might be seen from that point forward. Since the earliest patients were just becoming eligible to be reported on at around the time he said that, it was a very encouraging development. But nothing has been reported yet - so is TH-1902 not as potent in humans as in mice?
We know something about three patients in the phase 1b. Juniper's wife was one of the earlier patients and started treatment in very ealry June. She saw significant tumor shrinkage in some tumors after two treatments but was sadly unable to proceed in the trial due to other tumors which did not respond. My own cousin died shortly after her only treatment of sepsis from malignant acites so we could not glean anything from her experience. I heard of another patient being able to cut back pain medication after just one treatment but never got any further updates.
We know from the efficacy results in the pahse 1a that 3 patients had at least some benefit from the drug which at least tells us it works on some level. One of those patients may have met the criteria for proof of concept had they not caught covid after the third treatment and exited the study.
Two of those three patients were prostate cancer patients, an unexpected situation since prostate cancer was not thought to be a high sortilin overexpressor. All three patients were located at the Gettysburg clinic, which seems a bit odd to me.
The outlook for TH-1902 is undoubtedly good "if they can get there" on efficacy. That they have not had at least one protocol amendment yet is worrying to me. If TH-1902 is really effective, I would have thought we would have one by now but this may only reflect my impatience and the plodding nature of the FDA testing system.
Did TH need to increase the testing sites because the non-Gettysburg sites have not seen much success and are no longer referring patients to TH-1902's trial? Or did they need to add more sites because they are on the verge of of one or more step-ups in targetted patients because it looks increasingly likely they will show enough efficacy to get one or more protocol amendments?
Wew cannot know but the only reasonable conclusion I can draw from the accumulated weak evidence we have is the risks are rising that TH-1902 is not as special as we had hoped based on the excellent preclinical work that got Soleus to jump on board as the largest shareholder and the FDA to give it Fast Track status prior to any human trials. It may still be a good drug but the risk that it is not rises as each day passes with silence from the company regarding the trial.
If something is not going well in the trial right now, it is apparently not sufficiently bad that it would require disclosure to investors. And that may mean the info is inconclusive or there is just not enough of it to draw any concrete conclusions yet.
Management does seem confident and genuinely so. My friends who met with them the day of the third quarter earnings release came away sensing that confidence. Someone just stepped up and bought 1.6 million shares, so they must have sensed that confidence as well. But until we know for sure the drug works safely and has a good path towards eventual FDA approval, it is going to be a tad uncomfortable.
"There" in your statement "If they can get there" can also mean many different things as these phase 1b findings could direct future testing in many different directions. I remain hopeful the ultimate direction will be one that leads to broad, deep markets among those unfortunate cancer-stricken people who have few alternatives. But until the company tells us something, the stock is evidently going to continue to treat the cancer opportunity as a big zero. That will channge in an instant if they do produce positive efficacy results for TH-1902 but it appears no one is willing to give TH management any credit for getting things like this right until they confirm something actually positive on TH-1902.
Wino115 wrote: Today I am reminded of one element of the strategy in THTX's oncology push that is actually a very strong point --and that is addressing a market with very few products and large commercial potential.
I'm reminded of that today as I see Springworks has completely abandoned developing a new CAR-T product (in conjuction with Precision Bio) for multiple myeloma (bone marrow cancer) despite having just shown some pretty good numbers in the trial. The reason, "competitive dynamics" in that space. Looks like there's plenty of product options and JNJ has a very successful drug that they would have had to go up against. They just don't think they will see much in the way of revenue even if they are successful.
Because of the way the SORT1 platform is theorized to work --bypassing resistance and getting a lot of drug in safely -- it was a natural to look at heavily pre-treated, refractory cancers. There's many reasons why this makes sense and a few are about the commercialization strategy. TH1902 is looking to provide a safe/"big dose" therapy aimed at the stage of cancer's development where essentially there is no option like that with a high chance of actually working in these patients. If you can prove that up, the field is pretty wide open for you. Unlike today's example, we really don't face an issue with "competitive dynamics" negating this program.
We should add that as one more positive (along with safety signals seen so far) for the program. If we do see that efficacy we're all hoping for, you'll really have lined up all the kinds of things you would dream about for a successful platform -- it's safe, it's effective, and it's an unmet need in some large markets (we hope) with very little competition (at least for the time being). That would make for a compelling investment thesis if they can get there.