RE:All comers dose and safety vs targeting high sortlin expressWe now know that the concept behind TH-1902 works at some level due to the three responders as well as Juniper's wife's response. But we do not know if the drug works consistently enough or well enough to move forward in drug trials. It likely will, but that is yet to be proven. We do not yet have all the details about the phase 1a and by the time we get them, they may no longer be even relevant since phase 1b results rleassed before those phase 1a results might supercede them.
With the responders we have, there are some questions. Two of the three were prostate cancer patients and pre-clinical work did not indentify prostate cancer as one of those at the top of the pile in terms of sortilin overexpression. One of those patients saw a tumor totally vanish while the other saw a small reduction in tumor size and stable disease. It is great TH-1902 got this result in two prostate cancer patients, but one cannot help to wonder of the 15 non-responders in phase 1a, how many of them might have had a cancer type predicted to have more sortilin overexpression and yet did not respond. So, we do not have full info on phase 1a and we cannot answer those type of questions. So there may be a lot more to understand about this drug and it may not line up with what we expected to see. Given the way the press release was written, which "buried the lede" about seeing a patient with a 53% reduction in their targeted tumors, one has to think that those who saw all the results of the phase 1a might have intentionally downplayed things because they are not yet sure what exactly is going on. Notice how TH viewed the importance of what was discovered in the phase 1a from the intitial bullet points at the top of the press release and just under the title of the press release, which was about as bland a title as could be written:
- Confirmed safety profile at 300 mg/m2 or 1.5 times the therapeutic dose of docetaxel alone
- Confirmed low levels of free docetaxel consistent with observations in animal studies
- Early signs of efficacy observed in the dose escalation portion of the study
- Enrollment of clinical trial sites continue with 6 major cancer centers activated
So, first, safety - the main objective of the trial but also old news when this was put out.
Second, free docetaxel
It takes them to the third bullet point to mention the early signs of efficacy but again bury the lede by not highlighting the 53% responder until later in the press release.
Also, if you assume the patient with the 53% reduction had two tumors they were tracking, one disappeared but the other barely shrunk at all, which seems weird. What might account for this? And why does one prostate patient see a 53% reduction but the other only a single digit reduction in tumor size? Now, these are probably standard types of questions most drugs face following a phase 1a, so don't get too concerned. I was very pleased with the phase 1a results but it is just an issue of a phase 1a is not geared to answer the questions we would like answered so we get some interesting info and we have to try to figure out what to do with it while not having enough info to actually do so sensibly.
Further, the endometrial cancer patient was a cancer type we expected TH-1902 to work on and we would have hoped for a big decline in those tumors but we got a smaller shrinkage but a very stable situation, which is good. But ideally, I think we would have liked to have seen the 53% decline in tumore size in the endometrial patient and more stable in disease with the prostate cancer patients given the pre-clincial indications we had about how TH-1902 might work.
So, we know the concept behind TH-1902 works at least in some circumstances but those circumstances may not line up well with the pre-clinical expectations so there might be a reluctance to highlight them at this early stage in the testing process. Hence the decision to bury the lede? I am just speculating on that but it may be why the press release was structured in the way it was.
Taking that uncertainty out the equation, then yes, we should expect faster results from the phase 1b. Juniper's wife clearly had a pretty rapid response on some of her tumors, so that is an indication of what we are looking for and expect to happen. But, again, not all of her tumors reacted. Why? These are some of the things I am sure the scientists are trying to understand and if they are able to work out why this happens, perhaps they can make adjustments in future testing.
As for when the company shares any pahse 1b successes they changed the rules on that recently. INitially, they were adamanant they were required to share any sign of preliminary efficacy in phase 1b within 24 hours of discovering it because it would be a material event. Now, their commitment to that has wobbled and they are saying it is more likely they will not have a press release until they have sufficient evidence of efficacy in one tumor type to approach the FDA with a protocol amendment to take the number of patients in that tumor type up to 25. So, I was hoping for some initial indications of efficacy being announced sometime in the August/September time frame but the bar is higher to go for a protocol amendment so it will likely take longer for us to get the next milestone press release on TH-1902. How long is hard to know as they are not saying anything specific about the number of patients enrolled or the early benefit they may be seeing from the drug. Remember, it is an open label trial and they can say w hatever they want about it whenever they want.
So, in theory we should see faster responses and stronger results but the phase 1a data actually muddies the water a little bit on the strength of the responses we should expect and the change in the way t he company is choosing to announce info about t he phase 1b lengthens the time frame until we here something about it.
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BlitzBuuckeyeoh wrote: Should we possibly see much quicker and stronger results? If our concept works!
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