RE:Did it move tail risks? I think the way I'm seeing this is the end to 1a was imagined to come with enrolling 6 patients at 420 but as patients recieved more of that dose the accumulation of AEs has forced them to take a step back after just 4. The pain comes from a simple phrase like "step back" means 2 or 3 or 4 months. So that final step of 1a starts again now at 300 in effect. It's excruciating that it all takes so long, hard to hand out blame though for that.
I guess I'm a little less positive about the step back resolving the safety issues. If all they've had is 4 patients receiving two or three doses of 420 and we are looking at multiple different AEs that are as yet still poorly described then I think there's still a fair chance of accumulating more AEs at 300. I understand they are looking for a manageable scenario not a perfect scenario, hopefully they can achieve that.
We are still suffering from a lack of enrolment of meaningful numbers of patients at what they are calling "significant" doses. That still means safety and efficacy is really still poorly defined, I guess I'd go with you that they should find a good MTD to move forward with but we are still far from being told this drug has a strong looking therapeutic window.
I guess the shift in cancer types in the expansion phase partly mitigates that thing Jfm has been whining about. We can think of the expansion phase as being 'enriched' for SORT+ patients now compared to the previous design given the focus on high expressing cancers. I guess the negative is they supposedly had the previous selection of cancers to optimized for unmet need and favourable business opportunities so we have to see a little bit of compromise on those fronts in favour of prioritizing getting efficacy signals. Maybe I'm over-stating that, Christian's argument that given their new R&D that colorectal and pancreatic only make sense with a good Sort screening tool sounds valid.
When it comes to NASH all that's really happening is the messaging is moving away from an unlikely best case scenario to something that better fits the stark reality of their drug program and the wider NASH drug development ecosystem. They are a acknowledging the negative headwinds not just the positive one's :)
Wino115 wrote: To me, I just want to make sure they're putting TH1902 in a position to become a viable treatment in the future. Christian let it slip how they are hoping to use this treatment and it aligns with what Belevieu said before --they want the ability to use a good dose that gets concentrated and internalized over a longer period with no major safety issues. He let slip that the "issue" with refractory patients is to get something that helps put tumor on the defensive for as long as you possibly can --supress the tumor and stop spreading so the patient can live longer. By going to 300 and eliminating whatever they saw at 460 will create that therpeutic approach with what they saw was negligible safety issues.
I think it's pretty clear the 300 level should pass since they had already moved beyond that and we never heard issues with 300. So that's the final group going now. To me, that eliminates some of the downside since they are solid on the safety and have a dose that's large enough.
Sounds like any efficacy data will likely only be in 1b, so I can't change the probabilities much on the option value. But what they did do is the increase the size of the market they're going for by a bunch. Adding in the second HR+ breast cancer makes it much larger as does melanoma -- those are both very large markets. Same for lung. I'm not sure if the HR+ market would also allow them to move into more to 2L or 3L markets, but it's definitely no longer just $12bil market they are addressing. I would guess HR+, melanoma and lung alone would add another $4-5bil to that market size as a guess.
The quicker move to get a "parallel" development going in markets they don't want to set up in seems to point to a China deal happening sooner than I would have thought, so that's a positive given the current prices being paid for ADC deals. I guess you can add somethiing in for that now in a valuation model.
My net conclusion just around oncology is the negative tail of 1a not reaching a therapeutic dose or being unsafe is off the table, but the larger part around efficacy is still there since no data. The probability is the same for that reason, but the ultimate size of the prize -so the scale of the upside potential is much larger by 50% or so. If you were to actually throw that into the oncology option model you'd likely increase the option value by $.75 to $1.00.
But I doubt the market is actually trying to think this way, so don't expect to see that even though analytically, what they've said around TH1902 is a net-net positive. I guess the surprises will be China quicker than I thought, and the published data and on to the larger 1b in 2-3 months according to Christian. But rest was a bit of a ho-hum, kick the can down the road for me.