RE:RE:RE:Did it move tail risks?A few other intriguing points were hinted at. First off, in the pipeline they still have the docerubicin TH1904 in there, despite saying they won't bother given how broadly TH1902 appears to be working at. And they are now testing SN38 and have listed immunotherapy drugs and TKIs previously. This wasn't the normal slide they show it at, but we know there's more. But the point Paul made was, they have seen industry interest on the delivery vehicle but it has required them to educate the interested parties because none of them have any experience around SORT1+ since it's new and they're the first to target it.
The wildcard would be if they educate a partner around the deliver possibility, show them what they've learned thus far in 1a, it's not inconceivable you'd at least get a shot for combining it with some of the other more advanced drugs out there in a trial. It it's in a more specialty area, it's not something they'd get in to anyway (say, head neck tumors, etc...). Also, if it's a proprietary drug at the moment, they'd have to partner. Those would both validate it and provide a pipeline asset funded by someone else with upfront payments that would be meaningful to them given the size of past deals around platforms (re: Bicycle, Sutro, SeaGen, Daiichi Sankyo, etc...). That sounded more pertinent, given Pauls added discussion around educating firms on the sortilin issue, than in the past. I suppose this is where Dr. Rothenburg could come in very handy.
SPCEO1 wrote: It seems pretty obvious to me that the phase 1a trial has been messy but I suspect that is true for most. That messiness cost us time but all will be quickly forgotten if the overall result is positive. I think the reason we are not getting any clear info on the trial is that it has been a messy situationand they are not keen to show us that. So, all we get is partial positive info for the most part. Again, standard operating procedure from a biotech but it does get old.
The good news is there is obviously going to be a phase 1b unless something very dramatic happens in the next couple of months. Christian sounded very confident about the progress to be seen at the 300mg level so let's hope that is well-founded - I suspect it is as he has access to all the messiness of the phase 1a and evidently still believes that. So, we will most likely have a 300mg MTD which is plenty, we will have more shots on goal due to the expanded phase 1b trial and Christian noted again the liklihood that TH-1902 will allow for many more cycles. Basically, my guess is TH pushed hard to test at 420mg,it did not work well and it cost them time. But it likely gave them lots of additional data and raised their confidence about success being achieved at the 300mg level. I myself am perfectly happy with 300mg MTD as that should allow the drug to do its magic quite well. I am unhappy that they took a messy route to get hear and chewed up so much time in the process.
Now they have to get thsoe conference presentations put together in a way that will wow investors, produce a nicely curated view of the phase 1a trial that obscures the messiness, get a broker to bite and cover them with an optimistic report, raise the needed money, get the phase III NASH trial going and do a partnership deal with the Chinese and outlicensing deals with Western drug companies. That is a bigask and it all depends on cancer working well but I am not too concerned about that.
qwerty22 wrote: 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.