RE:RE:RE:RE:Full report from Doug Loe Not really, technically there is no lead at the moment. The results of Ph1 will determine which is the lead indication(s). At that point he can build his model around the market for those leads, I think he is right that you can't build a model based on all the indications in this first basket trial because it's unlikely all will proceed.
It seems their original plan was to go with tnbc as the only lead indication. For whatever reason, hopefully data driven, they changed their mind and choose a basket trial. I'm going to guess it's along the lines of Christian's excitement about pancreatic cancer and they just couldn't ignore that result so moved over to getting data from multiple indications from the get go. If this change is driven by something positive like that then it's a good decision. I imagine the path to approval is potentially shorter in pancreatic cancer given how badly the present drugs perform. There are some downsides as well though. If you went with a single indication then all the data you accrue is in that indication so potentially you get to answer some of the deeper questions faster for that indication but you lose the chance to see the broad applicability of the drug. Swings and roundabouts, it just slightly changes the data flow in first 12-24 months, not in a bad way just different.
Doug Loe is talking about one technical issue, lead indication, and putting a timeframe on getting that answer, he's not saying all the questions are going to take that long to get some answers, other things will certainly report before then. Maybe his focus is building his model and the things he needs for that and lead indication is one of those things.
His take on NASH is a little different. It seems if they'd stuck with HIV NASH he might have been prepared to derisk this more but the move to general NASH is worrying him. I guess I have to backtrack as well. Seems like he's OK with fat reduction as a efficacy signal (at least for NASH resolution) although he seems to have strong concerns with reversing fibrosis.
Wino115 wrote: Right, and I would assume TNBC is lead but that they would rank pancreatic and ovarian pretty close behind based on large population of unmet need. I suppose you could say the same for colorectal, but like you say, they can't do it all in the first trial. They can clearly tackle them quickly thereafter and will be trialing TH1904 at some point. I guess you go for the ones where the response rate is over a certain hurdle of response.
I am guessing the strategy is to go for the most prevalent but hardest to treat with unmet need so that you get all the accelerated approvals and breakthrough therapy designations. Then do the others right in the background until those are completed. That's where you could partner an indication out if you want someone else to run with it and it's a relatively smaller indication.
qwerty22 wrote: The data will come in stages. The types of info that support approval are ORR, DOR, PFS etc (go learn the language of RECIST). Before that we certainly will start to get reports on safety and an efficacy signal as they get something meaningful but that will be on small numbers of patients maybe over several indications and there is no way to construct ORR etc from those. The first stage data (roughly Ph1 part 1) (maybe mid/late 2021 thru to mid 2022) will be 'signals', indicatating if the drug can do what is expected. The 2nd stage (Ph1 part2) data (late 2022) might be the first chance to QUANTIFY that signal and relate it to other drugs for each indication, still slim data for doing that though. At that stage the promising indication can go into expansion trials (Ph2) that's when the meat goes on the bone.
He's only talking about "preferred target" here it makes sense that that particular decision will come at the end (interim) of Ph 1 part 2. If he has to piece together a model he can't do that without certain info in hand such as which indication they are chasing. Like him I like the basket trial approach but it does come with some downsides like a delay in ascribing a lead indication. If they'd just focused on tnbc then we'd know the lead indication from the start but we'd lose some of the benefits of a basket trial. It's highly unlikely they move forward with all 4/5 indications so which indications make it will need to be worked out from the data.
jeffm34 wrote: "We expect to revisit our assumption on preferred target indication for TH1902 once we have Phase I tumor response data to review, probably near end-of-F2022 if the trial commences enrollment in early FQ321 as Thera predicts."
He's not expecting to see tumour response data until the end of 2022?