Wino115 wrote: My take. In a word, at least they were up there with a few big boys...Madrigal, Harrison, etc... Regardless of what they said, which was all the stuff we already know, it's just good for them to be on these and keep hammering away. Just get up on that stage and pitch. It's a start.
A few key points I took away:
No change in Endpoints,Acc Approval still in the cards (Harrison)
High placebo reponse rates, so look for additional endpoints to show the delta more (Harrison).
I agree with this and that is also what THTX may be analyzing. Harrison mentioned Madrigal added a 2 step improvement and that it had to include one of the NAS categories moving to 0, but I couldn't quite hear his whole explanation. Something to the effect you want to see more movement in one of the subcategories (Steotosis, Inflammation, Balooning) to get better results versus placebo.
The point he was making here is that if you set the cutoff for efficacy higher then placebo starts to fail those more stringent settings and you remove the placebo effect from the study. The highest stringency for drugs that impact both Nash and fibrosis is to move from inflammation OR fibrosis to inflammation AND fibrosis because typically placebo can't resolve both, but you'd have to have confidence your drug could hit both. Harrisons point on how there won't be one drug because it's to heterogeneous a disease, that combos should be tried and that a tool that would be great is for there to be a screening system such that depending on your specific case, the doctor prescribes you one of the specific approved drugs. Meaning, there likely is a market for the leader (maybe #1,2) in each broad MOA category (PPARs, Thyroids, FGFs, GRGH, etc...) Since THTX is THE ONLY one using the growth hormone pathways, they may have it to themselves. The patents help there too. I guess the fact they were there with a fat buster 15 years ago has helped them since no one else could move in there and test/develop. In a way, they had a NASH patent (and now a real NASH patent with the extensions) well before anyone knew about NASH and what may work.
The key to combo is MOA. You can just randomly combo two drug that work and hope for the best or you take a ration approach. Look at the MOA, look at which two MOAs complement each other and make dat-driven decisions. This is the favoured approach of pharma, if you want to get considered for combos you need to understand how your drug works not just get an approval. The Ph3 is priority now but hopefully they don't just take a minimal approach here. I hope eventually we start hearing about maybe sponsored project in Grinspoon's label on mechanisms, hopefully they repeat the transcriptomics in the general population. If the indication ultimately ends up with a combo approach there is value in understanding the mechanisms at play. I like Harrisons point too that using these tools to pre-screen would be a smart idea. I've been saying that THTX ought to think through what type of patients may work best with tesamorelin given it's MOA and screen for them. If that is what is taking time, then I am perfectly ok with them to take the time to figure this out and get it in because it has to increase your chance of success to hit endpoints massively I would think. That's ok with me. Clearly they know high VAT works, obesity works, etc... but they may want to add a lot of other pre-screen criteria besides just NAS >=4 and F2,F3.
Also Harrisons comment on non-invasive techniques and need to be really clear on how you will get uniform biopsy results could also be adding time to this. I would also agree that you should get that up to industry standards at the outset and those standards do seem to be getting better lately. So they should be incorporating all that so they can look as good as a Madrigal at the end as far as the data and what they prove.
Nothing all that new for us on the THTX. A few comments though so Paul understands what he shoudl be doing. LEAH & PHILLIP Please tell him this politely, when you're on a stage for a NASH conference and you know you only have 10 minutes, structure your comments around those restrictions. Dispense with Trog and Egrifta with one line, same for Oncology. They only need to be mentioned along with your $65mil of revenue. That would take 30 seconds, not 3 minutes of your 10. FOCUS on the NASH stuff...this is a liver conference, not HIV or Oncology. I'm not saying ignore it, but it should have been 30 seconds, max. Leah you need to budget the time for them, that's what I used to do when my bosses would hone in on my pitches to big corporate pension funds. I'm happy for their help, but here's your 2 minutes and hand it to me for the guts of the pitch. They should have delved a bit more into the foundations of the studies, who they work with (CMO just offhand mentioned Grinspoon without any introduction. So no one knows you're working with Harvard Med and Grinspoon and Loomba!). I would have had a progression such as --experienced drug, fully know it's MOA for lipo, extending to liver, 15 years safe, 3-4 Phase 2 type trials, sizes, what you learned, summarize them all ("ultimately we've tested it on roughly 120 double-blinded placebo controlled studies, some NASH, some NAFLD, but all NAFL, results support following conclusions -- Fat reduced 35-40% vs. placebo, ALT, AST down, HDL/LDL/Trigl flat to better, IGF-1 whatever, etc... Laterst study goes into genetic MOA -- shows oxidative phos...etc... So we are changing the liver cells as far as lipogenesis etc... Very powerful and upstream action. No we are initiating a Phase 3 in NASH patients as designed with our Scientific Adv of NAMES.. Summarize, it's safe, we have a lot of data showing it's effective in the ways you'd want to see it, we are the only GRGH approach, have long patents, more MOAs the better as Harrison says, no reason to believe we won't see in better liver environment than HIV liver that drug continues to do what it did in past trials.
YES, YES, YES, YES, YES,!! Drop the mike... that would have been 10 minutes, punchy, and covered the key bits. They covered most of that, but not all and it wasn't with a solid, convincing flow. I just wish Dubuc or Leah would, litetlly, script it out and write it out like a speech. Here's the 10 minute Iinvestor speech, 10 min scientific speech, 3o min investor speech, 30 minute scientific speech, 10 minute NASH only Investor speech, 10 Minute ONcology Investor speech, 10 minute Overview Investor speech, 30 minute overview speech, etc.... Just write them out. I would write out my speeches fully, edit them and have the long version and the short version for my pitches. They really need to do this so they can be consistent and hit the most relevant points.
YES Overall, just the fact they were up there is a win.
YES Have to start somewhere and we're starting at the bottom!
SPCEO1 wrote: They are excited and they have been for some time. I am as well, but I really don't want to outrun my headlights on that as it is important to see human trial data first to make sure there is a path ahead for it.
BlitzBuuckeyeoh wrote: Sounded like they are really really excited with oncology pipeline also.