RE:RE:Expectations for Next Week If they are smart then the end of year timeline already has plenty of contingencies in it. Barring some extreme event (no evidence for that), then there should be no real reason to overrun. I'm hoping they don't need to use all the contingency time and we get surprised early. I see the timing of going public as separate to all the things that have to be done to move on to part 2. The priority should be to ensure part 2 happens on time so they should not be delaying the things happening in the background. They might leave going public as late as possible to tell a better story, that is a separate issue to keeping the clinical program on time.
Wino115 wrote: I think you have it. I did notice that there is a whole lot of data collected in these initial phases which needs to be understood by the investigators to inform the second leg discussions with the FDA. That takes time if it includes scans, safety issues, etc... I think Paul does wish to meet or pre-empt the deadlines he sets, so Nov/Dec is still in his sites.
There's a lot of ways to either show some POC or just infer it. We know we are working with resistance, heavily-treated patients at the very end of their treatment window. That's a daunting task to deal with in a trial but what they all go through. So even if you didn't get to the point where the axis of your large dosing combined with high sortilin and tumor shrinkage enough that the spread didn't kill the patient, you may still have some data that points to the concept being completely valid in humans --and that's a huge way to start.
For instance, if they show there was very little toxin ever seen in the plasma and they did not see any odd blood/urine readings to suggest it impacted any other vital organ (so fine kidney, liver, brain, eye, etc.. function), then you can infer the toxin mostly got in to the tumor or was washed out in urine. If higher doses didn't present larger issues, that sort of tells you the same. IF they didn't reach MTD, that's also solid info. IF they scanned tumors and just show they stopped growing, that's fine, let alone if they shrunk. If some of the metastices stopped even though the tumor was just steady, that's ok. If the response rate was overall high even though patients were too far gone to begin with, that's valuable info. If it was all just partial responses but in the right way, that's fine as there likely would be patients still on the drug and will continue on into Part 1b. So there's numerous scenarios, including just saying the dose is XXX, we had no safety issues and on to part 1b. Even just saying that would lead me to infer they have a large dose, it's getting in there and not causing problems, let's see how it works with patients not at the far end of the line where we can treat them with more drug, frequently, and over a longer time frame.
On pricing, I think you're too low even though their CGS will be lower than an ADC. Trodelvy is around $20k per 3 week cycle. And I think Keytruda is close to that. Kadcyla is around $140k for a year. It may be TH1902 can be configured to dose weekly for smaller amounts or every 2/3/4 weeks with larger amounts. If we see signs that there was no events to lead to discountinuation or suspension of the drug (like neutropenia), then you may have that window to do a smaller dose every week of the year to just keep the tumor from spreading anywhere else. In either case, I think you could see annual administration of at least what Trodelvy is (3-4 cycles @20k) or higher. So I would pencil in low case of $50k and high of $300. By way of example, if you did a cycle every 3 weeks for a year it would be $350k. If you did a lower dose every week (say $5k dose), you're still talking $250k.
I have relistened to that last conference and it's unclear if Paul says 10,000 or "ten(s) of thousands". He sort of quickly utters something. But looking at the market they're after and assuming he's talking about the first indication (likely TNBC), it would be more than 10,000 a year. The incidence globally of TNBC is 200,000 new cases a year. Even though they're 4L at this point, they are not tied in to it being HER2+/ER/etc.... -- it should work for any tumor that is at an advanced stage, possibly refractory, and expresses a lot of sortilin. So you could see it for one indication getting 20k patients a year and then if you add the other solid tumors in, 50-70k patients a year just for 4L.
If he did say 10,000, I think he's just talking about one indication and only for 4L and downplaying it if it's TNBC. TNBC is the biggest, but lung isn't far behind. The others (pancreatic, colorectal, endometrial and ovarian) are all smaller. If they work in melanoma, then that would also be larger.