RE:RE:10 349 125 shares now held by Soleus Interesting..what do they know that we don't? They're way more in the weeds in understanding the science and have likely used plenty of experts to review their thesis. Hopefully they're right, but everyone can be wrong sometimes! By the way, those warrants from the share offering are way under the strike price, so at this point fairly worthless except for time-value. I don' t recall the exercise but I believe it's 2024.
We shouldn't be surprised they haven't communicated as they've had to put a new financial and sales plan into effect while at the same time reviewing all the trial data and figuring out if the path forward they hope for is within reason scientifically and financially. I'm not worried about the financial cost as juniper showed it's not much except for paying the contract org and the clinics. I think we backended a full trial was around $200k an enrollee, but they've probably already paid for a lot of that. I doubt they have all the TH1902 issues worked out, so don't expect that this month. We should just get reassurance around growth, revenues, cost cuts. All we can ask for at this point.
Here's some news on PDCs that is bright and shows a few things --shows that PDCs can have a strong efficacy response rates, shows they can be durable in humans, shows the linkers can work inside the cell, and that results, both safety and efficacy, are different based on dose level (which we knew) and also dose schedules.
This morning Bicycle released Phase 1a dose escalation results for their PDC (BT8009) that targets Nectin-4 for solid tumors, with urothelial being the lead (competing with the SeaGen’s ADC Padcev). Their dosage trial has two dose levels and also has THREE dose schedules. So it’s not uncommon to be playing around with more than just dose levels.
The three dosages being trialed are 5mg every week, 7.5mg 21 day cycle, 10mg every other week. For the first dose they got 4/8 ORR (50%) in urothelial with two remaining on the therapy. For the second dose regime they got 1/2 and 2/4 (50%) in other cancers. Most common SAE was neutropenia (6% patients) at the 5mg levels. They haven’t released data on higher doses or all the urothelials that are ongoing now for 14 months. OVerall they did have 3 out of the 49 (6%) patients have a SAE caused by the drug that were serious. All were in the higher dose ones. Meaning, it seems the optimal regime is a smaller dose given weekly and not a larger dose given less frequently —what they are contemplating with TH1902 and we can only hope works better on efficacy. But the point being, unlike what we have been guessing at, it may just be going lower and doing it more often will not just have better tolerability, but may also see better efficacy in certain kinds of tumors or certain kinds of patients. Of course, as others will point out, maybe MMAE is more powerful warhead than docetaxol. Fair critique.
The responses were one complete and the rest partials. The 10mg every 2 wk regime in Breast got one PR, so they’re still playing around with dosage by cancer type —really just experimenting probably based on what they read in the PK/PD data. They also had a PR in NSCL and the two urothelials. They said the patients were all Nectin4 positive.
The investigators highlighted that what they’re after is safer approach “thus leading to longer duration of treatment.” —that all important treatment window. Honestly, while no one can argue with responses, the overall numbers show you just need to see a few. For instance, they dosed 24 patients for urothelial —only 8 got to the recommended dose they settled on of 5mg. 1 of the 8 had a complete and 3 were partial. There were other patients which I’m not sure why they didn’t include them, but they showed 3 stable disease and one non-evaluable. Not sure why they excluded them from the denominator.
The 3 different dose regimes all deliver the same amount of MMAE payload as the weekly 5mg over a 6 week period. So that’s the logic of the doses and what Marsolais said to analysts --that they can get the same or higher dose in over the same 3 week one dose approach. The response rates for the other two regimes were similar but pretty tiny cohorts. 1 of 2 had PR and 2 of 4 had PR. Overall there were 49 patients in the dose trial. If you just looked at the overall responses and not using their lower “intent to treat” numbers, you could say that they got responses in 7 out of the 49 patients (14%). If you use that number and assume THTX did 20 enrollees in the 1b part, you would have hoped to see 3 responses in there and I guess they didn’t; hence the pause and rethink. So the question will be, can a change in dosage get you to 3 or more responses with 20 new enrollees. Regardless, while you can’t argue with the responses for Bicycle’s PDC, it is amazing that it’s only on a trial of 8 patients in one cancer and 2 or 4 in the other two. The CR is powerful and the 4/8 is solid. The others are just way to tiny to extrapolate, but that’s what a 1b and 2 is for and these numbers were good enough for them to take a chance on moving it forward.
I guess my overall assessment is that
- PDCs can work (a CR is proof) - at least theirs did
- that CR shows their PDC is being internalized in the tumors
- lower more frequent doses seem to be their best approach balancing safe/eff
Questions would be:
- payload power —docetaxol vs. MMAE or others?
- ITT is smaller subset of overall enrollment
- just need that decent response rate for a particular cancer and make sure it’s positive for your target market!