RE:RE:RE:RE:Examples of efficacy from dose escalation studies I think what they have done with the timelines is they have given themselves until the end of the year for the data from this small number of patients to develop. If the drug is efficacious and they've picked up the right patients who can respond then what they should be seeing from late summer are efficacy signals emerging. Each new scan has the potential to add something important to the dataset. I think what they should be doing from now to the end of the year is looking at how that data is developing, looking at individual patients and making educated guesses about where their responses are going. Making judgement calls on whether the data is ready at this point to best represent the potential of the drug or whether waiting for a few patients to get more scans is a better option.
I think we can think of this in a very binary way. There is a response, there isn't a response. The truth is this is a constantly developing process, constantly adding new data. The PR is about picking a moment in that constantly changing story to represent the efficacious nature of the drug. They've given themselves until the end of the year but I can see that moment coming at any time depending on how the data is developing.
If they are smart I think they are assessing how the data is developing and looking for the sweet spot when the data tells the best story. They could have nothing now and they are waiting for something. They could have good PRs that they think with a few more doses might get all the way to CRs, they could have a bunch of SDs that they think could either improve to PRs or worsen to the cancer progressing. They could be amassing lots of other data they think adds to the story. I don't think it's about sitting on data, I think it's about making judgement calls on how the data is developing and picking the right moment to go public. The PR is a snapshot in a constantly changing story, they have to pick a good moment.
I expect they'll time other commercial considerations around that.
SPCEO1 wrote: Look how quickly you have forgotten what they did last year! Remember the press release with the news of the FDA approval of both the NASH phase III and cancer trials along with the 25% growth rate expectation for the legacy drug sales??? One of the drug trial approvals came before Christmas, the other after Christmas yet the company sat on both for a while and then added the fabrication about expected legacy sales before releasing it all at once just prior to the offering. And we have all the same people in charge that were in charge then so it seems reasonable to me to expect they might act in a similar manner again this time. Until they behave better and start establishing a better track record, one should probably assume more of the same.
Let's hope they do better this time around, regain their credibility and move onto many bigger and better things. If they have nothing in cancer to "tout" as Paul said yesterday, then Paul's credibility is going to fall another few notches lower since he has been consistently very positive in the way he has generally characterized the cancer phase 1a trial. Hopefully, the specific data coming from the trial, whenever they get around to telling us more, will back up those favorable comments.
On the issue of what data they may already have, if there was a response when they were doling out lower doses to the patients, as the pre-clinical work suggested there would be, they would already know that. One issue, however, is did those earlier patients who were treated with lower doses survive long enough to have enough treatments to show an effect. My sense at the cancer KOL was that they had already begun to see some efficacy signals and the talk about wanting to rpove such things up in the right way also indicates they have seen something.
Or they are just speking in an optimisitc manner that intentionally is creating a perception of success in the trial when no success has yet been seen? While they have shown a willingness to distort the truth in the past, I am hoping they learned from those mistakes.
palinc2000 wrote: I would expect if they had market moving ''good" info they would release it and not put a lid on it for months.....
SPCEO1 wrote: They likely are not giving any notable trial data yet because they are aiming at another fundraising at some point soon and are trying to hold as much good info as they can for that. Either there is no good info to report (which seems unlikely) or they are curating the info for a release at an optimal time in conjunction with a share sale. That is my best guess as to why they have taken the info approach they have on the phase 1a. Perhaps they will start releasing some data in November and then build on that through early next year. Ideally, they do an offering after getting a Breakthrough Therapy designation from the FDA. If they can through in a NASH partnership or other means of monetizing some value there before then, all the better. But the lack of info from THTX on the phase 1a is likely associated with their fund raising strategy.
Wino115 wrote: Just as an example, here's what analyst says about two dose escalation trials in Phase 1 for Prelude Therapeutics. The drug and cancers are different than what THTX is going after, but it does show that if they are doing scans around tumors, they may have data (even n=1 type data) that analysts are interested in. Here's how Barclays looked at these two recent dose escalation data points in regards to valuation and de-risking. Notice the number of responses isn't high. They look at one anecdotal complete reponse in ovarian and brain cancer and use that to assess a higher probability of success for this trial
TRIAL 1:
On clinical efficacy for PRT543, early Prelude responses in solid and hematologic tumor types help validate the approach for PRMT5 inhibition: 1) In solid tumors, initial Phase 1 data for PRT543 shows activity in HRD+ ovarian cancer, including one rapid and durable CR from first scan out to 9 months in a highly advanced patient. In 13 solid tumor patients, as of Sept 2020, Prelude has shown 1 CR (HRD+ ovarian cancer), 4 SDs (including 1 HRD+ ovarian), 4 PDs, and 4 awaiting assessment, and 2) In hematologic malignancies, of nine MF patients, there was an 11% (1/9) ORR and 89% (8/9) SDs. Of total evaluable hematologic patients (nine MF and two MDS), 73% (8/11) achieved SD. The fast response rate in ovarian, early in dose escalation is encouraging: The ovarian CR was at first scan with a drop in CA-125 to 2.6 U/mL (from 37.8 at baseline) and the second scan (eight weeks later) confirmed the CR with a final CA-125 of 4.6 U/mL. A third scan (at 24 weeks or ~six months) demonstrated continued CR and CA- 125 fell to 3.3 U/mL. The HRD+ ovarian patient with a CR has received nine months of therapy and remains a CR as of 12/16/20.
TRIAL 2: Here's for their brain cancer trial:
For Prelude’s oral brain-penetrant PRMT5 inhibitor, Phase 1 dose escalation data shows 17% (1/6) PR in GBM – though small numbers, the response has deepened and confirmed, which is encouraging for early dose escalation data: Of six GBM patients reported so far, one refractory GBM patient had a PR with -66% reduction initially, with a subsequently reduction to -77% from baseline by week 18, confirming the PR. The GBM patient has received five months of therapy and remains in PR as of 12/16/20. We note that, overall, Phase 1 dose escalation data has been reported from 17 patients (10 solid tumors, 6 GBM, 1 pending diagnosis) of PRT811.
SO the analysts conclusion on these two dose escalation data points of 1 deep response from a patient is that it de-risks the trial:
In summary, at AACR-NCI-EORTC (Oct. 7-10), for Prelude’s PRMT5 inhibitors in Phase 1 dose escalation, we expect to see additional responses — up from 1 CR with PRT543 in ovarian cancer and 1 PR with PRT811 in GBM, as well as a favourable safety profile.
Upside/downside: We assign a 65% likelihood to positive results, potentially driving the stock up +15%, while negative results could drive the stock down -10%. For PRT811 in GBM, we project peak probability-adjusted sales of ~$685mn by 2028, or $10 of our $80 price target.
So THTX should look at these competitor releases and feel comfortable given as much data as they can around the dose escalation so that the concept and MOA is understood, the safety is understood and the way the drug may develop in the next phases may help. They shouldn't be afraid to talk about scans and partial responses of even 1 if it's deep. All this data, whatever it is, helps to understand where it stands and how we should adjust our left and right tails. I hope they read what other companies do and how analysts may look at these things.