RE:Examples of efficacy from dose escalation studies It's worth looking at how much interest that early ovarian data from Sept 2020 caused.
After the data release they announced their IPO. This was initially priced at $18 to raise $150 mil, they ended up raising $181 mil. The SP shot up after that to as high as $88 over the rest of 2020 and they ended up with a 2nd financing in Jan 2021 at $60.
Pretty good for 1 CR!
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.