Sensei finds Faeth

Sensei Biotherapeutics looked buried last year after discontinuing its anti-VISTA MAb solnerstotug, but the group was resurrected on Wednesday with the acquisition of Faeth Therapeutics. The all-stock deal will give Sensei the PI3Kα inhibitor serabelisib and the mTORC1/2 blocker sapanisertib, which are being combined in a phase 2 endometrial cancer trial with results due this year.

The agreement coincided with a $200m private placement that might also help bring back solnerstotug: the company said the proceeds would also be used to complete an ongoing phase 1/2 solid tumour trial, although it’s unclear what future that asset might have given its underwhelming 14% ORR among 35 post-PD-(L)1 inhibitor solid tumour patients receiving a Libtayo combo, as reported at last year’s ESMO meeting.

Though the deal can be seen as a reversal of the private Faeth into Sensei's Nasdaq listing, the Sensei entiry remains, with its biotech focus and existing management team; management is being joined by Faeth's co-founder Anand Parikh, as chief operating officer. Faeth raised $92m from venture financiers, its most recent round being a $25m "strategic raise" in October.

Piktor this

The focus of the deal is clearly on serabelisib plus sapanisertib, a combo dubbed Piktor. The uncontrolled phase 2 trial, being conducted in collaboration with the Gynecologic Oncology Group, is evaluating Piktor plus paclitaxel in patients with endometrial cancer progressed after platinum-based chemo and/or checkpoint inhibitors. The primary endpoint is overall response rate.

The trial also incorporates a substudy evaluating Piktor plus paclitaxel plus an insulin-suppressing diet; it’s hoped the diet could prevent glucose and insulin increases in response to PI3K inhibitors, thereby potentially improving safety and efficacy.

In a phase 1 solid tumour trial, Faeth highlighted a 47% ORR among 15 evaluable patients; among these, four of five endometrial cancer patients responded, although one complete responder died from Covid.

Sensei also outlined plans to begin a phase 1 trial in ER-positive, HER2-negative breast cancer this year. Here, the company believes that the dual approach has been validated by Celcuity, whose pan-PI3K/mTOR inhibitor gedatolisib is being reviewed by the FDA for ER-positive, HER2-negative, PIK3CA wild-type breast cancer, based on the Viktoria-1 trial.

Sensei reckons Piktor could have the edge thanks to its specificity for PI3Kα, as well as its oral administration, versus gedatolisib’s intravenous delivery.

Still, the PI3Kα space has been moving increasingly towards mutant-selective (wild-type sparing) assets from the likes of Lilly and Relay – others like OnKure have gone further by developing mutation-specific projects. But Sensei believes that, by broadly hitting PI3Kα, it could prevent wild-type PI3K escape.

There aren’t too many groups active in PI3K plus mTOR inhibition, according to OncologyPipeline, although China’s Joyo Pharma recently listed a phase 3 study of its asset, WX390, plus Loqtorzi in cervical cancer. 

Ovarian plans

Sapanisertib plus paclitaxel has also shown promise in ovarian cancer, producing a mean PFS of 5.8 months, versus 4.0 months with paclitaxel alone, in the phase 2 investigator-sponsored Dice trial in platinum-resistant patients, presented at ESMO last year.

Faeth previously said it hoped to meet the FDA this year to discuss further development, including a potential registrational trial.

Both serabelisib and sapanisertib have had a long development path, having been licensed by Takeda from Intellikine in 2011. Serabelisib was then licensed to Petra Pharma in 2019, and sapanisertib to Calithera in 2021, before finding their way to Faeth.

Faeth has claims that, nevertheless, the assets’ composition of matter patents aren’t due to expire until August 2037.

PI3K & mTOR combos in active clinical development

Source: OncologyPipeline.