Janux impresses again

Janux impressed investors in February with JANX007, and now it's done it again. Updated phase 1 results with the PSMA-targeting masked T-cell engager in late-line castration-resistant prostate cancer have had sellside analysts throwing around superlatives and investors sending the group’s stock up 70% this morning.

The company already has its eye on second-line disease, and reckons it could go even earlier based on the latest data, which as well as raising hopes for JANX007 also further validate Janux’s masking approach. However, it’s worth noting that the results came in just 16 patients, and excluded those previously treated with Pluvicto, Novartis’s approved PSMA-targeting radioconjugate.

Janux’s market cap of $3.5bn looks generous for such early results, and probably factors in hopes of a buyout that may or may not emerge.

56% to 100%

In February Janux reported data from earlier dosing cohorts in the same study, showing PSA50 responses of 56% among patients receiving an initial dose of at least 0.1mg, and 83% among those initially receiving 0.2mg. Five of these 23 patients had received anti-PSMA radioligand therapy.

Now the company has revealed a 100% PSA50 among 16 pre-Pluvicto patients who received JANX007 target doses of 2-9mg once weekly. Notably, patients weren't selected for PSMA expression, and PSA90 data look equally impressive, as illustrated by a cross-trial comparison of agents both approved and in development for late-line mCRPC. 

Cross-trial comparison of selected agents in relapsed mCRPC

Notes: *pre-Pluvicto pts receiving target doses of 2-9mg; **1 confirmed & 3 unconfirmed PRs; ^cohorts 6-8 only; ^^cohorts 4-8 only. Source: OncologyPipeline & company presentation.

During a call to discuss the data, the Cantor Fitzgerald analyst Josh Schimmer called the results “unprecedented”, while Cowen analysts later wrote that JANX007 could be the best overall asset in development for CRPC.

However, Janux also treated post-Pluvicto patients, and didn’t give the PSA response numbers for these, or even say how many patients were in this group. On the call Janux said it was no longer focused on post-Pluvicto patients, adding that this was a small market.

However, response rates touted by Janux give another reason for pause. Among eight patients who were RECIST evaluable the group claimed an ORR of 50%. However, three responses were unconfirmed, and two of these will remain so, as the patients have been lost to follow-up, Janux disclosed on the call.

If including only the one confirmed response, and the one that could still be confirmed, this gives an ORR of 25% – still decent on a cross-trial basis, but nowhere near as impressive.

Janux said JANX007 was well tolerated, but didn’t give absolute numbers of adverse events, only treatment-related events that occurred in 15% of patients or more. And liver enzyme elevations occurred in 75% of patients – most low grade, but something to keep an eye on.

The company is continuing the dose-escalation phase of its trial, testing a 12mg weekly dose, but in the meantime has selected 6mg and 9mg for dose expansion, which is expected to begin next year.

The company is now focused on developing JANX007 in second and third-line pre-Pluvicto patients, with an eye on eventually moving into the first line. The group is also “very interested” in a combination with Xtandi, or other androgen receptor pathway inhibitors, in earlier lines of disease.