Almost exactly one year ago, Janux Therapeutics unveiled early data for its investigational T-cell engager that wowed investors and analysts alike. But the biotech’s newest update has failed to garner the same investor enthusiasm, with the company’s stock nearly halving following the data drop.
After market close Monday, Janux provided a further look at its PSMA x CD3 immunotherapy, coded JANX007, that is being tested in phase 1a/1b trials for patients with advanced castration-resistant prostate cancer.
As of Oct. 15, 109 patients were treated across dose-escalation and expansion studies. Patients enrolled in the phase 1a trial were heavily pre-treated, whereas those enrolled in the phase 1b expansion study hadn’t previously received any taxane chemotherapy.
Out of 27 eligible patients, eight (30%) demonstrated confirmed and unconfirmed partial responses, according to Janux’s Dec. 1 release. The company did not detail how many partial responses were confirmed versus unconfirmed, nor did it disclose which doses were tied to the RECIST responses.
Previously, confirmed and unconfirmed partial responses were reported in four of eight (50%) RECIST-eligible patients.
When looking at prostate-specific antigen (PSA) levels—a main measure of treatment efficacy for the disease—12 of 14 (86%) patients receiving Janux’s selected phase 1b dosing regimen achieved a 50% or greater reduction in PSA levels from baseline, while seven of 13 (54%) patients saw a 90% or more reduction.
The findings compare “very favorably” to Novartis’ Pluvicto and other investigational T-cell engagers, Evercore’s Jonathan Miller wrote in a Dec. 1 note, though the analyst noted that it failed to beat Janux’s own 100% PSA50 recorded last year, when all 16 patients in an interim cut achieved a 50% or greater reduction.
Since the market closed yesterday, Janux’s stock has plummeted 48%, falling from $33.99 per share to $17.7 as of 11 a.m. ET today.
Despite the negative investor reaction, Evercore’s Miller and William Blair analysts remain confident in JANX007’s continued development and best-in-disease potential.
In a Dec. 2 note, William Blair analysts acknowledged the “fair criticism” related to the lowered RECIST response rate and the company’s failure to disclose information about the confirmed versus unconfirmed responses.
However, William Blair deemed the stock drop an “overreaction” based on the totality of data, citing favorable cytokine release syndrome (CRS) mitigation strategies and different dosing regimens.
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Those considerations, paired with the initial data in patients with lower tumor burden, still suggest that JANX007 “has the potential to achieve a best-in-disease profile and achieve blockbuster sales,” the analysts wrote.
Janux’s new data reveal an overall progression-free survival (PFS) of 7.3 months across 108 patients receiving at least 2 mg of JANX007—a rate that aligns with previous estimates, appears competitive and should increase with optimal dosing strategies, according to William Blair.
When looking at the 6-mg or 9-mg cohorts—the doses that will be studied going forward—29 patients treated saw a median PFS of 7.9 months.
The figures generally fall in step with a phase 1 cut for Amgen’s bispecific T-cell engager xaluritamig, which recorded a median PFS of 7.8 months among 47 patients, as well as a subpopulation analysis of 33 patients receiving Johnson & Johnson’s bispecific pasritamig for a median PFS of 7.85 months.
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Looking at Janux’s new data, the biotech’s updated CRS mitigation efforts are tied to a “very strong safety profile,” according to William Blair analysts.
For competitive reasons, Janux isn’t sharing the specifics of the different protocols, but did disclose that one strategy resulted in zero grade 3 CRS cases, with most cases being grade 1.
While the specific protocol was only tested among 14 patients, replicating the profile in active trials “would be very encouraging and likely result in a therapy that can be given in the outpatient setting,” William Blair analysts wrote.
“Although specific timelines have not been given, we anticipate the next update with JANX007 in from the phase 1b trial will come in 2026 and will reestablish investor confidence in the program,” the analysts predicted.
