Janux lets the genie out of the bottle

One criticism of Janux Therapeutics is that it has selectively disclosed results with its PSMA-targeting masked T-cell engager JANX007, and on Monday evening the company came clean, putting out a larger dataset; its stock crashed 49% as a result on Tuesday morning.

One headline finding from the phase 1 Engager-PSMA-01 trial in late-line castration-resistant prostate cancer is that overall response rate now stands at 30% among 27 evaluable patients receiving ≥2mg – down from 50% among eight patients previously. And Janux has yet to fill in some blanks; the 30% figure includes unconfirmed, as well as confirmed responses, but the company isn’t breaking this down.

Furthermore, median radiographic progression-free survival among 108 subjects across various doses is now 7.3 months – from 7.5 months among 16 patients previously. 

As well as apparently deteriorating since the last update in May, a cross-trial comparison suggests that JANX007 isn’t as effective as other T-cell engager hopefuls in prostate cancer, such as Amgen’s Steap1-targeting xaluritamig, and Johnson & Johnson’s KLK2-targeting pasritamig. Those projects have produced median rPFS of 7.8 and 7.9 months respectively.

Meanwhile, Novartis’s PSMA-targeting radioligand therapy Pluvicto produced median rPFS of 9.3 months in the PSMAfore study. However, that trial recruited patients who had progressed on an androgen receptor pathway inhibitor, but hadn’t received prior taxane-based chemo. In Janux’s trial patients had received a median of four prior therapies.

Source: company presentation.

Also in Janux’s defence, the latest JANX007 results come from a mixture of patients, including those receiving suboptimal doses or suboptimal cytokine release syndrome management strategies.

CRS reared its head in May, when the company disclosed that it was trying to mitigate this side effect, without giving more details, or indeed a breakdown of CRS events.

Janux did provide more information on Monday: it has now moved away from a prophylactic Actemra regimen (coded CRS-P1), to another regimen called CRS-P2. The company didn’t give specifics of the latter, saying it wanted to keep this secret from its competitors.

The inclusion of CRS-P1 patients could explain why there was an 8% rate of grade 3 or higher CRS in Engager-PSMA-01, Janux’s chief executive, David Campbell, said during a conference call.

He also suggested that efficacy could improve once the company tested its go-forward dose(s), and moved into earlier therapy lines. Janux is now focused on the taxane-naive setting, where it disclosed early results from four patients, with three showing PSA50 responses, and one hitting PSA90.

Janux also plans to take JANX007 into PARP inhibitor-refractory patients, and raised the possibility of gunning for expedited approval here – although this plan looks to be at an early stage, with the group yet to discuss it with the FDA.

As for dose, Janux is prioritising 3mg, 6mg and 9mg once weekly, with 6mg looking most likely. The group is also moving forward with dosing once every two weeks.

Janux’s dose-optimisation efforts look logical, but the investor reaction shows how much more the markets had been expecting at this stage – especially for a company valued at $2bn.

Evolving data with JANX007 in Engager-PSMA-01

Notes: *pre-Pluvicto pts receiving target doses of 2-9mg; **depending on starting dose given; ***1 confirmed & 3 unconfirmed PRs; ^among 85 pts receiving ≥2mg; ^^includes confirmed & unconfirmed responses, no details given. Source: Janux release.