Janux tries to improve on the masking approach

Riding on a $1.5bn valuation as a result of its first masked therapeutic Janux is moving to try to repeat the trick. An R&D update on Thursday saw the group resurrect a previously disclosed preclinical anti-TROP2 asset, as well as proposing the addition of CD28-based co-stimulation to improve on JANX007, the molecule responsible for its current success.

A need to improve on JANX007 is evident given the market's disappointment at the project's latest results, and it's hard not to see the return to TROP2 as a distraction away from the lack of a JANX008 update for over a year now. The CD28 co-stimulation idea isn't new either, so the key message to investors seems to be: wait patiently for more clinical data some time later this year.

JANX007, a masked T-cell engager against PSMA, has impressed in prostate cancer, but the project's latest update in May prompted a 9% share price fall over concerns of cytokine release syndrome. Moreover, the phase 1 dataset is being disclosed selectively, with Janux switching focus from all-comers to pre-Pluvicto patients, and zeroing in on selected doses.

Need to do better

As a driver of Janux's valuation JANX007 is crucial, so the fact the group now sees the need to improve on it might raise eyebrows. 

This, the group revealed on Thursday, is to be done through a new masked molecule that also targets PSMA but, rather than being a T-cell engager, additionally hits the co-stimulatory protein CD28. Both these domains are masked, and for now this project is coded PSMA-TRACIr.

Janux's idea is that PSMA-TRACIr will be combined with JANX007 in a phase 1 prostate cancer trial that it hopes to begin in the second half of 2026. It claims that such a combo could allow dosing to be adjusted depending on patient characteristics, and suggests that it might allow relatively high doses to be explored.

In this way it drew a distinction between PSMA-TRACIr and non-masked anti-PSMA x CD28 projects like Amgen's acapatamab (discontinued in 2022) and Regeneron's nezastomig, which it claims are limited by severe toxicity. Of course, toxicity now hangs over JANX007 too, with Janux not disclosing the latest CRS numbers, while at the same time introducing a CRS-mitigation strategy.

Equally vexing is why Janux hasn't said anything about JANX008, a masked anti-EGFR T-cell engager, since dribbling out early phase 1 data in May 2024. This showed a single confirmed complete response in a NSCLC patient, and no responses in 10 further subjects with lung, colorectal, renal and head and neck cancers.

JANX008 was once a benchmark for CytomX investors, since their company was also developing a masked anti-EGFR T-cell engager, CX-904, and this was partnered with Amgen; however, despite showing hints of promise in pancreatic cancer CX-904 was discontinued in favour of an anti-EpCAM asset, CX-2051. For now Janux says updates on JANX007 and JANX008 will come "later this year".

TROP2 resurrection

Meanwhile, Janux is again advancing TROP2-TRACTr, a dual-masked T-cell engager against TROP2 that it claims could be more potent than anti-TROP2 ADCs like Trodelvy and Datroway, allowing for increased activity in patients with relatively low expression of TROP2.

This programme isn't new, having been listed as a preclinical asset in Janux's 2021 IPO document, before disappearing from the pipeline. Janux didn't say why it has decided now to resurrect it, and hasn't specified a timeline beyond saying it would carry out IND-enabling activities in the second half of 2025.

It will also be noted that Janux has spent years tinkering with a CD28 approach, its 2021 R&D pipeline including JANX009, a preclinical anti-PD-L1 x CD28 molecule. However, this was subsequently dropped.

Janux’s oncology pipeline

Source: OncologyPipeline.