Janux plans $200m offer on back of prostate cancer readout

Buoyed by data from a trial of its T-cell engager (TCE) therapy in prostate cancer that almost tripled its share price, Janux Therapeutics has moved quickly to file a stock offering that could add around $200 million to its cash position.

The San Diego biotech is offering $175 million in a public offering that could rise to $201.5 million if underwriters take up an option, less discounts and commissions.

The move comes right after Janux reported results from a phase 1 trial of JANX007, a PSMA-directed TCE, in metastatic castration-resistant prostate cancer patients who had received a median of five earlier therapies.

The first-in-human study is the first readout from the company’s pipeline of tumour-activated TCE (TRACTr) therapies, designed to overcome the limitations of the class in treating solid tumours.

While they have shown promise in blood cancers, TCEs have struggled to make ground in solid tumours, due to serious side effects like cytokine release syndrome (CRS), off-target effects on healthy tissues, and short half-lives. Janux uses a peptide masking technology to overcome these limitations, blocking the T-cell binding site until it is exposed by enzymes within the tumour.

Looking at data from the first 18 evaluable subjects enrolled in the phase 1 trial, five of six patients treated with JANX007 at the first step dose of 0.2 mg or more saw a reduction in PSA levels – a biomarker for prostate cancer activity – of at least 50%. No cases of CRS greater than grade 2 were seen in any of the patients.

According to Janux, that suggests a “potential best-in-class profile” for JANX007 in mCRPC, a view that seemed to be shared by investors as a buying frenzy drove the company’s stock up around 230% and its market cap to $2.3 billion.

Other biotechs that have been developing PSMA-directed TCEs for prostate cancer include Amgen with AMG 509, also in phase 1, as well as Harpoon Therapeutics (heading for a takeover by MSD) and Regeneron. Harpoon’s initial HPN424 candidate was abandoned after disappointing phase 1/2 efficacy, while Regeneron has been forced to change tack on the development of REGN5678 after two patient deaths in a phase 1/2 study.

The category could also see competition from Ambrx – in the process of being acquired by Johnson & Johnson in a $2 billion deal - whose PSMA-targeting antibody-drug conjugate (ADC) ARX517 showed encouraging phase 1/2 safety and efficacy results at last year’s ESMO congress.

Meanwhile, Janux also reported early data with its second TRACTr candidate, EGFR-targeting JANX008 in a basket study involving patients with various solid tumours, including colorectal, head and neck, lung, and kidney cancers. The results showed preliminary signs of efficacy and a good toxicity profile.

“The clinical data provide[s] compelling proof-of-concept for the TRACTr platform in a setting where many other approaches have failed due to material safety issues or lack of efficacy,” said David Campbell, Janux’s chief executive.

“Our TRACTr platform provides an entry point to multiple, large solid tumour indications that are intractable with conventional TCE approaches.”