Janux’s stock triples as early T-cell engager safety data shines

27 Feb 2024
firstwordpharma.com
Clinical ResultImmunotherapyDrug ApprovalPhase 1ADC
After the early wave of immunotherapies proved successful at treating certain cancers, the race has been on to broaden the treatable patient population by fine-tuning specificity and tamping down on toxicities, particularly in solid tumours – and Janux Therapeutics may have just taken the lead for next-generation T-cell engagers.
The biotech skyrocketed nearly 230% Tuesday after its two programmes seemed to avoid the severe safety side effects that have hampered the modality’s movement into solid tumours.
In a pair of Phase Ia, dose-escalating studies, Janux’s conditional T-cell engagers, called Tumor Activated T Cell Engagers (TRACTrs), did not lead to any cases of high-grade cytokine release syndrome (CRS), “a major toxicity issue that led to discontinuation of multiple T-cell engager clinical candidates,” H.C. Wainwright analysts wrote in a note.
“The positive initial data provides validation for the double-masking approach,” they added.
Janux’s ‘masking’ technology was developed to ensure tumour-specific activation and avoid on-target toxicities. Both of the clinical TRACTrs comprise a tumour antigen-binding domain and CD3, the latter of which is covered by a peptide mask that can only be removed by tumour-specific proteases. This prevents T-cell binding before the treatment reaches its target, avoiding an overactive immune response. Similarly, TRACTrs also have an albumin binding domain mask to extend half-life, and these can only be removed at the tumour as well.
Competitive prostate cancer data
The first programme, dubbed JANX007, is a PSMA-targeted TRACTr intended to treat advanced or metastatic castration-resistant prostate cancer (mCRPC).
So far, 23 patients have received the treatment, and a maximum tolerable dose has yet to be reached. Janux said reported incidents of CRS were “temporary and mild,” with no events higher than Grade 2.
At the ≥0.1mg starting dose, 10 of 18 (56%) patients saw a PSA reduction from baseline of at least half, and the next dose level of  ≥0.2mg led to the same PSA reduction in 5 of 6 (83%) evaluable patients.
The H.C. Wainwright analysts suggested these results compare favourably with Pluvicto (lutetium Lu 177 vipivotide tetraxetan), a PSMA-targeting radiotherapeutic from Novartis, which was approved by the FDA after demonstrating that 177 of 385 (46%) mCRPC patients experienced a PSA reduction of  50% or more.
Janux plans on sharing updated dose expansion data next half.
Lung cancer responds
Of the 11 treated patients, only two experienced CRS, and both cases were classified as Grade 1.
One patient with NSCLC who received a once-weekly 0.15mg dose of JANX008 had a confirmed partial response (PR), with 100% reduction of their lung lesion, elimination of liver metastasis, and no CRS. The PR was maintained through their week-18 scan.
Additionally, one patient experienced a 12% reduction of their RCC mass.
The company said it is continuing the dose escalation and optimisation of JANX008.
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