Prostate specific membrane antigen tumour activated T-cell engager therapy (Janux Therapeutics/Merck & Co)

The newest interim data from Janux Therapeutics’ Phase 1a prostate cancer trial have driven the company’s shares $JANX up 66% premarket Tuesday as investors mull the increasing probability of a buyout. JANX007 is a tumor-activated T cell engager, or TRACTr, targeting both prostate-specific membrane antigen (PSMA) and CD3. The Phase 1a trial is testing once-weekly doses of 2 mg to 9 mg in patients with advanced or metastatic castration-resistant prostate cancer (mCRPC). The trial subjects had received a median of four prior lines of therapy, but had not yet been treated with Novartis’ radiopharmaceutical Pluvicto. As of the Nov. 15 data cutoff, the Monday presentation shows that 16 patients had seen deep declines in prostate-specific antigen (PSA) levels; all achieved PSA50; 63% of patients achieved PSA90; and 31% hit PSA99. Three-quarters of the patients maintained PSA50 declines after at least three months, and 50% of patients maintained PSA90 declines at the same time point. Janux said that these deep and durable PSA responses came irrespective of resistance driver mutation status or prior treatment with a taxane or androgen receptor pathway inhibitors. In RECIST-evaluable patients, confirmed and unconfirmed partial responses were seen in four of eight patients for an ORR of 50%. The disease control rate was 63%. The safety of JANX007 also appears impressive. Cytokine release syndrome and related adverse events were “primarily limited to cycle 1 and grades 1 and 2,” according to Janux, as were treatment-related adverse events. The maximum tolerated dose was not reached. Janux still has some way to go, though: Investors will need to judge how Monday’s data might translate into progression-free survival, the approval endpoint used in second- and third-line mCRPC Phase 3 trials, where control arms generally produce six to eight months and Pluvicto yielded 12 months. Still, analysts from Leerink Partners suggested ahead of the readout that JANX007 could “effectively compete” with radioligand therapy, including Pluvicto, as well as antibody-drug conjugates. They suggest risk-adjusted peak sales of JANX007 could hit $1.5 billion in 2035. That will require further trials in earlier settings, and Janux says the new data have allowed it to pin down two once-weekly step dose regimens for Phase 1b studies in second- and third-line mCRPC patients. These will be 0.3/1.5/6 mg and 0.3/2/9 mg. Another question for investors is whether Janux will be the company to conduct such a study. The biotech was already being talked about as a takeover target , and potential buyers will find little in Monday’s data to put them off, even as the purchase price has climbed.

Shares of Janux Therapeutics surged to record highs following the release of study results for a drug that, if ultimately successful in testing, would represent a new type of therapy for prostate cancer.The findings come from an early-stage study testing the biotechnology companys therapy, dubbed JANX007, in 16 people with a form of advanced prostate cancer. Data Janux first disclosed earlier this year vaulted the companys market value past $2 billion. While early and from a small clinical trial, the new results announced Monday afternoon pushed Januxs shares nearly 75% higher, changing hands Tuesday morning at more than $70 apiece.The company is exceeding investor expectations and raising the bar in so-called metastatic, castration-resistant prostate cancer, wrote William Blair analyst Matt Phipps, in a Tuesday note to investors. He and multiple other Wall Street analysts raised their share price targets for Janux.Januxs drug is whats known as a T cell engager, a type of dual-acting antibody that draws immune cells to cancerous ones. Several T cell engagers are currently available to treat blood malignancies, but solid tumors have proven more elusive targets. T cell engagers are also associated with side effects, like a kind of overactive immune response known as cytokine release syndrome, that can require drugmakers to lower dosing.Januxs answer is a method of maskingits T cell engagers so they dont interfere with healthy tissue but still target malignant cells. The approach is designed to widen the range of effective and safe doses, sidestepping some of the problems other T cell engagers have had with solid tumors. The new results further demonstrated the therapeutic window-widening value proposition, wrote Leerink Partners analyst Jeffrey La Rosa on Tuesday.Janux is testing JANX007 in metastatic, castration-resistant prostate cancer, a target of several large companies and a market that analysts at the investment bank Stifel believe could surpass $10 billion annually in the U.S. alone by next decade. Novartis closely watched radiopharmaceutical drug Pluvicto, for instance, has already surpassed $1 billion in sales this year. The Swiss company has said yearly sales could reach $5 billion.In its Phase 1a study, Janux enrolled patients whod received a median of four prior treatments. As of a Nov. 15 cutoff, 16 who hadnt yet received Pluvicto achieved at least a 50% reduction in prostate-specific antigens, a marker indicative of a treatment benefit in prostate cancer.The durability of those responses looks promising, wrote Phipps, of William Blair, with three quarters of the patients with at least a 50% decline in PSA levels maintaining those results after at least three months. Half of the study volunteers who had 90% PSA declines saw their responses hold for at least three months as well. Four of the eight who could be evaluated for tumor responses had a partial response to treatment, Janux said.Notably, instances of CRS, as well as overall treatment-related side effects, were largely mild to moderate in severity. Janux said it hasnt yet found the maximal tolerated dose for JANX007, indicating it could test higher doses. Uncertainties remain, given the small patient numbers, still-early durability and relatively modest efficacy signal so far, wrote Leerinks La Rosa. Nonetheless, the company demonstrated best-in-disease effects on PSA and a best-in-class, differentiated safety profile, he added.Janux has selected doses for Phase 1b expansion trials in patients who are earlier in their disease course and havent yet received Pluvicto. Updated results are expected next year. '