Janux Therapeutics, Inc.

AbbVie’s head of hematology Mariana Cota Stirner, M.D., Ph.D., said the deal shows commitment to \"advancing innovative treatments for complex cancers like multiple myeloma.”\n T-cell engagers have been hot property in recent months, so it’s only right that one the biggest deals to kick off the J.P. Morgan Healthcare conference should see AbbVie expanding its interest in the tech.The Big Pharma is handing China’s Simcere Zaiming an undisclosed upfront payment with the potential of up to $1.05 billion in milestone payments for a phase 1-stage trispecific antibody. The candidate, dubbed SIM0500, targets GPRC5D, BCMA and CD3 and is already in phase 1 trials for multiple myeloma in the U.S. and China.It’s not AbbVie’s first foray into T-cell engager dealmaking—the pharma paid $65 million upfront in October to license EvolveImmune’s multispecific biologics for various targets in solid and hematologic malignancies. Even before that deal, AbbVie had been showing an interest in the modality, with then-CEO Richard Gonzalez telling analysts back in 2023 that the BCMA bispecific antibody T-cell engager ABBV-383 was driving the company’s “high level of interest” in the space.In this morning’s release, AbbVie’s head of hematology Mariana Cota Stirner, M.D., Ph.D., said the deal with Simcere Zaiming, a subsidiary of Simcere Pharmaceutical, showed that the U.S. pharma is “committed to advancing innovative treatments for complex cancers like multiple myeloma through our relentless R&D efforts and collaborations.”T-cell engagers are bispecific antibodies that bind to T cells and a molecule on a target cell, coercing the T cells to attack the target. The modality has been at the center of a string of biotech announcements in recent weeks, including Candid Therapeutics’ $925 million biobucks pact with WuXi Biologics, the launch of GSK-backed Ouro Medicines and the blockbuster hype surrounding Janux Therapeutics’ phase 1 prostate cancer asset.

Interim data on two T cell engagers that Vir Biotechnology licensed from Sanofi last year have begun to justify the biotech’s strategic shift into oncology. But the data are very early, and one of the assets appears less effective than a similar product being developed by Janux Therapeutics. The company’s stock $VIR climbed around 60% in early trading. VIR-5818 targets HER2, and is in a Phase 1 basket trial in several solid tumors expressing the antigen, including breast and colorectal cancer. Among the first 20 patients treated with weekly IV doses of at least 400 µg/kg, 10 had dose-dependent tumor shrinkage. And in a subset of six patients with HER2-positive colorectal cancer who had exhausted standard of care, confirmed partial responses (cPRs) were seen in 33%. One patient continued in cPR for over 18 months. The patients had received up to nine prior lines of therapy, and Vir CEO Marianne De Backer told Endpoints News that this included other HER2-targeting therapies. Early safety data showed that grade 1 or 2 cytokine release syndrome was seen in 20% and 10% of VIR-5818 recipients, respectively. No grade 3 or greater CRS was seen in any of the 79 patients dosed up to 1000 µg/kg, and most side effects were low-grade and manageable, the company said. This is important, De Backer said: “What has been holding the promise of T cell engagers back is [their] side effect profile. T cell engagers are very toxic.” Vir has mitigated this toxicity by using a so-called masking technology — PRO-XTEN, licensed from Sanofi along with the assets. T cell engagers are bispecific antibodies that bind to the tumor antigen and CD3 on T cells, attracting T cells to the tumor to kill it. The PRO-XTEN technology uses a protease-cleavable linker on both the tumor antigen and T cell binding domains of the antibody, keeping it in a dormant state until it reaches the protease-rich tumor microenvironment. This reduces systemic toxicity. Early Phase 1 data also released Wednesday suggests another asset, the PSMA-targeting VIR-5500, has potential in metastatic castration-resistant prostate cancer. But the data might not be quite as good as those released last month on Janux Therapeutics’ T cell engager. Data on the first 12 patients that were given VIR-5500 showed all had prostate-specific antigen reductions after an initial dose of at least 120 µg/kg. PSA50 response was confirmed in 58%. Recent interim data from the Phase 1a mCRPC trial of Janux’s JANX007, which also targets PSMA and CD3, showed that all 16 patients treated achieved PSA50 . JANX007 also uses a masking technology, though only for the T cell-binding domain. However, Vir said that an earlier cut of JANX007 data, in which 56% of 18 patients receiving lower doses achieved PSA50, was a fairer comparison. Vir said that no dose-limiting toxicities were seen with VIR-5500 doses up to 1000 µg/kg, and grade 1 or 2 CRS was seen in 17% and 11% of subjects, respectively, with no grade 3 or greater CRS. Weekly dose escalation in both studies is ongoing and dosing every three weeks will also be evaluated. The study of VIR-5818 also includes an arm in which the engager will be combined with Merck’s Keytruda and data are expected this year. Vir is also gearing up for a Phase 1 trial of the third asset it licensed from Sanofi, the EGFR-targeting VIR-5525. Initiation of this trial, expected in the first half of 2025, will trigger a $75 million milestone payment to Sanofi. Editor’s note: The headline and article were updated to include comments from Vir and note the company’s stock movement.

Plus, news about Innovent Biologics, Relmada Therapeutics, Zevra Therapeutics, Incyte and Bionical Emas: Enanta’s Ph2 win in RSV: The company’s oral N-protein inhibitor achieved a 1.4 log decline in viral load at day five versus placebo in the mid-stage trial in pediatric respiratory syncytial virus. A prespecified analysis of patients randomized within three days of symptom onset showed a decline of 1.2 log compared with placebo. Adverse events with Enanta’s zelicapavir and placebo were similar, and there were no treatment discontinuations or study withdrawals owing to side effects. — Elizabeth Cairns Carisma Therapeutics to lay off 34% of its workforce: The Philadelphia biotech will let go of 23 employees and stop developing its lead asset, a CAR-monocyte program called CT-0525. The biotech had expected to have initial data from its Phase 1 trial of the asset in the first quarter of 2025. It will now focus on an in vivo macrophage engineering platform for potential applications in fibrosis, cancer and autoimmune diseases. — Kyle LaHucik Innovent Biologics details early-stage data for its ADC: It said IBI343, Innovent’s anti-CLDN18.2 antibody-drug conjugate, produced an overall objective response rate of 32.6% in 43 patients with CLDN18.2-positive advanced pancreatic ductal adenocarcinoma who had been previously treated. The data, presented at the ESMO Asia Congress, also demonstrated a confirmed ORR of 23.3% and confirmed disease control rate of 81.4%. Among 26 patients, median progression-free survival was 5.3 months; overall survival data are not yet mature. — Elizabeth Cairns Relmada Therapeutics looks for alternatives: The Florida biotech is ending its Phase 3 trials in major depression disorder after saying last week that the rapid-acting NMDA drug was likely to fail . It will also seek strategic alternatives, which could include a sale of assets, reverse merger or other deals. Relmada said it will keep running its Phase 1 in metabolic disease. — Kyle LaHucik Zevra Therapeutics says goodbye to two execs: The biotech parted ways with its chief development officer Christal M.M. Mickle and chief scientific officer Sven Guenther as part of a reprioritization. It also let go an undisclosed number of people in CMC and clinical development. It had 65 full-time workers at the end of 2023. — Kyle LaHucik Incyte’s PD-1 antibody-chemo combo wins in non-small cell lung cancer: The Phase 3 trial met the primary endpoint of overall survival and all secondary endpoints in patients with previously untreated metastatic NSCLC. Patients taking the Zynyz-chemotherapy combination achieved a median overall survival of 18.1 months compared to 13.4 months in the placebo arm. Secondary endpoints included overall response rate and duration of response. Incyte plans to submit a supplemental BLA to the FDA next year. — Katherine Lewin Bionical Emas divests CRO to UK private equity firm: Kester Capital is buying Bionical’s clinical research organization, dubbed EMAS Pharma, which will now operate as an independent business. The sale will allow Bionical to focus on its “core” businesses, including its early access programs and clinical trial supply units. No financial details were disclosed. — Anna Brown Janux Therapeutics raised $402.5 million in its public offering, up from the $300 million it initially planned to raise. — Jaimy Lee