Bicara Therapeutics and Zenas Biopharma have provided fresh impetus to the IPO market with filings that illustrate what newly public biotechs may look like in the back half of 2024.
Both companies filed IPO paperwork on Thursday and are yet to say how much they aim to raise. Bicara is seeking money to fund a pivotal phase 2/3 clinical trial of ficerafusp alfa in head and neck squamous cell carcinoma (HNSCC). The biotech plans to use the late-phase data to support a filing for FDA approval of its bifunctional antibody that targets EGFR and TGF-β.
Both targets are clinically validated. EGFR supports cancer cell survival and proliferation. TGF-β promotes immunosuppression in the tumor microenvironment (TME). By binding EGFR on tumor cells, ficerafusp alfa may direct the TGF-β inhibitor into the TME to enhance efficacy and reduce systemic toxicity.
Bicara has backed up the hypothesis with data from an ongoing phase 1/1b trial. The study is looking at the effect of ficerafusp alfa and Merck & Co.’s Keytruda as a first-line therapy in recurrent or metastatic HNSCC. Bicara saw a 54% overall response rate (ORR) in 39 patients. Excluding patients with human papillomavirus (HPV), ORR was 64% and median progression-free survival (PFS) was 9.8 months.
The biotech is targeting HNSCC because of poor outcomes—Keytruda is the standard of care with a median PFS of 3.2 months in patients of mixed HPV status—and its belief that elevated levels of TGF-β explain why existing drugs have limited efficacy.
Bicara plans to start a 750-patient phase 2/3 trial around the end of 2024 and run an interim ORR analysis in 2027. The biotech has powered the trial to support accelerated approval. Bicara plans to test the antibody in other HNSCC populations and other tumors such as colorectal cancer.
Zenas is at a similarly advanced stage of development. The biotech’s top priority is to secure funding for a slate of studies of obexelimab in multiple indications, including an ongoing phase 3 trial in people with the chronic fibro-inflammatory condition immunoglobulin G4-related disease (IgG4-RD). Phase 2 trials in multiple sclerosis and systemic lupus erythematosus (SLE) and a phase 2/3 study in warm autoimmune hemolytic anemia make up the rest of the slate.
Obexelimab targets CD19 and FcγRIIb, mimicking the natural antigen-antibody complex to inhibit a broad B-cell population. Because the bifunctional antibody is designed to block, rather than deplete or destroy, B-cell lineage, Zenas believes chronic dosing may achieve better outcomes, over longer courses of maintenance therapy, than existing drugs.
The mechanism may also enable the patient’s immune system to return to normal within six weeks of the last dose, as opposed to the six-month waits after the end of depleting therapies aimed at CD19 and CD20. Zenas said the quick return to normal could help protect against infections and enable patients to receive vaccines.
Obexelimab has a mixed record in the clinic, though. Xencor licensed the asset to Zenas after a phase 2 trial in SLE missed its primary endpoint. The deal gave Xencor the right to acquire equity in Zenas, on top of the shares it received as part of an earlier agreement, but is largely backloaded and success based. Zenas could pay $10 million in development milestones, $75 million in regulatory milestones and $385 million in sales milestones.
Zenas’ belief obexelimab still has a future in SLE rests on an intent-to-treat analysis and results in people with higher blood levels of the antibody and certain biomarkers. The biotech plans to start a phase 2 trial in SLE in the third quarter.
Bristol Myers Squibb provided external validation of Zenas’ attempts to resurrect obexelimab 11 months ago. The Big Pharma paid $50 million upfront for rights to the molecule in Japan, South Korea, Taiwan, Singapore, Hong Kong and Australia. Zenas is also entitled to receive separate development and regulatory milestones of up to $79.5 million and sales milestones of up to $70 million.