Bicara and Zenas File for IPOs to Advance Late-Phase Prospects

Bicara Therapeutics and Zenas Biopharma have invigorated the IPO market with recent filings that offer a glimpse into the future of newly public biotech firms in the latter part of 2024. Both companies submitted their IPO paperwork on Thursday but have yet to specify their fundraising targets.

Bicara Therapeutics is seeking capital to advance a critical phase 2/3 clinical trial of ficerafusp alfa for head and neck squamous cell carcinoma (HNSCC). The company aims to use the late-phase trial data to support an FDA approval filing for its bifunctional antibody that targets EGFR and TGF-β. Both of these targets are clinically validated; EGFR aids in cancer cell survival and proliferation, while TGF-β fosters immunosuppression within the tumor microenvironment (TME). By binding to EGFR on tumor cells, ficerafusp alfa may direct TGF-β inhibition into the TME, thereby enhancing efficacy and minimizing systemic toxicity.

Bicara's hypothesis is supported by data from an ongoing phase 1/1b trial, which examines the combined effect of ficerafusp alfa and Merck & Co.’s Keytruda as a first-line therapy in recurrent or metastatic HNSCC. The phase 1/1b study reports a 54% overall response rate (ORR) among 39 patients. For those without human papillomavirus (HPV), the ORR increased to 64%, with a median progression-free survival (PFS) of 9.8 months. Bicara is targeting HNSCC due to poor patient outcomes—the standard care, Keytruda, has a median PFS of 3.2 months for patients with mixed HPV status—and believes that high levels of TGF-β account for the limited efficacy of existing treatments.

Bicara intends to launch a 750-patient phase 2/3 trial by the end of 2024 and perform an interim ORR analysis in 2027. The trial is designed to support accelerated approval. The company also plans to test the antibody in other HNSCC populations and additional tumor types, such as colorectal cancer.

Similarly, Zenas Biopharma is at an advanced stage of development. The biotech’s primary focus is to secure funding for multiple studies of obexelimab across various indications. This includes an ongoing phase 3 trial for immunoglobulin G4-related disease (IgG4-RD), phase 2 trials for multiple sclerosis and systemic lupus erythematosus (SLE), and a phase 2/3 study for warm autoimmune hemolytic anemia.

Obexelimab targets CD19 and FcγRIIb, mimicking the natural antigen-antibody complex to inhibit a broad B-cell population. Zenas believes that because the bifunctional antibody blocks rather than depletes B-cell lineage, chronic dosing could yield better outcomes over longer maintenance therapy periods than current drugs. The mechanism may also allow the patient's immune system to return to normal within six weeks of the last dose, in contrast to the six-month recovery period required after CD19 and CD20 depleting therapies. This quick immune system recovery could help patients avoid infections and permit timely vaccinations.

Obexelimab has had mixed results in clinical settings. Xencor licensed the asset to Zenas after a phase 2 trial for SLE failed to meet its primary endpoint. Xencor retains the right to acquire equity in Zenas, alongside shares from an earlier agreement, with potential payments contingent on the asset's success. Development milestones could reach $10 million, regulatory milestones $75 million, and sales milestones $385 million.

Zenas' confidence in obexelimab for SLE is based on an intent-to-treat analysis and outcomes for patients with higher levels of the antibody and specific biomarkers. The company plans to initiate a phase 2 trial for SLE in the third quarter.

Eleven months ago, Bristol Myers Squibb validated Zenas' efforts to revive obexelimab by paying $50 million upfront for rights to the molecule in Japan, South Korea, Taiwan, Singapore, Hong Kong, and Australia. Zenas could also receive up to $79.5 million in development and regulatory milestones, and up to $70 million in sales milestones.