An Investor’s Guide to Bispecific Antibodies

THE COWEN INSIGHT

This report provides a detailed overview of bispecific development. The FDA’s recent approval of Rybrevant marked the third US approval of a bispecific. With multiple bispecifics entering late-stage trials, we expect the pace of approvals to accelerate. In this primer, we mention 200+ bispecific assets, highlight key upcoming catalysts, and detail recent bispecific-focused partnerships.

Bispecifics Offer Novel Mechanisms of Action

Bispecific antibodies are antibody structures with the ability to bind two different targets. The mechanisms of action generally fall into three categories:

1. direct effector cells (Tcell and NK cells) to the tumor
2. co-stimulation of the tumor-infiltrating immune cells by targeting 4-1BB, CD40 and CD28
3. combine multiple proven mechanisms of action into a single molecule (PD-1xCTLA-4, PD-1xLAG-3, HER2xHER2, EGFRxcMET, CD28xPSMA, CD28xEGFR, CD28xMUC16, METxMET, etc.)

Three Bispecifics Now Approved, We Expect Pace To Accelerate

The FDA’s approval of Rybrevant for the treatment of patients with metastatic NSCLC with EGFR exon 20 insertion mutations in May 2021 marked the third US approval of a bispecific asset. Blincyto and Hemlibra are also approved.

The rapid adoption demonstrates the potential of the market. Blincyto (CD3xCD19) was first approved in the US in 2014 for the treatment of B-ALL. Despite the short half-life and requirements for continuous infusion, sales were $379MM in 2020, and we project revenues growing to $400MM in 2025. Hemlibra (FVIII mimetic) was approved in 2017. Sales of Hemlibra were CHF 2.2B in 2020, and we estimate sales of CHF 5.3B in 2025.

Upcoming Catalysts Can Benefit the Entire Field

High profile catalysts include regulatory action Faricimab (VEGFxAng2, late2021); filings for two CD3xCD20 assets, Mosunetuzumab (2H21) and Glofitamab(2022), and Tebentafusp (CD3xgp100, 2H21); pivotal trial initiations for Odronextamab (CD3xCD20, 2H21); and late-stage data updates for KN046 (PD-1xCTLA-4, 2H21), Flotetuzumab (CD3xCD123, 2H21), Elranatamab (CD3xBCMA, possibly 2022), and Zanidatamab(HER2xHER2, 2H21). We believe positive outcomes can drive up investor interest.

Significant Potential for Bispecific Focused Partnership

Strong M&A activities continue as companies seek to develop promising bispecific candidates and combine multiple approaches. Our review of the field identified 28 transactions focused on bispecific assets in the last year. We expect deal flow in the bispecific space to continue to grow.