CD19 Bispecifics: The Harbinger of Challenges for Autoimmune CAR-T Therapies

Below, I dive into the b-cell depletion bispecific antibody landscape and look at how this class of medicines could impact cell therapies in development for autoimmune diseases

harbinger of bad weather

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We got some interesting news about a week ago, with Cullinan Oncology announcing its intent to pivot its lead CD19xCD3 bispecific antibody into autoimmune diseases (AID). The molecule was in a P1 study for NHL, but the company decided to scuttle those studies and focus clinical development exclusively in AID, with the company initially targeting SLE and an IND set for Q3’24. Accordingly, the company has changed its name from Cullinan Oncology to Cullinan Therapeutics.

If you’ve been a loyal reader of Big Pharma Sharma, you’ll recall that we’ve predicted this move from the CD19xCD3 bispecifics for quite some time, ever since the first reporting of CD19 CAR-T data in autoimmune disease. The biology of B-cell depletion and facility of using an off-the-shelf antibody-based drug (especially in AID indications) just made too much sense for bsAbs not to move into AID.

I believe this move by Cullinan is a forbearer of more b-cell depleting bispecific antibodies entering the AID space to rival the remarkable early data CD19 CAR-Ts have generated to date, in a more convenient package. The German and Chinese autologous CAR-T data first awoke a rush for autologous CD19 CAR-T companies to enter AID, followed by allogeneic and in vivo CAR-T companies who said, “anything you can do, I can do better”. Now the doors have been blown open for bispecific antibodies to enter the party.

So how many more bispecifics could we see enter the space? Who else is well-equipped with clinical stage assets that can pivot or expand into AID and cause further crowding in this already heated space? What companies/assets could be targets for acquisition and partnership? Well, let’s take look.

B-Cell Depleting Bispecific Antibodies, Clinical Stage Competitive Landscape

Below I put together a landscape of bsAbs targeting CD19, CD20, and/or CD22. Certainly, there are more B-cell targets beyond these three (BCMA, BAFF-R, TACI, etc.), but these are the most abundant primary targets being used for B-cell depletion thus far. Additionally, the landscape below is restricted to clinical-stage assets. I also excluded monoclonal antibodies from this exercise, as the landscape began to become a bit unruly if included. However, in my analysis below, I make mention of a couple key monoclonal assets from Big Pharma players that could be relevant to the competitive dynamics in this space. Please take note of the color-coding and icons in the margin to navigate your viewing.