Epoch 19: The AutoImmune Renaissance

CD19, CAR-T, FcRN, T-Cell Engagers

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Hello Avatar! Welcome back for another week of biotech analysis. Today is Sunday, which means this is our Building Biotech newsletter that is focused on discussing biopharma strategy topics. Today we are going to cover AutoImmunity - a space that has heated up considerably over the past 1-1.5 years.  Recent advances and encouraging human data with B Cell depletion and FcRN focused strategies have resulted in a tsunami of investment dollars flooding into the space.  Today we will take you through the an intro to the biology, and overview of opportunities for therapeutic modulation being pursed, the epidemiology which enables a “pipeline in a pill” approach to build mega-blockbuster products profiles, and of course a lay of the land around the competitive landscape.  

If you're not subbed yet click the link below.  Every Thursday we are out with our FREE public/private biotech market update. Sundays are the days we focus on forward looking strategy.  Monday’s are for public equity research.  Tomorrow we will focus on Sana Biotechnology ($SANA) which is expected to share human data on initial cell persistence from HIP approaches in T1D. Why is this interesting to us?  Because allogeneic cell therapies have a massive unanswered question - durability.  Those of us that follow the space are aware of the immune silencing edits which have been implemented by Sana and their competitors.  They all make sense and look great on a ppt slide.  But will they work?  This data release will lend clarity to that question.  Options pricing suggest 90% volatility!  

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Enough shilling for the day, lots to cover this week, let's get started!

AUTOIMMUNITY

The history of using B cell depletion as a weapon against autoimmune diseases stretches back decades. Rituximab, a monoclonal antibody that latches onto the CD20 protein on B cells, emerged as a pioneering treatment. While it demonstrated remarkable efficacy in some conditions like rheumatoid arthritis, its effectiveness varied greatly across different autoimmune diseases. Additionally, targeting CD20 comes with a caveat - this protein is present on immature B cells in the bone marrow, crucial for a healthy immune system. This unintended depletion of immature B cells alongside mature autoreactive B cells limited the widespread adoption of rituximab and discouraged further exploration of CD20-targeted therapies.

However, the tide has begun to turn. Autoimmunity has to be right up there with obesity in terms of hottest areas in biotech in 2024. Recent research has shifted focus to CD19, another protein expressed on B cells. Unlike CD20, CD19 is absent on immature B cells, offering a potentially more specific and safer approach. Furthermore, advancements in understanding B cell subpopulations and their roles in autoimmunity are paving the way for the development of highly targeted therapies. 

Recent success using ex-vivo CD19 CAR-T, has reignited excitement in the field. In parallel, interesting work around FcRn blockers (and degraders) has continued to evolve.  The B Cell depletion story is now branching out into bi-functional antibodies - things are getting exciting for sure.

If you missed our recent write up on AutoImmunity which focused deeply on CAR-T we suggest you check it out here:

BACKGROUND ON B CELLS AND AUTOIMMUNITY 

So why all the focus on B Cells? Our immune system relies on B cells to produce antibodies and fight infections. However, in B-cell driven autoimmune diseases, these B cells turn against the body, creating harmful autoantibodies that attack healthy tissues. This malfunction can be triggered by various factors, including viral infections. The resulting diseases, like myasthenia gravis (MG) and systemic lupus erythematosus (SLE), cause significant damage. Today we explore the potential of targeting these disease-causing autoantibodies with therapeutic drugs, offering a new approach to combating B-cell autoimmune disorders.

THE INFLUENCE OF AUTOANTIBODIES ON HEALTH AND DISEASE