ASH 2023 non-LBA Most Interesting Abstracts

Below I walk through the non-late-breakers I am most intrigued by at the upcoming ASH 2023 meeting.

Introduction

Welcome back to another edition of BPS. As I noted last week, the floodgates of new oncology data are wide open, with ESMO in the rear view, SITC data matriculating right now, and ASH 2023 just around the corner. In a future post, I think I will look to pull out a few key themes and interesting data bites from SITC once I’ve fully sunk my teeth into that conference. From my high-level read, it has been light on major impactful clinical data, but full of interesting pre-clinical data readouts. For this week, however, I wanted to dive into ASH 2023 and flag a baker’s handful of abstracts of the non-LBAs that I’m most excited about analyzing once full data are released. Let’s get into it…

 CD19 CAR-T for Autoimmune Disease

Activity in this field has blown up over the course of the last 12 months. According to the Beacon Adoptive Cell Therapy Database, there are 157 cell therapies in development for the treatment of autoimmune diseases, with 28 of them targeting CD19. Existing CD19 CAR-T players, like Novartis, Kite, and BMS, have already stated their interest in expanding the benefit of CD19 CAR-Ts into autoimmune diseases. Next-gen CAR-T companies, like Gracell and Immpact Bio, have pivoted clinical development plans into autoimmune diseases. New companies like Cabaletta and Kyverna have sprouted up specifically to advance CD19 CAR-Ts for this therapeutic area. These maneuvers make great sense – in the same way CD19 CAR-Ts drive B-cell depletion that annihilates B-cell tumors, it can also clear autoreactive B-cells that cause certain autoimmune diseases. The same “reset button” we press on the B-cell compartment in blood cancers has now been shown in a few studies to provide long-lasting remissions in debilitating conditions like lupus and systemic sclerosis.

Both abstracts above (#4835 and #220) will have readthrough to each player looking to develop CD19 based programs in this space. Both data sets highlighted remission of systemic lupus (SLE) and independence from anti-inflammatory medications after treatment and follow-up. Data from the German study (#220) show 5 SLE patients with a minimum of 14 months follow-up still in remission. It’s clear to me that CD19 based B-cell depletion is demonstrating immense benefit for treatment refractory autoimmune patients. The question becomes how sticky are these responses long-term? Will patients need to keep going back to get new cells manufactured and dosed? Will they need to resume some level of anti-inflammatory medicine later? These are the near-term question I’m hoping to get more clarity on as these data sets mature. Longer term I’m curious about differential response across disease types (i.e., is SLE easier to treat than RA or sclerosis?) and how will payers manage cost in a world where autologous CD19 CAR-T are approved for the same indications that drugs like Remicade and Humira once dominated? I’d love to see how auto’ CD19 CAR-T stack up vs. CD19 bispecifics or Allo’ CD19 CAR-T in these diseases. If B-cell depletion is really what is driving benefit here, you might not need an autologous product to get to the same therapeutic goal – an off-the-shelf product, like a bsAb, that would not require chemo pre-conditioning could do the job just fine and be more palatable to the insurer and PBM  rebate and reimbursement spider web that controls access to medications in these markets in the US.