![]() Car-T therapies for autoimmune indications Not only does the competition already include Novartis, Bristol Myers Squibb is about to start phase 1 with the Nex-T manufactured BMS-986353 in lupus, and Johnson & Johnson recently licensed C-CAR039, an asset CBMG is testing in neuromyelitis optica, though the deal was limited to lymphoma. However, while an IND was signed off for autologous use last November, a trial has apparently not yet begun.Īs with oncology, biotech watchers will note the ever-present threat of big pharma. These include Descartes-08, a therapy in phase 2 development for myasthenia gravis by the private US company Cartesian Therapeutics.Īnother private biotech, Kyverna, licensed rights to an NCI-originated CD19 Car with a fully human binder over a year ago, and followed that with a tie-up with Intellia to develop an allogeneic version. Presumably for the latter reason numerous clinical trials are testing Cars that target BCMA – a marker found on plasma cells – instead of, or in addition to, CD19. He puts this down to the relative inaccessibility of B cells, or to CD20-negative plasma cells (a plasma cell is a B cell that has started producing antibodies) providing an added source of such autoreactive antibodies. Schett’s NEJM letter raised another key point: that mere depletion of B cells using MAbs has limited therapeutic activity in lupus. And it was a Chinese group, Iaso Biotherapeutics, that was the source of one of the elements of Cabaletta’s CABA-201. The industry pipeline reveals significant work with traditional Car-T therapies against lupus, as well as against Sjogren’s syndrome, myasthenia gravis and Crohn’s disease, much of this in China. The rest of the group’s pipeline is based on a slightly different approach that it calls chimaeric autoantibody receptor T cells, which express specific autoantigens and aim to cause antigen-specific B-cell depletion. While Schett did not respond to an interview request, his separate letter to the NEJM spells out the logic, saying lupus is known to be triggered by autoantibodies originating from autoreactive B cells.Ĭabaletta’s CABA-201, a CD19-directed project, aims to repeat Schett’s success in lupus, where a US IND has just been cleared. They might therefore also work in non-oncology diseases that originate at this cell type, of which lupus is perhaps the most obvious example. CD19 is a protein expressed on B cells, and CD19-directed Car-T therapies have been approved in B-cell malignancies, like acute lymphoblastic leukaemia and diffuse large B-cell lymphoma. Narasimhan put Novartis’s interest down to the academic paper, telling the group’s first-quarter analyst call: “Our Car-T teams are working around the clock now to expand as fast as we can given the very powerful case reports that we've seen.” The company’s YTB323 began a phase 1/2 lupus study in February, and Novartis is planning a push into other settings. Giving autologous CD19-directed Car-T therapy improved their clinical symptoms, and all five subjects saw remissions that started at three months and were maintained at eight. The paper described five patients with longstanding active systemic lupus erythematosus that was refractory to previous drug regimens. It was Schett’s group at Friedrich Alexander University Erlangen-Nuremberg that published a scientific paper detailing the use of anti-CD19 Car-T cells against lupus – the study that triggered much of the current frenzy. It is noteworthy that Cabaletta’s scientific advisory board includes Professor Georg Schett. We are putting immunology ahead of and multiple myeloma.” For biotech investors looking at this space the most relevant stock to watch is Cabaletta Bio, but there are others too. Perhaps the strongest signal here was sent by Novartis, whose chief executive, Vas Narasimhan, recently called autoimmune conditions “our top priority for Car-T therapy. ![]() The low-hanging fruit on that particular tree having now been picked, numerous companies are betting that autoimmune diseases could open up a new avenue of revenue generation – apparently on the strength of an academic paper. ![]() A quiet revolution is under way in Car-T therapy, and it has nothing to do with oncology.
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