Kyverna Therapeutics\' new CEO Warner Biddle has identified stiff person syndrome, a rare autoimmune neurological disorder launched into public attention by Céline Dion\'s diagnosis, as the initial indication for the company\'s lead CAR-T program, KYV-101.\n About 100 days into the CEO role at Kyverna Therapeutics, Warner Biddle has determined the strategic priorities for the California biotech, which aims to deliver the first approved CAR-T therapy in an autoimmune disease.The former Kite Pharma executive has identified stiff person syndrome (SPS), a rare autoimmune neurological disorder launched into public attention by Céline Dion’s diagnosis, as the initial indication for Kyverna’s lead CAR-T program, CD19-directed KYV-101.Lupus, which spurred the industry’s ongoing gold rush for developing cell therapies against autoimmune diseases and originally KYV-101’s first indication, is instead taking the third place on Kyverna’s priority list, as myasthenia gravis occupies the second spot.SPS is “our tip of the spear that will allow us to establish a base as the first autoimmune CAR company,” Biddle said in an interview with Fierce Biotech ahead of this year\'s J.P. Morgan Healthcare Conference. “And then we’ll be able to build on that, and we’ll be able to amplify our presence with another neuroinflammation franchise but with the patient population that’s going to be about 10 times larger than SPS.”The biotech chief will outline his plan in detail during this week\'s conference. Biddle joined Kyverna in September after a stint as the commercial chief at Gilead’s cell therapy arm Kite Pharma. The task in front of him is to blaze a winning trail for a bellwether biotech that has lost nearly 90% in stock price since a high-profile IPO in February 2024.Interest in CAR-T therapies for autoimmune disease exploded last year, following a series of promising results in patients with systemic lupus erythematosus (SLE) from academic studies out of Germany. The enthusiasm led to Kyverna’s upsized IPO in 2024.As one of the first companies to report clinical CAR-T data in lupus, Kyverna’s KYV-101 is considered a benchmark that followers must at least match up to in order to remain in the game. For patients with heavily pretreated lupus nephritis, a single infusion of KYV-101 has shown it could achieve deep B-cell depletion and put an end to disease activity, restoring stable kidney function and normal complement levels, while eliminating the need for immunosuppressants and toxic steroids.But the field is quickly getting crowded. Besides large pharmas such as Bristol Myers Squibb and Novartis, a growing list of biotechs, including the likes of Cabaletta Bio and Cullinan Therapeutics, are eyeing lupus either with CAR therapy or T-cell engagers.And a patient relapse—although from a lower dose of KYV-101—after five months of treatment speaks to the potential challenge and many unknowns of the cell therapy industry’s push into autoimmune diseases. Kyverna is currently finishing enrolling in KYV-101’s phase 1 lupus nephritis trial, with the goal to report data from nine patients—including six at the target dose of 100 million cells—in the second half of 2025, according to Biddle. The phase 1 results will then be used to design the pivotal clinical trial.The company is focusing on lupus nephritis instead of the larger SLE population “because we believe that lupus nephritis patients are at the highest risk of progressing to late-stage renal disease,” he said. Lupus nephritis is a serious complication of SLE, or commonly referred to as lupus. About 40% of lupus patients could develop nephritis, and 60% of them are expected to fail standard treatments, according to Kyverna.“We’re not moving away from lupus,” Biddle said. “It’s still a key priority for us.”As the red-hot lupus indication is already full of competition, with different programs likely fighting over trial participants, Biddle has decided to use SPS as an entry point.SPS is a progressive disorder marked by debilitating muscle stiffness in the torso, arms and legs with no approved therapies. The rare disease gained wider public knowledge after Céline Dion’s diagnosis and her comeback performance at the 2024 Paris Olympics opening ceremony.Because there’s a significant unmet need and patients experience deteriorating symptoms over a short period of time, Kyverna believes it can execute on a clinical trial relatively quickly, thereby giving KYV-101 the opportunity to be the first CAR-T to launch in an autoimmune disease, Biddle explained.While a late addition to KYV-101’s clinical program, the phase 2 SPS trial, coded KYSA-8, has already accrued 40% of patients with full enrollment expected mid-2025. Kyverna expects to report top-line data from the pivotal trial in the first half of 2026, followed by an application in 2026. As to myasthenia gravis, for which KYV-101 is undergoing phase 2 testing in the KYSA-6 trial, Kyverna intends to confirm a registrational path with regulators in the first half of 2025 and report interim phase 2 data in the second half of the year.“It’s important for us to be hyper focused in the short term,” Biddle said. “We’re going to be focusing on delivering meaningful short-term catalysts in a capital-efficient way. But there’s still lots of opportunities for growth, and we’re going to use a data-driven approach to prioritize future indications.”Besides those three priority indications, KYV-101 is also being tested in multiple sclerosis and systemic sclerosis. Kyverna in December reported initial data from five patients in the phase 2 KYSA-7 multiple sclerosis study, although it was hard to draw any conclusions on efficacy.The company’s second candidate, KYV-102, is designed to remove the apheresis process in CAR-T manufacturing. Kyverna aims to file for an investigational new drug application in the second half of 2025.With cash runway into 2027, Kyverna is “building the internal expertise in order to deliver these key milestones,” Biddle said, but added that the company is open to partnerships, “if they can add and contribute to the future growth of our company.”
