Kyverna Therapeutics Showcases miv-cel Data in SPS, gMG; CEO Eyes First Autoimmune CAR-T BLA

Key Points

• In the FDA‑aligned KYSA‑8 registrational trial in stiff person syndrome, mivocabtagene autoleucel (miv‑cel) met the primary endpoint at week 16 with a median 46% improvement in T25FW (81% of patients ≥20% improvement), sustained through 24 weeks in evaluable patients, and was well tolerated with no high‑grade CRS/ICANS.
• In the KYSA‑6 cohort for generalized myasthenia gravis, miv‑cel produced rapid, durable responses—100% of patients were clinically meaningful responders on MG‑ADL and QMG through 24 weeks—accompanied by deep B‑cell depletion and preservation of humoral responses to common vaccines.
• Kyverna is prioritizing an SPS BLA as it pursues what it calls a potential first approval for a CAR‑T in autoimmunity, targeting an initial US addressable population of ~2,000–2,500 patients with an early rollout at roughly 10 treatment centers.

Kyverna Therapeutics NASDAQ: KYTX highlighted new clinical data for its CD19-directed autologous CAR T-cell therapy mivocabtagene autoleucel (miv-cel), formerly KYV-101, during an American Academy of Neurology (AAN) conference call focused on stiff person syndrome (SPS) and generalized myasthenia gravis (gMG).

Chief Executive Officer Warner Biddle said the company presented “the first registrational primary analysis for an autoimmune CAR T,” calling it a milestone for Kyverna and the broader field. Biddle said the company’s top priority is its SPS biologics license application (BLA) submission as it works toward what it believes could be a first approval for CAR T in autoimmunity and a foundation for expansion into additional indications, including gMG and progressive multiple sclerosis over time.

KYSA-8 registrational trial in stiff person syndrome

Chief Medical and Development Officer Naji Gehchan said SPS is “highly debilitating and progressive,” with no FDA-approved therapies, and patients often rely on symptomatic drugs such as benzodiazepines along with chronic off-label immunotherapies. Gehchan cited a multicenter retrospective natural history study (University of Colorado and Johns Hopkins) that examined Timed 25-Foot Walk (T25FW) data from 153 patients over 10 years and found most patients had “no or minimal improvement” despite therapy, with increased reliance on walking aids over time.

Gehchan said KYSA-8 is an FDA-aligned, single-arm, multicenter, open-label, registrational phase 2 trial that enrolled 26 patients. He noted Kyverna has received RMAT and Orphan Drug designations for miv-cel in SPS. All patients discontinued immunotherapies prior to receiving a single dose of miv-cel.

Dr. Amanda Piquet, professor of neurology at the University of Colorado Anschutz and KYSA-8 lead investigator, reported that the primary endpoint was met at week 16. According to Piquet, miv-cel produced a 46% median improvement from baseline in T25FW at week 16, exceeding the 20% threshold considered clinically meaningful. She said 81% of patients achieved at least a 20% improvement, and “nearly a third” walked at the speed of a healthy adult by week 16.

Piquet added that among 12 patients requiring a walking aid at baseline, “two-thirds no longer needed assistance” at week 16. She said the T25FW improvement was sustained through 24 weeks in the 16 patients who reached that time point.

On secondary endpoints, Piquet said the trial showed statistically significant improvements in disability and mobility measures, including the Modified Rankin Scale and the Hauser Ambulation Index, and in SPS-specific measures including the Distribution-of-Stiffness Index and the Heightened Sensitivity Scale. She said 96% of patients improved in at least one primary or secondary endpoint. Piquet also cited a median 89-meter improvement in the six-minute walk test at 16 weeks and said SF-36 scores at week 16 were “comparable to healthy adults.”

Biomarkers, immune effects, and safety in SPS

Piquet described translational findings showing CAR T-cell expansion peaking at day 14, complete peripheral B-cell depletion, and a 56% reduction in GAD65 autoantibody levels. She said 54% of patients had B-cell reconstitution by week 16, with efficacy maintained despite reconstitution, and that no patients resumed chronic immunotherapies as of last follow-up. She also reported that reconstituting B-cell populations showed an increase in naïve phenotype and a decrease in memory phenotype, alongside an increase in regulatory T cells at week 16.

On safety, Piquet said miv-cel was “well-tolerated,” with no high-grade cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). She reported grade 3/4 neutropenia in four patients, described as manageable, and said serious treatment-related adverse events occurred in three patients and “fully resolved.”

KYSA-6 phase 2 trial in generalized myasthenia gravis

Kyverna also provided longer-term follow-up from KYSA-6, a phase 2 trial in seven refractory gMG patients who discontinued MG immunotherapies before receiving a single dose of miv-cel. Gehchan said the data cut-off was Feb. 25, with the longest follow-up up to 52 weeks, and 18-month follow-up is ongoing.

Dr. Sri Muppidi, clinical professor of adult neurology at Stanford Medicine and a KYSA-6 investigator, said the magnitude and durability of responses were “unprecedented.” He reported MG-ADL improved by 6.4 points at week 2 and by 8.5 points at week 24, while QMG improved by 8.6 points at week 2 and by 11.3 points at week 24. Muppidi said 100% of patients achieved clinically meaningful responses on MG-ADL, and 100% were responders on both MG-ADL and QMG.

Muppidi said 57% achieved minimal symptom expression at follow-up, and 100% had a clinically meaningful MG composite response, with a 16-point reduction. He emphasized that patients were able to discontinue prior immunosuppressive therapy—including non-steroidal drugs, high-dose steroids, FcRn inhibitors, and complement inhibitors—through week 24, which he said is not typical in other MG trials.

Safety and immune findings in gMG; commercial planning for SPS

In gMG, Muppidi reported no high-grade CRS or ICANS and said low-grade CRS was mostly fever and manageable. He cited grade 3 treatment-related events of neutropenia, lymphopenia, and low lymphocyte count in three patients, describing them as expected with lymphodepletion and CAR T and as fully resolved. He also said there were no serious adverse events, adding that a previously reported serious event was reclassified by the investigator as not serious.

Muppidi also described robust CAR T-cell expansion and deep B-cell depletion, with B-cell recovery detected in two patients at weeks 12 and 16. In patients with available antibody data, he said there was a robust and sustained reduction in AChR and MuSK antibody levels, while humoral immunity to common vaccinations appeared preserved.

Looking to commercialization in SPS, Biddle said Kyverna believes it has a strong evidence package for its BLA pathway and described SPS as a “compelling commercial opportunity.” He estimated approximately 6,000 diagnosed SPS patients in the U.S., with an initial focus on 2,000 to 2,500 patients (roughly 30% to 40%) who have had inadequate responses to off-label immunotherapies. Biddle said Kyverna plans to initially target about 10 centers, which he said would cover roughly half of the immediately addressable patient population, and then expand authorized treatment centers over time.

About Kyverna Therapeutics NASDAQ: KYTX

Kyverna Therapeutics is a clinical‐stage biotechnology company dedicated to developing engineered regulatory T‐cell (Treg) therapies for the treatment of autoimmune and inflammatory diseases. Leveraging a proprietary platform for the isolation, expansion and modification of Treg cells, the company aims to restore immune homeostasis in patients by delivering antigen‐specific cell therapies that selectively target diseased tissues while minimizing systemic immunosuppression.

The company's lead programs include an allogeneic Treg candidate in clinical development for ulcerative colitis, with additional preclinical assets focused on rheumatoid arthritis and other chronic inflammatory conditions.

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