Kyverna Therapeutics, Inc. Presents Registrational Trial Primary Analysis for Miv-Cel in Stiff Person Syndrome

Published: 2026-04-21 22:35:24 ET KYTX

Published on 04/21/2026 at 10:35 pm EDT

Kyverna Therapeutics, Inc. announced positive primary analysis results from its registrational trial, KYSA-8, of miv-cel (mivocabtagene autoleucel, KYV-101) in stiff person syndrome (SPS). In KYSA-8, a single dose of miv-cel delivered rapid, statistically significant and clinically meaningful improvements across all primary and secondary endpoints at 16 weeks, with the majority of patients regaining function, and all patients discontinuing chronic immunotherapies ? outcomes not previously observed in SPS.

Further, miv-cel was well-tolerated. KYSA-8 is a single-arm registrational Phase 2 trial evaluating miv-cel in patients with SPS. The primary endpoints are the change from baseline in the Timed 25-Foot Walk (T25FW) at 16 weeks and the incidence and severity of adverse events (AEs).

Secondary endpoints measuring disability, stiffness, hypersensitivity, and mobility include the Modified Rankin Scale (mRS), Distribution-of-stiffness Index (DSI), Heightened Sensitivity Scale (HSS), and Hauser Ambulation Index (HAI), respectively. Both DSI and HSS are SPS-specific clinical outcome measures designed to assess the extent of muscle stiffness and sensitivity to triggers of muscle spasms, respectively. A total of 26 patients who had an inadequate response to off-label immunomodulatory treatment options received a single dose of 1×108 miv-cel CAR T cells.

The data cut-off for the primary analysis was November 26, 2025, with a median follow-up of 6.5 months after miv-cel infusion (range, 4.4-12.2 months). Efficacy highlights from the primary analysis following a single dose of miv-cel are as follows: The trial met its primary endpoint, demonstrating a statistically significant improvement in the T25FW at Week 16 (p=0.0003), with a median improvement of 46% from baseline, regardless of baseline patient- and disease-related characteristics: 81% of patients achieved clinically meaningful improvement (=20% reduction from baseline), with nearly 1/3 of all patients walking at the speed of healthy adults by Week 16. Of the 12 patients requiring a walking aid at baseline, 67% no longer needed walking assistance at Week 16, reflecting meaningful functional independence.

All 26 patients remained free of chronic immunotherapies at Week 16 and through last follow-up. The trial met all secondary endpoints with significant (p<0.0001) mean improvements in mRS, HAI, DSI, and HSS of -0.8 (SD, 0.86), -1.6 (1.13), -1.5 (1.75), and -3.2 (2.01) points, respectively. Exploratory endpoints including additional efficacy measures, further supported the differentiated clinical profile of miv-cel: Sustained clinical benefit associated with deep, transient B-cell depletion and broad immune reset.

Significant reductions in GAD65-autoantibody titers associated with SPS, consistent with clinical results and miv-cel?s mechanism of action. Improvements in physical and mental functioning, including a more than 4-fold improvement over the minimal clinically important change in the 6-Minute Walk Test (6-MWT), and normalization toward healthy population benchmarks across the 36-Item Short Form Health Survey (SF-36) domains. Miv-cel demonstrated a well-tolerated safety profile consistent with its potential for outpatient administration: No high-grade cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) was observed.

Grade 3/4 neutropenia, a known AE associated with lymphodepletion and CAR T-cell therapy, was observed in four patients and was manageable. Serious treatment-related AEs occurred in three patients, all of which resolved fully without sequalae. Outcomes from a large, multicenter, retrospective natural history study examining the impact of SPS on walking speed, were also presented at AAN.

The study included 153 patients treated with off-label immunomodulators or symptomatic medications and with longitudinal T25FW assessments available. The majority of patients showed minimal (<20%) or no improvement in T25FW and required increasing reliance on walking aids over time. Changes in T25FW correlated with changes in disability assessed by mRS over time.

This analysis supports the use of T25FW as a valid longitudinal measure of mobility and confirms its association with disability in patients with SPS. These findings further highlight the limited impact of current treatment approaches and reinforce the potential for miv-cel to change the treatment paradigm in SPS. The registrational Phase 2 KYSA-8 trial is an open-label, single-arm, multicenter study evaluating the safety and efficacy of miv-cel in patients with SPS.

A total of 26 adult patients with SPS were dosed in the trial. Key inclusion criteria included a confirmed SPS diagnosis, stiffness index =2, and inadequate response to prior immunomodulatory therapies. Patients received lymphodepletion with low-dose cyclophosphamide and fludarabine followed by a single infusion of miv-cel at a target dose of 1×108 CAR T cells.

The primary endpoints were the change from baseline in the T25FW at Week 16 and safety. Secondary endpoints included the change from baseline in mRS, DSI, HAI, and HSS. Patients will be followed for one year.

Primary Endpoints Timed 25-Foot Walk (T25FW) Validated tool capturing improvement in walking ability Safety Incidence and severity of AEs Secondary Endpoints Modified Rankin Score (mRS) Change in degree of disability Hauser Ambulation Index (HAI) Change in time and degree of assistance to complete timed 25-foot walk Distribution of Stiffness Index (DSI) Change in muscle stiffness across body regions Heightened Sensitivity Scale (HSS) Change in muscle spasms SPS is a rare, progressive neurologic autoimmune disease characterized by muscle stiffness and painful muscle spasms, impacting mobility and gait.