Kyverna’s CAR-T KYV-101 Cleared for US Trial in Multiple Sclerosis, Marking Seventh IND Clearance

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The clearance continues a recent trend of IND clearances for CAR-T therapies in autoimmune disease.

Kyverna Therapeutics’ KYV-101, an investigational CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has received clearance of an investigational new drug (IND) application from the FDA for a new clinical trial in patients with multiple sclerosis (MS).1

Overall, the IND clearance marks the seventh for KYV-101. The open-label phase 2 trial, referred to as KYSA-7, will be one of several clinical trials currently evaluating or in preparation for evaluation of KYV-101 in autoimmune disease. KYV-101 has also been evaluated for the treatment of cancer, notably in a 20-patient phase 1 clinical trial (NCT02659943) for patients with B-cell malignancies.

“This approval is a critical necessary step that paves the way to enroll patients with treatment-refractory progressive MS for whom there are no currently available treatment options in the KYSA-7 trial,” Bruce Cree, MD, PhD, MAS, clinical research director and professor of clinical neurology at the University of California, San Francisco, said in a statement.1 “This study offers participants a new hope for arresting relentless disability worsening and a potentially durable, treatment-free remission.”

In addition to KYSA-7, Kyverna is currently preparing the KYSA-6 clinical trial for KYV-101 in myasthenia gravis (MG),which was cleared by the FDA in November of last year.2 KYV-101 is also being evaluated in patients with lupus nephritis in the phase 1 KYSA-1 trial (NCT05938725) in the United States and the phase 1/2 KYSA-3 clinical trial in Germany. For patients with diffuse cutaneous systemic sclerosis (scleroderma), KYV-101 will be assessed in the phase 1/2 KYSA-5 trial in the US, which is also currently in preparation.1,2 KYV-101 recently received fast track designation from the FDA for the MG designation in December 2023.3

Key Takeaways

  • Kyverna Therapeutics' investigational CD19-directed CAR T-cell therapy, KYV-101, has received FDA clearance for a new clinical trial (KYSA-7) for patients with multiple sclerosis (MS).
  • The KYSA-7 trial aims to address the lack of available treatment options for this population.
  • KYV-101 is also being evaluated in other autoimmune diseases, including myasthenia gravis (MG), lupus nephritis, diffuse cutaneous systemic sclerosis (scleroderma), with FDA fast track designation having been received for MG in December 2023.

“As a patient-centered organization, we are thrilled to see KYV-101 being cleared for a large patient demographic as part of our KYSA-7 trial,” Peter Maag, PhD, the chief executive officer of Kyverna, added to the statement.1 “This is a clear paradigm shift for autoimmune diseases, and a testament to our commitment to expand potentially life-changing therapeutic benefits to multiple indications.”

KYV-101 is an autologous version of a CD19-directed fully human CAR-T construct.4 It functions by eliminating B-cells in order to “reset” the immune system. Kyverna Therapeutics is among several other companies currently evaluating CD19-directed CAR-T therapies and other cell therapies for the treatment of B-cell driven autoimmune diseases. Some other companies with CAR-T therapies in development for MG and/or lupus include Cabaletta Bio, IASO Biotherapeutics, and Cartesian Therapeutics.5-7

CGTLive™ recently sat down with Tom Van Blarcom, PhD, the senior vice president and head of research at Kyverna Therapeutics, at the Cell Therapy for Autoimmune Disease Summit, held November 28-30, 2023, in Philadelphia, Pennsylvania, to discuss the potential of CAR-T in autoimmune disease. Van Blarcom highlighted the need for collaboration between oncologists, physicians who specialize in autoimmune disease, and companies like Kyverna to help bring novel cell therapies to patients.

“I think it’s a very exciting time seeing cellular therapies, in particular CAR T-cells, transition from the oncology setting into the autoimmune setting,” Van Blarcom told CGTLive. “One of the main things we're learning is that this [effort] has to be a really big partnership between oncology physicians who've been treating patients with CAR T-cells and these new physicians in rheumatology and neurology who have less or little-to-no experience with cellular therapies. Bringing both those communities together, as well as companies like [Kyverna] who are trying to develop these drugs, is a huge 3-way partnership...”

REFERENCES
1. Kyverna’s KYV-101 receives U.S. FDA clearance for treatment of patients with refractory, progressive multiple sclerosis in the KYSA-7 phase 2 trial. News release. Kyverna Therapeutics, Inc. January 4, 2024. Accessed January 8, 2024. https://kyvernatx.com/press-releases/kyvernas-kyv-101-receives-u-s-fda-clearance-for-treatment-of-patients-with-refractory-progressive-multiple-sclerosis-in-the-kysa-7-phase-2-trial/
2. Kyverna Therapeutics announces FDA Clearance of phase 2 IND for KYV-101, a fully human CD19 CAR T-cell therapy to treat Myasthenia Gravis. News release. Kyverna Therapeutics. November 13, 2023. Accessed January 8, 2024. https://www.prnewswire.com/news-releases/kyverna-therapeutics-announces-fda-clearance-of-phase-2-ind-for-kyv-101-a-fully-human-cd19-car-t-cell-therapy-to-treat-myasthenia-gravis-301986135.html
3. Kyverna Therapeutics granted FDA fast track designation for KYV-101 in the treatment of patients with refractory myasthenia gravis. News release. Kyverna Therapeutics. December 13, 2023. Accessed January 8, 2024. https://kyvernatx.com/press-releases/kyverna-therapeutics-granted-fda-fast-track-designation-for-kyv-101-in-the-treatment-of-patients-with-refractory-myasthenia-gravis/
4. Kyverna Therapeutics announces FDA clearance of IND for KYV-101, a novel fully human CD19 CAR T-cell therapy to treat scleroderma. News release. Kyverna Therapeutics. October 11, 2023. Accessed January 8, 2024. https://www.prnewswire.com/news-releases/kyverna-therapeutics-announces-fda-clearance-of-ind-for-kyv-101-a-novel-fully-human-cd19-car-t-cell-therapy-to-treat-scleroderma-301953561.html
5. Cabaletta Bio receives FDA clearance of CABA-201 IND application for treatment of generalized myasthenia gravis. News release. Cabaletta Bio, Inc. November 6, 2023. Accessed January 8, 2024. https://www.cabalettabio.com/news-media/press-releases/detail/99/cabaletta-bio-receives-fda-clearance-of-caba-201-ind
6. World's first CAR-T for NMOSD treatment, IASO Biotherapeutics' equecabtagene autoleucel, receives IND approval by NMPA. News release. IASO Biotherapeutics. August 19, 2022. Accessed January 8, 2024. http://www.iasobio.com/info.php?id=198
7. Cartesian Therapeutics announces dosing of first participant in a phase 2b randomized clinical trial for generalized myasthenia gravis. News release. Cartesian Therapeutics. January 31, 2023. Accessed January 8, 2024. https://www.cartesiantherapeutics.com/2023/01/31/cartesian-therapeutics-announces-dosing-of-first-participant-in-a-phase-2b-randomized-clinical-trial/
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