Kyverna’s CAR-T KYV-101 Gets FDA IND Clearance for Trial in Scleroderma


Kyverna is planning to conduct a phase 1/2 clinical trial (KYSA-5; NCT identifier pending) in patients with scleroderma.

Kyverna Therapeutics’ KYV-101, an investigational chimeric antigen receptor T-cell (CAR-T) therapy, has received clearance of its investigational new drug (IND) application by the FDA for a clinical trial in patients with diffuse cutaneous systemic sclerosis (scleroderma).1

In light of the IND clearance, Kyverna is planning to conduct a phase 1/2 clinical trial (KYSA-5; NCT identifier pending) in patients with scleroderma. The multicenter, open-label clinical trial will be the third clinical study that Kyverna has initiated for the evaluation of KYV-101 in an autoimmune disease; the company is also currently conducting the phase 1 KYSA-1 clinical trial (NCT05938725) in the United States and the phase 1/2 KYSA-3 clinical trial in Germany. Both KYSA-1 and KYSA-3 are evaluating KYV-101 for the treatment of active lupus nephritis in adult patients. 

In June 2023, Kyverna announced that the first patient had been enrolled in KYSA-1.2 Later, in September, Kyverna stated that in the first patient dosed in the trial, KYV-101 was generally well-tolerated at 28 days-posttreatment.3 Furthermore, the patient, who received KYV-101 in July at the University of Colorado Anschutz Medical Campus, did not experience any immune effector cell-associated neurotoxicity syndrome (ICANS).

"We are immensely proud of being able to bring KYV-101 to patients suffering from scleroderma," Peter Maag, PhD, the chief executive officer of Kyverna Therapeutics, said in a statement.1 "We are keen to initiate our KYSA-5 trial in this new patient population and generate data to support our KYV-101 design goals. With the deep B-cell depletion from KYV-101 treatment, patients with scleroderma may have a full reset of their immune system to stop the vicious cycle of their overactive immune system."

KYV-101 is an autologous version of a CD19-directed fully human CAR-T construct. It functions by eliminating B-cells in order to “reset” the immune system. The construct has previously been evaluated in a phase 1 clinical trial (NCT02659943) sponsored by the National Cancer Institute for patients with B-cell lymphomas and patients with chronic lymphocytic leukemia where it demonstrated antilymphoma activity that was associated with a reduction in cytokine-driven adverse events, including ICANS, and reduced immunogenicity, in comparison to a CAR-T product expressing FMC63-28Z and containing murine binding domains.3,4

"We welcome Kyverna's enthusiasm and interest to push forward with their CAR-T approach in scleroderma patients with the KYSA-5 trial," Luke Evnin, PhD, the chairman of the Scleroderma Research Foundation, added to the statement.1 "We await the results with optimism that CAR-T driven B-cell ablation may ultimately deliver efficacy with adequate safety for a broader range of our patients than immune-ablative chemotherapy alone."

In addition to the aforementioned milestones, Kyverna has also recently formed multiple collaborations to improve manufacturing operations.5 In September Kyverna announced that the Ingenui-T platform, the company’s process for autologous manufacturing of CAR-T products specifically directed at autoimmune indications, will be incorporated into its partner ElevateBio’s manufacturing and development operations, which are carried out under the name ElevateBio BaseCamp.

“We are excited by the potential to not only provide dramatic benefit to patients by eliminating the underlying disease pathology using CAR T-cell therapy, but also to bring innovation to other aspects of the patient journey,” Karen Walker, the chief technology officer at Kyverna said in a September 2023 statement.5 “Together with ElevateBio, we aim to deliver radical benefits to patients in less time, with lower impact, and at substantially reduced cost.”

In a separate agreement with Oxford Biomedica, Kyverna has also licensed the LentiVector platform for use in its CAR-T manufacturing processes.6 Kyverna stated that the LentiVector platform, a lentiviral-based gene delivery system, is expected to help the company in terms of scalability and reliability for its CAR-T manufacturing goals.

1. 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 October 11, 2023.
2. Kyverna Therapeutics announces first patient enrolled in phase 1 clinical trial of CD19 CAR T-cell therapy for Lupus Nephritis in the U.S. News release. Kyverna Therapeutics. June 29, 2023.
3. Kyverna Therapeutics announces achievement of 28-day post-infusion milestone for first U.S. patient dosed in phase 1 clinical trial of CD19 CAR t-cell therapy for lupus nephritis. News release. Kyverna Therapeutics. September 13, 2023. Accessed September 14, 2023.
4. Brudno JN, Lam N, Vanasse D, et al. Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nat Med. 2020;26(2):270-280. Doi: 10.1038/s41591-019-0737-3.
5. Kyverna Therapeutics and ElevateBio to Advance Kyverna’s Ingenui-T Cell Therapy Manufacturing. News release. Kyverna Therapeutics. September 26, 2023. Accessed October 11, 2023.
6. Kyverna Therapeutics and Oxford Biomedica Sign License and Supply Agreement for LentiVector® Platform. News release. Kyverna Therapeutics. September 20, 2023. Accessed October 11, 2023.
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