On July 15, 2026 Tempest Therapeutics, Inc. (Nasdaq: TPST) ("Tempest"), a clinical-stage biotechnology company developing a pipeline of advanced chimeric antigen receptor T-cell ("CAR-T") product candidates, reported details of its next-generation in vivo CAR-T platform. The company plans to advance TPST-4003, its lead in vivo CAR-T product candidate, into a first investigator-initiated clinical trial in patients with nervous system autoimmune diseases, initially focusing on myasthenia gravis ("MG") and multiple sclerosis ("MS"). The study is expected to enroll approximately 10 patients, with first patient dosing anticipated in the fourth quarter of 2026.
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TPST-4003 combines Tempest’s next-generation CD7-targeted mRNA lipid nanoparticle ("CD7-tLNP") delivery platform with the same dual-targeting CD19 B-cell maturation antigen ("CD19/BCMA") chimeric antigen receptor ("CAR") architecture used in TPST-2003, the company’s clinical-stage CAR-T program. Interim Phase 1/2a clinical data generated with TPST-2003 demonstrating the achievement of a 100% complete response rate, together with its successful U.S. manufacturing, provide important support of the underlying CAR construct, establishing a foundation for TPST-4003.
"We are excited to announce the strategic prioritization of our next-generation in vivo CAR-T pipeline and our plan to advance TPST-4003 toward an anticipated first patient dosing later this year," said Matt Angel, Ph.D., President and Chief Executive Officer of Tempest. "We believe our differentiated in vivo CAR-T platform may enable broader addressable T-cell coverage and support scalable repeat dosing once developed and commercialized, supporting future commercial attractiveness of in vivo CAR-T therapy. The lead product candidate in our pipeline, TPST-4003, is being designed to enable broad B-cell lineage depletion and reset with its dual CD19/BCMA targeting architecture, with the goal of potentially delivering improved efficacy and durability compared with single-target CAR approaches. We look forward to advancing TPST-4003 into clinical development later this year."
Planned Investigator-Initiated Trial of TPST-4003
The first planned investigator-initiated trial is expected to evaluate TPST-4003 in approximately 10 patients with nervous system autoimmune diseases, initially focusing on MG and MS. Initial study planning has involved discussions with six prospective clinical centers and principal investigators experienced in neurological autoimmune diseases. The company expects first patient enrollment and dosing to occur in the fourth quarter of 2026.
The study is expected to assess safety, cellular kinetics and pharmacodynamic activity following initial dosing. Key assessments are expected to include treatment-emergent adverse events and serious adverse events; the generation and expansion of peripheral blood CD4+ and CD8+ CAR-T cells and CD56+ CAR-NK cells; CAR transgene copy number; and the depth and kinetics of CD19+ B-cell depletion and B-cell subset reconstitution. Where clinically appropriate, exploratory assessments may also include the detection of CAR-positive immune cells in cerebrospinal fluid and the evaluation of B-cell depletion in lymphoid tissue.
Disease-specific clinical activity will be evaluated using established measures. Initial safety and pharmacodynamic data from the first patients are expected in the first half of 2027, followed by an interim clinical update including preliminary safety, pharmacodynamic and efficacy data in the second half of 2027.
Additional preclinical programs leverage advanced payloads and create a modular in vivo CAR-T portfolio. These include TPST-001 for non-B-cell hematologic malignancies and TPST-002 for solid tumors.
Tempest’s in vivo CAR-T platform, CD7-tLNP, is being designed to expand the potential of next-generation in vivo CAR-T therapy through three core differentiators:
Broader T-Cell Reach: The platform is being engineered to efficiently target both CD4+ and CD8+ T-cell populations, targeting broad CAR expression across the key cellular drivers of durable immunity. This comprehensive T-cell engagement is intended to support a more balanced and effective therapeutic response.
Better Delivery Logic: A differentiated targeting ligand, combined with rapid cellular internalization and a chemically optimized mRNA payload, is being designed to maximize intracellular delivery and CAR protein expression. Nucleoside-modified mRNA and optimized construct architecture together target a reduced innate immune sensing, extended functional mRNA activity, and robust yet transient CAR expression – enhancing delivery efficiency while preserving the advantages of an in vivo approach.
Scalable In Vivo CAR-T: By increasing CAR expression on a per-particle basis, the platform is being designed to achieve meaningful biological activity at lower doses, supporting improved manufacturing efficiency, reduced cost of goods, and the potential for scalable, repeatable treatment.
Together, we believe these capabilities may position the CD7-tLNP platform as a differentiated solution for the next generation of in vivo CAR-T therapies.
About TPST-4003
TPST-4003 is a preclinical, in vivo dual-targeting CD19/BCMA CAR-T product candidate that combines proprietary CD7-targeted mRNA/LNP delivery with a clinically validated dual-target CAR architecture utilized in the company’s TPST-2003 CAR-T program. Targeting broad B-cell lineage depletion and reset, TPST-4003 is being designed to address a range of autoimmune and oncology indications, initially including MG and MS.
(Press release, Tempest Therapeutics, JUL 15, 2026, View Source [SID1234669236])