New Risk • Aug 16
New major risk - Financial position The company has less than a year of cash runway based on its current free cash flow trend. Free cash flow: -US$21m This is considered a major risk. With less than a year's worth of cash, the company will need to raise capital or take on debt unless its cash flows improve. This would dilute existing shareholders or increase balance sheet risk. Currently, the following risks have been identified for the company: Major Risks Less than 1 year of cash runway based on free cash flow trend (-US$21m free cash flow). Negative equity (-US$1.1m). Shareholders have been substantially diluted in the past year (260% increase in shares outstanding). Revenue is less than US$1m. Minor Risks Currently unprofitable and not forecast to become profitable over next 2 years (US$22m net loss in 2 years). Market cap is less than US$100m (US$16.2m market cap). New Risk • Aug 14
New major risk - Revenue and earnings growth Earnings are forecast to decline by an average of 3.3% per year for the foreseeable future. This is considered a major risk. Ultimately, shareholders want to see a good return on their investment and that generally comes from sharing in the company's profits. If profits are expected to decline, then in most cases the share price will decline over time as well. In addition, if the company pays dividends it will also likely need to reduce or cut them, striking a dual blow to total shareholder returns. Currently, the following risks have been identified for the company: Major Risks Earnings are forecast to decline by an average of 3.3% per year for the foreseeable future. Shareholders have been substantially diluted in the past year (260% increase in shares outstanding). Revenue is less than US$1m. Minor Risks Currently unprofitable and not forecast to become profitable over next 2 years (US$22m net loss in 2 years). Market cap is less than US$100m (US$18.7m market cap). Announcement • Jul 15
Tempest Therapeutics Unveils Next-Generation In Vivo CAR-T Pipeline With First Clinical Study Planned For The Fourth Quarter Of 2026 Tempest Therapeutics announced 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 and multiple sclerosis. The study is expected to enroll approximately 10 patients, with first patient dosing anticipated in the fourth quarter of 2026. TPST-4003 combines Tempest’s next-generation CD7-targeted mRNA lipid nanoparticle delivery platform with the same dual-targeting CD19 B-cell maturation antigen chimeric antigen receptor 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. The first planned investigator-initiated trial is expected to evaluate TPST-4003 in approximately 10 patients with nervous system autoimmune diseases, initially focusing on myasthenia gravis and multiple sclerosis. 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. 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 myasthenia gravis and multiple sclerosis. 
