Reversing tumor immunosuppression with next-gen GPCR modulation

What It Covers

Sean Mac, CEO of Kynova Therapeutics, outlines the company's GPCR-based drug discovery platform, its lead anti-CCR8 antibody DT-7012 in Phase 1, a $32M Series B raise, and the strategic rebrand from Domain Therapeutics as the company targets immuno-oncology and inflammation.

Key Questions Answered

• •CCR8 Treg depletion mechanism: DT-7012 targets CCR8 to deplete T regulatory cells from the tumor microenvironment, restoring immune competitiveness against tumors. The Phase 1 trial in Australia has already confirmed Treg depletion in blood; the critical paired biopsy data confirming depletion within the tumor microenvironment itself is expected late Q2 or early Q3 2025.
• •GPCR platform differentiation: Unlike competing platforms that require locking the GPCR into a fixed configuration, Kynova's platform works with the native receptor. This enables discovery of allosteric modulators beyond standard antagonists, and allows measurement of downstream signaling — expanding viable targets into immuno-oncology and inflammation rather than only CNS and cardiometabolic areas.
• •Biotech-scale pivotal trial design: When selecting an indication for a pivotal trial, size the approvable dataset to be VC-fundable and choose indications with concentrated prescriber bases addressable by a biotech-scale salesforce. Kynova applied this framework to identify a path toward accelerated approval for DT-7012 before 2030, while still fitting within the pharma patent cliff window.
• •Mid-size pharma as deal targets: Beyond top-15 pharma, a growing tier of mid-size companies that have commercialized their first products now face the same pipeline renewal pressures. These players pursue deals in the $1–3B range, creating a broader M&A market that biotech companies should actively target alongside traditional large-pharma partnership conversations.
• •Non-dilutive capital sequencing: Securing a strong cash position first makes accessing non-dilutive capital significantly easier. Kynova pursues platform licensing deals and asset transactions alongside equity rounds, using incoming non-dilutive funds to extend runway and reduce reliance on Series C timing — a sequencing strategy applicable to any early-stage biotech managing cash between clinical milestones.