Investor Questions Video Series
1) What problem are we solving in late-line MSS metastatic colorectal cancer (mCRC)?
>90% of colorectal cancers are microsatellite-stable (MSS), 50-60% of them become metastatic with a 13% 5-year survival and , this large group does not significantly benefit from checkpoint inhibitors. After two standard lines, the benchmark is trifluridine/tipiracil plus bevacizumab, which improved median overall survival to ~10.8 months in the phase 3 SUNLIGHT trial, but responses remain modest and there is no patient-selection biomarker. Our program targets this late-line MSS mCRC setting, acts to prime immune response turning cold to hot tumors facilitating response to Check-Point inhibitors AND has a promising companion diagnostic can lift efficacy beyond current chemotherapy-based standards.
2) What is PolyPEPI1018 and how is it different from other cancer-vaccine approaches?
PolyPEPI1018 is an off-the-shelf peptide immunotherapy targeting multiple HLA genes in a given patient producing an market 10X boost in immunogenicity. PolyPEPI 1018 composed of six long peptides covering seven shared tumor antigens hitting twelve digitally selected epitopes commonly presented in mCRC. It’s designed to drive multi-antigen, CD8/Th1 responses. Treos is developing a biomarker companion diagnostic pre-identifies likely responders using the patient’s HLA genotype from a saliva sample potentially greatly enhancing responder included in a Phase 3 study. PolyPEPI1018 and the associated adjuvant manufacturing is straightforward, inexpensive at scale with a current cost-of-goods estimate of ~$20 per commercial dose, enabling global pricing flexibility.
3) What clinical signal have we seen so far?
Across three Treos-sponsored studies (OBERTO-101/201/301; n≈44) in advanced MSS mCRC, PolyPEPI1018 given with standard agents has shown a consistent immune response leading to Tumor Infiltrating Lymphocytes attacking and durable cancer responses relative to historical data. Importantly, patients with higher predicted PEPI counts—our AGP score from the CDx—tend to have better tumor shrinkage and longer survival. In OBERTO-201, patients with AGP ≥ 2 had a median OS of ~10.3 months vs ~4.6 months for AGP < 2 (HR ~3.5), supporting prospectively validating the cutoff in larger trials.
4) How does the companion diagnostic (CDx) work, and what’s the plan to validate it?
Our CDx calculates a patient’s AGP score—how many of the 12 vaccine epitopes included are predicted to bind that individual’s HLA alleles based on using HLA sequencing from saliva. The PEPI/AGP framework has been analytically validated (sensitivity/specificity ~93% against a reference standard) and clinically correlated with vaccine-specific T-cell responses and outcomes across multiple datasets. The next step is prospective (pre)qualification in our randomized phase 2, followed by clinical validation alongside phase 3 to support marketing authorization of both drug and CDx. We’re engaging experienced CDx partners and regulators to synchronize timelines.