Treos Bio Announces Positive Interim Results from a Phase 1/2 Clinical Trial

Treos Bio Limited reported positive interim results from its first-in-man Phase 1/2 study of its precision cancer vaccine with maintenance therapy in patients with metastatic colorectal cancer (mCRC).

The results were presented in a poster session entitled: A Phase 1 Study of PolyPEPI1018 Vaccine Plus Maintenance Therapy in Patients with Metastatic Colorectal Cancer with a Predictive Biomarker (OBERTO) at the 2019 American Society of Clinical Oncology (ASCO) annual meeting in Chicago on June 3.

PolyPEPI1018 is an off-the-shelf, long peptide vaccine comprised of 12 unique epitopes derived from seven conserved cancer testis antigens (CTAs) frequently expressed in mCRC. PolyPEPI1018 was designed to induce polyvalent T cell responses in a large subpopulation of CRC patients using its PEPI Test platform, which identifies Personal EPItopes (PEPIs) that are likely to induce antigen-specific T cell responses in a subject.

The Phase 1/2 study is an open-label, single-arm, multicenter study to evaluate the safety, tolerability, immunogenicity and preliminary efficacy of single (first part of the study) or multiple (second part of the study) subcutaneous injection of PolyPEPI1018 as an add-on immunotherapy to the standard-of-care maintenance therapy in patients with metastatic colorectal cancer (NCT03391232). Preliminary results of the first part of the study are now available and results of the second part of the study are expected to be published in the third quarter of this year.

Eleven patients were vaccinated with PolyPEPI1018 just after their transition to maintenance therapy with fluoropyrimidine and bevacizumab. Vaccination combined with maintenance therapy has been safe and well-tolerated, no grade 3 or higher adverse events definitely related to the vaccine occurred. Analysis of the first part of the study revealed that 100% of patients exhibited PolyPEPI1018-specific immune responses, 90% of them had both CD8+ and CD4+T cell responses (n=10). Detailed immunogenicity analysis for the first four subjects showed unprecedented immunological activity after a single dose of vaccine: polyfunctional CD8+ T cell responses were detected against up to five vaccine antigens per patient and both CD8+ and CD4+ T cell responses were detectable ex vivo. The PEPI Test correctly predicted the subjects’ antigen-specific T cell responses based on their complete HLA class I genotype determined from saliva sample (71% agreement with measured T cell responses).

Immunological data observed so far for PolyPEPI1018 off-the-shelf vaccine against mCRC outperformed reported immunogenicity of personalized neoantigen vaccines and enabled durable treatment effect as add-on to maintenance therapy.

“Despite the single dose of PolyPEPI1018, we have seen unexpected clinical signals in the first part of the study: of the 11 vaccinated patients, three had progressed disease (PD), five of them had stable disease (SD) and three of them experienced partial tumor remission (PR), one of them qualifying for curative surgery,” said Joleen M. Hubbard MD, the principal investigator of the OBERTO trial at the Mayo Clinic. “Based on these encouraging results, we amended the trial to administer three doses of PolyPEPI1018 given 12 weeks apart. This is the first presentation of clinical data from this program at a major medical conference and we plan to share updated data from this study later this year.”

“We obtained very encouraging clinical results in terms of patient responses and the ability of the PEPI Test to predict responses in line with our pre-clinical data, which support further development of PolyPEPI1018 together with candidate companion diagnostics for the selection of likely responders,” said Dr. Eniko R. Toke, Chief Scientific Officer of Treos Bio.

Treos Bio, headquartered in London, with operational subsidiaries in Budapest, Hungary and San Francisco. Treos Bio uses data science and proprietary biomarkers to develop its precision cancer vaccines, with substantially shortened development timelines and at lower costs. Treos Bio’s off-the-shelf cancer vaccines are designed to exclude autoimmunity and induce tumor specific immune responses to be safer and more effective in patients who cannot benefit from current immunotherapies. Treos Bio’s novel biomarkers will support the development of in vitro companion diagnostic tests to identify patients who are most likely to respond to treatment.

Treos Bio has completed preclinical development of additional members of the PolyPEPI cancer vaccine family with companion diagnostics to select likely responders. These patient-specific off-the-shelf vaccines are designed for a general population of patients with ovarian-, breast-, lung cancers, glioma, melanoma, and leukemia. Treos Bio patient focused vaccine design also supports the development of vaccines for single individuals and a population of individuals with a specific genetic background, including specific vaccines most effective in ethnic populations. For more information visit www.treosbio.com.