LONDON, May 29, 2020 (GLOBE NEWSWIRE) -- Treos Bio Limited, a clinical stage biopharma company developing precision peptide cancer immunotherapies, today presented positive final data from a Phase I/II study of PolyPEPI1018, its off-the-shelf multi-peptide treatment, in microsatellite stable metastatic colorectal cancer (MSS mCRC) patients during an online poster presentation released today at the 2020 ASCO Annual Meeting. OBERTO trial Principal Investigator Dr. Joleen Hubbard, Associate Professor Medical Oncology at the Mayo Clinic Rochester and a gastrointestinal oncologist, made the presentation. It can be viewed online at?https://meetinglibrary.asco.org/record/187919/video?and at?http://treosbio.com/index.php/publications-2/.

?Given the encouraging results of this clinical trial, we are moving forward with further studies of PolyPEPI1018 in conjunction with our companion diagnostic. We plan to conduct a randomized Phase II study of PolyPEPI1018 in maintenance therapy setting for first-line treatment of MSS mCRC, as well as a Phase I/II study in late-stage patients as an add-on to third-line therapy,? said Dr. Christopher Gallen, Executive Chairman of Treos Bio. ?Given the boosting effect on the pre-existing immunity, there is a strong rationale for a combination of PolyPEPI1018 with checkpoint inhibitors and Treos is also exploring options for clinical trials to test such combinations.?

PolyPEPI1018 is an off-the-shelf, synthetic, long peptide treatment containing immunogenic fragments of 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 Treos Bio?s proprietary?PASCal?computational tool, which identifies Personal EPItopes (PEPIs) that are likely to induce antigen-specific T Cell responses in a subject.

The Phase I/II OBERTO study was an open-label, single-arm, multicenter study to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of a single dose or of multiple doses of PolyPEPI1018 as an add-on to fluoropyrimidine/bevacizumab maintenance therapy in MSS mCRC patients after first-line induction chemotherapy (NCT03391232).

In the trial, 11 patients with MSS mCRC were injected subcutaneously with PolyPEPI1018 just after their planned transition to maintenance therapy with fluoropyrimidine/bevacizumab following the use of first-line combo chemotherapy and bevacizumab. The first part of the study included five patients who received a single dose of the immunotherapy within 21 days of transitioning to maintenance therapy. The second part included six patients who received three doses of the immunotherapy every 12 weeks. The primary endpoint was safety. The study showed that PolyPEPI1018 was safe and well tolerated. It also produced a robust immune response against multiple tumor antigens. Seven out of the 10 immune-evaluable patients had pre-existing immune responses against multiple targeted antigens, confirming the expression of target CTAs on the surface of the tumors. All pre-existing immune responses significantly boosted by the treatment.?De novo?antigen-specific T Cell responses were also induced against multiple antigens for eight out of 10 patients. Repeated treatments increased the magnitude of T Cell responses. Multi-antigenic CD8+ T Cell responses were detected for 80 percent of patients, exceeding the immune response rates reported for personalized neoantigen immunotherapies. Anticancer immunity was demonstrated to be HLA-genotype dependent, which predicted treatment benefit. Among four patients that had serial liver biopsies performed, increased immune cell infiltration was detected, which confirmed the conversion of previously immunologically cold tumors into hot tumors.

Immune responses induced by PolyPEPI1018 both at the peripheral and the tumor level indicate tumor response. Maintenance therapy, combined with multiple doses of PolyPEPI1018, led to objective responses and improved progression-free survival (PFS) for MSS mCRC patients. The median progression free survival (mPFS) in the multiple-dose group of 12.5 months compares favorably to results published from a recent trial conducted elsewhere in a relevant, large cohort using the same maintenance therapy but without an add-on immunotherapy (mPFS =7.4 months).

The poster also included details on two patients previously determined to have unresectable disease who responded so well to the treatment with PolyPEPI1018 that each of the two patients was able to undergo curative resection.

?The study showed that PolyPEPI1018 treatment both reactivates existing immune responses and induces efficient tumor-directed responses against multiple specific tumor antigens expressed in the metastases of colorectal cancer, which overrides immunological tolerance and allows clinically relevant anticancer effect,? said Mayo Clinic?s Dr. Hubbard. ?Importantly, a patient?s immunological and clinical responses could be predicted using a simple buccal cheek swab test, negating the need for a tumor biopsy to identify potential responders.?

About Colorectal Cancer Colorectal cancer is the third most common cancer worldwide, accounting for one-third of the cancer incidence and mortality burden worldwide together with lung and breast cancers with nearly 881,000 deaths in 2018 from colorectal cancer worldwide, according to GLOBOCAN. Microsatellite Stable Colorectal Cancer (MSS CRC) accounts for 85 percent of all CRC and 96 percent of metastatic CRC (MSS mCRC). While improvements in cancer care have boosted survival rates for all stages of colorectal cancer in the past two decades, the prognosis for patients with mCRC remains grim. The five-year relative survival rate for patients with metastatic colon cancer is just 14 percent. For patients with metastatic rectal cancer, the five-year relative survival rate is just 15 percent, according to the American Cancer Society.

About Treos Bio Limited Treos, headquartered in London, uses data science and proprietary biomarkers to develop its precision peptide cancer immunotherapies, with substantially shortened development timelines and at low costs. Treos? off-the-shelf cancer immunotherapies are designed to exclude autoimmunity and to induce tumor-specific immune responses, which are safer and more effective in patients who do not benefit from current immunotherapies. Treos? novel biomarkers will support the development of?in vitro?companion diagnostic tests to identify patients who are most likely to respond to treatment. The company is in clinical development of its PolyPEPI immunotherapy for metastatic colorectal cancer and has completed preclinical development of additional members of the PolyPEPI cancer immunotherapy family with companion diagnostics to select likely responders. These off-the-shelf immunotherapies are designed for a general population of patients with ovarian-, breast-, bladder-, gastric-, lung cancers and melanoma. Treos? patient-focused immunotherapy design also supports the development of immunotherapies for single individuals as well as for a defined population of individuals with a specific genetic background. More information can be found at?www.treosbio.com.

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