PolyPEPI 1018 / Treos Bio - LARVOL DELTA

PolyPEPI1018 vaccine in combination with TAS-102 in participants with late-stage microsatellite-stable metastatic colorectal cancer (MSS mCRC): A phase Ib study to evaluate safety, tolerability, immunogenicity and efficacy (OBERTO-201). (ASCO 2023) - P1 | "To our knowledge, this is the first study investigating combination of a cancer vaccine with TAS-102 chemotherapy in advanced MSS mCRC. Our results show that PolyPEPI1018 plus TAS-102 was well-tolerated with few grade 3 AEs beyond what is expected with TAS-102 monotherapy. Despite no objective tumor responses could be detected, correlative data suggest contribution of PolyPEPI1018-induced immunological responses to the improved clinical benefit and the combination warrants further testing."

Clinical • Combination therapy • Metastases • P1 data • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Musculoskeletal Pain • Oncology • Pain • Solid Tumor • KRAS

Phase Ib open-label study to evaluate safety, tolerability, immunogenicity, and efficacy of multiple subcutaneous injections of PolyPEPI1018 vaccine as an add-on immunotherapy to TAS-102 in participants with late-stage microsatellite-stable metastatic colorectal cancer (MSS mCRC; OBERTO-201). (ASCO-GI 2023) - P1 | "To our knowledge, this is the first phase Ib study investigating combination of a cancer vaccine with TAS-102 chemotherapy in advanced MSS mCRC. Our results show that PolyPEPI1018 plus TAS-102 was well-tolerated with few grade 3 AEs beyond what is expected with TAS-102 monotherapy. PolyPEPI1018 induced immunological responses at both peripheral and tumor level, albeit no objective tumor responses could be detected."

Clinical • Metastases • P1 data • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8

OBERTO-301: Safety and Activity of PolyPEPI1018 Plus Atezolizumab in Colorectal Cancer. (clinicaltrials.gov) - P2 | N=18 | Completed | Sponsor: Treos Bio Limited | Active, not recruiting ➔ Completed

Trial completion • Colorectal Cancer • Oncology • Solid Tumor

PolyPEPI1018 cancer vaccine in combination with anti-PD-L1 immunotherapy remodels the intratumoral T cell repertoire in MSS colorectal cancer: A retrospective analysis of OBERTO-301 study (ESMO-GI 2026) - P2 | "We evaluated immune changes in paired tumor biopsies from patients treated with the multi-antigen peptide vaccine PolyPEPI1018 plus atezolizumab in the OBERTO-301 study (NCT05243862). Conclusions PolyPEPI1018 in combination with anti-PD-L1 immunotherapy induces remodeling of the intratumoral T cell repertoire in MSS mCRC, with increased T cell infiltration and expansion of tumor-specific clonotypes, which translates to clinical benefit. These data provide mechanistic evidence that therapeutic vaccination targeting shared tumor antigens can convert immune-cold MSS mCRC into a more immunologically active tumor microenvironment."

Combination therapy • Retrospective data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • CTAG1B • KRAS

Treos Bio…announced new translational data from the Phase Ib/II OBERTO-301 study (NCT05243862), presented at the ESMO Gastrointestinal Cancers Congress 2026 (GlobeNewswire) - "The retrospective analysis evaluated paired baseline and on-treatment tumor biopsies and peripheral blood samples from OBERTO-301 patients treated with PolyPEPI1018 plus atezolizumab. Post-treatment tumor samples showed increased CD8+ T-cell density and PD-L1 expression, indicating conversion toward a more inflamed tumor microenvironment. T-cell receptor (TCR) sequencing demonstrated selective expansion of tumor-reactive T-cell clonotypes, including TCRs directed against PolyPEPI1018 antigens, additional tumor-associated antigens and neoantigens....Importantly, higher numbers of tumor-reactive TCR clonotypes and higher post-treatment CD8+ TIL density were associated with improved clinical outcomes, including longer overall survival and progression-free survival."

P1/2 data • Retrospective data • Colorectal Cancer

Durable pathological complete response associated with broad vaccine-induced T cell immunity in an MSS mCRC patient treated with PolyPEPI1018 peptide vaccine: a case report from the OBERTO-101 study (EACR 2026) - P1/2 | "Material and Following first-line induction therapy (FOLFOX/cetuximab) that led to partial response (PR), this patient entered OBERTO-101 and received maintenance therapy (5-FU/Leucovorin/cetuximab) and subcutaneous PolyPEPI1018 vaccination every 12 weeks (total 3 doses)... This patient case demonstrates that PolyPEPI1018 peptide vaccine can induce broad systemic and intratumoral T cell responses to confer deep, durable disease response by modulating the tumor immune microenvironment of CRC and liver metastases. This is the first report that showed tumoral expansion of T cells derived from peptide vaccination with non-mutated, shared tumor-associated antigens and its long-term clinical benefit in MSS mCRC."

Case report • Clinical • First-in-human • IO biomarker • Colorectal Cancer • Hepatology • Liver Cancer • Solid Tumor • CD8 • IFNG • TRB

TREOS Bio Announces Publication of Phase 1b Clinical Trial Results of PolyPEPI1018 Plus TAS-102 in Refractory MSS mCRC in JCO Oncology Advances (GlobeNewswire) - "In this single-arm trial (n=15) after two prior metastatic treatment lines, PolyPEPI1018 + TAS-102 was generally well tolerated....The combination achieved a 53.3% disease control rate (DCR); median progression-free survival (mPFS) was 4.0 months and median overall survival (mOS) was 8.7 months, representing promising improvements versus historical TAS-102 monotherapy. Patients with longer PFS and OS mounted broader cellular and humoral responses to PolyPEPI1018-targeted antigens. Exploratory analyses indicated more favourable outcomes in patients without active liver metastases at baseline; moreover, patients predicted based on HLA genotype to mount broader PolyPEPI1018-specific T-cell responses had longer survival (mOS 10.3 vs 4.6 months; HR=0.28)."

P1 data • Colorectal Cancer

TREOS Bio Partners with Charité Berlin and Junshi Biosciences to Launch Pivotal Phase II Clinical Trial in Refractory MSS Colorectal Cancer (GlobeNewswire) - "Bridge financing of $2.1 million supports initiation of pivotal Phase II study....The OBERTO-202 study will be conducted as an investigator-led trial at Charité – Universitätsmedizin Berlin, one of Europe's largest university hospitals, with Prof. Sebastian Stintzing as principal investigator and in collaboration with 14 other leading academic hospitals. The trial will evaluate PolyPEPI1018 and toripalimab in combination with standard of care (Lonsurf + Avastin) versus standard of care alone in approximately 140 patients with relapsed/refractory MSS CRC."

Commercial • Financing • New P2 trial • Colorectal Cancer

Evaluation of HLA genotype as predictive biomarker for immunological and clinical responses upon vaccination with PolyPEPI1018 cancer vaccine against colorectal cancer (ESMO 2024) - P1, P1/2, P2 | "Patients complete HLA genotype is the link between the vaccine-elicited robust immune responses and treatment benefit. Based on these encouraging initial results further development of PolyPEPI1018 vaccine with companion diagnostic is warranted."

Biomarker • Clinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8

A phase II, multicenter, open-label study of polyPEPI1018 in combination with atezolizumab in participants with relapsed or refractory microsatellite-stable metastatic colorectal (MSS mCRC) cancer (Oberto-301). (ASCO 2024) - P2 | " Patients with MSS mCRC who have progressed on 2-3 lines of prior chemotherapy regimen received PolyPEPI1018 (1.2 mg, sc) and atezolizumab (1,200 mg, iv) Q3W until disease progression or unacceptable toxicity. PolyPEPI1018 in combination with atezolizumab was well-tolerated with no Grade 3 AEs observed. Despite no objective tumor responses could be detected, correlative data suggest contribution of PolyPEPI1018-induced immune responses to the modulation of tumor microenvironment and to improved disease control. The study did not proceed to stage 2; it is on-going for the collection of survival data."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Colorectal Cancer • Microsatellite Instability • Oncology • CD4 • CD8 • MSI

PolyPEPI1018 Boosts Efficacy of Atezolizumab in Metastatic MSS CRC (Targeted Oncology) - "'Despite no ORR detected, consistent immunological and clinical efficacy data indicate an anti-tumor effect of the combination,' Joleen M. Hubbard, MD...'These data indicate that vaccination with PolyPEPI1018 may augment the efficacy of atezolizumab in MSS [metastatic] CRC and merit confirmation in a randomized trial.'"

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At ASCO 2024, Treos Bio Reports Key Survival Results for Chemo-Free Regimen of PolyPEPI1018 Peptide Immunotherapy and Roche’s PD-L1 Inhibitor in Late-Stage Colorectal Cancer (GlobeNewswire) - P2 | N=18 | OBERTO-301 (NCT05243862) | Sponsor: Treos Bio Limited | "Treos Bio Limited...announced the presentation of results from its phase 2 OBERTO-301 study of the company’s lead product candidate, PolyPEPI1018, in combination with atezolizumab in patients with late-stage microsatellite stable metastatic colorectal cancer (MSS mCRC) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting....The median overall survival (mOS) was 12.8 months (95% CI 8.8 - NE) and the 12-months survival was 60%; this compares favorably to the historical data of 7.1 months and 27% respectively for atezolizumab monotherapy in a similar patient population. Differences between the survival of patients with and without liver metastasis were not statistically significant (HR: 0.58 [95% CI 0.18 - 1.90]; P=0.36): Patients without active liver metastases (NLM) had a 12-month overall survival (OS) estimate of 67% and a median OS of 16.5 months."

P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Treos Bio to Present New Clinical Data on Off-the-Shelf Peptide Immunotherapy for Colorectal Cancer at 2024 ASCO Annual Meeting (GlobeNewswire) - "Treos Bio...investigators will present new results from a phase 2 trial of the company’s lead product candidate PolyPEPI1018 in combination with Roche’s PD-L1 inhibitor atezolizumab in patients with late-stage microsatellite stable metastatic colorectal cancer at the 2024 ASCO Annual Meeting....Investigators will present a poster with new data from OBERTO 301, a multicenter, open label, phase 2 trial evaluating the combination treatment of PolyPEPI1018 and atezolizumab in patients with MSS mCRC who have progressed on two or three prior treatment regimens."

P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Design and Development of PolyPEPI1018, an off-the-Shelf Peptide Vaccine against Colorectal Cancer (IO-SUMMIT EUROPE 2024) - "PolyPEPI1018 consistently induced multi-antigenic immune responses (both cellular and humoral) in high proportion of subjects, triggered recruitment and infiltration of T-lymphocytes into the tumor and increased expression of PD-L1. These studies show that PolyPEPI1018 has a role in improving clinical outcome for a subset of patients identified with a candidate genetic biomarker."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

Design and Development of PolyPEPI1018, an off-the-Shelf Peptide Vaccine against Colorectal Cancer (IO-SUMMIT EUROPE 2024) - "PolyPEPI1018 consistently induced multi-antigenic immune responses (both cellular and humoral) in high proportion of subjects, triggered recruitment and infiltration of T-lymphocytes into the tumor and increased expression of PD-L1. These studies show that PolyPEPI1018 has a role in improving clinical outcome for a subset of patients identified with a candidate genetic biomarker."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

A phase II, multicenter, open-label study of PolyPEPI1018 in combination with atezolizumab in participants with relapsed or refractory microsatellite-stable metastatic colorectal (MSS mCRC) cancer (Oberto-301): Initial results (ESMO 2023) - P2 | "Methods Patients with MSS mCRC who have progressed on 2-3 lines of prior chemotherapy regimen received PolyPEPI1018 (1.2 mg, sc) and atezolizumab (1,200 mg, iv) Q3W. PolyPEPI1018 induced immunological responses at both peripheral and tumor level, converted "cold" tumor into "hot", although to date no responses per RECIST have been noted. The study is on-going."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Colorectal Cancer • Microsatellite Instability • Oncology • CD8 • MSI

Presenting out latest research showing the PolyPEPI1018 peptide vaccine combined with immunotherapy induced immune responses both serologically and in the tumor microenvironment in MSS CRC ...

OBERTO-301: Safety and Activity of PolyPEPI1018 Plus Atezolizumab in Colorectal Cancer. (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: Treos Bio Limited | Recruiting ➔ Active, not recruiting | N=28 ➔ 18

Combination therapy • Enrollment change • Enrollment closed • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

OBERTO-201: A Vaccine (PolyPEPI1018 Vaccine) and TAS-102 for the Treatment of Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Jun 2023 | Trial primary completion date: May 2024 ➔ Jun 2023

Metastases • Trial completion • Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Treos Bio Announces Presentation of Final Results from Phase 1b Study of PolyPEPI1018 Immunotherapy for Late-Stage Metastatic Colorectal Cancer at 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - P1b | N=15 | OBERTO-201 (NCT05130060) | Sponsor: Mayo Clinic | "Treos Bio Limited...today announced the presentation of final results of the Phase 1b OBERTO-201 study of the Company’s lead product candidate, PolyPEPI1018, in combination with the oral chemotherapy TAS-102, for the treatment of patients with late-stage microsatellite stable (MSS) metastatic colorectal cancer (mCRC) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting....Final results from the study demonstrate that PolyPEPI1018 and TAS-102 were safe and tolerable in combination with safety and toxicity profiles similar to TAS-102 monotherapy. Overall, PolyPEPI1018 vaccination successfully induced both CD8+ and CD4+ T cells in each patient with available PBMC samples (n=5) as detected by ex vivo IFN-γ /GrB FluoroSpot. The vaccine induced IgG antibody responses against 3 of the 7 target shared antigens as measured by ELISA (n=15) and IgG antibody levels increased with multiple doses."

P1 data • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

OBERTO-201: A Vaccine (PolyPEPI1018 Vaccine) and TAS-102 for the Treatment of Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Mayo Clinic | Trial completion date: May 2024 ➔ May 2025 | Trial primary completion date: May 2023 ➔ May 2024

Metastases • Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Trial in progress: A phase II, multicenter, open-label study of PolyPEPI1018 in combination with atezolizumab in participants with relapsed or refractory microsatellite-stable metastatic colorectal (MSS mCRC) cancer (Oberto-301). (ASCO-GI 2023) - P2 | "In first line metastatic MSS CRC, PolyPEPI1018 in combination with fluoropyrimidine/bevacizumab vaccine was safe and demonstrated early evidence of clinical activity. The study is open with 10 patients enrolled at time of submission. Clinical trial information: NCT05243862."

Clinical • Combination therapy • IO biomarker • IO Companion diagnostic • Metastases • MSi-H Companion diagnostic • P2 data • PD(L)-1 companion diagnostic • Colorectal Cancer • Gastrointestinal Cancer • Oncology • MSI • PD-L1

OBERTO-201: A Vaccine (PolyPEPI1018 Vaccine) and TAS-102 for the Treatment of Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Mayo Clinic | Recruiting ➔ Active, not recruiting

Enrollment closed • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Dr. Hubbard on the Use of the PolyPEPI1018 Vaccine Plus Chemotherapy in Metastatic CRC (OncLive) - "Joleen M. Hubbard, MD, discusses key survival data from the phase 1b study of the PolyPEPI1018 vaccine and the impact of these findings on continued investigations of this vaccine in metastatic colorectal cancer."

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"PolyPEPI1018 + TAS102 doubles PFS for mCRC pts!" (,@Joleen__Hubbard)

Clinical • Colorectal Cancer