On December 7, 2023 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a clinical-stage immunotherapeutics company focused on oncology, reported the presentation of additional translational data from the AWARE-1 breast cancer window-of-opportunity study conducted in combination with SOLTI-Innovative Cancer Research at The San Antonio Breast Cancer Symposium (SABCS) (Press release, Oncolytics Biotech, DEC 7, 2023, View Source [SID1234638252]).

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"Translational data presented from the AWARE-1 study at SABCS showed that pelareorep induced the expansion of tumor-infiltrating lymphocytes, or TILs, in matched tumor biopsy and peripheral blood samples of newly diagnosed breast cancer patients. In addition, sequencing of the T cell receptors (TCRs) showed a more prominent expansion of existing TIL clones in the blood. We consider these results to be positive and important because they build on additional translational results reported this fall at two other medical meetings, The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) and The European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper), from the AWARE-1 and GOBLET studies respectively, and provide further support for pelareorep’s unique immunologic mechanism of action," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics. "Taken together, these translational data affirm pelareorep’s ability to enhance T cell infiltration into tumors and expand TILs in the peripheral blood, which have been correlated with tumor response. We intend to incorporate these learnings into the designs of our registrational studies in metastatic breast cancer and pancreatic cancer."

Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics, commented, "A review of the AWARE-1 study translational data presented at this year’s SABCS and previous scientific conferences demonstrates that pelareorep treatment, especially in combination with atezolizumab, results in:

•an increase in CelTIL score, which correlates with improved clinical outcomes in breast cancer
•increased CD8+ T cell infiltration into tumors
•the generation and expansion of T cell clones, especially TILs
•the upregulation of tumor PD-L1 expression

These findings confirm that pelareorep remodels the tumor microenvironment and stimulates tumor-directed immune responses, effects we believe are driven by the introduction of pelareorep’s double-stranded RNA into cancer cells."

Dr. Heineman concluded, "Results from multiple prior studies lead us to believe that pelareorep has the potential to fill very important treatment gaps for both breast and pancreatic cancer patients. The translational data reported this fall emphasize the importance of TIL clone expansion in pelareorep-treated patients and represents an important area for further exploration. We believe that analysis of TIL clone expansion could become a helpful precision tool to provide an early indication of treatment response and serve as a potential guide to patient care with pelareorep. We remain dedicated to expeditiously advancing the clinical development of pelareorep in support of our goal to provide cancer patients with improved treatment options."

Summary of Data and Findings for TIL-TCR-Seq from the AWARE-1 Study:

Samples: From the AWARE-1 window-of-opportunity study of patients with early-stage HR+/HER2- breast cancer:
•Collected from two patient cohorts, treated with pelareorep plus letrozole (cohort 1) or pelareorep plus letrozole and atezolizumab (cohort 2)
•Matched tumor and peripheral blood samples collected at two time points:
o#1 at the beginning of the study on Day 1 and

o#2: Day 21 – when tumors were surgically removed

Evaluation:
•Composite T cell scores, a tool to evaluate cellularity, previously analyzed according to the CelTIL scale; data provided in the poster for reference
•T cell fractions, to assess the TIL-fraction of T cells
•T cell Receptor Analysis, using T cell receptor sequencing (TCR Seq) as a proxy to analyze the number of TIL-specific clones and assess their origin, from pre-existing or new clones
•T cell data was analyzed to assess T cell clonal expansion according to origin (existing or new) at both time points (baseline and Day 21) and tissue samples (tumor biopsy or peripheral blood), using Adaptive Biotechnology’s Immunoseq’s protocol

Results: Pelareorep induced the expansion of existing TIL clones as well as new clones. These data are consistent with results from posters recently presented at SITC (Free SITC Whitepaper) and ESMO (Free ESMO Whitepaper) and affirm that pelareorep functions as an immunotherapeutic agent.
•CelTIL showed a composite increase in T cells: as previously reported, the majority of patients in both cohorts achieved an increase in CelTIL scores, with 60% of patients in Cohort 2 achieving a 30% increase in CelTIL scores, the primary endpoint of the study
•T cell fractions showed that TILs increased in both study cohorts (1.27 fold in Cohort 1, 2.74 fold in Cohort 2), with a greater increase in Cohort 2
•Clonal expansion results showed that pelareorep induced an expansion of TILs in tumor and peripheral blood with:
oIn tumors, new clones were more prominent
oIn peripheral blood, existing clones were more prominent
oIn cohort 2, there was greater overall expansion (qualified by the small numbers)

About AWARE-1
AWARE-1 was an open-label window-of-opportunity study in early-stage breast cancer. The study combined pelareorep, without or with atezolizumab, and standard of care therapy according to breast cancer subtype. Tumor tissue was collected from patients as part of their initial breast cancer diagnosis, again on day three following initial treatment, and finally at three weeks following treatment, on the day their tumor is surgically resected. Key objectives of the study were to confirm that pelareorep is acting as a novel immunotherapy, to evaluate potential synergy between pelareorep and checkpoint blockade, and to collect biomarker data. The primary endpoint of the translational study was overall CelTIL score (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study included safety and tumor and blood-based biomarkers. AWARE-1 met its primary endpoint of overall CelTIL score in 2021 (link to the PR, link to the poster). Additional biomarker data announced in 2022 showed pelareorep’s potential to improve the prognosis of breast cancer patients (link to the PR, link to the poster).

Poster Information
Poster Title T Cell Receptor Sequencing to Monitor Pelareorep-Induced Expansion of Tumor Infiltrating Lymphocytes
Presentation ID PO1-02-01
Session Poster Session 1
Poster Date & Time Wednesday, December 6, 2023 from 12 p.m. – 2 p.m. Central Time

A copy of the poster is available on the Oncolytics website and can be found by clicking here.