SAN DIEGO, Calif. and CALGARY, AB, Jan. 11, 2022 (Canada NewsWire via COMTEX) -- Oncolytics Biotech(®) Inc. /zigman2/quotes/204741333/composite ONCY +3.70% /zigman2/quotes/203812837/delayed CA:ONC +1.43% is providing a letter to shareholders, included below.
To the Shareholders of Oncolytics Biotech,
2021 generated ground-breaking data that creates the foundation for continued success in 2022 as we build our clinical opportunities and the data required to embark on our registrational study in metastatic breast cancer. This critical data encompasses data requested by the FDA and our global pharma collaborators, data that de-risks both our registrational program and clinical studies going forward. I would like to provide a summary of our 2021 accomplishments, an update on the final pieces of our metastatic HR+/HER2- breast cancer program, and provide some commentary on several of our promising programs in other indications.
Most importantly, the AWARE-1 study results presented this past year exceeded our expectations and provided us with additional confidence in our overall clinical development program. We are well on our way to completing enrollment in BRACELET-1, expected to occur in early 2022. The combination of clinical data from BRACELET-1 along with data from AWARE-1 will provide the final elements necessary to develop and launch a registrational study in metastatic breast cancer.
HR+/HER2- Breast Cancer Program: Our Primary Focus
If you have been following the Company, you're likely aware that we saw a near doubling of overall survival (OS) in metastatic HR+/HER2- breast cancer patients treated with pelareorep in IND-213, a randomized phase 2 study (link to the PR). After analyzing these data, we focused on achieving three key objectives set forth by regulators and our pharma partners, which represent important steps on the path to a registrational study. These objectives are to:
1. confirm that pelareorep works through an immunotherapeutic mechanism of action. Our enhanced understanding demonstrates pelareorep acts as an immunotherapeutic agent, part of an emerging drug class that provides much longer-lasting anti-cancer effects. This understanding allows us to better design clinical studies that are more likely to be successful; 2. determine whether pelareorep synergizes with immune checkpoint inhibitors (ICIs). Enhancing ICI activity exposes the Company to an oncology market expected to exceed $55 billion by 2025; 3. identify a biomarker to select patients who are likely to have better clinical outcomes. Biomarkers allow us to identify patients who are likely to respond to treatment, streamlining our registration program.
I am pleased to report that we are well on our way to achieving these three objectives. In April, at AACR (link to the PR), we presented data from cohort 1 and cohort 2 (both cohorts exclusively enrolled HR+/HER2- breast cancer patients) of our AWARE-1 study, which is being conducted in collaboration with Roche. Importantly, these data showed we had achieved the first two objectives referenced above. Specifically, we demonstrated that pelareorep treatment reverses immunosuppressive tumor microenvironments, generates and expands T cell clones, upregulates PD-L1 expression, promotes tumor infiltration of CD8+ T cells, and increases CelTIL score, a metric known to correlate with improved clinical outcomes. These effects were even more notable when pelareorep was combined with Roche's ICI atezolizumab, which demonstrates synergy between the two agents. This finding could be a significant advance, not only in breast cancer but in multiple other indications. Finally, in Q4 2021, after completing further analyses of samples from AWARE-1, we reported that changes in peripheral blood T cell populations acts as a putative predictive biomarker. This robust engagement of anti-tumor activity in AWARE-1 supports the hypothesis that the near doubling of overall survival seen in IND-213 was the result of the engagement of innate and adaptive immunity.
Based on the findings from IND-213 and AWARE-1, we continue to have confidence in the expected results from BRACELET-1, a randomized phase 2 study in metastatic HR+/HER2- breast cancer patients being conducted in collaboration with Pfizer and Merck Serono. To better understand and potentially optimize the overall clinical benefit observed in IND-213, BRACELET-1 was designed almost identically, but with an additional cohort to evaluate pelareorep in combination with the checkpoint inhibitor avelumab. Our principal objective for BRACELET-1 is to study our target patient population to inform the design of a registrational study, determine the number of patients required, and confirm what was seen in AWARE-1: the synergistic clinical benefits of pelareorep-ICI combination therapy in addition to using changes in peripheral blood T cell populations as a biomarker to select patients likely to have better outcomes.
We consider BRACELET-1 to be the last major step on our path to a registrational study, and we are on track to reach full enrollment in the trial in the first quarter of 2022. From there, we will need 16 weeks to conclude the patient scans required for a complete dataset for the primary endpoint, as well as additional time to compile and analyze the data. Considering all of this, we anticipate announcing BRACELET-1's top-line data in the fourth quarter of 2022. These timelines assume no or limited adverse impact from COVID-19. In the meantime, we plan to begin discussing our plans for a registrational study with the FDA and additional regulators while we are completing enrollment and performing data analysis.
Triple-Negative Breast Cancer: Expanding Pelareorep into an Additional Subtype
In December, we provided a positive safety update for the first five patients enrolled in IRENE (link to the PR), our study investigating pelareorep and an ICI in second- or third-line metastatic triple-negative breast cancer (TNBC). The absence of additional toxicity with this treatment combination in the TNBC subtype, in addition to the more established safety profile of pelareorep-ICI combinations in the HR+/HER2- subtype, means we could potentially expand into large ICI indication opportunities. We are excited about pelareorep's potential in TNBC and look forward to further results from IRENE.
GOBLET Trial: An Expansion of our Roche Collaboration into a New Indication
This past November, the first patient was dosed in GOBLET (link to the PR), our phase 1/2 trial to evaluate pelareorep in combination with atezolizumab for the treatment of colorectal, pancreatic, and anal cancer. This study is being conducted in collaboration with AIO and Roche and is exciting because it is an expansion of our relationship with Roche, our collaborator in AWARE-1, and represents an additional opportunity beyond breast cancer. GOBLET is supported by the encouraging AWARE-1 data and by data previously reported in pancreatic and colorectal cancer, which showed pelareorep-based combination treatments stimulated an adaptive immune response and:
-- led to a greater than 90% clinical benefit rate in KRAS-mutated colorectal cancer patients (link to the PR), and -- a greater than 80% increase in progression-free survival (PFS) in pancreatic cancer patients with low levels of CEACAM6 expression (link to the PR).
We are planning to provide a safety and enrollment update for this study in Q1 2022 and will provide more data as they become available.
Pelareorep and CAR T Cell Therapy in Solid Tumors: Potentially Opening a New Market
One development I found particularly exciting this past year was the announcement of data from preclinical studies of pelareorep and CAR T cell therapy in solid tumors (link to the PR). While CAR T cell therapy has historically been ineffective in solid tumors, combining CAR T cells with pelareorep in mice improved CAR T cell persistence and efficacy. This was further enhanced by an intravenous boost of pelareorep, which ultimately led to tumor cures. In that same study, boosting with a different oncolytic virus did not prevent recurrent tumor growth. If these results in solid tumors can be translated to the clinic, it would open a very significant new potential market that is currently unavailable, as CAR T therapy is now only used in hematological malignancies. As we've previously mentioned, this is largely a business development opportunity for Oncolytics, and 2021 involved working with our academic and industry collaborators to further evaluate and confirm the earlier results. We look forward to sharing additional updates as our work matures.