Scienza e Tecnologia
Oncolytics Biotech® Releases a Letter to Shareholders - 2021 Review and 2022 Outlook
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.
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:
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.
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.
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:
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.
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.
Pelareorep's development in China is positively progressing, with partner Adlai Nortye dosing the first patient in a bridging clinical trial evaluating the safety, tolerability, and preliminary efficacy of pelareorep-paclitaxel combination therapy in Chinese patients with advanced or metastatic breast cancer (link to the PR). This study, a Chinese FDA requirement, is very similar to our metastatic HR+/HER2- studies and is intended to accelerate pelareorep's clinical development in territories that include China , Hong Kong , Macau , Singapore , South Korea , and Taiwan . These are valuable and rapidly growing pharmaceutical markets, with China alone being the second-largest in the world after the United States .
Pelareorep's ability to recruit T cells into tumors, as demonstrated in AWARE-1, positions it as a potentially enabling technology for a wide cross-section of therapeutic agents. The findings highlighted below are from preclinical studies run by investigators at various institutions who have seen the value of pelareorep as an immunotherapeutic agent and have allocated their research budgets to evaluate combination therapies in their laboratories.
Over the last year, the data we generated and reported on have been invaluable, showing us that pelareorep generates a profound immunological response and synergizes with multiple oncology treatments. This leads us to an expanding list of potential combination partners and target indications. While breast cancer, specifically the HR+/HER2- subtype, a multi-billion-dollar opportunity, remains our primary focus, investigators continue to evaluate pelareorep as a potential immunotherapy backbone, and we continue to consider additional areas of study going forward. We believe we are on track to achieve several important milestones this year, the most significant of which will be our top-line data announcement for BRACELET-1, which is the last major step on our path to a registrational study. Based on our current timing expectations, we expect to report top-line data in Q4 2022. In lockstep with this, we will be furthering our regulatory plan with the FDA and potentially with other regulators to refine our phase 3 study design, an essential step before beginning a registrational study. Additionally, we expect to provide a GOBLET enrollment update, a multiple myeloma study update, disclose new data from our glioblastoma study, and provide more updates from other studies later this year.
Wishing everyone a happy new year and offering my thanks for your continued support,
Dr. Matt Coffey , President & CEO of Oncolytics Biotech
Director of IR & Communication
+1-858-886-7813
jpatton@oncolytics.ca
LifeSci Advisors
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tim@lifesciadvisors.com
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