Oncolytics Biotech Inc. operates as a clinical-stage biopharmaceutical company.
The company is developing pelareorep, a safe and well-tolerated intravenously delivered immunotherapeutic agent that activates the innate and adaptive immune systems and weakens tumor defense mechanisms.
Pelareorep is a proprietary isolate of reovirus, a naturally occurring, non-pathogenic double-stranded RNA (dsRNA) virus commonly found in environmental waters. Pelareorep has shown promising results in changing th...
Oncolytics Biotech Inc. operates as a clinical-stage biopharmaceutical company.
The company is developing pelareorep, a safe and well-tolerated intravenously delivered immunotherapeutic agent that activates the innate and adaptive immune systems and weakens tumor defense mechanisms.
Pelareorep is a proprietary isolate of reovirus, a naturally occurring, non-pathogenic double-stranded RNA (dsRNA) virus commonly found in environmental waters. Pelareorep has shown promising results in changing the tumor microenvironment (TME). This creates a more favorable TME, which in turn makes the tumor more susceptible to various treatment combinations. These treatments include chemotherapies and checkpoint inhibitors, as well as other immuno-oncology approaches, such as CAR T therapies, bispecific antibodies, and CDK4/6 inhibitors. Pelareorep induces a new army of tumor-reactive T cells, helps these cells to infiltrate the tumor through an inflammatory process, and promotes the overexpression of PD-1/PD-L1.
Business Strategy
The company’s business strategy is to develop and seek regulatory approval to market pelareorep in an effective and timely manner, and access additional technologies at a time and in a manner that is best for its development.
The key areas of the company’s strategy are continue to assess the safety and efficacy of pelareorep in human subjects through its clinical development program; maintain existing and establish new collaborations with experts to assist it with scientific and clinical developments of this new potential pharmaceutical product; implement strategic alliances with select biopharmaceutical companies and laboratories, at a time and in a manner whereby such alliances may complement and expand its own research and development efforts. Such alliances may also result in an eventual expansion to include providing additive sales and marketing capabilities; use the company’s broadening patent base and collaborator network as a mechanism to meet its strategic objectives; and develop relationships with companies that could be instrumental in assisting it to access other innovative therapeutics.
As its clinical development program advances, the company anticipates pelareorep's ability to enhance innate and adaptive immune responses within the TME will play an increasingly important role. This greatly increases opportunities for expansion of our clinical program along with business development and partnering opportunities to address a broad range of cancers in combination with a variety of other therapies.
The company’s primary focus is to advance its programs in hormone receptor-positive / human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) to phase 3 licensure-enabling studies. In addition, the company is exploring opportunities for registrational programs in gastrointestinal cancers through its GOBLET platform study.
The company’s business strategy is based on attaining a number of commercial objectives. The company is pursuing a strategy of establishing relationships with larger companies as strategic partners. It is anticipated that future clinical development into large international or pivotal trials would generally occur in conjunction with a strategic partner or partners, who would contribute expertise and financial assistance. In exchange for certain product rights and commitments to market the company’s products, the strategic partners would be expected to share in proceeds from the sale of its product or products.
Summary of Research and Development
Pelareorep’s anti-tumor activity is based on three complementary modes of actions, including selective viral replication in permissive cancer cells that leads to tumor cell lysis; activation of innate immunity in response to the infection, which results in a cascade of chemokines/cytokines, causing natural killer (NK) cells to be activated and attack cancer cells; and induction of adaptive immune responses capable of attacking tumors by targeting tumor and virus-specific antigens.
Preclinical and translational research to date indicates the following:
Pelareorep has anticancer effects in a variety of animal models demonstrating that it can reduce tumor burden and prolong survival in these models.
The anticancer effects in animal models can be enhanced when pelareorep is given in combination with chemotherapy, immunotherapy, radiotherapy, and other targeted cancer therapies, highlighting the ability of pelareorep to enhance the anticancer effects of a broad range of cancer therapeutics.
A toxic dose of pelareorep has not been reached/established in animal models and doses as high as 9.0 x 1010 TCID50 have been well-tolerated in humans; treatment with pelareorep causes manageable side-effects.
Clinical data as of 31 December 2023 indicate the following:
More than 1,500 patients have received at least one dose of study treatment in clinical studies with pelareorep. Of these, more than 1,100 patients received pelareorep, over 600 patients in Oncolytics-sponsored trials, and over 500 in investigator-sponsored trials received pelareorep.
Pelareorep has been administered as single or multiple doses (intratumoral or intravenous), either as a monotherapy or in combination with chemotherapy, immunotherapy (e.g., checkpoint inhibitors), and/or radiotherapy.
Pelareorep is generally well-tolerated and has a manageable side effect profile.
When combined with chemotherapy or immunotherapy, pelareorep does not appear to enhance either the frequency or severity of the adverse effects of these agents.
Efficacy results from clinical studies show that treatment with pelareorep can improve the outcome of cancer patients with a variety of different tumors:
In a randomized Phase 2 study with 74 mBC patients, known as IND.213, treatment with pelareorep plus paclitaxel versus paclitaxel alone demonstrated a statistically significant improvement in median overall survival (OS): 17.4 months versus 10.4 months, respectively (HR = 0.65; 80% CI 0.46–0.91; p=0.1). In a post hoc subgroup analysis of patients with HR+/HER2- diseases, the median OS benefit from the addition of pelareorep to paclitaxel was even greater compared to paclitaxel alone: 21.0 months versus 10.8 months, respectively (HR = 0.60; p=0.1). A second randomized Phase 2 study, (BReast cAnCEr with the Oncolytic Reovirus PeLareorEp in CombinaTion with anti-PD-L1 and Paclitaxel) BRACELET-1, in metastatic HR+/HER- breast cancer patients who had failed hormonal therapy showed that pelareorep combined with paclitaxel improved both median progression-free survival (PFS) (9.5 months vs. 6.3 months) and confirmed objective response rate (ORR) (37.5% vs. 13.3%) compared to paclitaxel alone.
In the AWARE-1 window-of-opportunity study, most HR+/HER2- early breast cancer patients treated with pelareorep showed an increase in CeLTIL score, a measure of tumor cellularity and tumor infiltrating lymphocytes (TILs) that is associated with a better prognosis in breast cancer. Importantly, addition of the immune checkpoint inhibitor atezolizumab to pelareorep increased both the magnitude of the increase in CeLTIL score and the proportion of patients with a positive CelTIL score thereby achieving the study’s primary endpoint. Biomarker data from AWARE-1 further demonstrated that pelareorep treatment reversed immunosuppressive tumor microenvironments, generated, and expanded T cell clones, upregulated PD-L1 expression, and promoted CD8+ T cell tumor infiltration into tumors. Many of these effects were even more prominent when pelareorep was combined with atezolizumab demonstrating synergy between the two agents.
In the GOBLET platform study results, the ORR and disease control rate (DCR) were 62% and 85%, respectively, in the first-line advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) patients treated with the combination of pelareorep, atezolizumab and gemcitabine/nab-paclitaxel. The observed ORR is substantially higher than the average ORR of ~25% reported in historical control trials of gemcitabine and nab-paclitaxel in metastatic pancreatic cancer. Additional data also included: Eight of thirteen evaluable patients achieved a partial response (PR); Three of thirteen evaluable patients achieved stable disease (SD); and The cohort exceeded the protocol-specified success criterion for Stage 1 of = 3/12 objective responses.
In a single-arm study of gemcitabine plus pelareorep, known as REO 017, first-line patients with metastatic pancreatic ductal adenocarcinoma, had a median overall survival (OS) of 10.2 months with 1-year and 2-year survival rates of 45% and 24%, respectively. These results were encouraging when compared to 20–22% and 2–5% benchmark 1-year and 2-year survivals, respectively, for metastatic PDAC patients treated with gemcitabine alone from two different phase 3 studies.
In a two-arm Phase 2 study (NCI 8601), patients with metastatic PDAC were randomized to receive either carboplatin, paclitaxel and pelareorep (test arm) or carboplatin and paclitaxel alone (control arm). The median OS was similar for both arms, but the probability of survival at Year 2 was 20% in the test arm vs. 9% in the control arm. Evaluation of patient samples collected during this clinical trial identified the immunomodulatory CEA cell adhesion molecule 6 (CEACAM6) as a potential predictive biomarker for response to pelareorep therapy. Specifically, low levels of CEACAM6 mRNA expression were associated with prolonged progression-free survival in pelareorep-treated patients (10.3 months in CEACAM6 low versus 5.7 months in CEACAM6 high patients, p=0.05); importantly, this effect was not seen in the control arm.
Preliminary results from the anal carcinoma cohort of the GOBLET platform study showed ORR of 37.5% in second-line or later patients with squamous cell carcinoma of the anus treated with pelareorep plus atezolizumab, which compares favorably to the 10-14% ORRs reported in recent clinical trials of checkpoint inhibitor therapy is a similar second-line or later anal carcinoma populations. This cohort has exceeded the Stage 1 success criterion of =2 responses in the first 10 patients.
Clinical Development
Breast Cancer Program
In 2023, the company announced BRACELET-1 (BReast cAnCEr with the Oncolytic Reovirus PeLareorEp in CombinaTion with anti-PD-L1 and Paclitaxel) data that showed pelareorep driving robust increases in PFS and confirmed overall response rate at the 2023 American Society of Clinical Oncology Annual Meeting (ASCO).
Additional key biomarker and safety findings included:
Association between T cell expansion and efficacy measures: A statistically significant increase in T cell fraction, a measure of T cell expansion, was observed in cohort 2 (paclitaxel + pelareorep) but not in cohort 3 (paclitaxel + pelareorep + avelumab).
Generally favorable and manageable safety profile: Pelareorep displayed a manageable safety profile consistent with what has been observed in prior clinical trials that have collectively treated over 1,100 patients.
The results of this study provided important confirmatory data in a patient population similar to its IND.213 study, in which the company observes a statistically significant near-doubling of median OS with pelareorep treatment in HR+/HER2- metastatic breast cancer (mBC). These data further de-risk its path to registration, increasing the likelihood of clinical success and potentially allowing for the use of progression-free survival (PFS) as a primary endpoint.
In addition to the data presented at ASCO, the company continues monitoring BRACELET-1 patients for survival to allow the assessment of median OS in all treatment groups, which it expects to occur in 2024. The company also review its BRACELET-1 data with key opinion leaders to investigate different trial designs as it moves toward defining its breast cancer licensure-enabling study.
In 2023, the company also presented data from its AWARE-1 study at the Society for Immunotherapy of Cancer 38th Annual Meeting (SITC 2023) and 2023 San Antonio Breast Cancer Symposium (SABCS). In the AWARE-1 study, early-stage HR+/HER2- breast cancer patients were enrolled in two cohorts; those in cohort 1 received pelareorep and letrozole, while patients in cohort 2 received pelareorep, letrozole, and atezolizumab.
SITC 2023
Samples from cohort 2 were evaluated using a biomarker panel of 37 conjugated antibodies that bind to tumor antigens and immune cells. Novel imaging mass cytometry (IMC) technology was used to visualize cellular interactions down to the single cell level and showed an increase in PD-L1 positivity and cytotoxic T cells. This translational data will be incorporated into the registrational program for HR+/HER2- metastatic breast cancer.
2023 SABCS
Samples from both AWARE-1 cohorts were evaluated, showing pelareorep induced the expansion of existing tumor infiltrating lymphocyte (TIL) clones, which are presumed to be anti-tumor T cells and new clones. These data are consistent with results from posters recently presented at the (Society for Immunotherapy of Cancer) SITC and European Society for Medical Oncology (ESMO) meetings and affirm that pelareorep functions as an immunotherapeutic agent.
As previously reported, the majority of patients in both cohorts achieved an increase in CelTIL scores, which is correlated with improved patient outcomes, with 60% of patients in Cohort 2 achieving a 30% increase in CelTIL scores, the primary endpoint of the study.
Tumor 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, which included pelareorep and the checkpoint inhibitor.
Clonal expansion results showed that pelareorep induced an expansion of tumor-infiltrating lymphocytes (TILs) in tumor and peripheral blood with tumors, new clones were more prominent; peripheral blood, existing clones were more prominent; and cohort 2 containing atezolizumab, there was greater overall expansion.
Gastrointestinal Cancer Program
In addition to its breast cancer program, the company continues to explore pelareorep in gastrointestinal cancers through its GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) platform study. In 2023, the company completed enrollment in the advanced/metastatic PDAC cohort/Stage 1 and third-line metastatic colorectal (CRC) cohort/Stage 1 and continued to monitor patients and patient outcomes. In its advanced anal cancer cohort, the company continues enrolling patients and evaluating patient outcomes. The company also presented data from its advanced/metastatic PDAC, third-line metastatic CRC, and anal cancer cohorts at various conferences throughout the year.
GOBLET's PDAC cohort survival data reported at ESMO.
Updated data from GOBLET's PDAC cohort was presented at the European Society for Medical Oncology (ESMO) Congress 2023 showing an objective response rate and interim survival data exceeding historical control trials1-4.
A summary of the findings was as follows:
Tumor Responses:
ORR of 62% (54% confirmed by two or more consecutive scans).
A DCR of 85%.
T Cell populations analysis of the changes of T cell clones and tumor-infiltrating lymphocytes (TILs) showed:
Expansion of pre-existing and new T cell clones, including the expansion of TIL-specific clones.
A correlation between the expansion in the blood of TIL-specific clones and tumor response.
Safety:
The treatment combination has been well tolerated with no safety concerns.
Most common grade 3 and 4 treatment-related adverse events were related to red and white blood cell counts (anemia, neutropenia and decreased neutrophil counts), but were transient.
GOBLET's third-line metastatic colorectal (CRC) cohort efficacy data reported at ESMO.
This arm was the second consecutive arm within the GOBLET platform study to meet its respective success criteria and to be eligible to move to full enrollment. The interim results from the third-line metastatic CRC cohort included:
6 of 15 enrolled patients had SD as their best response, including 4 patients demonstrating stable disease (SD) at week 16.
These patients demonstrated a 40% disease control rate (DCR), a progression-free survival (PFS) of 2.8 months, a median OS of 8.0 months, and a 12-month survival rate of 33%.
The data suggested that pelareorep was taken by tumor cells and stimulated T cell expansion even in heavily pre-treated colorectal cancer patients.
GOBLET's anal cancer cohort efficacy data reported at International Multidisciplinary Anal Cancer Conference (IMACC).
Interim data presented at the 2nd International Multidisciplinary Anal Cancer Conference (IMACC) 2023 on patients with second-line or later, unresectable squamous cell carcinoma of the anal canal (SCCA) achieved the pre-defined success criteria. A summary of interim data and findings from the SCCA arm included:
Tumor Responses: Interim ORR of 37.5% based on one patient with a complete response (ongoing at 12 months) and two patients with a partial response (PR) (one at week 8, one ongoing at week 16).
Safety: No safety signal was observed, consistent with previously reported cohorts from the GOBLET study.
As well, in 2023, the company were selected by the Pancreatic Cancer Action Network (PanCAN) as the recipient of its US$5 million Therapeutic Accelerator Award. This grant will enable the company to continue its research on a clinical trial with pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX) chemotherapy with or without Tecentriq in pancreatic cancer patients.
The company has entered into agreements with Pfizer Inc (Pfizer) and Roche to supply their ICIs, avelumab and atezolizumab, respectively, for use in its ongoing Oncolytics-sponsored studies. Specifically, avelumab is being used in the company’s ongoing Phase 2 study in breast cancer (BRACELET study), and atezolizumab was used in its window-of-opportunity study in breast cancer (AWARE study) and is being used in its ongoing Phase 1/2 study in gastrointestinal cancer (GOBLET study). In addition, other ICIs that are being used or has been used in combination with pelareorep in investigator-sponsored studies include retifanlimab (Incyte) in a Phase 2 study in breast cancer (IRENE study) and nivolumab (BMS) in a Phase 1 study in myeloma.
Patents and Trade Secrets
The company relies on its patent portfolio to protect the development of pelareorep. The company has 150 issued patents including 15 issued in the U.S. and 7 in Canada. The company also has 16 patents pending in the U.S., Canada, and other jurisdictions.
Regulations
The company’s toll manufacturers are subject to periodic inspection by the FDA, the United States Drug Enforcement Administration, or DEA, and other domestic and foreign authorities where applicable, and must comply with cGMP regulations.
History
Oncolytics Biotech Inc. was founded in 1998. The company was incorporated under the Business Corporations Act (Alberta) in 1998.
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