On April 12, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), together with SOLTI, reported new clinical data from the AWARE-1 window-of-opportunity breast cancer study showing patients receiving pelareorep plus checkpoint blockade therapy met the trial’s primary endpoint (Press release, Oncolytics Biotech, APR 12, 2021, View Source [SID1234577890]). These data are featured in an electronic poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 during Week 1, which is taking place virtually from April 10-15, 2021.

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In the poster, data from the twenty HR+/HER2- early-stage breast cancer patients included in AWARE-1’s first two cohorts are presented. These patients were treated with pelareorep and letrozole without (cohort 1) or with (cohort 2) the PD-L1 inhibitor atezolizumab (Tecentriq) prior to surgery. Evaluation of cohorts 1 and 2 is the core objective of AWARE-1, as HR+/HER2- is the breast cancer subtype Oncolytics intends to examine in a future registrational study.

Pelareorep treatment in cohort 1 upregulated tumor PD-L1 expression, induced the generation and expansion of T cell clones, promoted tumor infiltration of CD8+ T cells, and increased the CelTIL score, a measure of tumor cellularity and inflammation associated with favorable clinical outcomes. These desired outcomes were further enhanced in cohort 2 patients, demonstrating pelareorep and atezolizumab synergistically combine to generate an anti-cancer immune response in the tumor and peripheral blood. Notably, cohort 2 met the pre-specified success criteria for the study’s primary endpoint (50% of patients with ≥ 30% increase in CelTIL score), with six of ten patients achieving at least a 30% increase in CelTIL score following treatment.

"These exciting AWARE-1 data confirm pelareorep promotes a pro-inflammatory tumor microenvironment, allowing it to synergistically interact with checkpoint inhibitors to train the immune system to fight cancer," said Aleix Prat, M.D., Ph.D., Translational Principal Investigator of AWARE-1, SOLTI President and Head of the Medical Oncology Department at Hospital Clinic in Barcelona. "The data show combining pelareorep with anti-PD-L1 therapy led to increases in CelTIL score and an improvement in the ratio between cytotoxic CD8+ T cells to regulatory T cells. These striking immunological changes are associated with greater therapeutic efficacy and improved clinical outcomes. Collectively, the AWARE-1 results highlight pelareorep’s potential to address the unmet need for techniques to enhance checkpoint inhibitor efficacy and strongly support the continued clinical evaluation of pelareorep-checkpoint inhibitor combinations."

Key data and conclusions from the AACR (Free AACR Whitepaper) poster include:

Treatment with pelareorep alone or in combination with atezolizumab increased tumor PD-L1 expression and led to the conversion of PD-L1 negative tumors into PD-L1 positive tumors
Pelareorep profoundly reverses immunosuppressive tumor microenvironments and promotes immune effector cell infiltration into solid tumors, positioning it as an enabling technology for a variety of immunotherapeutic agents
Tumor-cell specific pelareorep replication was observed in all evaluated patients following intravenous pelareorep administration
60% of cohort 2 patients (n=10) saw a CelTIL increase of at least 30% from baseline (pre-pelareorep administration) to surgery (21-days post-administration), exceeding the study’s pre-specified success criteria
70% of all cohort 1 and 2 patients (n=20) saw an increase in CelTIL from baseline to surgery
The addition of atezolizumab enhances pelareorep’s ability to generate and expand new anti-viral and anti-tumor T cell clones in the tumor and periphery
Compared to cohort 1, cohort 2 patients had a higher ratio of CD8+ T cells to regulatory T cells, suggesting pelareorep and checkpoint inhibition enhances inflammation within the tumor microenvironment
Thomas Heineman, M.D., Ph.D., Global Head of Clinical Development and Operations at Oncolytics, commented, "Based on these new results, we have successfully achieved two key objectives of the AWARE-1 study. We’ve demonstrated synergy between pelareorep and checkpoint blockade therapy, and we’ve shown pelareorep triggers an adaptive T cell immune response specifically targeting tumors."

Matt Coffey, Ph.D., M.B.A., President and Chief Executive Officer of Oncolytics Biotech Inc. added, "Achieving the primary endpoint in AWARE-1 is a key milestone validating our clinical development strategy. Data indicating that pelareorep and atezolizumab synergistically interact de-risks both our lead breast cancer program and our additional clinical trials evaluating pelareorep-checkpoint inhibitor combination therapies. The data also highlight pelareorep’s ability to profoundly reverse immunosuppressive tumor microenvironments and promote immune effector cell infiltration into solid tumors, positioning it as an enabling technology for a variety of immunotherapeutic agents. Moving forward, we expect these data to facilitate the advancement of our lead breast cancer program towards a registrational study while simultaneously bolstering our business development efforts across several indications and immunotherapy treatment regimes."

The electronic poster, titled "A window-of-opportunity study with atezolizumab and the oncolytic virus pelareorep in early breast cancer (AWARE-1)" is available for on-demand viewing on the AACR (Free AACR Whitepaper) Annual Meeting 2021 e-poster website and on the Posters & Publications page of Oncolytics’ website (LINK).

Key Opinion Leader Event

Oncolytics will host a Key Opinion Leader (KOL) event today at 2:00 pm ET with Aleix Prat, M.D., Ph.D., Translational Principal Investigator of AWARE-1, SOLTI President and Head of the Medical Oncology Department at Hospital Clinic in Barcelona and Dr. Richard Vile, a Professor of Immunology at the Mayo Clinic, who led the preclinical CAR T study with pelareorep presented earlier this year (link to press release, link to poster). To access the webcast, please click this link.

About AWARE-1

AWARE-1 is an open label window-of-opportunity study in early-stage breast cancer enrolling 38 patients into five cohorts:

Cohort 1 (n=10), HR+ / HER2- (pelareorep + letrozole)
Cohort 2 (n=10), HR+ / HER2- (pelareorep + letrozole + atezolizumab)
Cohort 3 (n=6), TNBC (pelareorep + atezolizumab)
Cohort 4 (n=6), HR+ / HER2+ (pelareorep + trastuzumab + atezolizumab)
Cohort 5 (n=6), HR- / HER2+ (pelareorep + trastuzumab + atezolizumab)
The study combines pelareorep, without or with atezolizumab, and the standard of care therapy according to breast cancer subtype. Tumor tissue is 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 of their mastectomy. Data generated from this study are intended to confirm that pelareorep is acting as a novel immunotherapy, to evaluate potential synergy between pelareorep and checkpoint blockade, and to provide comprehensive biomarker data by breast cancer subtype. The primary endpoint of the study is overall CelTIL score (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study include CelTIL by breast cancer subtype, safety, and tumor and blood-based biomarkers.

For more information about the AWARE-1 study, refer to View Source

Tecentriq (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

About Breast Cancer

Breast cancer is the most common cancer in women worldwide, with over two million new cases diagnosed in 2018, representing about 25 percent of all cancers in women. It is the second leading cause of death from cancer in women in America, with an estimated 42,000 deaths in the US in 2020.1

Breast cancer starts when cells in the breast begin to grow out of control. These cells usually form a tumor that can often be seen on an x-ray or felt as a lump. The malignant tumor (cancer) is getting worse when the cells grow into (invade) surrounding tissues or spread (metastasize) to distant areas of the body.

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

On April 12, 2021 C4X Discovery Holdings plc (AIM: C4XD), a pioneering Drug Discovery company, reported that its subsidiary, C4X Discovery Limited ("C4XD", "C4X Discovery" or the "Company"), has signed an exclusive worldwide licensing agreement with Sanofi (NASD: SNY, PAR: SAN – "Sanofi "), worth up to €414 million, for C4XD’s oral pre-clinical IL-17A inhibitor programme (Press release, C4X Discovery, APR 12, 2021, View Source [SID1234577886]). Under the terms of the agreement, C4XD will receive an upfront payment of €7 million and could receive up to a further €407 million in potential development, regulatory and commercialisation milestones, of which €11 million is in pre-clinical milestones, in addition to single digit royalties.

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Under the license, Sanofi will develop and commercialise an oral therapy for the treatment of inflammatory diseases, a multi-billion dollar market. The IL-17 family of cytokines are strong inducers of inflammation and are implicated in a variety of autoimmune diseases including psoriasis, psoriatic arthritis and ankylosing spondylitis. Current treatments targeting IL-17 are monoclonal antibodies administered via an injection. There is an urgent need for safe and efficacious oral small molecule therapies to increase the number of patients able to access IL-17 targeted drugs and expand availability into new inflammatory disease indications. C4XD’s small molecule IL-17A inhibitor programme can selectively block IL-17 activity in vivo whilst maintaining molecular size of the molecule in the traditional "drug-like" range suitable for oral administration. Sanofi will continue to work with the C4XD team to access its unique and proprietary 4D Conformetrix technology, as the programme advances towards clinical studies.

Clive Dix, CEO of C4X Discovery, said: "We are proud to be working with Sanofi to create much needed oral therapies in the underserved inflammatory disease space. While antibody therapies have demonstrated the potential of IL-17 inhibition in the generation of highly effective treatments, the injectable route means many patients currently do not have access to the medicines that can change their lives. We believe that our small molecule programme has the potential to create high value, efficacious and convenient oral IL-17 therapeutics for this large market. The Psoriasis market alone is estimated to be worth c.$24 billion per annum by 20271, and when combined with Sanofi’s development expertise our programme has the potential to address a number of indications.

"This is the second significant agreement for a C4XD programme and marks a major milestone for the Company, not only validating the strength of our Drug Discovery expertise, but also our strategy to drive shareholder value through early-stage revenue generating deals. With Indivior progressing our molecule for opioid addiction through a Phase I clinical trial and now our partnership with Sanofi driving potential next generation oral IL-17 therapies, we look forward with confidence to further develop our portfolio and deliver additional novel small molecule drug candidates tackling significant patient needs."

On April 12, 2021 XNK Therapeutics AB ("XNK" or the "Company"), a Swedish clinical stage immunotherapy company treating cancer by developing novel NK cell-based therapies, reported the completion of a private placement of SEK 64 million (Press release, CellProtect Nordic Pharmaceuticals, APR 12, 2021, View Source [SID1234577885]). The purpose of the issue is primarily to finance the Company’s research and development efforts.

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"XNK has made significant progress with its technology platform and this new funding will be key to continue the clinical development of our leading investigational drug candidate," said Johan Liwing, CEO of XNK.

On April 11, 2021 StoneWise, a medical technology company that accelerates novel drug discovery with artificial intelligence, reported that it has completed its series B and B+ financing to raise a total of US$100 million (Press release, Stonewise, APR 11, 2021, View Source [SID1234654561]).

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The series B financing was led by Legend Capital, while the series B+ funding was co-led by Greater Bay Area Community Development Fund and Lightspeed China. New investors include CDH VGC Fund and Eastern Bell Capital. Existing shareholders HillHouse Ventures, SIG, Long Hill Capital, and Linear Capital made additional investments.

The proceeds will be used to recruit and retain world-leading talents and upgrade the AI-enabled drug discovery platform so as to advance innovation and improve R&D efficiency.

"We will use the proceeds from these two rounds of financing to strengthenour talent team, accelerate technology iteration, and support project execution," says Zhou Jielong, founder of StoneWise. "We expect more eminent professionals to join us in the early stage of pharmaceutical development. Together, we will identify promising drug candidates faster, advance the use of AI in drug innovation, and improve life quality," he continues.

StoneWise completed four rounds of financing in 2020. Its investors include high impact players in both the pharmaceutical and the AI sectors. The latest financing will empower StoneWise to leverage its molecular design platform and knowledge graph to gear up AI-driven discovery of novel drugs.

It takes up to 15 years and around US$2.6 billion on average to develop a new drug. As one of the global pioneers to apply AI to small molecule drug R&D, StoneWise makes drug development more time-efficient and cost-effective with its drug discovery platform.

The platform provides pharmaceutical companies an integrated solution, featuring a vast range of tools such as a wide range of AI models, interactive medical knowledge graph, deep learning-driven scaffold hopping/derivatization, and generative molecular creation and design.

Richard Li, President of Legend Capital says, "Drug innovation is at the core of pharmaceutical development, and it is also a major entry point for AI application. StoneWise is an industry leader in terms of new technology development, strategic planning and project execution. We are confident that via integrating AI with computational chemistry, pharmacology, molecule dynamics, quantum mechanics, and other cutting-edge technologies, StoneWise will strive to lead AI-driven drug innovation."

"Drug discovery industry faces challenges such as long R&D cycles, low success rates, and sky-rocketing costs, which can be more effectively addressed by AI technologies. Up to now, multiple drugs developed with the support of AI entered into clinical development stages," says Mingyu Wang, senior partner of CDH VGC. "StoneWise’s AI platform has been well received by many pharmaceutical companies. We are confident on its growth potential and expect a continuous output of high-quality drug candidates., and a significantly improved drug discovery R&D system."

On April 11, 2021 Checkmate Pharmaceuticals, Inc. (NASDAQ: CMPI) ("Checkmate"), a clinical stage biopharmaceutical company focused on developing its proprietary technology to harness the power of the immune system to combat cancer, reported the presentation of new translational data from Checkmate’s Phase 1b trial of vidutolimod (CMP-001) in combination with pembrolizumab in patients with advanced anti-PD-1 refractory melanoma (Press release, Checkmate Pharmaceuticals, APR 11, 2021, View Source [SID1234577914]).

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Vidutolimod (CMP-001) demonstrates improved response in noninflamed anti–PD-1 refractory melanoma and response is associated with serum CXCL10 (Abstract #: 5231: NCT02680184)

During the 2021 AACR (Free AACR Whitepaper) Virtual Clinical Trials with Novel Immuno-oncology Strategies Session on April 11 from 4:00 – 5:45pm ET, Jason Luke, MD, Director, Cancer Immunotherapeutics Center, UPMC Hillman Cancer Center, and Associate Professor of Medicine, University of Pittsburgh School of Medicine, presents new translational data from an ongoing Phase 1b study of vidutolimod in combination with pembrolizumab in patients with PD-1 blockade refractory advanced melanoma.

Key highlights from these clinical data include:

93% of patients had progressive disease as their last response assessment on prior PD-1 blockade therapy, 42% had an elevated LDH, and the median sum of the target lesions longest diameter was 6.7 cm, indicating advanced disease
Response rates to vidutolimod in combination with pembrolizumab were similar across baseline patient characteristics including BRAF mutation, LDH level, number of prior systemic cancer treatments, best response to prior PD-1 blockade therapy, and prior ipilimumab
Responders and non-responders were not distinguished by baseline tumor characteristics including PD-L1 CPS, IFNg transcriptional signature, CD8+ T cells, or nonsynonymous mutations
All patients showed the expected rapid induction of anti-Qb antibodies to the virus-like particle (VLP), which facilitate the pharmacodynamic response to vidutolimod, and the antibody titers were not associated with clinical response
Clinical activity of vidutolimod in combination with pembrolizumab was associated with serum CXCL10 induction magnitude, induction of an inflammatory gene expression profile, and CD8+ T cells in injected and noninjected tumors
"These translational data provide new insights into the rapid pharmacodynamic responses to vidutolimod and support the conclusion that clinical responses to treatment are not associated with the previously-described predictive markers for response to PD-1 blockade such as inflamed tumors," said Dr. Jason Luke.