On January 4, 2024 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a clinical-stage immunotherapeutics company focused on oncology, reported on significant 2023 accomplishments and reported corporate priorities and anticipated clinical development milestones for 2024 (Press release, Oncolytics Biotech, JAN 4, 2024, View Source [SID1234638978]).

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Overview: "2023 was an outstanding year for Oncolytics and the development of pelareorep as a potential cancer therapy. To date, we have studied pelareorep in more than 1,100 patients, and it has been shown to be well-tolerated with mild side effects. Promising clinical and translational results from our Phase 2 programs and mechanism of action learnings from a wide range of tumor types, as detailed below, provided consistent data and efficacy signals with durable responses that support the use of pelareorep as an immunotherapeutic agent, either as a monotherapy or in combination with other agents. These data readouts from multiple clinical studies at numerous sites and from diverse cancer indications that are clinically important make a compelling argument for pelareorep as a true backbone immunotherapy with the potential to help countless patients across a range of tumors," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics. "We believe our cash balance and strong data, supported by our active business development program, position us well for 2024."

Positive Clinical and Translational Data: "Positive, early results from the Phase 1/2 GOBLET study in three gastrointestinal cancers – pancreatic, anal, and colorectal – showed that the combination of pelareorep and atezolizumab produced clinically meaningful improvements in response rates and survival timelines that are notably improved compared to historical results with no toxicity concerns. Translational data from studies in solid tumors, breast, pancreatic, and colorectal cancers showed that treatment with pelareorep remodels the tumor microenvironment and stimulates tumor-directed immune responses, affirming its mechanism of action as an immunotherapeutic agent. Together, these data provide a strong foundation to support advancing pelareorep into registrational-track studies, starting in 2024," continued Dr Coffey.

2024 Outlook: Dr. Coffey concluded by saying, "Looking ahead to 2024, we expect to initiate the first Phase 3 study for pelareorep in pancreatic cancer. The transition to a late-stage biopharmaceutical company will mark an important inflection point for investors, clinical collaborators and potential partners by providing a line of sight towards the path to regulatory approval and achieving our mission of developing pelareorep as an immunotherapeutic agent for cancer. We are excited to launch a new Phase 1/2 pancreatic cancer study investigating, for the first time, pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX). Finally, our discussions with regulators on a pivotal Phase 3 trial have been productive to date, and we expect to provide guidance on the registration path for metastatic breast cancer in the first half of 2024. We look forward to updating our stakeholders on our progress as the year unfolds."

Immunotherapeutic Mechanism of Action: Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics, said, "Translational data from multiple studies in 2023 have helped define pelareorep’s role in shaping the tumor microenvironment and have provided a better understanding of its ability to induce the expansion of T cell populations. Notably, the positive association between tumor response and TIL clone expansion could become a useful marker of clinical outcomes in future studies and during patient care. Moreover, these findings further distinguish pelareorep’s mechanism of action from that of other immunotherapeutic agents and provide support for its immunologic effects, which are largely driven by the introduction of its double-stranded RNA genome into cancer cells."

Financial Strength and Partnering Outlook: Kirk Look, Oncolytics’ Chief Financial Officer, commented, "Our $40 million cash balance as of September 30, 2023, and the grant funding from The Pancreatic Cancer Action Network (PanCAN) provides us with over 12 months of runway to support our operations, including the initiation of our first Phase 3 study and the BRACELET-1 survival data. We continue to have active conversations with potential partners and work diligently with clinical collaborators, including Roche and Pfizer. We believe the positive, extended dataset, including continued and durable responses, survival results, and translational observations, will provide potential partners with a well-defined and unique target product profile that will add to our discussions."

Anticipated Milestones are expected to include:

•H1 2024: Guidance on the registration path for HR+/HER2- mBC (metastatic breast cancer)
•H1 2024: Initiation of the PanCAN-supported Phase 2 Pancreatic Ductal Adenocarcinoma (PDAC) trial incorporating mFOLFIRINOX +/- atezolizumab and pelareorep
•Mid-2024: Initiation of the adaptive Phase 3 trial for pelareorep in PDAC
•Overall survival results from the BRACELET-1 study
•Expand enrollment following achievement of success criteria from the GOBLET Phase 1/2 study anal cancer cohort

Highlights of Oncolytics Biotech’s 2023 Achievements:

HR+/HER2- Metastatic Breast Cancer Program and the BRACELET-1 study
•Promising Randomized Phase 2 Data Readout Supports Previous Near Doubling of Median Overall Survival: Data presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting showed that pelareorep in combination with paclitaxel (cohort 2) resulted in a near tripling of confirmed overall response rate, a 50% increase in median progression-free survival, and a hazard ratio of 0.29 (link to the PR) compared to paclitaxel monotherapy (cohort 1).

Overall survival (OS) data continues to mature since multiple patients continue to be followed for survival in the pelareorep + paclitaxel cohort. Positive results would provide Oncolytics with two successful randomized Phase 2 studies showing a meaningful OS benefit for pelareorep. The data reported so far supports the initiation of a pivotal study in mBC and makes the case for an overall survival and progression-free survival dual endpoint in a registrational trial, which could substantially reduce the time to potential approval.

Gastrointestinal Cancers and the GOBLET study cohorts
•Pancreatic Cancer Survival Data Reported at ESMO (Free ESMO Whitepaper) Supports Decision to Move to Phase 3: Updated data presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 showed a 62% objective response rate, nearly triple what has been seen in historical control trials. In addition, interim survival data, including median progression-free survival and median overall survival timelines, exceed historical control trials by 25% or more (link to the PR, link to the poster). Patients in this single-arm, open-label study with advanced PDAC were treated with pelareorep, atezolizumab, gemcitabine, and nab-paclitaxel.

We continue to follow the survival of several patients in this cohort as well as patients from the GOBLET study with third-line colorectal cancer, which also met the pre-defined success criteria (link to the PR, link to the poster). Having received Fast Track designation from the FDA for the treatment regimen of pelareorep, atezolizumab, gemcitabine, and nab-paclitaxel in metastatic PDAC patients last year, we were very pleased to report additional promising data for this combination, paving the way to initiate our adaptive Phase 3 trial which will now be conducted by Oncolytics, building on the positive feedback from our work with PanCAN.

Also, thanks to a US$5 million grant from PanCAN, we will examine the potential of pelareorep in combination with mFOLFIRINOX +/- atezolizumab. With these data plus the results from the adaptive Phase 3 PDAC study (pelareorep + gemcitabine + nab-paclitaxel + atezolizumab), we hope to show efficacy data for pelareorep in combination with the two most commonly used treatment regimens for pancreatic cancer patients, which could help pave the way for future broad adoption by physicians and impact a substantial number of patients.

•Anal Cancer Data – Positive Early Results in an Underserved Patient Population: Data presented at the 2nd International Multidisciplinary Anal Cancer Conference (IMACC 2023) achieved the pre-defined Simon-two-step success criteria and showed a near tripling of objective response rates compared to historical control trials in addition to a complete response (link to the PR, link to the poster). Patients in this single-arm, open-label study with second-line, unresectable squamous cell carcinoma of the anal canal (SCCA) were treated with pelareorep and atezolizumab, marking an exciting signal of efficacy in an indication where checkpoint inhibitors have had limited impact historically, and there are few treatment options.

Having met the success criteria for efficacy for this cohort, we will work closely with AIO-Studien-gGmbH (AIO), which is managing the GOBLET study, to expand the number of patients who can be treated and, hopefully, accelerate the enrollment process. With continued positive data, this could become another high-priority indication for the company.

Other Opportunities: Preclinical data published in Science Translational Medicine (link to the PR) from studies in murine tumor models showed that combining CAR T cells with pelareorep improved CAR T cell persistence and efficacy in solid tumors. An intravenous boost of pelareorep enhanced this effect and led to tumor cures in >80% of cases. We believe there is a significant opportunity here as CAR T cell therapy is currently only effective in hematological cancers, and solid tumors are the vast majority of cancers diagnosed each year. While we do not have an active program underway, we continue to have discussions on the best way to advance this effort.

I would like to take this moment to wish everyone a Happy New Year and thank our shareholders for their support. We look forward to providing additional positive updates in 2024.

On January 4, 2024 Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standards of care to cure cancer and infectious diseases, reported that it has entered into a clinical study and collaboration agreement with Repare Therapeutics Inc. ("Repare") (Nasdaq: RPTX), a leading clinical-stage precision oncology company (Press release, Debiopharm, JAN 4, 2024, View Source [SID1234638995]). This clinical collaboration aims to explore the synergy between Debio 0123, a potential best-in-class, brain-penetrant, and highly selective WEE1 inhibitor, and lunresertib, a first-in-class, selective and potent oral, small molecule inhibitor of PKMYT1 with demonstrated anticancer activity.

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"We are delighted to enter into this clinical collaboration with Repare, the leader in PKMYT1 inhibition, to reinforce our commitment to the DDR space with our potential best-in-class WEE1 inhibitor. We believe this synthetic lethality approach will bring an innovative precision medicine therapy to patients"

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Under the clinical study and collaboration agreement, the combination of lunresertib and Debio 0123 will be evaluated in a new arm of Repare’s ongoing global MYTHIC study (NCT04855656) under Repare’s sponsorship. The Phase 1/1b clinical trial is anticipated to initiate in the first half of 2024. Debiopharm and Repare will collaborate on the design of the trial arm for the development of the combination and will share all costs equally. Debiopharm and Repare will each supply their respective drugs, and each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.

"We are delighted to enter into this clinical collaboration with Repare, the leader in PKMYT1 inhibition, to reinforce our commitment to the DDR space with our potential best-in-class WEE1 inhibitor. We believe this synthetic lethality approach will bring an innovative precision medicine therapy to patients," said Bertrand Ducrey, CEO of Debiopharm. "This is the first time that Debiopharm has initiated a collaboration to combine two investigational compounds, demonstrating our excitement by the potential of this therapeutic approach in hard-to-treat cancers."

At the AACR (Free AACR Whitepaper)-NCI-EORTC conference held in Boston in October 2023, Repare presented data showing that the combination of lunresertib and Debio 0123 is highly synergistic, and drives rapid and deep tumor regressions (Gallo et al., Poster #A023). Unpublished data independently generated by Debiopharm confirmed the dramatic synergy of the Debio 0123/lunresertib combination in vivo, further supporting the rationale for this clinical collaboration. In addition, several recent preclinical studies published by Repare and its collaborators have demonstrated proof-of-concept for the combination of WEE1 and PKMYT1 inhibition in relevant cancer cell lines and animal models of cancer (Sokhi et al. "Investigating Wee1 and Myt1 combined inhibition as a potential cancer therapeutic strategy", AACR (Free AACR Whitepaper) 2023, Poster #5511; Benada et al., 2023).

"Combining with Debiopharm’s highly selective WEE1 inhibitor is the ideal strategy to further extend our leadership in PKMYT1 inhibitor development," said Lloyd M. Segal, CEO of Repare. "The compelling mechanistic rationale and preclinical data Repare and Debiopharm have each generated for this combination give us confidence in its potential to deliver transformative benefit to patients with high unmet medical need."

On January 4, 2024 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported that Pascal Touchon, President and Chief Executive Officer, will present at the 42nd Annual J.P. Morgan Healthcare Conference on Thursday, January 11, at 9:45 a.m. PST / 12:45 p.m. EST in San Francisco, California (Press release, Atara Biotherapeutics, JAN 4, 2024, View Source [SID1234638963]).

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A live webcast of the presentation will be available by visiting the Investors and Media section of atarabio.com. An archived replay of the webcast will be available on the Company’s website for 30 days following the live presentation.

On January 4, 2024 OnKure, Inc. reported that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application of OKI-219, a potential best-in-class, mutant selective PI3Ka H1047R inhibitor, for clinical evaluation (Press release, OnKure, JAN 4, 2024, View Source [SID1234638979]). H1047R is the most common mutation in PI3Ka, being found in 15% of breast cancer and 4% of cancers overall.

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There is a significant need for improved therapies targeting PI3Kα with safer and more effective drugs. OKI-219 is a highly selective inhibitor of PI3Ka H1047R, with over 100-fold selectivity for the wild-type enzyme, potentially sparing on-target toxicities that arise from inhibition of the wild-type form of the protein in normal tissues. OKI-219 shows strong, single-agent activity, including regressions at low doses in multiple PI3Ka H1047R xenograft models that are heterozygous for PI3Ka H1047R, the most common profile seen clinically for this mutation, and supporting the potential activity of highly mutant-selective inhibitors. Notably, in preclinical models, OKI-219 shows no evidence of toxicities related to PI3Ka wild-type inhibition as measured by markers of hyperglycemia, even at doses that are >15x higher than minimally active doses for antitumor activity.

Mutational activation of PI3Kα is associated with lower activity of both estrogen receptor (ER)-targeted and HER2-targeted agents in breast cancer. OKI-219 shows synergistic activity in combination with selective estrogen receptor degraders (SERDs), overcoming SERD resistance and driving strong regressions. Similarly, the combination of OKI-219 + tucatinib drives strong regressions in models of HER2+/ PI3Ka H1047R breast cancer that are resistant to HER2- inhibitors.

OnKure plans to initiate a first-in-human clinical trial, OKI-219-101 (PIKture-01), in the first quarter of 2024 that will include a dose escalation in patients with advanced solid tumors harboring the PI3Ka H1047R mutation. Subsequent evaluation of OKI-219 in combination with the SERD fulvestrant in ER+/ PI3Ka H1047R advanced breast cancer, and with the HER2-monoclonal antibody trastuzumab in HER2+/ PI3Ka H1047R advanced breast cancers will follow.

About PI3Ka and OKI-219

PI3Ka is the most frequently mutated oncogene in cancers, and PI3Ka H1047R is the most common mutation in this gene, being found in 15% of breast cancer and 4% of cancers overall. While novel drugs targeting PI3Ka have been approved, the lack of mutant selectivity of these therapeutics drives considerable on-target toxicity by inhibiting the normal version of this protein in various tissues. To address this challenge, OnKure is discovering and developing a platform of highly mutant-selective PI3Ka inhibitors with the goal of improving efficacy and safety with molecules that fully inhibit the mutant oncogene while sparing the wild-type enzyme in normal tissues. OKI-219 is a potential best-in-class, orally bioavailable, highly selective inhibitor of PI3Ka H1047R with over 100-fold selectivity for the mutated form of the enzyme compared to wild-type. OnKure believes that the wild-type sparing properties of OKI-219 should significantly improve the activity and safety relative to currently approved agents. OKI-219 is currently in Phase 1 of clinical development in solid tumor patients with PI3Ka H1047R mutations.

On January 4, 2024 Avistone Biotechnology Co., Ltd. (also referred to as Avistone Biotechnology or Avistone), an innovative biotechnology company focused on precision oncology therapeutics, reported that they had recently completed their Series B financing of 1 billion Chinese yuan (~$140 million USD) (Press release, Avistone Pharmaceuticals, JAN 4, 2024, View Source [SID1234638997]). The Series B financing was jointly led by SDIC CS Capital and IDG Capital, with participation from Yanchuang Capital and Cathay Capital. Existing shareholder Bain Capital continues to make additional investments.

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This round of financing will be used to support clinical research and development of the Avistone pipeline, including both drug monotherapy studies and internal combinations; to accelerate the screening of new molecules; to support clinical studies and expansion in the United States of America; and to support commercialization of PLB1001 (Vebreltinib) in China. In China, Avistone has established a commercial sales and marketing team covering 25 provinces, nearly 1,000 hospitals, and hundreds of commercial companies and retail outlets.

Dr. Hepeng Shi, founder, chairman and CEO of Avistone Biotechnology, said: "We thank our Series B investors for trusting and investing in Avistone. This very important financing will support the commercialization of our recently approved molecule, PLB1001 (Vebreltinib), in MET Exon 14 Skipping Non-Small Cell Lung Cancer (NSCLC) and will provide funding for our pipeline. We will continue to pursue our vision to become a leading biotechnology company with a deep pipeline and focus on innovation. We aspire to be highly trusted by the patients and families that we serve along with the physicians, practitioners, and scientists that we work with."

SDIC states: "We are pleased to lead the B-round financing for Avistone. The Company has demonstrated impressive execution capabilities and has led effective translational medical work. We firmly believe that the company will continue to produce more clinically advanced innovative products in the future. We are committed to collaborating closely with the Avistone team to foster the company’s growth, ultimately benefiting patients and contributing to the advancement of China’s innovative pharmaceutical industry."

IDG Capital noted that, "We believe that the demand for better products is a prevailing trend in the biopharmaceutical industry, and Avistone has consistently aimed for and practiced this goal. Dr. Shi’s team swiftly achieved breakthroughs from 0 to 1 in product development, showcasing strong execution and product layout capabilities. Additionally, we have high expectations for Avistone’s outstanding commercialization capabilities. We believe that in the future, Avistone can achieve more innovative breakthroughs, and IDG Capital is committed to ongoing support, contributing to the advancement of the innovative pharmaceutical industry alongside Avistone."

Jonathan Zhu, Partner and Co-Head of Asia Private Equity at Bain Capital, expressed that "We are delighted to witness Avistone’s breakthroughs in targeted oncology drug development, positioning itself as a leading domestic innovative pharmaceutical enterprise with successful ventures into Class 1 innovative drugs. We have observed the growth and development of Avistone and have strong confidence in the company’s research and development capabilities, execution efficiency, and pipeline layout strategy. Our continued investment in Avistone underscores our belief in Dr. Shi’s leadership and his team’s ability to efficiently develop groundbreaking innovative biopharmaceuticals. This establishes them as a pioneering platform for tumor-targeted drug innovation rooted in China and globally oriented."