On January 19, 2023 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported that the Company has received an approximately $1.5 million (¥200 million) research service payment from Ono Pharmaceutical Co., Ltd. ("Ono") (Press release, Repare Therapeutics, JAN 19, 2023, View Source [SID1234626410]). The payment reflects achievement of a specified research trigger, under the companies’ 2019 Strategic Partnership Agreement ("Ono Agreement"). Under the terms of the Ono Agreement, Repare is primarily responsible for carrying out research activities for its Polθ program, now known as RP-2119, until the first submission of an IND in the U.S. or Japan. "This reflects an important milestone in our RP-2119 Polθ program, as we undertake our IND-enabling studies and prepare for our previously guided initiation of clinical trials in the summer of 2023," said Kim A. Seth, Chief Business Officer of Repare.

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Ono Strategic Partnership Agreement

In January 2019, Repare entered into an exclusive strategic research, development and commercialization partnership with ONO Pharmaceutical Co., Ltd., for Repare’s small molecule Polθ inhibitor program, now known as RP-2119, in Japan, South Korea, Taiwan, Hong Kong, Macau and ASEAN countries, excluding mainland China. Repare retains all rights to develop and commercialize the products outside the ONO territory, including the US, Canada and EU. Under the terms of the Ono Agreement, Ono paid Repare approximately $8.1 million, comprised of an initial upfront fee and research service payments, and agreed to make additional research service payments upon (i) certain specified research triggers and (ii) the election by Ono to collaborate on the development and commercialization of a proposed product candidate. In October 2021, upon the occurrence of a specified research trigger, Repare became eligible to receive a portion, amounting to ¥100 million ($0.9 million), of the research service payments.

On January 19, 2023 LinKinVax, a clinical-stage biotechnology company specialized in innovative protein-based vaccines, and Gustave Roussy, first leading cancer center in Europe, ranked third Best Cancer Hospital in the world,reported a collaboration to conduct a first-in-human Phase I/IIa clinical trial with CD40HVac, a new therapeutic vaccine candidate against head and neck cancer associated with human papillomavirus (HPV) (Press release, LinKinVax, JAN 19, 2023, View Source [SID1234626409]).

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The objectives of the study (EUCT n° 2022-502930-25-00), sponsored by Gustave Roussy, are to demonstrate the safety and immunogenicity of the CD40HVac vaccine candidate with the Poly-ICLC adjuvant (Hiltonol) against oncogenic HPV in patients with head and neck cancer, and to determine the recommended Phase 2 dose based on the safety profile of the vaccine candidate and its ability to induce immune responses. Several exploratory objectives are also planned to estimate progression-free survival and overall survival.

LinKinVax develops CD40HVac, a therapeutic vaccine for HPV-associated malignancies, based on an innovative technology directly targeting dendritic cells (DC), which play a crucial role in the immune system by stimulating and regulating immune responses. A recent U.S. population-based study conducted by the Centers for Disease Control and Prevention (CDC) showed that 66% of cervical cancers, 55% of vaginal cancers, 79% of anal cancers, and 62% of oropharyngeal cancers are attributable to HPV 16 and 18.

Although many HPV-induced tumors can be cured with modern multidisciplinary treatment approaches, it is important to develop new and effective therapeutic vaccines against HPV-associated malignancies to better address the needs of patients.

Prof. Yves Levy, Chief Medical and Scientific Officer LinKinVax, commented: "This partnership with Gustave Roussy to launch of the first phase 1 study is a crucial step for the development of our CD40HVac vaccine in immuno-oncology. It represents a bridge between basic research and clinical research designed to accelerate innovation for the benefit of patients. Together with Gustave Roussy, we look forward to making what we hope will be a major contribution to the treatment of HPV related cancers".

Dr. Caroline Even, Department of Head and Neck Oncology at Gustave Roussy (Villejuif- Paris) added: "Both Gustave Roussy and LinKinVax place innovation at the heart of a human, scientific and technological revolution in the fight against cancer, thereby responding to the ongoing challenge of giving patients access to the most recent treatment advances. We hope that this first project will be inaugural of a long-standing and synergistic collaboration between LinKinVax and Gustave Roussy"

On January 19, 2023 Cyteir Therapeutics, Inc. ("Cyteir") (Nasdaq: CYT) reported the strategic prioritization of clinical development of CYT-0851, an investigational monocarboxylate transporter inhibitor, as a potential combination therapy for the treatment of ovarian cancer (Press release, Cyteir Therapeutics, JAN 19, 2023, View Source [SID1234626408]). The prioritization follows encouraging preliminary clinical activity in a small number of patients observed in the Phase 1 dose escalation cohort with CYT-0851 in combination with capecitabine in advanced ovarian cancer. Cyteir plans to expand its evaluation of CYT-0851 in combination with capecitabine to treat advanced ovarian cancer and enroll additional patients in the first half of 2023 to further support these early signals. If successful, the combination of CYT-0851 with capecitabine has the potential to be an all-oral treatment for ovarian cancer. In conjunction with focusing clinical activities on ovarian cancer, Cyteir is reducing headcount by approximately 70% and deferring research and development in other areas, which is expected to extend Cyteir’s cash runway into 2026.

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CYT-0851 Development to Prioritize Combination Therapy

Phase 1 dose escalation cohorts with CYT-0851 in combination with capecitabine for the treatment of advanced ovarian cancer have shown encouraging preliminary clinical activity. To date, thirteen patients have been treated with CYT-0851 (from 100-400mg daily) and capecitabine, including five patients with advanced ovarian cancer. Responses and disease stabilization observed in these ovarian cancer patients in the 300mg and 400mg CYT-0851 dose levels are encouraging, and have led to Cyteir’s decision to focus on further development of this capecitabine combination in advanced ovarian cancer. Overall, CYT-0851 continues to be generally well tolerated with no new safety concerns.
In the first quarter of 2023, Cyteir expects to determine a maximum tolerated dose ("MTD") for CYT-0851 in combination with capecitabine and focus its efforts on enrolling and treating additional patients with advanced ovarian cancer at the MTD. If the data from these additional patients further support Cyteir’s focus on ovarian cancer, Cyteir intends to pursue development and potential registration of CYT-0851 in combination with capecitabine as an all-oral treatment for platinum resistant ovarian cancer.

In addition, Cyteir is evaluating CYT-0851 in Phase 1 dose escalation cohorts in combination with gemcitabine. To date, ten patients have been treated with CYT-0851 (from 100-200mg daily) and gemcitabine. Cyteir will continue the ongoing dose escalation cohorts with CYT-0851 and gemcitabine in solid tumor patients to identify an MTD, which could provide an additional opportunity to develop CYT-0851 as a combination therapy to treat patients with platinum resistant ovarian cancer.

Enrollment in the Phase 2 monotherapy cohorts with CYT-0851 will be suspended due to insufficient monotherapy activity observed to date. Cyteir plans to disclose the Phase 1 combination data for CYT-0851 in mid-2023.
"We are encouraged by these early signals and believe that an initial focus on the combination of CYT-0851 and capecitabine represents the greatest likelihood of success and an opportunity to serve patients with advanced ovarian cancer that have a high unmet medical need. This combination, if successful, has the potential to be an all-oral treatment regimen for patients with platinum resistant ovarian cancer," said Markus Renschler, MD, Cyteir’s President and CEO. "This strategic prioritization and the difficult decision to reduce our workforce is expected to extend our cash runway into 2026 and, if supported by the data and regulatory feedback, allows us to advance CYT-0851 into a potentially registrational trial as early as the second half of 2024. I personally would like to thank all of our dedicated employees and express my gratitude for their hard work in advancing our pipeline, and I wish them the best in the future."

In the United States, it is estimated that a total of approximately 13,000 patients are available for drug treatment per year who are platinum resistant and have progressed after two lines of prior therapy, or have progressed after at least three prior lines of therapy.

Deferral of R&D Activities Beyond Clinical Development of CYT-0851 to Extend Cash Runway

In conjunction with focusing development activities on CYT-0851, Cyteir announced that it will be suspending all preclinical research. Specific actions include:

Ceasing drug discovery projects focused on identifying inhibitors of DNA damage repair; and
Reducing company headcount to approximately 15 full-time employees.
Based on current estimates, including assumptions for continuation of clinical development of CYT-0851 towards registration as a combination therapy, Cyteir expects that these actions will extend its cash runway into 2026. As of December 31, 2022, on an unaudited basis, Cyteir had approximately $147 million in cash and cash equivalents. Cyteir estimates that it will incur aggregate charges of approximately $2.5 million to $3 million, all of which are anticipated to result in future cash expenditures, primarily for one-time employee severance and benefit costs, the majority of which are expected to be incurred in the first quarter of 2023.

On January 19, 2023 EpicentRx, a leading edge, clinical stage biopharmaceutical company, reported the publication of Phase 2 results of the PREVLAR trial which demonstrated that RRx-001 protects against severe oral mucositis in patients receiving radiation and chemotherapy for head and neck cancer (Press release, EpicentRx, JAN 19, 2023, View Source [SID1234626407]). The study was published in the International Journal of Radiation Oncology, Biology and Physics, also known as The Red Journal.

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PREVLAR, a multi-institutional, randomized trial compared the safety and efficacy of three dosing schedules of RRx-001 to mitigate oral mucositis in patients receiving concomitant chemoradiation for the treatment of oral and oropharyngeal cancers. Among the findings reported by Dr. David Sher from University of Texas Southwestern in Dallas and his colleagues in their paper "PREVLAR: Phase 2 randomized trial to assess the safety and efficacy of RRx-001 in the attenuation of oral mucositis in patients receiving head and neck chemoradiotherapy" was the observation that pre-radiation RRx-001 alone favorably impacted the incidence and duration of severe oral mucositis (SOM) safely. Importantly, RRx-001 patients responded no differently to their cancer than did patients in a control arm when evaluated two years after the completion of their chemoradiation treatment.

SOM is among the most common and symptomatically severe complications of concomitant chemoradiation used routinely to treat cancers of the head and neck. SOM occurs in approximately 70% of head and neck cancer patients. The sores or ulcerations associated with mucositis are often present throughout the mouth and throat and are associated with unmanageable pain, impaired nutrition, and dehydration, which result in more emergency room visits and hospitalizations. Most impactful on survival are the negative effects of SOM on patients’ ability to tolerate optimal treatment of their cancers.

The potential of RRx-001 as a protective agent for non-cancer, normal cells is related to its joint activities as an NLRP3 inflammasome inhibitor and activator of the Nrf2 antioxidant transcription factor. A larger Phase 2 randomized study named KEVLAR is planned with RRx-001 for further clinical evaluation of oral mucositis prevention.

Dr. Stephen Sonis, Harvard Professor of Oral Medicine and member of the Distinguished Faculty of the Dana-Farber Cancer Institute, and manuscript co-author, commented that "the results noted in PREVLAR suggest that RRx-001 may provide protection from severe radiation-associated mucositis with a dosing schedule that is highly desirable for both patients and radiation oncologists. I look forward to further study of this treatment in the subsequent KEVLAR study."

About RRx-001
The lead EpicentRx small molecule, RRx-001 is a highly selective NLRP3 inhibitor with vascular normalization and tumor associated macrophage polarization properties that resensitizes tumors to previously administered therapies. RRx-001 is under investigation in a Phase 3 trial for the treatment of small cell lung cancer (SCLC), and in a Phase 2 trial for protection against oral mucositis in first line head and neck cancer. It is also under development as a medical countermeasure for nuclear and radiological emergencies and as a treatment for neurodegenerative diseases like Parkinson’s and ALS/MND.

On January 19, 2023 NeoPhore Limited, a small molecule neoantigen immuno-oncology company, reported the completion of its £21.5m (US $28.5m) Series B financing, with a £6m (US $7.5m) financing extension (Press release, NeoPhore, JAN 19, 2023, View Source [SID1234626406]). The syndicate comprised its Series B subscribing investors including CRT Pioneer Fund, Claris Ventures, 2Invest, 3B Future Health Fund and Astellas Venture Management.

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NeoPhore is focused on the discovery and development of novel first-in-class small molecule drugs targeting the DNA mismatch repair (MMR) pathway to treat cancer. The additional funding will be used to progress NeoPhore’s expanding pipeline of drugs, encompassing multiple biological targets and modalities of treatment, to the start of IND-enabling studies in 2024.

Dr Robert James, Chairman of NeoPhore, said: "This additional support from NeoPhore’s existing investors is a strong testament to the Company’s novel and differentiated immunotherapy approach. We believe that by altering the tumour genotype to elicit immunological responses, we can offer huge clinical benefit in the level and durability of anti-tumour responses in a wide range of indications for the benefit of cancer patients. 2022 was a year of remarkable progress for NeoPhore in which it demonstrated, for the first time that we are aware of, a number of exciting therapeutic consequences of inhibiting mismatch repair with a small molecule."

In January 2022, NeoPhore achieved all of its investment related scientific milestones significantly ahead of schedule. In February 2022, NeoPhore expanded its research partnership with St George’s, University of London after a successful collaboration investigating novel cancer immunotherapies, and in July 2022, the Company entered a three-year research collaboration agreement with Memorial Sloan Kettering Cancer Center (MSK) to further validate the potential of NeoPhore’s proprietary DNA mismatch repair inhibitor (MMRi) compounds to enhance tumour immunogenicity and induce tumour immunity.

Dr Matthew Baker, Chief Executive Officer of NeoPhore, added: "2022 was a year of progress for NeoPhore. Collaborating with such prominent leaders in the field allowed us to advance our goal of developing next-generation immuno-oncology therapeutics. It is known that drugs designed to spark cancer neoantigen creation and subsequently stimulate the immune system, can improve outcomes for patients who do not benefit from the current generation of cancer immunotherapies. We welcome the continued support from our investors that enables us to further develop our drug discovery pipeline."