On June 24, 2024 Daiichi Sankyo reported that (TSE: 4568) EZHARMIA (valemetostat tosilate) has been approved in Japan for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) (Press release, Daiichi Sankyo, JUN 24, 2024, View Source [SID1234644516]). EZHARMIA is now the first dual inhibitor of EZH1 and EZH2 to be approved for PTCL after receiving SAKIGAKE designation for this indication.

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PTCL is a group of rare and often aggressive blood cancers, which represent about 10 to 15% of all nonHodgkin lymphomas (NHL).1 PTCL is more common in Asia, including in Japan, compared to other parts of the world. 2 A majority of patients with PTCL experience disease progression following initial treatment with a multi-drug chemotherapy-based regimen and median overall survival following relapse is approximately 5.8 months.

The approval of EZHARMIA by the Japan Ministry of Health, Labour and Welfare (MHLW) is based on results of the VALENTINE-PTCL01 phase 2 trial, which were presented at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. In VALENTINE-PTCL01, an objective response rate (ORR) of 43.7% (n=52, 95% CI: 34.6-53.1) was observed for EZHARMIA in 119 efficacy evaluable patients with relapsed or refractory PTCL as assessed by CT-based blinded independent central review (BICR). Seventeen complete responses (CRs) and 35 partial responses (PRs) were observed. Responses were seen across a variety of PTCL subtypes including angioimmunoblastic T-cell lymphoma (AITL), PTCL not otherwise specified (PTCL-NOS) and other PTCL subtypes.

"This second indication for EZHARMIA in Japan is an important advance for the treatment of relapsed or refractory peripheral T-cell lymphoma, as new and effective treatment options are needed to improve patient outcomes," said Toshinori Agatsuma, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo.

"EZHARMIA exemplifies the innovative research being conducted by Daiichi Sankyo aimed at creating new medicines with potential to change the standard of care for patients with cancer." 2 The safety profile of EZHARMIA in VALENTINE-PTCL01 was consistent with previous clinical trials. Treatment-related adverse events occurred in 106 of 133 patients (79.7%) with the most common including platelet count decrease (44.4%), anemia (27.1%), dysgeusia (24.8%) and neutrophil count decrease (21.1%).

About VALENTINE-PTCL01 Trial

VALENTINE-PTCL01 is a global, open-label, single-arm, two-cohort phase 2 study evaluating the efficacy and safety of EZHARMIA in patients with relapsed or refractory PTCL and adult T-cell leukemia/lymphoma (ATLL) who received at least one systemic therapy and were ineligible for hematopoietic stem cell transplant at the time of screening. One cohort enrolled patients with PTCL and a second cohort enrolled patients with ATLL.

The primary endpoint of VALENTINE-PTCL01 is ORR assessed by CT-based BICR. Secondary endpoints include duration of response, CR, PR, duration of CR and progression-free survival – all assessed by both BICR and investigator assessment – as well as ORR assessed by investigator, overall survival, safety and pharmacokinetics. Exploratory endpoints include PET-CT-based BICR and biomarker mutational status. Responses were evaluated based on Lugano 2014 response criteria. VALENTINE-PTCL01 enrolled 133 patients at multiple sites in Asia, Europe, North America and Oceania. For more information about this study, visit ClinicalTrials.gov.

About Peripheral T-Cell Lymphoma

PTCL is a group of rare and often aggressive blood cancers, which represent 10 to 15% of all NHLs.1 Approximately 553,000 new cases of NHL were diagnosed worldwide in 2022.3 There are at least 29 recognized subtypes of PTCL, which occur with significant geographic variation.4 PTCL is more common in Asia, including in Japan, compared to other parts of the world.

Prognosis of PTCL is generally poor, with a five-year overall survival rate of 32% in AITL and PTCLNOS, and 7% or lower in certain subtypes. A majority of patients with PTCL experience disease progression following initial treatment with a multi-drug chemotherapy-based regimen and median overall survival following relapse is approximately 5.8 months.1 Development of more effective medicines for PTCL continues to be an unmet clinical need, particularly in the relapsed or refractory setting.
About EZH1 and EZH2

The EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste homolog 2) enzymes help regulate the expression of genes involved in maintaining healthy hematopoietic stem cells (immature blood cells).6 Both enzymes are recurrently mutated or overexpressed in hematologic malignancies, including T-cell lymphomas, and research shows they contribute to the silencing of tumor suppressor genes and drive oncogenic growth.

About EZHARMIA

EZHARMIA (valemetostat tosilate) is first-in-class dual inhibitor of EZH1 and EZH2 that was discovered by Daiichi Sankyo. EZHARMIA is approved in Japan for the treatment of patients with relapsed or refractory PTCL and for the treatment of patients with relapsed or refractory ATLL. It is an investigational medicine in all countries outside of Japan.

About EZHARMIA Clinical Development Program

A global clinical development program is underway for EZHARMIA in hematologic and solid cancers. In addition to VALENTINE-PTCL01, EZHARMIA is being evaluated in the VALYM phase 2 trial in patients with relapsed or refractory B-cell lymphomas, which is being conducted under a strategic research collaboration with the LYSA-LYSARC-CALYM group in Europe, and a phase 1b study in combination with DXd antibody drug conjugates ENHERTU (trastuzumab deruxtecan) and datopotamab deruxtecan (Dato-DXd) in patients with solid cancers.

On June 24, 2024 Oncoinvent ASA, a clinical stage radiopharmaceutical company advancing alpha emitter therapy across a variety of peritoneal metastases, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to Radspherin for the treatment of patients with peritoneal metastases from ovarian cancer (Press release, Oncoinvent, JUN 24, 2024, https://www.oncoinvent.com/press-release/oncoinvent-receives-fda-fast-track-designation-for-radspherin-as-treatment-for-peritoneal-carcinomatosis-from-ovarian-cancer/ [SID1234644515]).

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"Fast Track designation for Radspherin is a key milestone for Oncoinvent, particularly as we are on the verge of initiating a Phase 2b trial to evaluate Radspherin in peritoneal metastases from ovarian cancer, and later also in peritoneal metastases stemming from colorectal cancer patients," said Anders Månsson, Chief Executive Officer of Oncoinvent. "Importantly, this designation reinforces the urgent need for safe and effective therapies for patients suffering from peritoneal metastases. These metastases have a particularly negative impact on life expectancy and effective treatment therefore has a significant chance of affecting overall survival in these patients. We believe we are well positioned to execute the clinical development of Radspherin in our upcoming trial and look forward to advancing this innovative product candidate to benefit patients battling this type of cancer, for whom there are limited treatment options."

The randomized, controlled Phase 2b trial will assess the efficacy and safety of Radspherin in patients with peritoneal metastases from ovarian cancer. The primary objective is to compare progression free survival (PFS) between patients who receive Radspherin after complete surgical resection following pre-operative chemotherapy and patients who only undergo pre-operative chemotherapy and surgery. Positive data from the Phase 1/2a safety interim analysis demonstrated that Radspherin was well tolerated with no dose-limiting toxicity observed with the administration of the recommended dose of 7MBq.

Fast Track designation is a process that is designed to facilitate the development and expedite the review of therapies intended to treat serious conditions and address unmet medical needs to potentially bring important new medicines to patients earlier. Companies whose programs are granted Fast Track designation are eligible for more frequent interactions with the FDA during clinical development. Provided relevant criteria are met, programs with Fast Track designation are eligible for accelerated approval and priority review as well.

On June 24, 2024 Merck, a leading science and technology company, reported the discontinuation of the Phase III randomized TrilynX study evaluating xevinapant plus chemoradiotherapy (CRT) in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) (Press release, Merck KGaA, JUN 24, 2024, View Source [SID1234644514]). The decision follows a pre-planned interim analysis performed by the study’s Independent Data Monitoring Committee, which found that the trial would be unlikely to meet its primary objective of prolonging event-free survival. Top-line safety data were overall compatible with the chemo-radio sensitizing properties of xevinapant. The company will conduct an in-depth review of the data and will share the results in a peer-reviewed forum.

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LA SCCHN has proven to be a difficult-to-treat form of cancer. CRT has remained the standard of care for decades, despite multiple studies designed to improve outcomes with new treatment approaches, including multiple immunotherapy trials.

"We sincerely thank the patients, caregivers and clinical investigators who participated in this trial," said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck. "While we are disappointed by these results, we remain steadfast in our commitment to develop transformative medicines within our oncology portfolio for areas of high unmet need."

Given the totality of the data, the company decided to also stop the Phase III clinical trial X-Ray Vision (xevinapant plus radiotherapy, compared to placebo plus radiotherapy) in patients who underwent resection of locally advanced head and neck cancer.

Merck is working to develop and deliver new treatment options that exploit the vulnerabilities of tumor cells. The company is exploring modalities including antibody drug conjugates (ADCs) and DNA damage response (DDR) inhibitors, across multiple tumor types, including many that have proven difficult to treat where there are significant unmet needs for patients. The company’s support for the head and neck cancer community remains steadfast with Erbitux, approved in combination with radiotherapy for the initial treatment of locally advanced SCCHN, and which continues to be studied in more than 200 active clinical trials, including at least 15 Phase III studies.

On June 24, 2024 Silence Therapeutics plc, Nasdaq: SLN ("Silence" or "the Company"), an experienced and innovative biotechnology company committed to transforming peoples’ lives by silencing diseases through precision engineered medicines, reported that it will receive a $2.0 million cash payment from Hansoh Pharmaceutical Group Company Limited ("Hansoh") following the achievement of a second undisclosed milestone related to the first target under the collaboration (Press release, Silence Therapeutics, JUN 24, 2024, View Source [SID1234644509]).

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"This represents an important milestone in our efforts to advance this program into the clinic with Hansoh," said Craig Tooman, President and CEO of Silence. "This is an exciting time for Silence and our mRNAi GOLD platform as we continue to advance and expand our pipeline targeting a wide range of genetic diseases."

Silence and Hansoh entered a collaboration in October 2021 to develop siRNAs ("short interfering RNAs") leveraging Silence’s proprietary mRNAi GOLD platform for three undisclosed targets. Under the terms of the agreement, Silence has exclusive rights to the first two targets in all territories except the China region. Hansoh has the exclusive option to license rights to those two targets in the Greater China, Hong Kong, Macau and Taiwan, and global rights to the third target.

Hansoh made a $16 million upfront payment to Silence and the Company is eligible to receive up to $1.3 billion in development, regulatory and commercial milestones. Silence is also eligible to receive royalties tiered from low double-digit to mid-teens on Hansoh net product sales. Today’s announcement represents the fourth research milestone payment achieved under the collaboration.

On June 24, 2024 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation (RPDD) to SLS009, a highly selective CDK9 inhibitor, for the treatment of pediatric acute lymphoblastic leukemia (ALL) (Press release, Sellas Life Sciences, JUN 24, 2024, View Source [SID1234644508]).

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"We are pleased that the FDA has granted Rare Pediatric Disease Designation to SLS009 for the treatment of pediatric ALL, the most common cancer diagnosed in children," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "We remain steadfast in our commitment to advancing SLS009 through the clinical development process across multiple indications and striving to improve the lives of patients, including children, and their families affected by ALL. We look forward to exploring SLS009 as a potential treatment option in pediatric ALL and this designation will significantly help expedite clinical development."

Childhood ALL is a life-threatening disease with a high unmet medical need. Despite significant advances in the treatment of pediatric ALL, relapse continues to be the most common cause of treatment failure. There are patient subpopulations with high-risk and very high-risk features in need of less toxic therapies that would ultimately extend their long-term event-free survival (EFS) which remains around 50% for very high-risk groups. In clinical trials, SLS009 has demonstrated a very favorable safety profile with complete absence, to date, of any non-hematologic clinical higher-grade toxicities.

Rare Pediatric Disease (RPD) Designation is granted by the FDA for serious or life-threatening diseases that affect fewer than 200,000 people in the United States, and in which the serious or life-threatening manifestations primarily affect individuals less than 18 years of age. If, in the future, a New Drug Application (NDA) for SLS009 for the treatment of pediatric AML is approved by the FDA, SELLAS might be eligible to receive a Priority Review Voucher (PRV) that could be redeemed to receive a priority review for any subsequent marketing application. PRVs may be used by the sponsor or sold to another sponsor for their use and have recently sold for approximately $100 million.