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HUTCHMED Completes Patient Enrollment of a Bridging Study of Tazemetostat in Patients with Relapsed/Refractory Follicular Lymphoma in China

On September 12, 2023 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that it has completed patient enrollment of a bridging study of tazemetostat in China (Press release, HUTCHMED, SEP 12, 2023, View Source [SID1234635103]).

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The bridging study is a multicenter, open-label, Phase II study to evaluate the efficacy, safety and pharmacokinetics of tazemetostat for the treatment of patients with relapsed/refractory follicular lymphoma ("R/R FL"). The primary objective is to evaluate the objective response rate ("ORR") of tazemetostat for the treatment of patients with R/R FL whose disease harbor EZH21 mutations (Cohort 1). The secondary objectives included duration of response ("DoR"), progression-free survival (PFS), and overall survival (OS) of tazemetostat for the treatment of R/R FL patients whose disease do or do not harbor EZH2 mutations (Cohort 2), as well as to evaluate the safety and pharmacokinetics. The lead principal investigator is Dr Junning Cao of Shanghai Fudan University Cancer Center. A total of 42 patients were enrolled. Additional details may be found at clinicaltrials.gov, using identifier NCT05467943.

Tazemetostat is a first-in-class methyltransferase inhibitor of EZH2 developed by Epizyme, Inc. ("Epizyme"), an Ipsen company. It is approved by the U.S. Food and Drug Administration ("FDA") for the treatment of certain patients with advanced epithelioid sarcoma ("ES") and certain patients with R/R FL under the FDA accelerated approval granted in January and June 2020, respectively. HUTCHMED entered into a strategic collaboration to research, develop, manufacture and commercialize tazemetostat in China, Hong Kong, Macau and Taiwan.

In May 2022, tazemetostat was approved by the Health Commission and Medical Products Administration of Hainan Province of China to be used in the Hainan Boao Lecheng International Medical Tourism Pilot Zone ("Hainan Pilot Zone"), under the Clinically Urgently Needed Imported Drugs scheme, for the treatment of certain patients with ES and FL consistent with the label as approved by the FDA.

In March 2023, tazemetostat was approved and launched in Macau. A market authorization application has been under review in Hong Kong since December 2022.

Tazemetostat was included in the Chinese Society of Clinical Oncology (CSCO) guidelines for ES in 2022 and for FL in 2023.

About FL and ES

FL is a subtype of non-Hodgkin’s lymphoma ("NHL"). FL accounts for approximately 17% of NHL. In 2020, there were an estimated 16,000 and 13,000 new cases of FL in China and the U.S., respectively.

ES is a rare, slow-growing type of soft tissue cancer. Radical tumor resection is the primary treatment for patients with ES. However, ES is known for its high propensity for locoregional recurrence and distant metastases. The survival of patients with ES is often unsatisfactory with very limited treatment options.

About TAZVERIK (tazemetostat)

TAZVERIK is a methyltransferase inhibitor indicated in the United States for the treatment of:

● Adults and pediatric patients aged 16 years and older with metastatic or locally advanced ES not eligible for complete resection.

● Adult patients with R/R FL whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies.

● Adult patients with R/R FL who have no satisfactory alternative treatment options.

These indications are approved under accelerated approval by the U.S. FDA based on ORR and DoR. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

The most common (≥20%) adverse reactions in patients with ES are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with FL are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

View the U.S. Full Prescribing Information here:

View Source

TAZVERIK is approved in Japan with the indication of relapsed or refractory EZH2 gene mutation-positive FL (only when standard treatment is not applicable).

TAZVERIK is a registered trademark of Epizyme Inc., an Ipsen company.

About Tazemetostat Clinical Development in China

HUTCHMED and Ipsen are developing tazemetostat in various hematological and solid tumors in Greater China. We are participating in Ipsen’s SYMPHONY-1 (EZH-302) study, leading it in China. We also initiated a Phase ІІ study in combination with our phosphoinositide 3-kinase delta (PІ3Kδ) inhibitor amdizalisib in patients with R/R FL in February 2023. We are generally responsible for funding all clinical trials of tazemetostat in China, including the portion of global trials conducted there.

SYMPHONY-1 (EZH-302) is an international, multicenter, randomized, double-blind, active-controlled, 3-stage, biomarker-enriched, confirmatory Phase 1b/3 study, which is designed to evaluate the safety and efficacy of tazemetostat in combination with rituximab + lenalidomide (R2) in patients with R/R FL after at least one prior line of therapy (clinicaltrials.gov identifier: NCT04224493).

China combination study in R/R FL is an open-label, Phase ІІ study in approximately 140 patients to evaluate the safety, tolerability and preliminary anti-tumor efficacy of tazemetostat in combination with amdizalisib in patients with R/R lymphoma. The first patient was dosed in February 2023 (clinicaltrials.gov identifier: NCT05713110).

HOOKIPA Announces Grant of Inducement Awards Under Nasdaq Listing Rule 5635(c)(4)

On September 12, 2023 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported that the Compensation Committee of the Company’s Board of Directors approved the grant of non-statutory options to new employees to purchase an aggregate of 100,000 shares of the Company’s Common Stock under HOOKIPA’s 2023 Inducement Plan (Press release, Hookipa Biotech, SEP 12, 2023, View Source [SID1234635102]). The award was granted as an inducement material to the employees’s acceptance of employment with HOOKIPA in accordance with Nasdaq Listing Rule 5635(c)(4). The options have an exercise price equal to $ 1.00 per share. The options have a ten year term and vest over four years, with 25% vesting on the one-year anniversary of the grant date and the remainder vesting in equal quarterly installments for three years thereafter, subject to the employee’s continued service with HOOKIPA on each such vesting date. The options are subject to the terms and conditions of HOOKIPA’s 2023 Inducement Plan approved by the Board of Directors in April 2023 and the terms and conditions of award agreements covering the grants.

Exelixis and Insilico Medicine Enter into Exclusive Global License Agreement for ISM3091, a Potentially Best-in-Class USP1 Inhibitor

On September 12, 2023 Exelixis, Inc. (Nasdaq: EXEL) and Insilico Medicine ("Insilico") reported that the companies have entered into an exclusive license agreement granting Exelixis global rights to develop and commercialize ISM3091, a potentially best-in-class small molecule inhibitor of USP1, which has emerged as a synthetic lethal target in the context of BRCA-mutated tumors (Press release, Exelixis, SEP 12, 2023, View Source [SID1234635101]).

Under the terms of the agreement, Insilico granted Exelixis an exclusive, worldwide license to develop and commercialize ISM3091, and other USP1-targeting compounds, in exchange for an upfront payment to Insilico of $80 million anticipated in the third quarter 2023. Insilico is also eligible to receive future development, commercial, and sales-based milestone payments, as well as tiered royalties on net sales.

"ISM3091 represents a potentially best-in-class approach to inhibiting USP1, an important oncology target with broad applicability in BRCA-mutant tumors," said Dana Aftab, Ph.D., Executive Vice President, Discovery and Translational Research and Chief Scientific Officer, Exelixis. "We believe preclinical data on ISM3091’s potent anti-tumor activity, tolerability, and pharmacokinetics set the compound apart from competing USP1 inhibitors and make it an important addition to Exelixis’ growing clinical-stage pipeline. Following the FDA’s clearance of Insilico’s IND earlier this spring, we’re looking forward to accelerating phase 1 trial enrollment."

"ISM3091 is the third clinical-stage program made possible by Chemistry42, Insilico Medicine’s generative AI platform for small molecule drug discovery," said Alex Zhavoronkov, Ph.D., founder and CEO of Insilico Medicine. "The compound’s novel structure, anti-tumor activity, and excellent drug-like properties give it significant potential as a differentiated program directed at BRCA-mutant tumors, which include forms of ovarian, prostate, and breast cancer. This program attracted significant interest from multiple potential partners in the pharmaceutical industry, but we were most impressed by the level of technical expertise and development and commercial capabilities of Exelixis. With a track record of commercial and clinical development success in oncology, Exelixis is the best partner to take ISM3091 forward, and we’re excited to see the program take flight as a component of the company’s pipeline behind cabozantinib, its global oncology franchise."

USP1 facilitates DNA damage repair by removing ubiquitin from multiple substrates including proteins that stabilize the replication fork. A small molecule discovered using Insilico Medicine’s generative AI platform with extensive multiparameter optimization capabilities, ISM3091 was designed to inhibit the activity of USP1. In preclinical experiments, ISM3091 was found to be potently efficacious against multiple tumor cell lines and in vivo models with BRCA mutations, as well as in homologous recombination DNA repair (HRR)-proficient models, both as a single agent and in combination with PARP inhibitors. It is also well tolerated in different species with a high margin of safety. Insilico disclosed select data in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2023. On April 17, 2023, the FDA cleared the initial IND for ISM3091 for the treatment of patients with solid tumors.

Defence’s Broad and Versatile Accum® Technology Platform Focus on Cancer Therapeutics

On September 12, 2023 Defence Therapeutics Inc. ("Defence" or the "Company"), one of the leading Canadian biotechnology companies, reported its continuation to bringing innovative strategies aimed at targeting various indications related to immune-oncology (Press release, Defence Therapeutics, SEP 12, 2023, View Source;utm_medium=rss&utm_campaign=defences-broad-and-versatile-accum-technology-platform-focus-on-cancer-therapeutics [SID1234635100]).

Whether using an antibody, cell-based vaccine or small molecule therapeutics, the common denominator in all of Defence’s development products is the Accum technology, a platform specifically designed to strategically enhance and increase the efficacy of any existing bio-drug against cancer. This Accum technology can be exploited to design a multitude of products including: i) antibody-drug conjugates ("ADCs"), ii) protein/cellular vaccines, and iii) the design of anti-cancer small chemotypes.

The Accum-ADC program

ADCs were originally made to target breast cancer. The treatment regimens used with these ADCs usually require large doses, while the therapeutic response is limited or weak. By bio-conjugating ADCs with Accum, Defence has demonstrated improved potency of commercially available ADCs by 20 to 100 folds. Although Defence is using this approach to optimize commercially available ADCs such as Enhertu, the company is actively working on developing two in-house ADCs using its own proprietary monoclonal antibodies targeting two tumor-specific cell surface proteins and payloads. In addition, Defence is partnering with Orano, a world-renowned multinational company, to develop the next-generation radio-immunoconjugates using Defence’s intracellular targeting Accum technology to provide distinctive best-in-class ADC therapies.

Protein- and cell-based vaccines targeting cancer

Although ADCs represent great tools to directly attack and kill cancer cells, they are ideal against a hand-full types of cancer and lack the ability to trigger a long-lasting memory response. This forms the basis of Defence’s vaccine program. Defence engineered and tested a dual acting vaccine targeting cervical cancer. In this context, the term "dual" refers to the vaccine ability to protect and/or treat established cervical (or head and neck – also induced by HPV) cancer. This protein-based vaccine is based on the use of a single protein (in contrast to a mix of 9 viral-derived capsid proteins). In preclinical models, Defence demonstrated that the vaccine synergises with various immune-checkpoint blockers resulting in survival rate between 70 and 100%. With the completion of all GLP studies, Defence is actively working to manufacture the vaccine to initiate a Phase I clinical trial against head and neck cancer in 2024, either by itself or in partnership.

Another successful Defence’s vaccine example demonstrating yet again the versatility of the Accum technology is the design of the ARM vaccine, relying on the use of a type of stem cell pharmacologically re-programmed to behave as antigen presenting cells. The use of this universal off-the shelf vaccine has shown impressive cure rates (80-100%) in solid T-cell lymphoma and melanoma models. In parallel to its manufacturing for Phase I clinical trial targeted in Q1 of 2024, Defence is currently testing the vaccine against two hard-to-treat diseases: pancreatic and ovarian cancer. What makes the ARM vaccine special could be summarized in twofold: i) its impressive therapeutic potency, and ii) its adaptability to treat any solid or liquid tumor given granted access to patients-tumor samples.

The AccuTOXTM program: a new line of anti-cancer therapeutics

Although the goal of using Accum has been mostly to improve biomolecules accumulation in target cells, the Defence team discovered that delivery of unconjugated Accum or its derivatives can exert potent anti-cancer properties. This observation gave rise to the AccuTOXTM moiety, a lead Accum variant capable of halting pre-established lymphoma, melanoma and cervical cancer when give with different immune-checkpoint blockers. More specifically, the AccuTOXTM was shown to cause DNA damage and trigger a form of immunogenic cell death capable of activating the immune system in parallel. AccuTOXTM destroys tumor cells from the inside-out and stimulate an immune response to protect the host from subsequent tumor re-growth. With manufacturing fully completed, IND filling is expected in Q4 of 2023 to start a Phase I clinical trial against a basket of solid tumors at City of Hope National Medical Center and Beckman Research Institute.

Accum Drug the Undruggable

Defence Therapeutics is on the verge of very important inflection points. Its pipeline is well positioned to prevent cancer and/or enhance the efficacy of any bio-drug designed to target cancer. With all these products and an active program on mRNA cancer vaccines, Defence is in a strong position to truly make a difference in helping reduce cancer death rate. Defence is focussing and dedicating its leadership against one of the biggest enemies of humanity: cancer.

According Market.us, the global oncology market recorded a valuation of USD 208 billion in 2022 and is expected to reach USD 628 billion by the end of 2032, expanding at a CAGR of 12% over the decade.

Collaboration between CYTEA

On September 12, 2023 CYTEA|BIO, reported its collaboration with EFS Besançon (PIBT) and Bionoveo (Press release, CYTEA BIO, SEP 12, 2023, View Source [SID1234635099]). This partnership is aimed at propelling the development and manufacturing of our state-of-the-art cell therapy products. These groundbreaking therapies signify a novel category of medical progress, harnessing the potential of allogeneic natural killer (NK) cells sourced from human umbilical cord blood (UCB) armed with a chosen monoclonal antibody (mAb), expertly designed with a high-affinity Fc region.

Alan Cookson, the CEO of CYTEA|BIO, remarked, "Through this collaboration, our commitment lies in advancing the realm of cell therapy and addressing a pressing, unmet medical necessity for patients grappling with glioblastoma. At the forefront of our inaugural clinical trial stands our flagship product, CYT-102, holding the promise of enhanced treatment outcomes and renewed hope."

This collaboration marks a milestone where expertise converges, aspirations align, and medical innovation takes center stage. Together, we are venturing into uncharted territories, guided by our dedication to scientific excellence and patient well-being. The synergy between CYTEA|BIO, EFS Besançon, and Bionoveo resonates with the potential to redefine medical standards and reinvigorate the lives of countless individuals.

As we embark on this remarkable journey, the path ahead may present challenges, yet it is illuminated by the prospect of reshaping the landscape of healthcare. Through relentless determination and collaborative spirit, we strive to make a lasting impact. The core of our endeavor remains rooted in compassion, guided by purpose, and driven by a commitment to improving lives. The future is promising, and we are poised to drive positive change.