On July 4, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported that the New Drug Application ("NDA") for tazemetostat for the treatment of adult patients with relapsed or refractory ("R/R") follicular lymphoma ("FL") has been accepted for review and granted Priority Review by the China National Medical Products Administration ("NMPA") (Press release, Hutchison China MediTech, JUL 4, 2024, View Source [SID1234644677]).

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

This China NDA is supported by results from a multicenter, open-label, Phase II bridging study in China, and clinical studies conducted by Epizyme outside China.

Tazemetostat was approved for use in the Hainan Boao Lecheng International Medical Tourism Pilot Zone (Hainan Pilot Zone) in May 2022, 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. Tazemetostat was approved in the Macau Special Administrative Region ("SAR") in March 2023 and in the Hong Kong SAR in May 2024.

About Follicular Lymphoma
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.[1],[2],[3]

About Tazemetostat Clinical Development in China
Tazemetostat is a first-in-class methyltransferase inhibitor of EZH2 developed by Epizyme, an Ipsen company. HUTCHMED entered into a strategic collaboration to research, develop, manufacture and commercialize tazemetostat in China, Hong Kong, Macau and Taiwan.

42 patients were enrolled in the Phase II bridging study in China. The primary objective was to evaluate the objective response rate ("ORR") of tazemetostat for the treatment of patients with R/R FL whose disease harbor EZH2 mutations. The secondary objectives included duration of response ("DoR"), progression-free survival (PFS), overall survival (OS), safety and pharmacokinetics of tazemetostat for the treatment of R/R FL patients whose disease do or do not harbor EZH2 mutations. Results of the study will be submitted for presentation at an upcoming medical conference (NCT05467943).

HUTCHMED is participating in Ipsen’s SYMPHONY-1 study, leading it in China. This is an international, multicenter, randomized, double-blind, active-controlled, 3-stage, biomarker-enriched, confirmatory Phase Ib/III study, which is designed to evaluate the safety and efficacy of tazemetostat in combination with rituximab and lenalidomide (R²) in patients with R/R FL after at least one prior line of therapy (NCT04224493).

About Tazemetostat approval in the United States
Tazemetostat 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.

Please see the U.S. Full Prescribing Information for TAZVERIK (tazemetostat).

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.

On July 4, 2024 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the phase II/III SKYSCRAPER-06 study, evaluating tiragolumab plus Tecentriq (atezolizumab) and chemotherapy versus pembrolizumab and chemotherapy as an initial (first-line) treatment for people with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer, did not meet its primary endpoints of progression-free survival (PFS) at its primary analysis with a hazard ratio (HR) of 1.27 [95% CI: 1.02,1.57] and overall survival (OS) at its first interim analysis with a HR of 1.33 [95% CI: 1.02, 1.73], which was immature (Press release, Hoffmann-La Roche, JUL 4, 2024, View Source [SID1234644669]). The combination of tiragolumab plus Tecentriq and chemotherapy showed reduced efficacy in both PFS and OS compared to the comparator arm in the intent-to-treat population, which includes the phase II and phase III cohorts. The overall safety profile remains consistent with the safety profile previously observed for the combination of tiragolumab plus Tecentriq and chemotherapy, and no new or unexpected findings were identified. Based on these results, patients and investigators will be unblinded and we intend to halt the study. A communication will be sent to the investigators and results will be shared with health authorities and subsequently presented at an upcoming medical meeting.

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"These results are disappointing as it was our hope that this combination might yield improved outcomes for people living with metastatic non-squamous lung cancer," said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. "We are thankful to all of the patients and healthcare professionals involved in the study, and we will leverage the learnings to inform our scientific understanding of the anti-TIGIT pathway and new avenues in cancer research."

Ongoing phase III studies are investigating treatment settings and indications distinct from SKYSCRAPER-06. Based on today’s results, we will evaluate any relevant changes needed to the ongoing tiragolumab programme.

About SKYSCRAPER-06 study
SKYSCRAPER-06 is a global phase II/III, randomised, placebo-controlled and double-blinded study evaluating tiragolumab plus Tecentriq (atezolizumab) and chemotherapy as an initial (first-line) treatment versus pembrolizumab and chemotherapy in 542 people with non-squamous non- small cell lung cancer. Primary endpoints are overall survival (OS) and progression-free survival (PFS).

About tiragolumab
Tiragolumab is an investigational novel immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint which suppresses the immune response to cancer. Based on preclinical research, tiragolumab is thought to work as an immune amplifier with other cancer immunotherapies such as Tecentriq (atezolizumab). The TIGIT pathway is distinct but complementary to the PD-L1/PD-1 pathway. Dual blockade with tiragolumab and Tecentriq may help overcome immune suppression and restore the immune response.

About Tecentriq (atezolizumab)
Tecentriq is a cancer immunotherapy approved for some of the most aggressive and difficult-to-treat forms of cancer. Tecentriq was the first cancer immunotherapy approved for the treatment of a certain type of early-stage (adjuvant) non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and hepatocellular carcinoma (HCC). Tecentriq is also approved in countries around the world, either alone or in combination with targeted therapies and/or chemotherapies, for various forms of metastatic NSCLC, certain types of metastatic urothelial cancer (mUC), PD-L1-positive metastatic triple-negative breast cancer (TNBC), BRAF V600 mutation-positive advanced melanoma and alveolar soft part sarcoma (ASPS).

Tecentriq is a monoclonal antibody designed to bind with a protein called programmed death ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted therapies and various chemotherapies across a broad range of cancers.

In addition to intravenous infusion, Tecentriq has been approved as a subcutaneous formulation in over 40 countries. The approved indications for Tecentriq SC mirror those of Tecentriq IV.

On July 3, 2024 Pentixapharm AG, a clinical-stage biotech company discovering and developing novel targeted radiopharmaceuticals against a range of malignancies, reported the execution of an agreement, effective July 1st, to acquire the target discovery business of Berlin-based Glycotope GmbH.

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The deal encompasses a portfolio of preclinical antibodies against multiple oncology targets that can be developed into radiopharmaceuticals. It also includes Glycotope’s laboratories, cell banks, tumor target data base, and the equipment needed to exploit the discovery platform, along with a range of patents, licenses, and other tangible assets. In total, Pentixapharm will be able to add an integrated team of 40 seasoned executives, R&D specialists, and administrators to its staff.

"The acquisition will broaden Pentixapharm’s Intellectual Property portfolio beyond the one built around the CXCR4 receptor. This will immediately double the development pipeline and significantly expand the associated business and clinical development opportunities," explained Hakim Bouterfa, CEO of Pentixapharm AG. "Glycotope’s pipeline comprises several candidates that can be used immediately for proof-of-concept studies as next generation radiopharmaceuticals. We look forward to maximizing the synergy of Pentixapharm’s know-how and Glycotope’s target discovery for the benefit of patients in both diagnostics and therapeutic applications."

"The transaction provides Pentixapharm not just with a chance to build a clinical pipeline beyond the company’s current CXCR4-ligand based programs, but also substantially strengthens its administrative and managerial capacities," noted Andreas Eckert, Chairman of the Supervisory Board of both Pentixapharm and mother company Eckert & Ziegler SE (EZAG). "It adds a critical number of talents to the planned secession of Pentixapharm to Frankfurt Stock Exchange, thereby facilitating a seamless separation from EZAG. The offices and laboratories included in the deal are large enough to allow a consolidation of all Berlin-based activities into one location."

The transaction will also affect the composition of the Pentixapharm Management Board once the company becomes listed on the Frankfurt Stock Exchange. Hakim Bouterfa, current CEO of Pentixapharm, is designated to move to the Company’s Supervisory Board. He will be succeeded by Dirk Pleimes, currently Pentixapharm’s Chief Medical Officer. Patrik Kehler, former Chief Scientific Officer (CSO) of Glycotope, will assume the CSO position at Pentixapharm, while Glycotope’s former CEO, Henner Kollenberg, will take over the responsibility for administrative and business development issues as Chief Business Officer.

Patrik Kehler, newly appointed Chief Scientific Officer of Pentixapharm, explained: "The target discovery unit’s development activities focus on tumor-associated carbohydrate structures, so-called GlycoTargets. Their major advantage is the reduced normal tissue binding compared to conventional antibodies. Based on their superior tumor-specificity, they are suitable for development in an array of different modes of action. In the radiopharmaceuticals field, they have the potential to close the treatment gap that exists for the majority of solid tumors."

(Press release, PentixaPharm, JUL 3, 2024, View Source [SID1234663465])

On July 3, 2024 ImmuneOnco Biopharma reported that Timdarpacept (IMM01) combined with Tislelizumab for refractory cHL Phase III clinical trial successfully completed the first patient enrollment on July 1, 2024 (Press release, ImmuneOnco Biopharma, JUL 3, 2024, View Source [SID1234655701]).

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IMM01 is the first SIRP-α-FC fusion protein to enter the clinical stage in China and is developed to use in combination with other drugs to treat a variety of blood and solid tumors. The results of two Phase II clinical trials of IMM01 were released in oral presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 annual meeting. One is the new updated data of Phase II trial for IMM01 combined with Tislelizumab in cHL patients who have failed prior PD-(L)1 antibody therapy, after 6.87 months of follow-up, ORR reached 66.7%, CR 24.2%, DCR 93.9%, median PFS and median DOR were not reached. In addition, IMM01 combined with Tislelizumab was well tolerated. Another is the phase 2 study of IMM01 combined with azacitidine (AZA) as the first-line treatment in adults with higher risk myelodysplastic syndromes (MDS). After 12.8 months follow-up, ORR reached 64.7%, including 29.4% CR), 15.7% mCR with hematologic improvement (HI): 5.9% HI and 13.7% mCR alone. 12-month PFS reached 54.4%. The updated data show that MM01 combined with AZA were well tolerated and effective in patients with treatment-naive higher-risk MDS.

Founder and chairman of ImmuneOnco Dr. Tian, Wenzhi said: "We are very pleased to see the completion of the first patient enrollment in our Phase III registration clinical trial of Timdarpacept (IMM01) combined with Tislelizumab for cHL refractory to PD-(L)1 monoclonal antibody. This therapy tries to meet ’unmet clinical need’ since there is very limit treatment options for those young-age onset patients. Timdarpacept activates macrophages to turn "cold tumors" into "hot tumors", and macrophages will present more tumor antigens to T lymphocytes to induce tumor-specific T cell responses, thereby restoring and expanding the sensitivity and therapeutic response to Tislelizumab This is well supported by our clinical data. In contrast, PD-1 antibody combined with another T cell-associated immune checkpoint antibody is difficult to achieve such clinical manifestations. We firmly believe that the development of Timdarpacept in combination with Tislelizumab for refractory cHL will have great market competitiveness. We will quickly advance the phase III registered clinical trial and strive to bring benefits to cHL cancer patients as soon as possible."

Chief Medical Officer/Senior Vice President of ImmuneOnco, Dr. Lu, Qiying, said: "the project of IMM01, the company’s key product, combined with Tislelizumab successfully completed the enrollment of the first patient in phase III clinical trial for the cHL patients refractory to PD1/PD-L1 therapy. this is another important milestone indicating that the clinical development of IMM01 has fully entered the registered clinical trial stage. This is globally first registration of trial large molecule drug against CD47 for cHL. From approval of CDE on May 16 to First Patient in on July 1, our team took one and half month to get the work done , indicating that the team had strong execution ability and worked efficiently. We are confident that we can quickly promote the clinical development of IMM01 products to bring new treatment options for cancer patients to solve the unmet clinical needs."

On July 3, 2024 (the "Effective Date"), Eagle Pharmaceuticals, Inc. (the "Company") and Curia Global, Inc., f/k/a Albany Molecular Research, Inc. ("AMRI") and Curia New Mexico, LLC (together with AMRI, "Curia") reported to have entered into a Settlement Agreement and Release ("Settlement Agreement") relating to the settlement of all their claims and counterclaims in Curia Global, Inc. v. Eagle Pharmaceuticals, Inc., AAA Case No. 01-23-0000-2937, American Arbitration Association (the "AAA Arbitration"), and Curia Global, Inc. v. Eagle Pharmaceuticals, Inc., Index No. 651064/2023, Supreme Court of the State of New York, County of New York (the "NY Court Action") and other claims and disputes relating to these proceedings.

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As previously disclosed, the AAA Arbitration relates to disputes arising from the parties’ Vasopressin Commercial Supply Agreement, dated April 15, 2018 ("Vasopressin CSA"), and the NY Court Action relates to disputes arising from the parties’ PEMFEXY Master Development and Supply Agreement, dated March 26, 2021 (the "PEMFEXY MSA"). The Company and Curia have agreed to a mutual release of all claims arising from or concerning the Vasopressin CSA (other than any future indemnity claims that may be asserted related to defects or product liability), or the allegations, claims or counterclaims in the AAA Arbitration or the NY Court Action, in addition to payment, covenants, representations and other terms, the material terms of which are summarized below. The parties’ releases are subject to the payment of the full settlement amount and the passage of a specified time period thereafter with no Events of Default (as described below). The Settlement Agreement provides that the settlement is not an admission of liability or wrongdoing by either party. The PEMFEXY MSA remains in effect.

Pursuant to the Settlement Agreement, the Company agreed to pay Curia $26.5 million in accordance with the following payment schedule: $10.0 million within one business day of the Effective Date (paid on July 5, 2024); $10.0 million on or before February 17, 2025; and $6.5 million on or before July 7, 2025. In addition, Curia has filed a Stipulation of Discontinuance with Prejudice in the NY Court Action pursuant to the Settlement Agreement and the parties have agreed to take all other necessary steps to cause the prompt dismissal with prejudice of all claims in the NY Court Action, including the withdrawal of the appeal in the NY Court Action.The parties have jointly submitted a request to the arbitrators in the AAA Arbitration to issue a final award on consent recording the settlement.

Pursuant to the Settlement Agreement, an Event of Default occurs upon a failure by the Company to pay when due any of the settlement payments described above, and specified bankruptcy and insolvency events with respect to the Company.

The foregoing description of the material terms of the Settlement Agreement does not purport to be complete and is qualified in its entirety by reference to the Settlement Agreement, which the Company intends to file with the Securities and Exchange Commission as an exhibit to the Company’s Annual Report on Form 10-K for the year ended December 31, 2023.