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 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE), reported that the Company has entered into a commercial and revenue sharing agreement with leading global cancer center (Press release, OSE Immunotherapeutics, JUN 24, 2024, View Source [SID1234646936]).

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This exclusive and worldwide agreement with Memorial Sloan Kettering Cancer Center (MSK) covers OSE Immunotherapeutics’ patent rights and jointly owned OSE/MSK patent rights in the field of Chimeric Antigen Receptor (CAR) cell therapy for the treatment of Interleukin-7 Receptor (IL-7R) expressing cancers, in particular hematological tumors such as Acute Lymphoblastic Leukemia. As part of this agreement, MSK will lead the research, development, and commercialization efforts, and subsequently share potential future revenues with OSE Immunotherapeutics.

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, said: "We are very pleased to reinforce our collaboration with one of the world’s most renowned US cancer hospitals in oncology and in particular in the field of CAR-T cell therapies. Based on their pioneering expertise in this area, we look forward to the clinical exploration of a potential breakthrough therapy option for IL-7R expressing cancer patients".

"I am excited for the next steps in translation of IL-7R targeted CARs to clinical trials treating IL-7R expressing tumor bearing patients at MSK," said Prasad S. Adusumilli, MD, FACS, Deputy Chief and Attending, Thoracic Service, and Vice Chair for Translational Research, Department of Surgery, at MSK. Dr. Adusumilli holds the Min H. & Yu-Fan C. Kao Chair in Thoracic Cancer at MSK. His laboratory team investigated and developed therapeutic strategies using IL-7R CAR T cells.

This new agreement is based on the initial multi-year research collaboration between MSK and OSE Immunotherapeutics to explore the preclinical potential of a non-antagonist IL-7R monoclonal antibody directed against the alpha chain of IL-7R used either as a therapeutic antibody or for the design of innovative CAR-T cells for cancer indications expressing high level of IL-7R.

On June 24, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that it will host a R&D update in Shanghai, China, and via webcast on Tuesday, July 9, 2024 (Press release, Hutchison China MediTech, JUN 24, 2024, View Source [SID1234644501]) (Press release, Hutchison China MediTech, JUN 24, 2024, View Source [SID1234644501]).

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During the event, the senior management team will share insights into the Company’s R&D strategy and vision. Additionally, the team will provide updates on certain programs within HUTCHMED’s extensive and innovative pipeline. This will include updates on the Phase III ESLIM‑01 and Phase II/III ESLIM‑02 studies of our Syk inhibitor sovleplenib in immune thrombocytopenia ("ITP") and warm antibody autoimmune hemolytic anemia, ("wAIHA") respectively; the surufatinib Phase II/III study for metastatic pancreatic ductal adenocarcinoma ("PDAC"); and the Phase III RAPHAEL study of our IDH1/2 inhibitor HMPL-306 in acute myeloid leukemia ("AML").

The in-person event will take place from 3:00 p.m. to 5:00 p.m. HKT in Chinese (Putonghua) in Shanghai. A live webcast will be held simultaneously. Attendance for the in-person event is by invitation only.

An English language webcast will take place from 8:30 p.m. HKT / 8:30 a.m. EDT / 1:30 p.m. BST on Tuesday, July 9, for approximately two hours.

Both webcasts will be live and can be accessed via www.hutch-med.com/event. Investors interested in listening to a webcast should log on before the start time to download any software required. A replay of the event will be available shortly thereafter for approximately 90 days.

On June 24, 2024 Biond Biologics Ltd. ("Biond" or the "Company"), a private clinical-stage biopharmaceutical company developing novel immunotherapies for cancer and a platform for the intracellular delivery of biologics, reported that the first patient has been dosed in a first-in-human clinical trial testing BND-35, a humanized ILT3/LILRB4 antagonist antibody (Press release, Biond Biologics, JUN 24, 2024, View Source [SID1234644517]).

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The first patient was administered BND-35 as a monotherapy at the Institute of Oncology, Davidoff Center, Rabin Medical Center, Israel, one of the six Israel and US trial study sites. The phase 1, open-label, dose escalation study aims to explore the safety, tolerability, anti-tumor activity, pharmacokinetics and exploratory biomarkers for BND-35 as a monotherapy and in combination with two approved drugs, a PD-1/PD-L1 inhibitor or the anti-EGFR drug, cetuximab. The decision to test the combination of BND-35 with cetuximab was driven by supportive pre-clinical data and a deep understanding of the BND-35 mechanism of action. BND-35 augments antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity, which are mediated by binding of Fc receptors (FcR) on immune cells to antibodies as cetuximab and additional tumor targeting antibodies. Each arm of the trial includes the patient populations most likely to benefit from ILT3/LILRB4 blockade based on translational research findings.

"The BND-35 trial design introduces a novel combination therapy that targets the immunosuppressive cell milieu within the tumor microenvironment (TME)," commented Professor Salomon Stemmer, M.D., Head of Research, Development and Innovation and Deputy Director of Davidoff Center at the Rabin Medical Center, and a clinical investigator in the trial. "There’s a pressing need for innovative treatments for cancers that are resistant to existing therapies. Given its promising preclinical efficacy, we’re eager to assess BND-35’s potential in overcoming ILT3/LILRB4-mediated immunosuppression."

"ILT3 is a unique receptor expressed on various suppressive myeloid cells within the TME and the binding of various ligands to ILT3 maintains the TME in an immunosuppressive state. BND-35 has been demonstrated to effectively block the interaction between ILT3 and its various ligands, thereby enhancing the immune system’s ability to fight tumors, resulting in increased physiological anti-tumor responses and enhanced tumor cell destruction by immune cells," stated Tsuri Peretz, project manager for the BND-35 program.

About ILT3/LILRB4/LILRB4

BND-35 is a novel anti-ILT3/LILRB4 antagonist antibody developed for the treatment of solid tumors. BND-35 binds ILT3/LILRB4 with high affinity and blocks its interaction with ligands present in the TME In vitro and ex vivo studies have demonstrated that BND-35 as monotherapy or in combination with anti-PD-1/PD-L1 pathway inhibitors as well as with anti-EGFR agents, enhances the pro-inflammatory activity of various myeloid cells and inhibits the immunosuppressive activity of suppressive myeloid cells, thereby restoring T cell and NK cell activity.

BND-35-induced immune activity enhancement was demonstrated in a unique system of patient-derived tumoroids. In vivo, blocking ILT3/LILRB4 activity with BND-35, as monotherapy or in combination therapy, resulted in decreased tumor growth and induced a pro-inflammatory phenotype in tumor-resident T cells and myeloid cell populations. Further information about the trial is available in View Source;rank=1 (Trial Identifier: NCT06274437).

On June 24, 2024 Illumina, Inc. (NASDAQ: ILMN) reported the successful completion of the spin-off of GRAIL (Press release, Illumina, JUN 24, 2024, View Source [SID1234644502]). This milestone follows the company’s previously announced plans to divest GRAIL, and GRAIL is now a public and independent company. GRAIL will begin regular way trading on Nasdaq on Tuesday, June 25 under the ticker symbol "GRAL." Illumina will continue to trade on Nasdaq under the ticker symbol "ILMN."

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"With the completion of the spin-off of GRAIL, we have achieved our goal of divesting GRAIL in a manner that allows its breakthrough technology to continue benefiting patients," said Jacob Thaysen, CEO of Illumina. "Illumina will maintain a minority share of 14.5% in the company. GRAIL plays a critical role in the fight against cancer, and while the company is no longer part of Illumina, we remain confident in its future and will continue to support GRAIL with our sequencing technology, end-to-end workflows, and suite of services."

Later this week, Illumina will file an 8-K/A providing historical unaudited pro forma financial information and will provide supplemental non-GAAP information on its investor relations website at View Source

Illumina also announced it will issue results and host its earnings call for the second quarter of 2024 following the close of market on Tuesday, August 6, 2024. Illumina will also host a virtual Strategy Update on Tuesday, August 13, 2024, beginning at 8:00 am Pacific Time (11:00 am Eastern Time) and running for approximately two hours. Additional details for these events will be announced in the coming weeks and provided on Illumina’s investor relations website, View Source Replays of these events will be posted on Illumina’s investor relations website after each event and for at least 30 days following.

"As we turn the page, we are excited to share our plan to accelerate topline growth, achieve operational excellence, deliver for our customers, and maximize value for shareholders in our upcoming strategy update," said Thaysen. "Illumina is prepared to lead the next era of innovation in next generation sequencing by continuing to focus on strengthening our business and catalyzing the industry with an even greater focus on our customers’ priorities."

Financing Information

As previously disclosed, on June 17, 2024, Illumina entered into a 364-day delayed draw credit agreement that provided for a senior unsecured term loan credit facility in an aggregate principal amount of up to $750 million. The credit facility was drawn in full on June 20, 2024, and the proceeds, together with cash from Illumina’s balance sheet, were used to fund cash to the balance sheet of GRAIL in connection with Illumina’s divestment of GRAIL. The current borrowing rate under the credit facility is approximately 6.70%.

Distribution Details

The separation was achieved through the distribution of 85.5% of the outstanding shares of GRAIL to holders of Illumina common stock at 12:01 a.m. ET on June 24, 2024 (the "Distribution Date"). In addition to retaining their shares of Illumina common stock, Illumina shareholders received one share of GRAIL common stock for every six shares of Illumina stock held as of close of business on the record date of June 13, 2024. Illumina retained 14.5% of the outstanding shares of GRAIL common stock.

On Tuesday, June 25, 2024, the first trading day following the Distribution Date, GRAIL will begin trading "regular way" on Nasdaq under the ticker symbol "GRAL." There will no longer be two markets in Illumina common stock and Illumina will continue to trade on Nasdaq under the ticker symbol "ILMN."

Fractional shares of GRAIL common stock were not distributed to Illumina shareholders and are instead being aggregated and sold in the open market. The net proceeds will be distributed pro rata, in cash, to Illumina shareholders who would otherwise have received a fractional share of GRAIL common stock.

For U.S. federal income tax purposes, Illumina’s U.S. shareholders (other than those subject to special rules) generally should not recognize a gain or loss as a result of the distribution of GRAIL shares, except with respect to cash received in lieu of fractional shares. Illumina shareholders are urged to consult with their tax advisors with respect to the U.S. federal, state, and local or foreign tax consequences, as applicable, of the spin-off.

For more information about the distribution, please contact the distribution agent, Computershare Trust Company, N.A., at 150 Royall Street, Canton, MA 02021 or at the telephone number 877-373-6374.