On June 7, 2021 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, reported that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental Biologics License Application (sBLA) for anti-PD-1 antibody tislelizumab for the treatment of patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors (Press release, BeiGene, JUN 7, 2021, View Source [SID1234583657]).

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"We are excited by the acceptance of our filing for tislelizumab in patients with MSI-H or dMMR solid tumors, which underscores our ongoing commitment to pursuing the full potential of tislelizumab, a potentially differentiated checkpoint inhibitor, and expanding its access where there is unmet medical need. This submission also marks the seventh indication submitted to health authorities, including three approvals for our tislelizumab program," commented Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. "Results from our Phase 2 trial demonstrated that tislelizumab’s treatment effect was consistent and durable across tumor types and endpoints. We are encouraged by the data and plan to continue our communications with the CDE, hoping to bring this medicine to more patients."

The sBLA is supported by clinical results from a single-arm, multi-center, open-label, pivotal Phase 2 clinical trial (NCT03736889) to evaluate efficacy and safety of tislelizumab as monotherapy in patients with previously treated locally advanced unresectable or metastatic MSI-H or dMMR solid tumors, with an enrollment of 80 patients in China. Patients received tislelizumab 200 mg intravenously every three weeks until disease progression, unacceptable toxicity, or withdrawal. Radiological imaging was performed at nine weeks and then every six weeks for the first year of therapy and every 12 weeks thereafter. The primary efficacy analysis set included patients who received any dose of tislelizumab with measurable disease per independent review committee (IRC) at baseline. The primary endpoint of this trial is objective response rate (ORR) as assessed by IRC per RECIST v1.1; secondary endpoints include time to response (TTR), duration of response (DoR), disease control rate (DCR), and progression-free survival (PFS) as assessed by investigator and IRC, overall survival (OS), and safety and tolerability. Results of this study were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

About Microsatellite Instability-High or Mismatch Repair Deficient Solid Tumors

Microsatellite instability-high (MSI-H) cancer cells have a greater than normal number of genetic markers called microsatellites, which are short, repeated sequences of DNA. Cancer cells that have large numbers of microsatellites may have defects in the ability to correct mistakes (also known as mismatch repair deficiency, or dMMR) that occur when DNA is copied in the cell. MSI-H and dMMR tumors are found most often in colorectal cancer and other types of gastrointestinal cancer and endometrial cancer, although they may also be found in cancers of the breast, prostate, bladder and thyroid. i

About Tislelizumab

Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The China National Medical Products Administration (NMPA) has granted tislelizumab approval in three indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy; and conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies and for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

In addition, four supplemental Biologics License Applications for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy, for patients with previously treated with at least one systemic therapy hepatocellular carcinoma and for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.

BeiGene has initiated or completed 17 potentially registration-enabling clinical trials in China and globally, including 13 Phase 3 trials and four pivotal Phase 2 trials.

In January 2021, BeiGene and Novartis entered into a collaboration and license agreement granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

Tislelizumab is not approved for use outside of China.

About the Tislelizumab Clinical Program

Clinical trials of tislelizumab include:

Phase 3 trial comparing tislelizumab with docetaxel in the second- or third-line setting in patients with NSCLC (NCT03358875);
Phase 3 trial comparing tislelizumab to salvage chemotherapy in patients with relapsed or refractory classical Hodgkin Lymphoma (cHL; NCT04486391);
Phase 3 trial in patients with locally advanced or metastatic urothelial carcinoma (NCT03967977);
Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced squamous NSCLC (NCT03594747);
Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced non-squamous NSCLC (NCT03663205);
Phase 3 trial of tislelizumab in combination with platinum-based doublet chemotherapy as neoadjuvant treatment for patients with NSCLC (NCT04379635);
Phase 3 trial of tislelizumab combined with platinum and etoposide versus placebo combined with platinum and etoposide in patients with extensive-stage small cell lung cancer (NCT04005716);
Phase 3 trial comparing tislelizumab with sorafenib as first-line treatment for patients with hepatocellular carcinoma (HCC; NCT03412773);
Phase 2 trial in patients with previously treated unresectable HCC (NCT03419897);
Phase 2 trial in patients with locally advanced or metastatic urothelial bladder cancer (NCT04004221);
Phase 3 trial comparing tislelizumab with chemotherapy as second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC; NCT03430843);
Phase 3 trial of tislelizumab in combination with chemotherapy as first-line treatment for patients with ESCC (NCT03783442);
Phase 3 trial of tislelizumab versus placebo in combination with chemoradiotherapy in patients with localized ESCC (NCT03957590);
Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for patients with gastric cancer (NCT03777657);
Phase 2 trial of tislelizumab in patients with relapsed or refractory cHL (NCT03209973);
Phase 2 trial in patients with MSI-H/dMMR solid tumors (NCT03736889); and
Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment in patients with nasopharyngeal cancer (NCT03924986).
BeiGene Oncology

BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines to patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy volunteers. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 40 countries. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. The Company currently markets three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis Pharma AG granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

On June 7, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company that strives to create new value through the pursuit of advances in life sciences and technologies, reported the dosing of the first patient with relapsed or refractory marginal zone lymphoma enrolled in the recently added second arm of the global Phase 2 TIDAL study of zandelisib, a selective phosphatidylinositol 3-kinase ("PI3K") delta inhibitor (Press release, MEI Pharma, JUN 7, 2021, View Source [SID1234583656]). Both arms of the TIDAL study are evaluating zandelisib as a monotherapy for the treatment of adults with follicular and marginal zone lymphomas. Subject to results from TIDAL, data from each study arm are intended to support separate accelerated approval applications with the U.S. Food and Drug Administration (FDA) under 21 CFR Part 314.500, Subpart H.

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The TIDAL study (Trials of PI3K DeltA in Non-Hodgkin’s Lymphoma), to be conducted in the U.S., Europe, Asia and Oceania, is a global Phase 2 study evaluating zandelisib as a monotherapy across two study arms: the first study arm for the treatment of adults with relapsed and refractory follicular lymphoma and the second study arm for marginal zone lymphomas, in both cases after failure of at least two prior systemic therapies including chemotherapy and an anti-CD20 antibody. The primary efficacy endpoint will be the rate of objective responses to therapy and other endpoints will include duration of response and tolerability of zandelisib.

"Relapsed and refractory marginal zone lymphoma is an incurable disease for which there are limited available therapeutic options for patients who may not have responded to conventional therapies," said Pier Luigi Zinzani, M.D., Ph.D. Professor, Institute of Hematology Seràgnoli University of Bologna, Bologna, Italy, and co-chair of the global TIDAL study. "Given the positive and encouraging results to date with zandelisib, we are eager to further evaluate the potential benefit zandelisib may offer patients with marginal zone lymphoma."

"The initiation of the marginal zone lymphoma study arm in TIDAL is an important step in our commitment, in partnership with Kyowa Kirin, to identify and explore the full potential of zandelisib across multiple B-cell malignancies, including combinations with other therapies, and to meet the need for new innovative medicines across a range of hematological cancers.," said Richard Ghalie, M.D., chief medical officer, of MEI Pharma. "We continue to anticipate multiple important milestones from the zandelisib program this year, including topline data from our Phase 2 TIDAL study in fourth quarter and clinical data updates from the ongoing Phase 1b study at ASCO (Free ASCO Whitepaper), EHA (Free EHA Whitepaper) and ICML. We also will continue expansion of the zandelisib clinical program evaluating additional indications and combinations, including the start around mid-year of COASTAL, a Phase 3 study evaluating zandelisib in combination with rituximab in patients with second line follicular and marginal zone lymphoma."

"I am delighted that this important milestone was achieved for zandelisib in the marginal zone lymphoma study arm of the global TIDAL study," said Yoshifumi Torii Ph.D., Executive Officer, Vice President, Head of R&D Division of Kyowa Kirin. "Under the partnership with MEI, we continue to work with medical professionals and patients to demonstrate zandelisib’s potential to help those in need with B-cell malignancies."

About Zandelisib
Zandelisib (formerly called ME-401), a selective PI3Kδ inhibitor, is an investigational cancer treatment being developed as an oral, once-daily, treatment for patients with B-cell malignancies. In March 2020 the U.S. FDA granted zandelisib Fast Track designation for treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least 2 prior systemic therapies..

In April 2020, MEI and Kyowa Kirin entered a global license, development, and commercialization agreement to further develop and commercialize zandelisib. MEI and Kyowa Kirin will co-develop and co-promote zandelisib in the U.S., with MEI booking all revenue from the U.S. sales. Kyowa Kirin has exclusive commercialization rights outside of the U.S. and will pay MEI escalating tiered royalties on ex-U.S. sales.

Other than the TIDAL study, ongoing zandelisib studies also include a Phase 2 pivotal study in Japan in patients with indolent B-cell non-Hodgkin’s lymphoma (iNHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM) conducted by Kyowa Kirin.

About the TIDAL Phase 2 Study
The TIDAL study (Trials of PI3K DeltA in Non-Hodgkin’s Lymphoma) is a global Phase 2 study evaluating zandelisib as a monotherapy across two study arms: the first study arm for the treatment of adults with relapsed and refractory follicular lymphoma and the second study arm for marginal zone lymphomas, in both cases after failure of at least two prior systemic therapies including chemotherapy and an anti-CD20 antibody. The primary endpoints of the study are the objective response rate and the tolerability of zandelisib.

Subject to the results, data from each study arm are intended to support separate accelerated approval marketing applications with FDA under 21 CFR Part 314.500, Subpart H.

The study is evaluating zandelisib administered once daily at 60 mg for two 28-day cycles and then on an intermittent schedule (IS) of once daily dosing for the first seven days of each subsequent 28-day cycle. Approximately 120 follicular lymphoma and 64 marginal zone lymphoma patients will be enrolled and treated with the IS regimen. The primary efficacy endpoint will be the rate of objective responses to therapy and other endpoints will include duration of response and tolerability of zandelisib.

The TIDAL study is being conducted in the US, Europe, Asia and Oceania. More information about this trial is available at ClinicalTrials.gov.

About Marginal Zone and Follicular Lymphomas*
Marginal zone lymphoma (MZL) is a group of indolent, or slow growing, lymphomas. The disease forms on B-cells, a type of white blood cell called a lymphocyte. MZL accounts for approximately 5% to 10% percent of all non-Hodgkin lymphoma cases; over 77,000 cases of non-Hodgkin lymphoma are diagnosed in the U.S. each year. The average age at diagnosis for most marginal zone lymphomas is 60 years.

Follicular lymphoma (FL) is the most common indolent lymphoma, comprising about 20-30% of all non-Hodgkin lymphomas. The disease also forms on B cells, is chronic in most cases and tends to progress slowly. Most people diagnosed with FL are over 65 years of age. Sometimes follicular lymphomas can change into diffuse large B-cell lymphoma, a fast-growing (aggressive) type of NHL.

On June 7, 2021 Iksuda Therapeutics (Iksuda), the developer of a new generation of antibody drug conjugates (ADCs) with raised therapeutic index, reported it has completed a US $47 million (circa GB £34 million) financing round, co-led by Mirae Asset Capital and its subsidiaries, Celltrion and Premier Partners, with the Company being advised by Ashfords LLP (Press release, Iksuda Therapeutics, JUN 7, 2021, View Source [SID1234583655]). The funding will support the advancement of Iksuda’s lead ADC assets and expansion of its payload and conjugation platform technologies.

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Iksuda’s lead pre-clinical candidate, IKS03, is a best-in-class CD19-targeted ADC candidate for B-cell cancers. The investment will enable progression of IKS03 to first-in-human phase 1 clinical trials. It will also be used to accelerate the Company’s earlier-stage programmes including IKS04 and IKS012 to IND filing.

Iksuda’s ADC programmes target tumours that currently have limited treatment options and high relapse rates. The Company’s drug development pipeline is centred on the improved safety and efficacy conferred by tumour activated, prodrug payloads in combination with stable conjugation technologies, including its proprietary novel PermaLink platform. Iksuda’s research-stage pipeline utilises its proprietary Protein Alkylating (ProAlk) tumour-activated payload platform, recently licensed from Göttingen University1. The novel mode of action for the ProAlk tuneable payload series differs from the field’s primary focus of intra- or DNA inter-strand cross-linking, conferring benefits against drug and tumour resistance mechanisms, and enabling the development of more powerful, more tolerable ADCs.

Dr Dave Simpson, Chief Executive Officer, Iksuda Therapeutics, said: "This is a transformational investment milestone for Iksuda, enabling us to focus on the progression of our industry-leading ADC programmes and bring them to the clinic, whilst supporting our commercial growth. The funding not only reflects the potential of our technologies, but also the unmatched expertise of the Iksuda team. We are grateful for the support of this group of investors and delighted to welcome them to the team."

Ji Kwang Chung, Investor, Mirae Asset Capital, commented: "We have been highly impressed with Iksuda’s approach and progress to date, and with the Company’s leadership. We are delighted to lead this investment round, and to contribute to enabling the team to progress its very promising pipeline of ADC candidates."

Woosung, Kee, CEO, Celltrion Inc., added: "By pursuing tumours that are resistant to current treatment approaches, Iksuda is extending the boundaries of ADC technology, and consequently the treatment options for patients. This ideally complements Celltrion’s drive to pioneer uncharted areas of innovative therapies, incorporating unique and successful next-generational approaches that promote health and welfare globally. We have been very impressed with Iksuda’s progress to date and look forward to working together to support their mission."

On June 7, 2021 Silence Therapeutics plc, AIM:SLN and Nasdaq: SLN ("Silence" or "the Company"), a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, reported that it will present data showing the potential for SLN124 to address a range of hematological diseases by targeting the liver-expressed gene TMPRSS6 during two poster sessions at the European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress to be held on June 9-17, 2021 (Press release, Silence Therapeutics, JUN 7, 2021, View Source [SID1234583654]).

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The presentations include a preclinical safety assessment of SLN124 which will show data that are consistent with recent positive topline clinical data from the GEMINI phase 1 study of SLN124 in healthy volunteers announced last month (press release linked here). SLN124 is being evaluated in the ongoing GEMINI II phase 1 study in patients with thalassemia and myelodysplastic syndrome. A second poster will present encouraging preclinical evidence that using siRNA to target TMPRSS6 could be a viable therapeutic avenue for treatment of the rare blood disorder, polycythaemia vera (PV).

E-posters will be available for registered attendees through the EHA (Free EHA Whitepaper) Virtual Congress platform starting Friday, June 11, 09:00 CEST.

Details on the presentations are as follows:

Title: Non-clinical safety of SLN124, a GalNAc conjugated 19-mer double stranded siRNA targeting TMPRSS6 facilitating evaluation in clinical studies

Abstract #: EP846 (link here)

Session Topic: Iron metabolism, deficiency and overload

Title: Anti-TMPRSS6 RNAi Therapy as a Novel Treatment Option for Polycythaemia Vera

Abstract #: EP1057 (link here)

Session Topic: Myeloproliferative neoplasms – Biology & Translational Research

About SLN124

SLN124 is a gene ‘silencing’ therapy – one that is designed to temporarily block a specific gene’s message that would otherwise trigger an unwanted effect. In this case, SLN124 aims to temporarily ‘silence’ TMPRSS6, a gene that prevents the liver from producing a particular hormone that controls iron levels in the body – hepcidin. As hepcidin increases, it is hoped that iron levels in the blood will decrease, which could in turn allow more healthy red blood cells to be produced, thereby improving anemia.

​In preclinical studies, SLN124 showed a strong safety profile and positive effects on improving levels of red blood cells and reducing harmful iron levels. Data from the recently completed GEMINI phase 1 study of SLN124 in healthy volunteers demonstrated SLN124 was safe and effective in reducing plasma iron levels and had a long duration of action. These data support the ongoing GEMINI II phase 1 study of SLN124 in people with thalassemia or myelodysplastic syndrome (MDS), whose bodies produce fewer healthy red blood cells than normal and who can store too much iron in their bodies. For more information on the GEMINI II study, please click here.

On June 7, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, reported that it will host a key opinion leader webinar focusing on ficlatuzumab, the Company’s investigational potent humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets hepatocyte growth factor (HGF), being studied in head and neck squamous cell carcinoma (HNSCC) on Wednesday, June 16, 2021 at 2:00 p.m. Eastern Time (Press release, AVEO, JUN 7, 2021, View Source [SID1234583653]).

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The webinar will feature a presentation by Julie E. Bauman, M.D., MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Deputy Director, University of Arizona Cancer Center. Dr. Bauman will discuss the current treatment landscape and unmet medical need in HNSCC and the results from a randomized confirmatory Phase 2 study of ficlatuzumab as a single agent or in combination with cetuximab (ERBITUX), an EGFR-targeted antibody, in patients who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab (pan-refractory) with metastatic HNSCC that were presented in a poster discussion at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Dr. Bauman will be available to answer questions following the formal presentations.

AVEO’s management team will provide an overview of the Company’s development plan for ficlatuzumab, for which it anticipates making a decision by mid-year on the initiation of a Phase 3 study in an HPV negative HNSCC patient population after receiving feedback from the U.S. Food and Drug Administration (FDA).

A live webcast of the webinar can be accessed by visiting the investors section of the Company’s website at www.aveoncology.com. A replay of the webcast will be available for a limited time.