Harbour BioMed Announces Dosing of First Patient in Combination Therapy Phase Ib/IIa Trial of Next-Generation Anti-CTLA-4 Antibody

On January 24, 2022 Harbour BioMed ("HBM", HKEX: 02142) reported that, it has successfully completed the dosing of first patient in phase Ib/IIa trial at the stage of dose expansion of its anti-CTLA-4 antibody (HBM4003) in combination therapy with toripalimab (anti-PD-1 antibody) for patients suffering from advanced melanoma and other solid tumors (Press release, Harbour BioMed, JAN 24, 2022, View Source [SID1234606750]).

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As the first heavy chain only fully-human antibody on clinical stage in the world, HBM4003 showed its good safety profile and strong efficacy on its monotherapy study of phase I trial. HBM is making all efforts to push forward to the studies of this product in combination therapy as treatment for multiple solid tumors, including melanoma, NSCLC, HCC, NET/NEC.

About HBM4003

HBM4003 is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, HBM4003 has demonstrated significantly improved depletion specific to high CTLA-4 Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect presents a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug in monotherapy and combo-therapy.

Arrowhead Pharmaceuticals Announces Closing of Agreement with GlaxoSmithKline

On January 24, 2022 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported that the exclusive license agreement between Arrowhead and GlaxoSmithKline (LSE/NYSE: GSK) announced on November 22, 2021, has now closed (Press release, Arrowhead Pharmaceuticals, JAN 24, 2022, View Source [SID1234606734]). Closing of the transaction was subject to customary closing conditions and expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended.

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Innovent Announces the Approval of Pemazyre® (pemigatinib) in Hong Kong Market for the Treatment of Adults With Locally Advanced Or Metastatic Cholangiocarcinoma With A FGFR2 Fusion Or Rearrangement That Have Progressed After At Least One Prior Line Of Systemic Therapy

On January 24, 2022 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases reported that the Hong Kong Department of Health (DH) has approved Pemazyre (pemigatinib) for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy (Press release, Innovent Biologics, JAN 24, 2022, View Source [SID1234606751]).

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Pemazyre, discovered by Incyte and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan, is the first tyrosine kinase inhibitor approved for the treatment of cholangiocarcinoma, a type of biliary tract cancer, in Hong Kong market, marking a new milestone following the successful approval of Pemazyre in Taiwan in June 2021 and the New Drug Applicant(NDA) acceptance by China’s NMPA in July 2021.

The approval was based on the FIGHT-202 study, which is a Phase 2, multi-center, open-label, single-arm study (NCT02924376) evaluating the safety and efficacy of Pemazyre – a selective fibroblast growth factor receptor (FGFR) inhibitor – in adult (age ≥18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGFR2 fusion or rearrangement. The major efficacy outcome measure was overall response rate (ORR) determined by an independent review committee Per RECIST V1.1. As data cut of (April 4th,2020), a total of 108 subjects with FGFR 2 fusion/rearrangement was enrolled in the study and received 13.5mg pemigatinib per day, the ORR was 37.0% (95% CI: 27.94%, 46.86%), including 4 complete responses. The median duration of response (DOR) was 8.08 months with responses lasting ≥ 6 months in 26 of the 40 (66.0%) responding patients and ≥ 12 months in 15 (37.5%) patients. The safety analysis, including 147 patients, demonstrated that pemigatinib was generally well tolerated. Hyperphosphatemia was the most common (58.5%) treatment-emergent adverse event (TEAE). TEAEs grade 3 or higher were reported in 68.7% of patients; the most frequent of which were hypophosphatemia (14.3%), arthralgia (6.1%), stomatitis 6.1%), hyponatremia (5.4%), abdominal pain (5.4%) and fatigue (5.4%).

For more information FIGHT-202, please visit View Source or https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30109-1/fulltext.

Dr. Yongjun Liu, President of Innovent, stated: "The approval of Pemazyre in Hong Kong, following the approval in Taiwan earlier this year, further broadens Innovent’s product portfolio and market coverage. Currently Innovent has developed a robust pipeline of 26 clinical assets and more than 80 projects in preclinical stage, along the way we have established strategic collaborations with a dozen of global and regional partners. We look forward to launching more innovative drugs to help fulfill unmet needs, overcome current therapeutic limitation and improve the life quality of patients."

"Cholangiocarcinoma is the second most common malignancy originated in the liver with a high incidence in Asia. This cancer is usually not diagnosed until it has already developed into an advanced unresectable and/or metastatic stage. There are limitations on current treatment options, which call for innovative drugs that could greatly enhance disease control as well as provide better life quality," stated Dr. Hui Zhou, Senior Vice President of Innovent. "Data from previous clinical trials of Pemazyre in participants with advanced cholangiocarcinoma with FGFR2 fusion that have progressed after at least one prior line of systemic therapy has not only shown satisfactory safety results but also revealed compelling efficacy signals. In addition, Pemazyre is an orally administered medication that could improve convenience and patient compliance. The approval is a new milestone for Innovent; we look forward to hearing good news from NMPA as well and to bringing the therapeutic benefit of Pemazyre in the treatment of eligible patients with cholangiocarcinoma in the Greater China market."

About Advanced Cholangiocarcinoma and FGFR2 Rearrangement

Cholangiocarcinoma is a malignant tumour originated from biliary epithelium cells and it is categorized as intrahepatic or extrahepatic based on anatomical location of origin. The incidence of cholangiocarcinoma has been increasing progressively over the past decade. Surgery is the first priority for patients with resectable disease. However, most cholangiocarcinomas has been in advanced and/or metastatic status at diagnosis and lost the chance for surgical resection. The treatment options for patient who relapse after surgery or have advanced / metastatic disease are limited and the recommended therapy method is systemic chemotherapy with gemicitabine plus cisplatin, which has a medium overall survival of less than a year.

Aberrant signaling through FGFR resulting from gene amplification or mutation, chromosomal translocation, and ligand-dependent activation of the receptors has been demonstrated in multiple types of human cancers. Fibroblast growth factor receptor signaling contributes to the development of malignancies by promoting tumor cell proliferation, survival, migration, and angiogenesis. Results from early clinical studies of selective FGFR inhibitors, including Pemazyre, have shown a tolerable safety profile for the class and preliminary signs of clinical benefit in participants with FGF/FGFR alterations.

About Pemazyre (pemigatinib)

In April 2020, the U.S. Food and Drug Administration (FDA) approved Incyte’s Pemazyre (pemigatinib), a selective, oral inhibitor of FGFR isoforms 1, 2 and 3, for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement as detected by an FDA-approved test. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer with a FGFR2 fusion gene, worsening after cancer chemotherapy. In Europe, Pemazyre is approved for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or rearrangement that have progressed after at least one prior line of systemic therapy.

Pemazyre is marketed by Incyte in the United States, Europe and Japan.

In December 2018, Innovent and Incyte entered into a strategic collaboration for three clinical-stage product candidates discovered and developed by Incyte, including pemigatinib (FGFR1/2/3 inhibitor). Under the terms of the agreement, Innovent has received the rights to develop and commercialize the three assets in Mainland China, Hong Kong, Macau and Taiwan. In March 2020, Innovent announced that the first patient was dosed in the pivotal registrational trial evaluating pemigatinib in patients with advanced cholangiocarcinoma in China.

In June 2021, Taiwan Food and Drug Administration (TFDA) approved Pemazyre (pemigatinib) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or rearrangement.

In July 2021, the National Medical Products Administration (NMPA) of China accepted the New Drug Application (NDA) for Pemazyre(pemigatinib) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement.

In Jan 2022, the Hong Kong Department of Health (DG) approved Pemazyre(pemigatinib) for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.

PAT-DX1 Engineering Update

On January 24, 2022 Patrys reported the completion of the first engineering run for its lead asset PAT-DX1 (Press release, Patrys, JAN 24, 2022, View Source [SID1234606695]).

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The purification of PAT-DX1 from the cell harvest resulted in lower drug product recoveries than expected. Our team is now working with the Contract Development Manufacturing Organisation (CDMO) to implement improvements to the large-scale purification process.

This will mean an extension of the anticipated timeline to start our first in human study for PAT-DX1.

BeiGene Announces Positive Findings from Phase 3 Trial of Tislelizumab in Combination with Chemotherapy in First-Line Gastric or Gastroesophageal Junction Cancer

On January 24, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported positive findings from the global Phase 3 RATIONALE 305 trial of tislelizumab versus placebo in combination with chemotherapy as a first-line treatment for patients with locally advanced, unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (Press release, BeiGene, JAN 24, 2022, View Source [SID1234606735]). At the interim analysis, tislelizumab in combination with chemotherapy met the primary endpoint of overall survival (OS) in patients with PD-L1 expression, with additional follow-up needed to assess OS benefits in the intention-to-treat (ITT) population. The safety profile of tislelizumab was consistent with that observed in previous trials, with no new safety signals identified with the addition of chemotherapy.

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"The addition of tislelizumab to chemotherapy significantly extended the overall survival for previously untreated patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumor expressed PD-L1. We will continue to follow up to determine OS benefits across the patient population in the trial," commented Yong (Ben) Ben, M.D., Chief Medical Officer, Solid Tumors at BeiGene.

RATIONALE 305: Tislelizumab vs. Placebo in Combination with Chemotherapy in First-Line G/GEJ Adenocarcinoma

RATIONALE 305 is a randomized, double-blind, placebo-controlled global Phase 3 trial (NCT03777657) comparing the efficacy and safety of tislelizumab combined with platinum and fluoropyrimidine chemotherapy and placebo combined with platinum and fluoropyrimidine chemotherapy as a first-line treatment for patients with locally advanced, unresectable or metastatic G/GEJ adenocarcinoma. The primary endpoint of the trial is OS. Secondary endpoints include progression-free survival (PFS), overall response rate (ORR), duration of response (DoR), and safety. A total of 997 patients from 13 countries and regions globally, including close to 50 percent from outside of China, were enrolled and randomized 1:1 to receive either tislelizumab and chemotherapy or placebo and chemotherapy.

About Gastric Cancer

Gastric cancer (GC) is the fifth most common cancer worldwide and the third leading cause of cancer death, with more than one million cases and approximately 770,000 deaths in 2020.1 Adenocarcinoma is the major histologic subtype of GC, representing 90% of cases.2 About two-thirds are GC and the remainder are gastroesophageal junction (GEJ) cancers.3

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 approved tislelizumab in six indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy, for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, and for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy. NMPA also granted conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies, 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, and for the treatment of patients with hepatocellular carcinoma (HCC) who have received at least one systemic therapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

In addition, three supplemental Biologics License Applications for tislelizumab are under review by the Center for Drug Evaluation (CDE) of the NMPA, including for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors, for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have disease progression following or are intolerant to first-line standard chemotherapy, and for first-line treatment of patients with recurrent or metastatic nasopharyngeal cancer (NPC).

In the U.S., a Biologics License Application for tislelizumab as a treatment for patients with unresectable recurrent locally advanced or metastatic ESCC after prior systemic therapy is currently under review by the U.S. Food and Drug Administration with a PDUFA target action date of July 12, 2022.

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 for patients across the globe. We have a growing R&D and medical affairs team of approximately 2,900 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 14,500 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. 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. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU and U.K., Canada, Australia and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the 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, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, including a biologics license application (BLA) under FDA review, BeiGene and Novartis announced an option, collaboration and license agreement in December 2021 for BeiGene’s TIGIT inhibitor ociperlimab that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis Oncology products across designated regions of China.