On April 28, 2022 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported it will be participating in the upcoming BofA Securities 2022 Healthcare Conference in Las Vegas, Nevada (Press release, Guardant Health, APR 28, 2022, View Source [SID1234613176]).

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Guardant Health’s management is scheduled to participate in a fireside chat on Tuesday, May 10 at 10:40 a.m. Pacific Time / 1:40 p.m. Eastern Time. Interested parties may access a live and archived webcast of the presentation on the "Investors" section of the company website at: www.guardanthealth.com.

On April 28, 2022 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing next-generation multifunctional biotherapeutics, reported that it has completed enrollment in its global HERIZON-BTC-01 pivotal clinical trial evaluating the antitumor activity of zanidatamab monotherapy in patients with previously treated advanced or metastatic HER2-amplified biliary tract cancers (BTC), including gallbladder cancer and cholangiocarcinoma (bile duct cancer) (Press release, Zymeworks, APR 28, 2022, View Source [SID1234613175]). Efficacy and safety results from HERIZON-BTC-01 are expected to be announced by early 2023.

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"Completing enrollment in our first pivotal trial is a tremendous accomplishment for Zymeworks. I’m extremely proud of our team and our collaborators at BeiGene for their hard work in reaching this milestone ahead of expectations," said Neil Josephson, M.D., Chief Medical Officer. "Currently there are limited options for patients with advanced HER2-amplified biliary tract cancer who experience disease progression after front-line therapy. Zanidatamab has the potential to meet the urgent global clinical need for a safe and effective therapy for patients with this difficult to treat cancer."

Biliary tract cancers, including gallbladder cancer and cholangiocarcinoma, account for approximately 3% of all adult cancers and is often associated with a poor prognosis1. Globally, more than 210,000 people are diagnosed with BTC every year2 and most patients (> 65%) with BTC are diagnosed with tumors that cannot be removed surgically. The human epidermal growth factor receptor 2 (HER2) is a well-described target for anti-cancer therapy. About 5% to 19% of patients with BTC have tumors that express HER23, suggesting that these patients may have the potential to benefit from HER2-targeted therapy. Currently no HER2-targeted therapy has been approved for the treatment of BTC.

HERIZON-BTC-01 is a global, multicenter, open-label, single-arm study (NCT04466891) with a primary endpoint of confirmed objective response rate (ORR) by independent central review (ICR) per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary endpoints are duration of response (DOR), proportion of subjects with a DOR ≥16 weeks, disease control rate (DCR), progression-free survival (PFS), overall safety (OS) and safety. HER2 amplification, as determined by in situ hybridization (ISH) in tumor tissue, was an inclusion criterion for all subjects enrolled into the two study cohorts: Cohort 1, the primary efficacy cohort, with tumor tissue showing HER2 immunohistochemistry (IHC) 2+ or 3+ staining, and cohort 2 with tumor tissue showing HER2 IHC 0 or 1+ staining. The study was initiated in July 2020 and has active sites in North America, Asia Pacific, Europe and South America.

About Zanidatamab

Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. Zanidatamab’s unique binding properties result in multiple mechanisms of action including HER2 -receptor clustering, internalization, and downregulation; inhibition of growth factor-dependent and -independent tumor cell proliferation; antibody-dependent cellular cytotoxicity and phagocytosis; and complement-dependent cytotoxicity. Zanidatamab is currently being evaluated in two pivotal clinical trials, one for the first-line treatment of advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (HERIZON-GEA-01) and one for previously treated HER2-amplified biliary tract cancer (HERIZON-BTC-01). Zanidatamab is also being evaluated in several Phase 2 clinical trials for HER2‑expressing gastroesophageal, colorectal, and breast cancers. The FDA has granted zanidatamab Breakthrough Therapy designation for patients with previously treated HER2 gene-amplified biliary tract cancer, as well as two Fast Track designations, one as monotherapy for refractory biliary tract cancer and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma. These designations mean zanidatamab is eligible for Accelerated Approval, Priority Review and Rolling Review, as well as intensive FDA guidance on an efficient drug development program. Zanidatamab received Break Through Designation from the Center of Drug Evaluation (CDE) in China for treating patients with biliary tract cancer who have failed prior systemic therapies. Zanidatamab has also received Orphan Drug designations from the FDA as well as the European Medicines Agency for the treatment of biliary tract and gastric cancers.

Zymeworks has an existing intermediate-size Expanded Access Protocol (EAP) for use of zanidatamab in patients with HER2-positive advanced solid tumors who are not eligible for other zanidatamab clinical trials, and who in the opinion of the treating oncologist, would potentially benefit from treatment with zanidatamab. Additional information is available on our website at View Source

About the Zymeworks-BeiGene Collaboration

In November 2018, Zymeworks and BeiGene entered into license and collaboration agreements in which BeiGene was granted an exclusive license for the research, development, and commercialization of zanidatamab and ZW49 in Asia (excluding Japan), Australia, and New Zealand. The companies are collaborating on joint global development for selected indications, with the goal of developing zanidatamab and ZW49 worldwide across multiple HER2-expressing cancers and lines of therapy.

On April 28, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) seeking approval of niraparib in combination with abiraterone acetate, in the form of a dual action tablet (DAT)* plus prednisolone, for the treatment of patients with prostate cancer who have progressed to metastatic castration-resistant prostate cancer (mCRPC) and are positive for homologous recombination repair (HRR)+ gene alterations (Press release, Johnson & Johnson, APR 28, 2022, View Source [SID1234613174]). When approved by the European Commission, niraparib in combination with AAP will be the first dual action tablet formulation in the European Union specifically targeting HRR gene alterations in mCRPC.

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The combination of niraparib, a PARP (poly adenosine diphosphate-ribose polymerase) inhibitor, and abiraterone acetate, a CYP17 inhibitor, targets two oncogenic drivers in patients with mCRPC, AR-axis and HRR gene alterations. The DAT formulation is also intended to be more convenient for patients, and thus aims to improve treatment compliance. Prostate cancer is one of the most common cancers in Europe with approximately 473,000 patients diagnosed in 2020.2 Up to approximately 30% of patients with mCRPC have HRR gene alterations which are associated with a worse prognosis compared to patients without HRR gene alterations.1

"People with prostate cancer harbouring BRCA alterations face a more aggressive form of disease with worse outcomes and faster progression, sadly leading to a shorter life expectancy," commented Professor Gerhardt Attard=, Primary Study Investigator and Clinician Scientist and Team Leader at University College London Cancer Institute. "This submission is an important step towards improving the outcomes for people with metastatic prostate cancer harbouring BRCA alterations using a targeted therapy that significantly delays the time to their cancer progressing."

The EU MAA is supported by data from the MAGNITUDE study (NCT03748641), a Phase 3, randomised, double-blind, placebo-controlled, multicentre study evaluating the safety and efficacy of niraparib combined with abiraterone acetate plus prednisone (AAP) in patients with mCRPC. The study showed that at the final analysis for radiographic progression-free survival (rPFS), the treatment combination of niraparib and AAP demonstrated a statistically significant improvement in patients with HRR gene alterations as compared to placebo and AAP.1 First results from the study were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) – Genitourinary Cancers Symposium (ASCO GU 2022) Annual Meeting (Abstract #12). The study continues to collect data on the secondary endpoints, which include time-to-initiation of cytotoxic chemotherapy, time to symptomatic progression and overall survival.1

"The data supporting this submission demonstrate the benefit of niraparib in combination with AAP in patients with specific gene alterations and reinforce the importance of biomarker testing in helping to provide an individualised treatment for these patients," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "We are committed to advancing targeted therapeutic options for patients with prostate cancer as we build upon our deep understanding of the disease, with a focus on improving outcomes for patients."

"The submission of niraparib in combination with AAP to the European Medicines Agency marks an important milestone in addressing specific genetic alterations in prostate cancer," said Mathai Mammen, M.D., Ph.D., Executive Vice President, Pharmaceuticals, R&D, Johnson & Johnson. "We are determined to transform this complex disease through innovation, science and ingenuity."

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About Niraparib
Niraparib is an orally administered, selective poly-ADP ribose polymerase (PARP) inhibitor, that is currently being studied by Janssen for the treatment of patients with prostate cancer.1 Additional ongoing studies include the Phase 3 AMPLITUDE study evaluating the combination of niraparib and AAP in a biomarker-selected patient population with metastatic hormone-sensitive prostate cancer (mHSPC).3

In April 2016, Janssen Biotech, Inc. entered a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (acquired by GSK in 2018), for exclusive rights to niraparib in prostate cancer. In the European Union, niraparib is indicated for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy; for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy (Zejula SmPC 2021). Niraparib is currently marketed by GSK as ZEJULA.4

About abiraterone acetate
Abiraterone acetate is an orally-administered androgen biosynthesis inhibitor. In the European Union, abiraterone acetate is indicated with prednisone or prednisolone for the treatment of newly diagnosed high risk mHSPC in adult men in combination with ADT; the treatment of mCRPC in adult men who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated; and the treatment of mCRPC in adult men whose disease has progressed on or after a docetaxel based chemotherapy regimen (ZYTIGA SmPC 2020).5

Abiraterone acetate is currently marketed by Janssen Janssen-Cilag International NV as ZYTIGA.5

About Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer (mCRPC) characterises cancer that no longer responds to ADT and has spread to other parts of the body. The most common metastatic sites are bones, followed by lungs and liver.6 Prostate cancer is the most common cancer in men in Europe.7 More than one million men around the world are diagnosed with prostate cancer each year.8 Patients with mCRPC and HRR gene alterations have a worse prognosis than those without HRR alterations.9

About MAGNITUDE
MAGNITUDE (NCT03748641) is a Phase 3 randomised, double-blind, placebo-controlled, multicentre clinical study evaluating the safety and efficacy of the combination of niraparib and AAP for patients with mCRPC, with or without certain HRR gene alterations. The study includes two cohorts in which patients were randomised to receive either niraparib and AAP or placebo and AAP cohorts: one cohort of patients with predefined HRR gene alterations (including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2 alterations) and one cohort of patients without HRR gene alterations. In a third, open-label cohort, all patients received the dual action tablet formulation of niraparib and AAP.1

The primary endpoint of the MAGNITUDE trial is rPFS. Secondary endpoints include time-to-initiation of cytotoxic chemotherapy, time to symptomatic progression and overall survival.1

On April 28, 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 that the BTK inhibitor BRUKINSA (zanubrutinib) has been approved in Uruguay for the treatment of adult patients with previously treated mantle cell lymphoma (MCL), relapsed or refractory marginal zone lymphoma (MZL), and Waldenström’s macroglobulinemia (WM) (Press release, BeiGene, APR 28, 2022, View Source [SID1234613173]). BeiGene and Adium entered into an exclusive distribution agreement for Adium to commercialize BRUKINSA in Latin America.

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"Tolerability of treatments for B-cell malignancies is an important consideration with BTK inhibition, and BRUKINSA was designed with that in mind to maximize BTK occupancy and minimize off-target binding. Today, we have a new treatment option for patients with MCL, MZL and WM in Uruguay, providing hope for improved treatment outcomes," said Dr. Karina Cicinelli, Corporate Medical Director at Adium.

"We are proud of the progress BeiGene has made in Latin America over the past year, with this approval in three indications in Uruguay following recent launches in Brazil, Chile and Ecuador. With Adium’s established commercial presence in Latin America, we hope patients with MCL, MZL, and WM will soon have access to this important treatment option," commented Eduardo Molinari, Senior Director of New Market Development in Latin America at BeiGene.

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA has previously been approved for three indications in the United States: for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (Nov. 2019)*; for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) (Aug. 2021); and for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (Sept. 2021)*.

BRUKINSA is supported by a broad clinical program which includes more than 3,900 subjects in 35 trials across 28 markets. To date, BRUKINSA has received more than 20 approvals covering more than 40 countries and regions, including the United States, China, the EU and Great Britain, Canada, Australia and additional international markets. Currently, more than 40 additional regulatory submissions are in review around the world.

* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

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.

On April 28, 2022 Chimera Bioengineering ("Chimera") a biotherapeutics company building next-generation CAR-T therapeutics focused primarily on solid tumors, reported the appointment of Vlad Hogenhuis, M.D., as Chief Executive Officer (CEO) (Press release, Chimera Bioengineering, APR 28, 2022, View Source [SID1234613172]). Previously, Dr. Hogenhuis was Chief Operating Officer at Ultragenyx Pharmaceuticals and Head of Specialty Pharma and Oncology at GSK. The Company also announced it won AFCR’s 2021 BRACE Award Venture Competition, in recognition of Chimera’s breakthrough science for the development of transformative cancer therapeutics. Chimera’s lead candidate, CBIO-007, is a conditionally armed CAR-T cell therapy in preclinical development as a potential treatment for major solid tumors, such as lung, breast, colorectal, pancreatic, prostate, and ovarian cancers. CBIO-007 was generated from Chimera’s proprietary GOLD Platform technology, which creates conditional, location-specific activation of tumor microenvironment (TME)-modifying payloads by CAR-T cell therapies.

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"When I was evaluating opportunities, I was immediately struck by the elegance and enormous potential impact of Chimera’s approach to enhance CAR-T efficacy while minimizing their toxicity," said Dr. Hogenhuis. "We are thrilled to have won AFCR’s BRACE Award, which has not only connected us to investors and advisors, it also has provided key funding and validation of our approach and current dataset. We’ve generated compelling preclinical data confirming delivery of potent immunomodulatory payloads to solid tumors without systemic exposure, and this data gives us confidence that Chimera’s GOLD Platform technology can unlock the potential of CAR-T to treat a broad range of cancers, including solid tumors."

AFCR’s BRACE Award is a first-of-its-kind program for early stage oncology technology companies focused on Asian-prevalent cancers. With this honor, AFCR, Bluedot Bio, and other new investors contributed $7.5 million of new capital, joining Chimera’s existing investors, including Viking Global Investors, Founders Fund, and Illumina Accelerator, to bring the company’s total amount raised to $26 million, since the company was founded in 2015. Since that time, Chimera has established a pipeline of therapies from its proprietary GOLD Platform technology, which creates conditional, location-specific activation of tumor microenvironment (TME)-modifying payloads by CAR-T therapies. The company’s preclinical dataset on its lead candidate, CBIO-007, in pancreatic, prostate, and triple negative breast cancer xenograft tumor models, demonstrates that CBIO-007 efficiently eliminates tumors, while unarmed CAR-T cells are unable to control them.

AFCR’s Chief Executive Officer and Founder Sujuan Ba, Ph.D., said, "AFCR’s BRACE Award Venture Competition is designed to accelerate the commercialization of innovative cancer research discoveries for cancer patients, in Asia and worldwide, and we believe Chimera’s novel approach to spatially controlling CAR-T cells, for safer, more potent therapies, has the potential to improve the treatment of a broad range of cancers from hematologic cancers to solid tumors."

"During the evaluation of Chimera for AFCR’s BRACE Award, I was impressed with Chimera’s insightful approach to counteract the suppressive tumor microenvironment by leveraging natural mechanisms in the engineering of T cells to selectively deliver a payload only when they are activated by tumor cells," said Raju Kucherlapati, Ph.D., Paul C. Cabot Professor of Genetics at Harvard Medical school, who led the committee for the AFCR’s BRACE Award Venture Competition and founded several biotechs, including Cell Genesys, Abgenix (acquired by Amgen) and Millennium (acquired by Takeda). "Furthermore, Chimera’s initial data in preclinical models provides support for the ability of their GOLD Platform technology to direct the curative potential of CAR-T therapies to treating solid tumors, which continues to be a leading cause of death around the world."

About Chimera’s GOLD Platform Technology

Chimera’s GOLD Platform harnesses programmable, RNA-based gene regulation circuits inherent to immune cells to control CAR-T therapies conditionally armed with therapeutic payloads that target the tumor microenvironment (TME). Chimera applies its proprietary GOLD Platform to engineer potent CAR-T cell therapies for solid tumors that target the immunosuppressive TME, which has historically limited conventional CAR-T therapeutic efficacy. In preclinical studies, the GOLD Platform spatially restricts to the site of solid tumors the delivery of high levels of powerful therapeutic payloads by armed CAR-T cells, weakening the TME and maximizing CAR-T potency. Specifically, Chimera demonstrated in head-to head preclinical experiments with unarmed as well as a constitutively armed IL-12 payload that GOLD-controlled CAR-Ts eliminated xenograft tumors from prostate, pancreas, and triple negative breast cancer cell lines. Chimera’s chimeric receptor engagement-dependent payload delivery approach is designed to prevent toxic, systemic payload exposures that can decrease the therapeutic index of armed CAR-T cells.