On December 8, 2021 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported new clinical data for the HER2-targeted bispecific antibody, zanidatamab, in heavily pretreated HER2-positive breast cancer (Press release, Zymeworks, DEC 8, 2021, View Source [SID1234596623]). The data are being presented at the San Antonio Breast Cancer Symposium (SABCS) taking place in San Antonio, Texas and virtually, December 7-10, 2021. In addition, Zymeworks will present a Trial in Progress poster detailing the ongoing clinical trial evaluating zanidatamab in combination with the CD47-blocker, evorpacept (ALX148).

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Summary of Clinical Trial Results

The data presented at SABCS are from a clinical study of 24 patients with heavily pretreated HER2-positive metastatic breast cancer who received zanidatamab in combination with either vinorelbine (n=12), capecitabine (n=8), or paclitaxel (n=4). Patients received multiple prior regimens containing HER2-targeted agents including trastuzumab (96%), pertuzumab (96%), and T-DM1 (96%), and many also received a tyrosine kinase inhibitor.

In 22 efficacy-evaluable patients, treatment with zanidatamab and chemotherapy resulted in a cORR of 36.4% and DCR of 86.4%, and the majority of patients experienced a decrease in their tumor size. The mPFS is 7.3 months across all treatment regimens with 42% of patients still on study at the time of data cutoff. Zanidatamab in combination with single agent chemotherapy is well tolerated, with the majority of treatment-related adverse events considered mild to moderate in severity (Grade 1 or 2).

"Zanidatamab together with chemotherapy shows encouraging antitumor activity and a manageable safety profile in patients with HER2‑positive breast cancer that has progressed after treatment with multiple HER2-targeted agents," said Neil Josephson, M.D., Chief Medical Officer at Zymeworks. "We were impressed by the activity and durability of disease control with zanidatamab, with over half of patients experiencing a confirmed response or stable disease lasting over 6 months. These results, together with data presented earlier this year in both HER2‑expressing biliary tract cancer and gastroesophageal adenocarcinoma, build on our belief that zanidatamab has the potential to be a foundational therapy across multiple HER2-expressing solid tumor indications. We look forward to sharing additional data with zanidatamab in HER2‑positive breast cancer from our other ongoing trials in the first half of 2022, including in combination with Ibrance and fulvestrant in late-line hormone receptor positive disease as well as in combination with docetaxel in the first-line setting."

"Zanidatamab continues to generate clinical data that differentiate it from existing and emerging HER2-targeted standards of care," said James Priour, Chief Commercial Officer at Zymeworks. "Expanding on our commitment to complete ongoing pivotal trials in biliary tract and gastric cancers, we see breast cancer as the next indication to pursue a potential label. As we await additional data in early lines of breast cancer, these data in late-line present an additional registrational opportunity. With the majority of HER2-positive breast cancer patients benefitting from new therapies and surviving longer than ever before, there is a significant commercial opportunity in the third- and fourth-line setting. We believe the data presented today demonstrate that zanidatamab and chemotherapy could be a new option for these patients."

SABCS Presentations

The following presentations are available to conference registrants on the SABCS conference website as well as to the general public at View Source

Zanidatamab in Combination with Chemotherapy in Late-Line HER2-Postive Breast Cancer – Clinical Results Presented Today

Title: Zanidatamab (ZW25), a HER2-targeted bispecific antibody, in combination with chemotherapy (chemo) for HER2-positive breast cancer (BC): Results from a phase 1 study.
Lead Author: Philippe L. Bedard, M.D., Princess Margaret Cancer Center, Toronto, ON Canada.
Abstract: #93
Program Number: P2-13-07

Zanidatamab in Combination with Evorpacept (ALX148) – Trial in Progress Poster Presented Today

Title: Zanidatamab (ZW25) in Combination with Evorpacept (ALX148) in Advanced Human Epidermal Growth Factor Receptor 2 (HER2)-expressing Cancers, Including Breast Cancer: a Phase 1b/2, Multicenter, Open-Label, Dose-Finding and Cohort-Expansion Study (ZWI-ZW25-204)
Lead Author: Sara A. Hurvitz, M.D., University of California, Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles, CA, US
Abstract: #182
Program Number: OT1-14-01

Zymeworks is presenting a trial in progress poster at the SABCS for a Phase 1b/2 multi-center clinical study in HER2-expressing cancers, including breast cancer. This study is evaluating the novel combination of zanidatamab, a HER2-targeted bispecific antibody, and evorpacept, a CD47-blocker, for the treatment of advanced and/or metastatic HER2-positive and HER2-low breast cancer and other HER2-expressing cancers. Treatment with zanidatamab in combination with evorpacept has the potential to augment immune clearance of HER2-expressing cancer cells, by blocking the CD47 signal that inhibits phagocytosis of these cells.

The study is currently open for enrollment. For further information (including updates to active sites), visit www.clinicaltrials.gov [NCT05027139]

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 with 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 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.

About Evorpacept

Evorpacept is a next-generation CD47 blocking therapeutic that combines a high-affinity CD47 binding domain with an inactivated, proprietary Fc domain. Evorpacept is designed to avoid the limitations caused by hematologic toxicities inherent in other CD47 blocking approaches, and to leverage the immune activation of broadly used anti-cancer agents through combination strategies. ALX Oncology is developing evorpacept in multiple Phase 1 and Phase 2 clinical trials globally across a range of hematologic and solid malignancies in combination with a number of leading anti-cancer agents. The FDA has granted two Fast Track designations to evorpacept, one for the first-line treatment of patients with head and neck squamous cell carcinoma, and one for the second-line treatment of patients with HER2-positive gastric or gastroesophageal junction carcinoma. The FDA’s Fast Track designation provides the opportunity for more frequent meetings with the FDA over the course of drug development and allows for eligibility for Accelerated Approval and Priority Review if relevant criteria are met, as well as for Rolling Review.

On December 8, 2021 City of Hope, a world-renowned, National Cancer Institute (NCI)-designated comprehensive cancer research and treatment organization, reported it has entered into a definitive agreement to acquire Cancer Treatment Centers of America (CTCA), a network of oncology hospitals and outpatient care centers across the United States (Press release, City of Hope, DEC 8, 2021, View Source [SID1234596622]). City of Hope’s strategic acquisition of CTCA will advance the missions of both organizations, building a national, integrated cancer research and treatment system to transform the future of cancer care.

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"This is a defining moment in the fight against cancer and a powerful opportunity to reach more cancer patients with the leading treatments, care and advanced research they critically need," said Robert Stone, president and CEO of City of Hope and the Helen and Morgan Chu Chief Executive Officer Distinguished Chair. "CTCA has a strong commitment to patient-centric cancer care, and combining its network and services with City of Hope’s scientific expertise, clinical trials and patient care strengths will significantly increase the number of people who can access the latest lifesaving treatments."

City of Hope’s acquisition expands and accelerates the organization’s ability to rapidly translate research and science into lifesaving care through its unique model — connecting breakthrough discoveries and academic medicine expertise with excellent, community-based specialized cancer care to the benefit of patients and families served. This acquisition also expands the portfolio, reach and impact of City of Hope’s leading-edge cancer services and capabilities, including research and development, into more communities across the country.

"Building on more than three decades of unparalleled patient experience and quality care, we’re excited to become a part of City of Hope, and to take a step closer to reaching so many more cancer patients with our unique, patient-centered model," said Pat Basu, M.D., M.B.A., president and CEO of CTCA. "Through the shared, patient-centric values of both organizations and expanded access as a result of the collaboration, cancer patients across the nation will be the ultimate beneficiaries of this relationship."

City of Hope is a national leader in advancing cancer research and treatment protocols, conducting nearly 1,000 clinical trials annually that can enroll approximately 25% of its patients. With more than 450 patent portfolios, 95 active investigator-initiated investigational new drugs (INDs) and approximately 50 IND applications submitted to the U.S. Food & Drug Administration every year, City of Hope is among the leading innovators in cancer research. The organization is also a pioneer in bone marrow and stem cell transplants with one of the largest, most successful programs of its kind in the U.S., having performed more than 17,000 procedures.

With CTCA, City of Hope builds on and accelerates its vision to forge partnerships and find new avenues for its expertise to positively impact as many lives as possible. In addition to the ongoing, significant expansion of its clinical network in Southern California, City of Hope previously acquired Translational Genomics Research Institute (TGen), which provides breakthrough genomics research. TGen’s capabilities are fully leveraged to provide highly specialized care and precision medicine treatment to City of Hope patients across its clinical care network. And in 2019, City of Hope launched AccessHopeTM to extend the reach of its clinical and research expertise directly to partner employers, including 17 of the Fortune 500 companies, so they can provide their employees with cancer information and expert clinical decision support.

Combined, City of Hope and CTCA will include approximately 11,000 team members, comprising the collaborative expertise of 575 physicians across a network of locations in California, including a new campus in Irvine opening in summer 2022, as well as Arizona, Illinois and Georgia. Basu will remain CEO of CTCA and report to Robert Stone.

"Cancer treatment is changing rapidly. Today, through advances such as immunotherapy, precision medicine and other treatments available through clinical trials, there are better survival rates and fewer side effects than ever before. A critical part of cancer care is closing the gap to access that exists for too many patients, particularly in underserved communities," continued Stone. "By joining forces with CTCA, we’re taking a major step forward in our mission to democratize cancer care and bring today’s treatments and tomorrow’s discoveries to even more people who need them now."

The transaction is expected to close in early 2022, subject to regulatory approvals. After close, City of Hope intends to convert CTCA to a nonprofit organization.

On December 8, 2021 McKesson Corporation (NYSE: MCK) reported that it will host an Investor Day beginning at 1:00 p.m. ET, where executive leadership will provide an overview of the company’s progress towards its goal of delivering sustainable growth and details around the company’s long-term financial outlook (Press release, McKesson, DEC 8, 2021, View Source [SID1234596621]).

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The Investor Day event will showcase how McKesson will deliver long-term growth:

Highlighting significant progress in executing against its priorities by focusing on people and culture, sustainable core growth, streamlining the portfolio, and expanding its oncology and biopharma services ecosystems. The success is evidenced by its strong financial performance and outstanding operational excellence.
Reaffirming its commitment to the growth pillars of oncology and biopharma services. The company’s differentiated set of assets and capabilities uniquely positions the company to win in these growing markets and improve the health outcomes of patients.
Providing a financial overview and long-term outlook that highlights the focus on shareholder value creation and supports a compelling investment thesis.
Increasing fiscal 2022 Adjusted Earnings per Diluted Share guidance range to $22.35 to $22.95, from the previous range of $21.95 to $22.55, to reflect an additional $0.40 related to the U.S. government’s COVID-19 vaccine distribution program.
Announcing a new $4.0 billion increase to the share repurchase program authorized by the Board of Directors.
"We are excited to share our vision and strategy with the investment community. As we focus on the next chapter of growth and innovation, McKesson will leverage the breadth and depth of its core growth to further develop and build differentiated oncology and biopharma services ecosystems," said Brian Tyler, chief executive officer. "We remain committed to delivering superior shareholder returns through sustainable earnings growth and a disciplined approach to capital deployment."

Webcast and Presentations

The video webcast will be available live from 1:00 p.m. to 4:00 p.m. ET on Wednesday, December 8, 2021 at investor.mckesson.com/events-and-presentations. After the event, the archived video webcast will be available on McKesson’s Investor Relations website, along with the company’s slide presentation, at investor.mckesson.com.

Non-GAAP Financial Measure

This press release includes a forecast of Adjusted Earnings per Diluted Share, which is not a financial measure calculated in accordance with U.S. generally accepted accounting principles (GAAP). The company is unable to provide a quantitative reconciliation of this forward-looking Non-GAAP measure to the equivalent forward-looking GAAP measure without unreasonable effort, because the company does not forecast GAAP earnings per share and cannot reliably forecast LIFO inventory-related adjustments, certain litigation loss and gain contingencies, restructuring, impairment and related charges, and other adjustments, which are difficult to predict and estimate. These items are inherently uncertain and depend on various factors, many of which are beyond the company’s control, and as such, any associated estimate and its impact on GAAP performance could vary materially. Refer to investor.mckesson.com and the company’s slide presentation noted above for definitions and explanations of the Company’s Non-GAAP financial measures.

On December 8, 2021 H3 Biomedicine Inc. (H3), a U.S.-based precision medicine research & development subsidiary of Eisai Co., Ltd., reported the presentation of two posters at the 2021 San Antonio Breast Cancer Symposium (SABCS) being held in a hybrid format on December 7- 10, 2021 (Press release, H3 Biomedicine, DEC 8, 2021, View Source;positive-HER2-negative-Breast-Cancer-at-San-Antonio-Breast-Cancer-Symposium [SID1234596620]). The presentations include interim investigational data from H3’s ongoing clinical development program, H3B-6545, a potential first-in-class, orally available Selective ERα Covalent Antagonist (SERCA), in women with ER-positive, HER2-negative breast cancer.

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"At H3, we are developing a pipeline of targeted medicines with the potential to impact the future of cancer treatment," said Ping Zhu, Ph.D., President and Chief Scientific Officer of H3. "Our ongoing clinical study of H3B-6545 is evaluating its potential to address current unmet medical needs in breast cancer either as a single agent or in combination with therapies such as palbociclib. We look forward to showcasing its progress at SABCS 2021."

H3B-6545 PRESENTATIONS

Abstract Number: 976

Title: H3B-6545, a Novel Selective Estrogen Receptor Covalent Antagonist (SERCA), in Estrogen Receptor Positive (ER+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Advanced Breast Cancer – A Phase II Study
Program Number: P1-17-10
Poster Session: 1
Date and Time: Wednesday, December 8, 2021, 7:00am – 8:30am CT
Presenter: Erika P. Hamilton, Sarah Cannon Research Institute, Tennessee Oncology

Abstract Number: 1166
Title: H3B-6545 in Combination with Palbociclib in Women with Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer, Phase 1b Study
Program Number: P1-17-03
Poster Session: 1
Date and Time: Wednesday, December 8, 2021, 7:00am – 8:30am CT
Presenter: Stephen Johnston, Royal Marsden NHS FDN Trust, London, UK

About H3B-6545

Estrogen receptor alpha (ERα) plays an important oncogenic role in the genesis and progression of luminal breast cancers,1 and historically has been a target of endocrine therapies. However, recently, hotspot mutations in ERα have been detected in nearly 30% of endocrine-therapy resistant metastases. Functional studies have shown that these ERα mutations can confer ligand-independent activation of the ERα pathway and can promote partial resistance to existing classes of ER-directed therapies.2,3 H3B- 6545, a first-in-class small molecule selective estrogen receptor covalent antagonist (SERCA) demonstrates activity in tumor models that harbor wild-type or mutant ERα.4 H3B-6545 activity against ERα mutants resistant to standard therapy provides an opportunity to target a currently unmet medical need both as a single agent and in combination with other breast cancer therapies.

This release discusses investigational uses of agents in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such investigational agents will successfully complete clinical development or gain health authority approval.

On December 8, 2021 Metagenomi, a genetic medicines company with a versatile portfolio of next-generation gene editing tools, reported that the company will share data related to their novel, compact, and hypo-immune gene editing systems at the 63rd Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), which is taking place in Atlanta, GA and virtually, December 11–14 (Press release, Metagenomi, DEC 8, 2021, View Source [SID1234596619]).

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"The development of CAR T therapies and other genetically engineered cell therapies in recent years has resulted in significant benefits for patients, yet there remains a large unmet need for gene editing systems that can be used to develop novel immunotherapy approaches to treat blood cancers," said Brian C. Thomas, PhD, CEO and Co-Founder of Metagenomi. "At ASH (Free ASH Whitepaper), we are presenting data on our novel nucleases that display highly efficient and specific gene editing both in vivo and ex vivo and hold significant potential to drive the development of new and efficacious therapies for patients."

In a poster titled "A Novel Type V CRISPR System with Potential for Genome Editing in the Liver," it is shown that Metagenomi’s novel Type V CRISPR-associated nuclease was highly active in the liver of mice when systemically administered via lipid nanoparticles (LNP). The nuclease was derived from a unique natural environment and is phylogenetically distinct from previously identified Type V systems. Moreover, no antibodies to the nuclease were detected in serum from 50 healthy human donors, while between one third and half of the same serum samples contained antibodies that bind to spCas9, which is derived from a Streptococcus bacteria that commonly infects humans. In summary, this novel Type V CRISPR-associated nuclease is a promising new gene editing system for in vivo editing of the liver.

In a separate poster titled "Novel CRISPR-Associated Gene Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genomic Engineering for Cell Therapy Development," three novel gene editing systems were used to make reproducible and efficient edits to human immune cells, demonstrating utility for the next generation of cell therapy development for blood cancers. Metagenomi’s novel gene editing systems were used to disrupt the T cell receptor alpha-chain constant region and the T cell receptor beta-chain constant region in approximately 90 percent of cells. Beta-2 microglobulin was edited in 95 percent of T cells. A chimeric antigen receptor (CAR) construct was also shown to be integrated in up to 60 percent of T cells. Novel gene editing systems were deployed in NK cells to disrupt CD38 — a cell surface immune modulator that can be targeted in the development of cancer immunotherapy — and to integrate a CAR construct that led to robust CAR-directed cellular cytotoxicity. B cell editing occurred in approximately 80% of target cells with successful transgene integration. What’s more, as these gene editing systems are taken from environmental samples as opposed to human pathogens, pre-existing immunity is expected to be rare. In summary, these novel systems were shown to result in highly efficient and specific gene edits in human immune cells and display the potential for use in cell therapy development.

Details of the presentations are below:

Presentation Title: A Novel Type V CRISPR System with Potential for Genome Editing in the Liver
Session Title: 801. Gene Therapies: Poster I
Presenting Author: Morayma Temoche-Diaz, PhD
Publication Number: 1862
Session Time: Saturday, December 11, 5:30 p.m. ET

Presentation Title: Novel CRISPR-Associated Gene-Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genome Engineering for Cell Therapy Development
Session Title: 801. Gene Therapies: Poster III
Presenting Author: Gregory Cost, PhD, Vice President of Biology, Metagenomi
Publication Number: 3984
Session Time: Monday, December 13, 6:00 – 8:00 p.m. ET