On January 20, 2022 Eisai (Headquarters: Tokyo, CEO: Haruo Naito) and Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada) reported the publication of results from the Phase 3 Study 309/KEYNOTE-775 trial in the January 19, 2022 edition of the New England Journal of Medicine (Press release, Eisai, JAN 19, 2022, View Source [SID1234605576]). The pivotal study evaluated the combination of LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A. versus chemotherapy (treatment of physician’s choice of doxorubicin or paclitaxel) for patients with advanced endometrial carcinoma following at-least one prior platinum-based regimen in any setting.　　

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The publication includes previously reported data that was first presented in an oral plenary session at the virtual Society of Gynecologic Oncology (SGO) 2021 Annual Meeting on Women’s Cancer.1 Results showed that the LENVIMA plus KEYTRUDA combination demonstrated statistically significant improvements in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to chemotherapy. Objective response rate (ORR) data and additional detailed efficacy and safety data, including subgroup analyses, are also featured in the publication.

"While rates of endometrial carcinoma continue to rise globally, patients with advanced or recurrent disease have limited options available to them once the disease progresses following platinum-based chemotherapy," said Dr. Gregory Lubiniecki, Vice President, Oncology Clinical Research, Merck Research Laboratories. "KEYNOTE-775/Study 309 is an important Phase 3 study that supported recent approvals of KEYTRUDA plus LENVIMA for certain types of advanced endometrial carcinoma in the U.S. and other countries around the world, where it became the first immunotherapy and tyrosine kinase inhibitor combination approved for these patients."　　　　　

"The Phase 3 Study 309/KEYNOTE-775 trial demonstrates the ongoing commitment that Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A. share in addressing the unmet needs of people living with difficult-to-treat cancers, including advanced endometrial carcinoma," said Corina Dutcus, M.D., Senior Vice President, Clinical Research, Oncology Business Group at Eisai Inc. "The publication of this study in the New England Journal of Medicine reflects the importance of our joint research in exploring the potential of the LENVIMA plus KEYTRUDA combination."　

The publication contains results for the all-comer population, including the mismatch repair deficient (dMMR) patient population for which LENVIMA plus KEYTRUDA is not approved in the U.S.

Based on the results from the Phase 3 Study 309/KEYNOTE-775 trial, LENVIMA plus KEYTRUDA has been approved in the U.S. for patients with advanced endometrial carcinoma that is not microsatellite instability-high or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. LENVIMA plus KEYTRUDA is also approved in the European Union and Japan for certain patients with advanced or recurrent endometrial carcinoma regardless of mismatch repair status. Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A. are studying the LENVIMA plus KEYTRUDA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in more than 10 different tumor types across more than 20 clinical trials.

About Study 309/KEYNOTE-775 Trial

Study 309/KEYNOTE-775 (ClinicalTrials.gov, NCT03517449(New Window)) is a Phase 3 multicenter, open-label, randomized, active-controlled study conducted in 827 patients with advanced endometrial carcinoma who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings. Participants may have received up to two platinum-containing therapies in total, as long as one was given in the neoadjuvant or adjuvant treatment setting. The study excluded patients with endometrial sarcoma, carcinosarcoma, pre-existing Grade ≥3 fistula, uncontrolled blood pressure (>150/90 mmHg), significant cardiovascular impairment or event within previous 12 months or patients who had active autoimmune disease or a medical condition that required immunosuppression. The primary efficacy outcome measures were OS, and PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors Version (RECIST) v1.1. Secondary efficacy outcome measures included ORR as assessed by BICR.

　　

Patients were randomized 1:1 to receive LENVIMA (20 mg orally once daily) plus KEYTRUDA (200 mg intravenously every three weeks) or investigator’s choice, consisting of either doxorubicin (60 mg/m2 every three weeks) or paclitaxel (80 mg/m2 given weekly, three weeks on/one week off). Treatment with LENVIMA plus KEYTRUDA continued until RECIST v1.1-defined progression of disease as verified by BICR, unacceptable toxicity, or for KEYTRUDA, a maximum of 24 months. Administration of LENVIMA plus KEYTRUDA was permitted beyond RECIST-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was tolerated.

About Endometrial Carcinoma2,3,4,5,6

Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium and is the most common type of cancer in the uterus. In 2020, it was estimated there were more than 417,000 new cases and more than 97,000 deaths from uterine body cancers worldwide (these estimates include both endometrial carcinomas and uterine sarcomas; more than 90% of uterine body cancers occur in the endometrium, so the actual numbers for endometrial carcinoma cases and deaths are slightly lower than these estimates). In Japan, there were more than 17,000 new cases of uterine body cancer and more than 3,000 deaths from the disease in 2020. In the U.S., it is estimated there will be nearly 66,000 new cases of uterine body cancer and nearly 13,000 deaths from the disease in 2022. In Europe, it is estimated there were more than 130,000 new cases of uterine body cancer and more than 29,000 deaths in 2020. The five-year relative survival rate for metastatic endometrial carcinoma (stage IV) is estimated to be approximately 17%.

About LENVIMA (lenvatinib) Capsules

LENVIMA, discovered and developed by Eisai, is an orally available kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, LENVIMA decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.　　

Currently, LENVIMA has been approved for monotherapy as a treatment for thyroid cancer in over 75 countries including Japan, in Europe, China and in Asia, and in the United States for locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer. In addition, LENVIMA has been approved for monotherapy as a treatment for unresectable hepatocellular carcinoma in over 70 countries including Japan, in Europe, China and in Asia, and in the United States for first-line unresectable hepatocellular carcinoma. LENVIMA has been approved for monotherapy as a treatment for unresectable thymic carcinoma in Japan. It is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 60 countries, including in Europe and Asia, and in the United States the treatment of adult patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma. LENVIMA has been approved in combination with KEYTRUDA (generic name: pembrolizumab), for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) in United States and in Europe. LENVIMA has been approved in combination with KEYTRUDA as a treatment for advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation in the United States, and has been approved for the similar indication (including conditional approval) in over 10 countries such as Canada and Australia. In some regions, continued approval for this indication is contingent upon verification and description of clinical benefit in the confirmatory trials. In Europe, it has been approved in combination with KEYTRUDA (generic name: pembrolizumab) as the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation. In Japan, it has been approved for the treatment of unresectable advanced or recurrent endometrial　carcinoma that progressed after cancer chemotherapy.

About KEYTRUDA (pembrolizumab) Injection, 100mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck & Co., Inc., Kenilworth, N.J., U.S.A. has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

On January 20, 2022 TriSalus Life Sciences, an immunotherapy company on a mission to extend and improve the lives of patients living with liver and pancreatic tumors, reported a strategic research collaboration with the University of Colorado Anschutz Medical Campus to advance research of immuno-oncology treatments for patients with liver and pancreatic tumors (Press release, TriSalus Life Sciences, JAN 19, 2022, View Source [SID1234605649]). This collaboration will leverage TriSalus’ immunotherapy platform, which integrates immunotherapeutics and innovative drug delivery technology to address the unique challenges of treating tumors in the liver and pancreas and improve outcomes for patients.​

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Over the next three years, TriSalus will collaborate with the University of Colorado Anschutz Medical Campus on studies using TriSalus’ proprietary Pressure-Enabled Drug Delivery (PEDD) method for the administration of an investigational toll-like receptor 9 (TLR9) agonist, SD-101. Pre-clinical and clinical studies involving this platform aim to build upon the scientific knowledge around treatments available for cancers of the liver and pancreas and enable more patients to benefit from immunotherapy. In collaborating with TriSalus, CU Innovations has led the establishment of the business relationship while the CU Anschutz research team will focus on creating clinical research to advance TriSalus’ approach.

"This collaboration bolsters the instructional and research objectives of the University of Colorado Anschutz Medical Campus while fostering the development of scientific knowledge that can improve patient care," said Gordon McLennan, MD, vice chairman for clinical research and section chief of interventional radiology at the University of Colorado School of Medicine. "As a world-class medical institution at the forefront of transformative science, education and healthcare, we look forward to collaborating with TriSalus Life Sciences to help bring potentially transformative treatments to patients living with liver and pancreatic cancers."

Despite progress in cancer treatment, patients with liver and pancreatic tumors still experience poor outcomes, as these tumors remain stubbornly difficult to treat. Two of the most significant barriers that prevent optimal delivery and performance of therapeutics for these tumors include immune response suppression and ineffective drug delivery due to high intratumoral pressure. Together, these barriers prevent therapeutics from getting inside tumors and limit the effectiveness of immunotherapy for patients.

"Supporting pre-clinical and clinical research that pushes the boundaries of current knowledge will help us to advance promising therapies for patients with liver and pancreatic tumors, who are in desperate need of more effective treatments," said Christopher Lieu, MD, associate director of clinical research at the University of Colorado Cancer Center.

TriSalus’ platform consists of an investigational immunotherapy, SD-101, that aims to reactivate the immune system within these organs for targeted tumor killing, and the Pressure-Enabled Drug Delivery method, that modulates pressure and flow within blood vessels to improve therapy uptake and tumor response.

"Collaborating with the University of Colorado Anschutz Medical Campus exemplifies our commitment to overcome current limitations of immunotherapy treatment for liver and pancreatic tumors," said Steven C. Katz, MD, FACS, chief medical officer at TriSalus. "By combining our collective expertise in cancer research, together we can help realize the potential for the TriSalus platform to bring meaningful benefit to patients."

The collaboration with University of Colorado Anschutz Medical Campus extends TriSalus’ ongoing partnerships with the country’s leading cancer centers. To learn more about clinical trials underway, visit trisaluslifesci.com.

On January 19, 2022 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM; HKEX: 13) reported that updated analysis of the ongoing international Phase I/Ib trial of fruquintinib will be presented at the upcoming 2022 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, taking place on January 20-22, 2022 (Press release, Hutchison China MediTech, JAN 19, 2022, View Source [SID1234605536]). The meeting will be held virtually and in person at the Moscone Center in San Francisco, California, US.

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Further details of the presentation are as follows:

Title: Phase I/Ib trial of fruquintinib in patients with advanced solid tumors: preliminary results of the dose expansion cohorts in refractory metastatic colorectal cancer
Presenter: Arvind Dasari, MD, MS, MD Anderson Cancer Center
Session: Poster Session C: Cancers of the Colon, Rectum, and Anus
Abstract No.: 93
Date & Time: Saturday, January 22, 2022
Location: Moscone Center – West, Level 1, West Hall and virtually

About Colorectal Cancer ("CRC")
CRC is a cancer that starts in either the colon or rectum. CRC is the third most common cancer worldwide, estimated to have caused more than 915,000 deaths in 2020.[1] In the U.S., an estimated 150,000 people were diagnosed with CRC and 53,000 people died from CRC in 2021.[2] In Europe, CRC is the second most common cancer, with an estimated 507,000 new cases and 240,000 deaths in 2020.[2] In Japan, CRC is the most common cancer, with an estimated 147,000 new cases and 59,000 deaths in 2020.[2]

About Fruquintinib
Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.

About Fruquintinib Approval in China
Metastatic CRC in China: Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA) in September 2018 and commercially launched in China in late November 2018 under the brand name ELUNATE. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. ELUNATE is indicated for the treatment of patients with metastatic CRC who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study[3], a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).

About Fruquintinib Development Beyond CRC Monotherapy
The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:

Gastric Cancer ("GC") in China: In October 2017, HUTCHMED initiated the FRUTIGA study, a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for second-line treatment of advanced gastric or esophagogastric junction ("GEJ") adenocarcinoma. The trial is designed to enroll patients who did not respond to first-line standard chemotherapy. Subjects receive either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. Patients are randomized at a 1:1 ratio and stratified according to factors such as stomach vs. GEJ tumor type and performance status. The primary efficacy endpoint is overall survival (OS). Secondary efficacy endpoints include progression-free survival (as defined by RECIST 1.1), objective response rate, disease control rate, duration of response, and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers related to the antitumor activity of fruquintinib will also be explored (clinicaltrials.gov identifier: NCT03223376). In June 2020, HUTCHMED completed a planned interim data review. Based on the preset criteria, the Independent Data Monitoring Committee (IDMC) recommended that the trial continue.

Immunotherapy combinations: HUTCHMED has entered into collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd) and sintilimab (IBI308, developed by Innovent Biologics, Inc. and marketed as TYVYT in China).

Metastatic breast and endometrial cancers in the U.S.: HUTCHMED initiated this open-label, multi-center, non-randomized, Phase Ib/II study in the U.S. to assess the safety and efficacy of fruquintinib in combination with tislelizumab in patients with advanced, refractory triple negative breast cancer ("TNBC") and endometrial cancer ("EMC"). This study is being conducted to investigate if the addition of fruquintinib can potentially induce activity to immune checkpoint inhibitor therapy in TNBC and EMC. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04577963. Safety and preliminary efficacy of fruquintinib were demonstrated in advanced solid tumors, including TNBC, in a Phase I study conducted in China (NCT01645215) and a Phase I/Ib study is ongoing in the United States (NCT03251378).

Gastric, colorectal and non-small cell lung cancers in China & Korea: BeiGene, Ltd. initiated this open-label, multi-center, Phase II study to assess the safety and efficacy of fruquintinib in combination with tislelizumab in patients with advanced or metastatic, unresectable GC, CRC or non-small cell lung cancer ("NSCLC"). Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04716634.

Solid tumors in China: HUTCHMED initiated this open-label, multi-center, non-randomized, Phase II study to assess the safety and efficacy of fruquintinib in combination with sintilimab in patients with advanced EMC, cervical cancer, CRC, GC, hepatocellular carcinoma (HCC), NSCLC or renal cell carcinoma (RCC). Additional details of the study may be found at clinicaltrials.gov, using identifier NCT03903705. Preliminary results of certain cohorts were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper) and the Chinese Society of Clinical Oncology Annual Meeting (CSCO).

On January 19, 2022 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported a corporate update on its key strategic priorities for 2022 and 2023 in addition to confirming its upcoming clinical development milestones for zanidatamab and ZW49 (Press release, Zymeworks, JAN 19, 2022, View Source [SID1234605664]).

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"Upon assuming my new role effective January 15th, we have moved quickly to review and confirm key strategic priorities for the near term and to establish a renewed and smaller leadership team focused on accomplishing those priorities in a prompt, high-quality and cost-efficient manner," stated new Chair and Chief Executive Officer, Kenneth Galbraith. "We have already begun the process to reset and focus the organization on: (i) timely execution of our clinical development programs for zanidatamab and ZW49 in collaboration with our Asia-Pacific partner, BeiGene; (ii) a streamlined R&D strategy for our technology platforms and preclinical product candidates; (iii) actively seeking additional opportunities to establish further partnerships and collaborations in order to grow our business; and (iv) improving our financial position in order to properly fund our key priorities for 2022 and 2023."

Mr. Galbraith continued, "As an initial step, we have reset and focused the Company’s operations around our core activities and most promising R&D opportunities. These measures, including the reduction in our workforce announced today, provide opportunities to reduce our future planned expenditures while continuing to fund our key priorities for 2022 and 2023. I am looking forward to reporting our progress against these key priorities over the course of 2022 and 2023 as we reset, focus and build a leading biopharmaceutical company around a renewed organization, and an exciting and expanding pipeline of product candidates with the potential to make a significant difference for patients around the world with difficult-to-treat cancers."

Key Strategic Priorities for 2022 and 2023

Fully recruit the HERIZON-BTC-01 pivotal clinical study for zanidatamab by mid-2022;
Fully recruit the HERIZON-GEA-01 pivotal clinical study for zanidatamab by the end of 2023;
Complete or close out other ongoing early-stage clinical studies for zanidatamab as data become available, and use these data to identify and support strategic decisions regarding future clinical development opportunities beyond the ongoing pivotal clinical studies;
Finalize a clear clinical development path for ZW49 based on additional clinical data expected in 2022 from the ongoing Phase 1 clinical trial;
Select and advance two new antibody-drug conjugate or multispecific product candidates leveraging Zymeworks’ novel, therapeutic platforms (Azymetric, ZymeLink, EFECT and ProTECT) to IND-enabling studies to provide the ability to submit two Investigational New Drug (IND) applications by the end of 2024;
Execute on new partnerships and collaborations to support the development and commercialization of zanidatamab and Zymeworks’ early-stage R&D pipeline and technology platforms;
Continue to support and advance Zymeworks’ core technology platforms and collaborations; and
Improve Zymeworks’ financial position over 2022 and 2023 through a combination of alternatives, including forming additional partnerships and collaborations, monetizing existing assets and products and securing additional financing.
"By focusing on our key priorities, we can work towards improved operational execution in a cost-effective manner over 2022 and 2023, and position the Company for appropriate and well-managed growth of our clinical and preclinical pipeline as opportunities arise," said Mr. Galbraith.

R&D Update

"2022 will be an important year for the development of our lead clinical-stage product candidate, zanidatamab, as we continue our efforts in conjunction with our Asia-Pacific partner, BeiGene, to make this potential new therapy available to patients around the world suffering from Biliary Tract Cancer (BTC) and Gastroesophageal Adenocarcinomas (GEA). We look forward to reporting new clinical data at upcoming medical conferences throughout 2022, and announcing next steps in the months ahead for both zanidatamab and ZW49," stated Dr. Neil Josephson, Chief Medical Officer (CMO) of Zymeworks.

Biliary Tract Cancer (BTC)

HERIZON-BTC-01, a pivotal study evaluating zanidatamab in previously-treated advanced HER2-amplified BTC, continues to enroll patients in line with our expectations, including in the Asia-Pacific region with our partner BeiGene
The Company refines its guidance of completing the enrolment in the HERIZON-BTC-01 pivotal clinical study by mid-2022
Gastroesophageal Adenocarcinoma (GEA)

HERIZON-GEA-01, a pivotal study evaluating zanidatamab in 1L HER2-positive GEA, continues to enroll patients in line with our expectations, building off the encouraging clinical data in the 1L GEA setting for zanidatamab in combination with chemotherapy presented at ESMO (Free ESMO Whitepaper) in September 2021
The Company confirms its guidance of completing enrolment in the HERIZON-GEA-01 pivotal clinical study before the end of 2023
The Company confirms its guidance for providing clinical data for zanidatamab in combination with chemotherapy and tislelizumab in 1L HER2-positive GEA in H1 2022 in conjunction with its Asia-Pacific partner BeiGene
Other Clinical Development Opportunities for Zanidatamab

Early clinical studies continue to advance in important patient populations, including studies conducted in collaboration with BeiGene, ALX Oncology and Pfizer, that will play a role in determining and supporting investment in future clinical development opportunities for zanidatamab beyond the current pivotal studies for BTC and GEA
Zymeworks confirms its guidance for providing data for:
zanidatamab in combination with chemotherapy in 1L HER2-positive breast cancer in H1 2022 in conjunction with its Asia-Pacific partner BeiGene, and
zanidatamab in combination with Ibrance and fulvestrant in 3L+ HER2-positive HR‑positive breast cancer in H1 2022
ZW49

Dose escalation for the QW dosing schedule as well as expansion cohorts for the Q3W dosing schedule continue to progress
The Company confirms its guidance of providing updated clinical data in H2 2022 that will inform and support clear decisions to be made in 2022 regarding the clinical development path for ZW49 in conjunction with its Asia-Pacific partner BeiGene
Leadership Team

"In connection with our renewed focus on key strategic priorities for 2022 and 2023, Mr. Neil Klompas, our newly-promoted Chief Operating Officer (COO), Dr. Neil Josephson, our recently-promoted CMO, and I have re-established the leadership team comprised of highly qualified and experienced individuals who will work together with us to reset, focus and build our Company," stated Mr. Galbraith. "Mr. Klompas will work with me to directly manage and guide our commercial strategy for zanidatamab, our expanded outreach in business development and corporate development, our renewed early-stage R&D strategy for the technology platforms, our efforts to improve our financial position and leadership of our corporate operations. Dr. Josephson will work with me to manage our important clinical-stage development programs for zanidatamab and ZW49, and provide an important leadership function with our talented employees based in Seattle and other regions in the United States."

"I look forward to working with both of them in their new leadership positions. In addition, we will be immediately commencing a search for an experienced Head of Research and Development to lead our R&D operations and continue building our world-class technology platforms."

The leadership team is comprised of:

Neil Klompas, CPA, CA – Chief Operating Officer and Chief Financial Officer

Neil Josephson, MD – Chief Medical Officer

Bruce Hart, PhD – Senior VP, Regulatory Affairs

Mark Hollywood – Senior VP, Technical and Manufacturing Operations

Kaycia Wilde, PhD – VP, Clinical Operations

John Fann, PhD – VP, Technical Operations and Process Science

Milan Mangeshkar, PhD – VP, Biometrics

Surjit Dixit, PhD – VP, Technology

David Poon, PhD – VP, Business Development and Alliance Management

Daniel Dex, JD – VP, Legal and Corporate Secretary

Jennifer Kaufman-Shaw, JD, PhD – VP, Intellectual Property

Additional information regarding the background and experience of our leadership team is available on our website in the "Leadership" section.

In conjunction with the renewed focus on key priorities and desire for cost-efficiency in our operations, ten members (or 50%) of the former senior management team (including the Chief People Officer, Chief Commercial Officer and Chief Scientific Officer/EVP Early Development), will be leaving the Company. Additionally, in line with these reductions in the senior management team, a Company-wide reduction in workforce will be initiated with a target of reducing employee headcount by at least 25% by the end of 2022.

Mr. Galbraith said, "While we sincerely understand and appreciate the personal impact of these changes on employees in our organization, starting immediately, a smaller, more focused workforce is essential for us to improve our operating performance and accomplish our key priorities in a more cost-efficient manner. I am confident in the ability of our Board of Directors, our new leadership team and our dedicated employees to work effectively together as we move forward to carry out the work that we do every day for the benefit of patients in need, our collective success as a workforce, and in the interests of our stockholders to build a successful and valuable biotechnology company."

Updated Financial Position

The Company provided an update on its financial resources, including having cash, cash equivalents and short-term investments of approximately $250 M (unaudited) as of December 31, 2021, and reiterated its guidance on a financial runway to fund current operations through at least late 2022. The Company intends to report full Q4 and FY 2021 results and provide any further corporate updates on February 24, 2022.

"We will continue to actively consider a variety of initiatives and options to further improve our financial position during 2022 and 2023, including spending reductions and deferrals, establishing additional collaborations and partnerships, monetizing existing assets and product candidates, and various new financing alternatives in order to provide the necessary funding to continue to pursue our key priorities, and to improve our financial condition for the longer term," stated Mr. Klompas. "We will be looking at outlicensing, partnership and funding opportunities as they relate to several of our non-core early-stage R&D programs, including product candidates and intellectual property for targeting IL-12, CD47, and MET, as well as a novel ACE2 decoy program targeting SARS-CoV-2. We believe that prudent measures to grow our business in a well-managed and orderly fashion are aligned with the interests of patients in need, our employees and our stockholders, and we look forward to updating our progress on these efforts as and when appropriate."

To help improve its financial condition for the longer-term, Zymeworks anticipates that it may, from time to time and subject to market conditions and other factors, consider raising additional capital to further support its business, operations and programs.

On January 19, 2022 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage biopharmaceutical company dedicated to delivering targeted therapies for rare cancers, reported the publication of a review article in the Journal of Hematology & Oncology that outlines the potential ability of momelotinib—a novel JAK1, JAK2 and ACVR1 / ALK2 inhibitor—to address the critical unmet need of anemia for myelofibrosis patients (Press release, Sierra Oncology, 19 19, 2022, View Source [SID1234605666]). Srdan Verstovsek, MD, PhD, Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center and co-Primary Investigator of the pivotal Phase 3 MOMENTUM study, co-authored the article.

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"We are delighted to see this publication that reinforces momelotinib as the potential JAK inhibitor of choice for myelofibrosis patients with anemia—a need that is currently not met with approved JAK inhibitors. We look forward to sharing MOMENTUM topline data the end of January 2022," said Stephen Dilly, MBBS, PhD, President and Chief Executive Officer at Sierra Oncology.

Myelofibrosis is characterized by constitutional symptoms, including fatigue, body and bone pain and excessive sweating or fever; splenomegaly (enlarged spleen); and anemia. Moderate-to-severe anemia afflicts 40-60% of myelofibrosis patients at the time of diagnosis and increases to up-to 90% of patients over time.1 Anemia is a predictor of reduced overall survival and is associated with a nearly four-fold increase in the risk of death compared to no anemia, with a median survival of just 2.1 years.2,3

While JAK inhibitors are the mainstay of treatment options for myelofibrosis patients, currently approved JAK inhibitors cause myelosuppression, worsening anemia and creating poorer outcomes for patients. This profile creates a critical gap in the myelofibrosis treatment landscape and the need for a therapy that can address all three hallmarks of disease.

The authors noted in the publication, "Momelotinib’s mechanism of action uniquely positions it amongst approved and late-stage JAK inhibitors to be able to significantly alleviate the inflammation-driven, iron-restricted anemia of MF [ myelofibrosis] and eliminate/prevent RBC [red blood cell] transfusion dependence in a significant portion of MF patients besides treating the other two cardinal features of MF (splenomegaly and constitutional symptoms)."

To read the full article, titled "Momelotinib: an emerging treatment for myelofibrosis patients with anemia," please visit the Journal of Hematology & Oncology website.

About Momelotinib

Momelotinib is a selective and orally bioavailable JAK1, JAK2 and ACVR1 / ALK2 inhibitor for the potential treatment of myelofibrosis. Myelofibrosis results from dysregulated JAK-STAT signaling and is characterized by constitutional symptoms, splenomegaly (enlarged spleen) and progressive anemia.

Momelotinib is currently under investigation in the MOMENTUM clinical trial, a global, randomized, double-blind Phase 3 study for symptomatic and anemic myelofibrosis patients. The study enrolled 195 patients based on a planned 180 patients across 21 countries. Topline data are anticipated by the end of January 2022, and assuming positive results, the company intends to file an NDA with the FDA in the second quarter of 2022.