On December 14, 2021 Everest Medicines Limited (HKEX 1952.HK, "Everest", or the "Company"), a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products to address critical unmet needs in Asia Pacific markets, reported that the Ministry of Food and Drug Safety (MFDS) of South Korea accepted its New Drug Application (NDA) for Sacituzumab Govitecan ("SG") for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease (Press release, Everest Medicines, DEC 14, 2021, View Source [SID1234597153]).

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The MFDS in South Korea previously granted Fast Track Designation and Orphan Drug Designation to SG for the treatment of mTNBC in April 2021.

"We’re extremely proud of this acceptance as breast cancer is the leading cause of death from cancer in South Korean women and one of the fastest growing cancers in the world," said Kerry Blanchard, MD, PhD, Chief Executive Officer of Everest Medicines. "Historically, women with metastatic TNBC have had fewer treatment options available and this application acceptance means we are one step closer in making SG available for women with this aggressive cancer in South Korea."

Under the trade name Trodelvy, the U.S. FDA previously granted accelerated approval to SG in April 2020 and then expanded its previous indication with full approval in April 2021 for adult patients with unresectable locally advanced or mTNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease. In May 2021 Everest announced that the China National Medical Products Administration accepted its BLA with priority review for SG for adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.

In November 2021, Everest announced topline results for its Phase 2b EVER-132-001 study of SG, which met its primary endpoint with a 38.8% overall response rate (ORR). This study evaluated 80 people in China, and the results were consistent with those from the global Phase 3 ASCENT study, thus showing similar efficacy in the Chinese population.

About Triple-Negative Breast Cancer (TNBC)

TNBC is the most aggressive type of breast cancer and accounts for approximately 15% of all breast cancers. The median age of breast cancer diagnoses tends to be younger in Asian than western countries, and the percentage of the TNBC molecular subtype has been increasing in the past 10 years. TNBC cells do not have estrogen and progesterone receptors and have limited human epidermal growth factor receptor 2 (HER2). Due to the nature of TNBC, effective treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of metastatic breast cancer.

About Sacituzumab Govitecan

Sacituzumab govitecanis (SG) is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the TROP-2 receptor, a protein overexpressed in multiple types of epithelial tumors, including mTNBC and metastatic urothelial cancer (UC), where high expression is associated with poor survival and relapse. SG is approved for adults with second-line metastatic TNBC in the United States, the European Union, Australia, Canada, Great Britain and Switzerland under the trade name Trodelvy and approval is based on data submitted from the Phase 3 ASCENT study. Review is also underway in Singapore and China through Everest Medicines. Trodelvy is also approved under the accelerated approval pathway for use in metastatic UC in the United States and continues to be developed for potential use in other TNBC and metastatic UC populations. It is also being developed as an investigational treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer. Additional evaluation across multiple solid tumors is also underway.

SG was also granted Pediatric and Rare Severe Disease Priority Review Designation by the Taiwan Food and Drug Administration (FDA) in July 2021. In addition, Everest announced in January 2021 that it submitted a New Drug Application (NDA) to the Health Sciences Authority (HSA) of Singapore for SG for the treatment of patients with metastatic TNBC who have received two prior therapies, at least one for metastatic disease. That application is currently under review.

Under a licensing agreement with Gilead Sciences, Inc., Everest Medicines has exclusive rights to develop, register, and commercialize SG for all cancer indications in Greater China, South Korea, and certain Southeast Asian countries. In October 2020, SG was included in the updated 2020 China Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer, compiled by the Breast Cancer Expert Committee of the National Cancer Control Center, the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association, and the Cancer Drug Clinical Research Professional Committee of the Chinese Anti-Cancer Association.

On December 14, 2021 Sumitomo Dainippon Pharma Oncology, Inc., a clinical-stage biopharmaceutical company focused on research and development for novel cancer therapeutics, reported that the Phase 3 WIZARD 201G study will terminate following its second interim analysis after determining there is a low probability of meeting the primary endpoint of overall survival at the final analysis (Press release, Sumitomo Dainippon Pharma, DEC 14, 2021, View Source [SID1234597152]). This study evaluated the safety and efficacy of Ombipepimut-S Emulsion (DSP-7888)*, an investigational WT1 immunotherapeutic cancer vaccine, in combination with bevacizumab versus bevacizumab alone in patients with recurrent or progressive glioblastoma (GBM) following initial therapy.

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"Patients with recurrent or progressive glioblastoma have a high unmet medical need and we intended to develop a new treatment option for this population," said Patricia S. Andrews, CEO and Global Head of Oncology, Sumitomo Dainippon Pharma Oncology (SDP Oncology). "We are disappointed with the results of this Phase 3 trial and would like to express gratitude to the trial’s participants, investigators, and staff for their efforts and contributions to the study. SDP Oncology is committed to continuing our pursuit of advancing our pipeline to bring forward innovative treatments for patients with cancer."

The multicenter, open-label, randomized Phase 3 WIZARD 201G study evaluated the efficacy and safety of Ombipepimut-S Emulsion in combination with bevacizumab versus bevacizumab alone at 185 events in the second interim analysis of a pivotal trial with an enrollment planned for 338 patients. Patients were randomized one-to-one in the study. The study’s primary endpoint was overall survival with an adaptive design and two planned interim analyses. The overall safety profile was generally tolerable. The most common adverse events occurring in patients in the Ombipepimut-S Emulsion in combination with bevacizumab arm were injection site reactions, hypertension, headache and fatigue. Final data and analyses of this study will be published for the oncology community.

The study of Ombipepimut-S Emulsion in combination with checkpoint inhibitors in solid tumors with an expansion arm in platinum-resistant ovarian cancer (NCT03311334) will continue as planned.

*Adegramotide/nelatimotide is assigned as the international nonproprietary name (INN).

About Ombipepimut-S Emulsion (DSP-7888)

Ombipepimut-S Emulsion (DSP-7888) is an investigational WT1 immunotherapeutic cancer vaccine containing two peptides that induce WT1-specific cytotoxic T-lymphocytes (WT1-CTL) and helper T-cells to attack WT1-expressing cancerous cells found in various types of hematologic and solid tumors. Researchers have identified that adding a peptide to induce helper T cells may improve outcomes compared to a treatment regimen based on a killer peptide alone.1

Ombipepimut-S Emulsion is in a Phase 1/2 study (estimated enrollment number of patients: 84; NCT03311334) in the United States in combination with nivolumab or pembrolizumab in patients with advanced solid tumors with a Phase 2 expansion arm in platinum-resistant ovarian cancer in combination with pembrolizumab. In 2017, the U.S. Food and Drug Administration granted Orphan Drug Designations for Ombipepimut-S Emulsion in brain cancer and in myelodysplastic syndrome (MDS).

About Glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive form of primary brain cancer.2 In 2018, approximately 11,000 men and women in the U.S. were diagnosed with GBM.3 GBM is a highly infiltrative form of cancer and is not surgically curable, which leads to a high recurrence rate and poor prognosis. The overall 5-year survival rate is approximately 5.7%.3 Treatment barriers to GBM include its ability to create an immunosuppressive tumor microenvironment (TME) that is further protected by the confines of the blood-brain-barrier.4

On December 14, 2021 JW Therapeutics (HKEx: 2126), an independent innovative biotechnology company focused on developing, manufacturing and commercializing cell immunotherapy products, reported the primary clinical response on Carteyva (relmacabtagene autoleucel injection) in adults with relapsed/refractory follicular lymphoma (r/r FL) in China at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, JW Therapeutics, DEC 14, 2021, View Source [SID1234597151]).

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As of the data cut-off of September 10, 2021, 28 patients were treated with Carteyva with at least three months of follow-up.

Of 27 efficacy evaluable patients, as assessed by the investigator, best overall response rate (ORR) was 100% (27/27) and best complete response rate (CRR) was 92.6% (25/27). With a median follow-up of 8.84 months, the median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were not reached.

In 28 patients who received Carteyva, any grade and severe (grade≥3) cytokine release syndrome (CRS) were 42.9% and 0%, respectively, and any grade and severe (grade≥3) neurotoxicity (NT) were 17.9% and 3.6%, respectively.

Dr. Mark J. Gilbert, Chief Medical Officer of JW Therapeutics, commented: "Most patients with r/r FL remain incurable and eventually relapse or progress. Results from this pivotal study provide evidence that Carteyva can result in high tumor remission rates and a manageable toxicity profile in r/r FL patient. Encouraged by these findings, we are looking forward to expanding the indications of Carteyva use into r/r FL, hopefully benefiting more patients soon."

Reference:

Song, Y. et.al.; 63rd Annual ASH (Free ASH Whitepaper) Meeting, 2021, abstract #2434, Atlanta, GA December 10th-14th

About Relmacabtagene Autoleucel Injection (trade name: Carteyva)

Relmacabtagene autoleucel injection (abbreviated as relma-cel, trade name: Carteyva) is an autologous anti-CD19 CAR-T cell immunotherapy products that was independently developed by JW Therapeutics based on a CAR T cell process platform of Juno Therapeutics (a Bristol Myers Squibb company). The first product of JW Therapeutics, relma-cel was approved by the China National Medical Products Administration (NMPA) in September 2021 for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, making it the first CAR-T product approved as a Category 1 biologics product in China. Currently, it is the only CAR-T product in China that has been simultaneously included in the National Significant New Drug Development Program, granted priority review and breakthrough therapy designations.

On December 14, 2021 City of Hope, a world-renowned cancer research and treatment organization, reported study results of a Phase 2 clinical trial showing monotherapy with sotorasib resulted in anti-tumor activity and a favorable benefit-risk profile among heavily pretreated patients with advanced colorectal cancer (Press release, City of Hope, DEC 14, 2021, View Source [SID1234597147]). The research was published today in Lancet Oncology.

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Colorectal cancer is the third most common cancer diagnosed in the United States and the second leading cause of cancer death, according to the Centers for Disease Control and Prevention.

The research study focused on a subset of colorectal cancer patients who carry a mutated gene called KRAS G12C, which is estimated to inflict about 4% of people with colorectal cancer tumors, said Marwan Fakih, M.D., lead study author and co-director of the Gastrointestinal Cancer Program at City of Hope. KRAS mutations have been linked to worse overall survival in colorectal cancer, partly because they are resistant to targeted therapies that inhibit the EGFR protein, a pathway that enables cancer cell growth.

"For this chemotherapy-resistant population, the study results exceeded the historic benefits linked to approved third- and fourth-line therapies for advanced colorectal cancer," said Fakih, professor in City of Hope’s Department of Medical Oncology & Therapeutics Research and the Judy & Bernard Briskin Distinguished Director of Clinical Research. "This Lancet Oncology study is a proof of principle that targeting KRAS G12C with a small molecule KRAS G12C inhibitor, sotorasib, can lead to tumor shrinkage and meaningful duration of disease control in a patient population that otherwise has very limited treatment options."

While the response rate in the study did not meet expectations, the ongoing, single-arm Phase 2 CodeBreaK 100 trial showed an objective response rate of 9.7% among the 62 patients enrolled, with six patients achieving a partial response. Disease control (complete response, partial response or stable disease) was achieved in 82% of patients. Median progression-free survival and overall survival were four months and nearly 11 months, respectively.

Patients had received a median of three prior treatment regimens of systemic anti-cancer therapy, with 73% of patients receiving three or more previous lines of treatment prior to participating in this study. Most treatment-related side effects were minor (grade 1-2) and included diarrhea and nausea.

"These data from the Phase 2 CodeBreaK 100 show encouraging clinical activity and a positive benefit-risk profile with sotorasib in advanced colorectal cancer in this heavily pretreated patient population, with the response rate exceeding the current standard of care therapies," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Amgen remains deeply committed to bringing new treatment options to colorectal cancer patients who harbour the KRAS G12C mutation, and we believe the path forward is combination therapy, so we look forward to investigating sotorasib in combination with panitumumab in our Phase 3 trial."

Currently, overall response rate for patients with recurrent metastatic colorectal cancer who take approved options, such as trifluridine and regorafenib, ranges from 1-4%, Fakih said. Their estimated median progression-free survival and overall survival range from two to three months and six to nine months, respectively. The CodeBreaK 100 data for this patient population demonstrates better response rate and longer survival than current approved medicines.

"We are now working on potentially improving the efficacy of sotorasib by combining it with panitumumab, therefore resulting in a more complete blockade of the EGFR pathway and improving oncological outcomes. We have recently reported the preliminary results of a sotorasib plus panitumumab combination therapy in KRAS G12C mutated metastatic colorectal cancer, which resulted in an overall response rate of 33% in patients who have never received sotorasib," said Fakih. "We are looking forward to the launch and completion of a randomized Phase 3 clinical trial to test and potentially confirm the superiority of sotorasib and panitumumab over standard of care and to enable the approval of this combination in this patient population with unmet needs."

The ongoing clinical trial can be found on ClinicalTrials.gov.

The study, "Sotorasib for previously treated colorectal cancers with KRAS p.G12C mutation (CodeBreaK100): an interim analysis of a single-arm, Phase 2 trial," was supported by industry sponsor Amgen Inc.

On December 14, 2021 Geron Corporation (Nasdaq: GERN), a late-stage biopharmaceutical company focused on the development and commercialization of treatments for hematologic malignancies, reported three poster presentations related to imetelstat, the Company’s first in class telomerase inhibitor, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Geron, DEC 14, 2021, View Source [SID1234597146]). The posters are available at www.geron.com/r-d/publications.

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"The posters for this year’s ASH (Free ASH Whitepaper) Meeting highlight our ongoing Phase 3 development of imetelstat in lower risk MDS and refractory MF, as well as exploratory work in new indications to maximize the potential value of imetelstat," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "We believe the unique telomerase inhibition MOA of imetelstat has the potential to transform the standard of care in hematologic malignancies."

Clinical Posters

Lower Risk Myelodysplastic Syndromes (MDS)

Abstract Title: On-Target Activity of Imetelstat Correlates with Clinical Benefits, Including Overall Survival (OS), in Heavily Transfused Non-Del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) Abstract #2598

The poster reports new analyses to assess the correlation between imetelstat’s inhibition of telomerase with the efficacy and safety data from the IMerge Phase 2 clinical trial. These correlative analyses indicating that patients who achieved optimal pharmacodynamic (PD) effect achieved higher rates of red blood cell transfusion independence (RBC-TI), longer RBC-TI and a trend toward improved overall survival. Importantly, these patients did not have higher rates of Grade 3+ neutropenia, thrombocytopenia or liver function elevations compared to patients who did not achieve optimal PD effect.

These data provide further evidence for the on-target mechanism of action (MOA) of imetelstat through telomerase inhibition and links imetelstat’s on-target activity with clinical benefits.

To confirm these and other results from IMerge Phase 2, the Company is conducting a double-blind, randomized, placebo-controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 170 transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS), also referred to as lower risk MDS, who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint is the rate of RBC-TI for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

IMerge Phase 3 is fully enrolled and patient enrollment has been closed. Based on current planning assumptions, the Company expects top-line results from IMerge Phase 3 in early January 2023.

Refractory Myelofibrosis (MF)

Abstract Title: A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy (BAT) in Patients with Intermediate-2 (Int-2) or High-risk Myelofibrosis (MF) Refractory to Janus Kinase Inhibitor (JAKi) Abstract #1503 Trials in Progress

IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is planned to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis who are refractory to prior treatment with a JAK inhibitor, also referred to as refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete response, partial response, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

IMpactMF is currently enrolling patients. For further information about IMpactMF, including enrollment criteria, locations and current status, visit ClinicalTrials.gov/NCT04576156.

Pre-Clinical Poster – Pediatric Acute Myeloid Leukemia

Abstract Title: Imetelstat Significantly Reduces Leukemia Stem Cells in Patient-Derived Xenograft Models of Pediatric AML Abstract #3352

Acute myeloid leukemia (AML) is the deadliest malignancy in children. To improve survival in pediatric AML, novel targeted therapies and other alternative treatment methods are needed. Due to the significant unmet medical need in this disease, the use of imetelstat was evaluated to determine whether the drug 1) has anti-leukemia activity and 2) could be used as a therapeutic for pediatric AML.

The poster describes results from pre-clinical studies of imetelstat in pediatric AML cell lines (in vitro studies) and patient derived (PDX) mouse models (in vivo studies). The efficacy of imetelstat either as a single agent or in combination with chemotherapy or azacitidine was also evaluated. In cell line experiments, imetelstat treatment resulted in cell apoptosis/death of leukemia stem cells (LSCs) in a time- and dose-dependent manner and with minimal effect on normal bone marrow samples. In the in vivo studies, imetelstat treatment reduced LSC numbers and prolonged survival in mice. Observations of prolonged survival in mice were also seen when combining imetelstat with chemotherapy or azacitidine.

These data suggest imetelstat may represent an effective therapeutic strategy to target the LSC population in pediatric AML patients.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.