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Cogent Biosciences Provides Corporate Updates and Reports Second Quarter 2021 Financial Results

On August 16, 2021 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported financial results for the second quarter ended June 30, 2021 and provided corporate updates (Press release, Cogent Biosciences, AUG 16, 2021, View Source [SID1234586605]).

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"People fighting advanced systemic mastocytosis live every day in need of additional treatment options. We initiated the Phase 2 APEX clinical study for our lead program bezuclastinib, designed to specifically target the underlying genetic cause of advanced systemic mastocytosis with the goal of providing new therapeutic options for patients," said Andrew Robbins, President and CEO of Cogent Biosciences. "In addition, we look forward to advancing bezuclastinib into two new clinical studies by the end of 2021, including the SUMMIT study for patients with non-advanced systemic mastocytosis, while actively progressing novel discovery programs with the recently formed Cogent Research Team."

Recent Program and Corporate Highlights

APEX Study in AdvSM Patients Initiated
Cogent initiated APEX, a Phase 2 clinical study of bezuclastinib in patients with AdvSM. APEX is an open-label, global, multicenter study that will evaluate the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. Learn more about the APEX study at www.cogentclinicaltrials.com
Cogent expects to report preliminary clinical data from the APEX study in the first half of 2022, including levels of serum tryptase, a validated biomarker of mast cell activity.
SUMMIT Study of bezuclastinib in NonAdvSM Patients on track to start 2H 2021
Following recent positive interactions with FDA, Cogent is on track to initiate SUMMIT, a randomized, double-blind placebo-controlled Phase 2 clinical study of bezuclastinib in patients with NonAdvSM.
FDA Granted Orphan Drug Designation for bezuclastinib in GIST (Gastrointestinal Stromal Tumors)
FDA granted orphan drug designation for bezuclastinib for the treatment of GIST with an estimated 4,000 to 6,000 GIST cases diagnosed annually in the United States.
Cogent remains on track to initiate a new study of bezuclastinib and sunitinib in GIST patients during 2H 2021.
Cogent Research Team continues to evolve efforts in pioneering best-in-class, small molecule therapeutics
Based in Boulder, Colorado, the Cogent Research Team continues to focus on developing best-in-class, small molecule therapeutics to expand Cogent’s pipeline and deliver novel precision therapies for patients living with unmet medical needs.
Announced long-term lease on ~40,000 sq. ft. facility which will serve as laboratory and office space headquarters for Cogent Research Team.
Formed the Cogent Scientific Advisory Board
Comprised of world-class experts involved in the discovery and development of novel therapeutics for patients with genetically-driven diseases, this group has been brought together to provide external perspective for the Cogent Research Team as it develops a robust portfolio of novel, small molecule discovery programs designed to address significant patient unmet needs.
Dr. Ryan Corcoran, MD, PhD – Director of the Gastrointestinal Cancer Center Program and Scientific Director, Termeer Center for Targeted Therapy at the Massachusetts General Hospital Cancer Center and Associate Professor of Medicine at Harvard Medical School
Dr. Michael Vasconcelles, MD – Chief Medical Officer of Flatiron Health, a healthcare technology and services company focused on accelerating cancer research and improving patient care
Dr. Srdan Verstovsek, MD, PhD – United Energy Resources, Inc. Professor of Medicine and a hematologist-oncologist at the MD Anderson Cancer Center, Houston, Texas, USA
Dr. Kwok-Kin Wong, MD, PhD – Director, Division of Hematology and Medical Oncology, Anne Murnick Cogan and David H. Cogan Professor of Oncology, Department of Medicine, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health
Second Quarter 2021 Summarized Financial Results

R&D Expenses: Research and development expenses were $12.4 million for the second quarter of 2021 as compared to $5.1 million for the second quarter of 2020. R&D expenses include non-cash stock compensation expense of $1.0 million for the second quarter of 2021 compared to $0.5 million for the second quarter of 2020.
G&A Expenses: General and administrative expenses were $4.9 million for the second quarter of 2021 as compared to $2.8 million for the second quarter of 2020. G&A expenses include non-cash stock compensation expense of $1.6 million for the second quarter of 2021 compared to $0.4 million for the second quarter of 2020.
Net Loss: Net loss was $16.5 million for the second quarter of 2021 as compared to a net loss of $7.4 million for the second quarter of 2020. During the second quarter of 2021, the company spent $12.6 million of its cash and cash equivalents.
Cash and Cash Equivalents: As of June 30, 2021, Cogent had cash and cash equivalents of $218.1 million. The company believes that its cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into 2024.

Exact Sciences receives regulatory approval for the Oncotype DX Breast Recurrence Score® Program in Japan

On August 16, 2021 Exact Sciences Corp. (Nasdaq: EXAS) reported that Japan’s Ministry of Health, Labor and Welfare (MHLW) has approved the Oncotype DX Breast Recurrence Score Program (Press release, Exact Sciences, AUG 16, 2021, View Source [SID1234586599]). The test helps guide chemotherapy treatment recommendations and provides risk of distant recurrence in patients with hormone receptor-positive, HER2-negative early-stage breast cancer with up to three positive lymph nodes. MHLW approval is a critical step in making Oncotype DX accessible to breast cancer patients in Japan.

Breast cancer is the most common cancer in Japanese women, and more than 90,000 new breast cancer cases were diagnosed in Japan in 2020.i The Oncotype DX Breast Recurrence Score Program approved in Japan combines the Oncotype DX Breast Recurrence Score test and software developed for the Japanese market. Exact Sciences plans to pursue coverage under Japan’s universal healthcare insurance system and launch the test through its Japanese affiliate, Exact Sciences K.K.

"MHLW’s approval of Oncotype DX is great news for breast cancer patients in Japan and reflects the powerful evidence backing the Oncotype DX test," said Kevin Conroy, chairman and CEO. "Our international team is enabling new areas of growth for our current advanced cancer tests and will accelerate access to future innovative tests for patients around the world."

The Oncotype DX test provides information allowing doctors and patients to personalize treatment plans with greater confidence.ii While chemotherapy is routinely offered, research shows that only a minority of patients with early-stage breast cancer will actually benefit.iii Oncotype DX is the only test validated to determine which patients will benefit from chemotherapy and provides critical information beyond traditional prognostic factors.iv-viii The test is supported by prospective outcomes data from the TAILORxvii and RxPONDERviii studies, which show that most patients with either node-negative or node-positive disease can be spared chemotherapy when decisions are guided by Oncotype DX.

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. In breast cancer, the Oncotype DX Breast Recurrence Score test is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. In prostate cancer, the Oncotype DX Genomic Prostate Score test predicts disease aggressiveness and further clarifies the current and future risk of the cancer prior to treatment intervention, and the Oncotype DX AR-V7 Nucleus Detect test helps determine which patients with metastatic castration-resistant prostate cancer (mCRPC) are resistant to androgen receptor (AR)-targeted therapies. The Oncotype DX AR-V7 Nucleus Detect test is performed by Epic Sciences at its centralized, CLIA-certified laboratory in San Diego and offered exclusively by Exact Sciences. The Oncotype MAP Pan-Cancer Tissue test is a rapid, comprehensive tumor profiling panel that aids therapy selection for patients with advanced, metastatic, refractory, or recurrent cancer. With more than 1 million patients tested in more than 90 countries, the Oncotype tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype tests, visit www.OncotypeIQ.com, www.MyBreastCancerTreatment.org or www.MyProstateCancerTreatment.org.

Kumquat Biosciences and Eli Lilly have reached a partnership to jointly develop tumor immune small molecule drugs

On August 16, 2021 Recently, Loxo Oncology, a research and development group of Eli Lilly, and Kumquat Biosciences (Kumquat) reported that the two parties have reached an exclusive collaboration agreement to jointly discover, develop and commercialize a series of innovative small molecule drug candidates that cause tumor-specific immune responses (Press release, Shanghai Medicilon, AUG 16, 2021, View Source [SID1234586598]).

As a collaborative partner of Kumquat, Shanghai Medicilon Inc. (Medicilon) congratulates the Kumquat Biosciences on the new progress of small molecule immuno-oncology (IO) platform.

Kumquat Biosciences and Eli Lilly have reached a partnership to jointly develop tumor immune small molecule drugs
According to the agreement, Kumquat will use its small molecule immuno-oncology (IO) platform to discover the innovative clinical drug candidates, from which Eli Lilly could select a certain number of drug candidates for further development and commercialization of global market except Greater China Region. Kumquat reserves the right to develop and commercialize each drug candidate selected by Eli Lilly in the Greater China region, however Eli Lilly has the right to participate in the joint commercialization of these drugs in the Greater China region. In addition, Kumquat could choose to jointly develop and commercialize certain drug candidates selected by Eli Lilly in the United States.

The collaboration between the two parties is the starting point after Kumquat has focused on small-molecule tumor immunotherapy. As a collaborative partner, Medicilon has the honor to witness the growth of Kumquat. Currently, Medicilon has over 50 researchers providing chemical FTE services for Kumquat. Medicilon is continuing to empower Kumquat with the flexibly adjustable solutions, controllable project progress, and customizable synthesis lines.

Guided by customer needs with the mission of innovative drug research, the FTE team of Medicilon is committed to providing high-quality emerging compounds for new drug research and development organizations. The pharmaceutical service includes medicinal chemistry, compound library design and synthesis, synthetic chemistry and synthetic process research and development. This collaboration model is cost effective and could be flexibly adjusted based on customer and project needs.

"Congratulations to Kumquat and Eli Lilly for reaching collaboration," Medicilon Founder & CEO Dr. Chunlin Chen said, "Medicilon wishes Kumquat shine in the field of tumor immunotherapy, achieve more innovative research and development results, and bring hope to the tumor patients around the world."

ANTICANCER AGENT “TAZVERIK® TABLETS 200mg” (TAZEMETOSTAT HYDROBROMIDE) LAUNCHED IN JAPAN FOR EZH2 GENE MUTATION-POSITIVE FOLLICULAR LYMPHOMA

On August 16, 2021 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has obtained manufacturing and marketing approval for the EZH2 inhibitor "Tazverik Tablets 200 mg" (tazemetostat hydrobromide) in Japan with the indication of relapsed or refractory EZH2 gene mutation-positive follicular lymphoma (only when standard treatment is not applicable) (Press release, Eisai, AUG 16, 2021, View Source [SID1234586585]).

This approval is based on the results of a multicenter, open-label, single-arm clinical phase II trial (Study 206)1 in Japan conducted by Eisai and other studies2 conducted by Epizyme, Inc. (Headquarters: Massachusetts, United States) outside Japan. Study 206 enrolled patients with EZH2 gene mutation-positive, primarily follicular lymphoma, who had relapsed or were refractory. The primary endpoint of this study was objective response rate (ORR), and secondary endpoints included safety. This study achieved the primary endpoint target and exceeded a prespecified tumor response threshold with statistical significance: ORR in patients with EZH2 mutation-positive relapsed or refractory follicular lymphoma (n=17) was 76.5% (90% confidence interval (CI): 53.9-91.5) as measured by independent review. Treatment-emergent adverse events (incidence of 25% or more) observed in this study were dysgeusia (52.9%), nasopharyngitis (35.3%), lymphopenia (29.4%) and blood creatine phosphokinase increased (29.4%). Eisai will conduct a post-marketing special use results survey (all-case surveillance) in all patients who are administered "Tazverik" until a pre-determined number of patients has been reached in accordance with an approval condition imposed by the MHLW.

Created by utilizing Epizyme’s proprietary product platform, "Tazverik" is a first-in-class small molecule inhibitor of the epigenetic enzyme EZH2. It is one of the histone methyltransferases in the epigenetics-related protein group, and is thought to regulate the expression of cancer-related genes and suppress the growth of cancer cells by specifically targeting EZH2, which contributes to the cancer growth process.3 Eisai is responsible for the development and commercialization of this agent in Japan, while Epizyme, Inc. is responsible for all regions outside of Japan. In the United States, "Tazverik" received accelerated approval for the indication of epithelioid sarcoma in January 2020, and follicular lymphoma in June 2020 (Notes to editors 1).

Follicular lymphoma is a low-grade B-cell lymphoma that accounts for 10-20% of non-Hodgkin’s lymphomas. Follicular lymphoma is generally indolent and sensitive to chemotherapy. However, development of a new treatment strategy is required for follicular lymphoma which still remains difficult to cure, as recurrence often occurs repeatedly. 7-27% of follicular lymphomas are reported to have gain-of-function mutations in the EZH2 gene,4,5 and it is estimated that there are approximately 600 to 2,400 patients with follicular lymphoma with EZH2 gene mutations in Japan. A companion diagnostic test for EZH2 gene mutations, "cobas EZH2 Mutation Test" by Roche Diagnostics K.K. (Headquarters: Tokyo) was approved in May 2021.
　

Eisai aims to make continuous efforts to meet the diversified needs of and increase the benefits provided to patients with cancer, their families, and healthcare professionals, by delivering "Tazverik" as a new treatment option for EZH2 gene mutation-positive follicular lymphoma.　

1. About "Tazverik Tablets 200 mg" (tazemetostat hydrobromide, Development Code: E7438, Epizyme, Inc.’s Development Code: EPZ-6438)

"Tazverik" is a first-in-class, oral small molecule inhibitor that targets EZH2. Eisai and Epizyme, Inc. have conducted joint research and development with utilizing Epizyme, Inc.’s proprietary product platform, based on the alliance agreement concluded in March 2011 targeting EZH2 for research, development, and sales. This agent selectively inhibits EZH2 in a competitive matter with S-adenosylmethionine (a methyl group donor) to suppress methylation of H3K27. Due to the alteration in the alliance agreement between the two companies in March 2015, Eisai is responsible for development and commercialization of this agent in Japan, while Epizyme, Inc. is responsible for all regions outside Japan.

At the Kawashima Industrial Park located in Gifu Prefecture, Japan, the production site for this agent in Japan, Eisai has successfully developed the innovative pharmaceutical manufacturing technology so-called "Continuous Manufacturing", and has applied it to production. Continuous Manufacturing contributes to quality improvement and stable supply of pharmaceutical products by integrating manufacturing automation and real-time quality monitoring technology. In addition, Continuous Manufacturing is a technology that is attracting attention as a new pharmaceutical manufacturing method that can achieve high production efficiency with space saving and energy saving, and has a low environmental load. Eisai was one of the first to adopt Continuous Manufacturing system (CTS-MiGRA) and applied this technology to the production of this agent.

The accelerated approval was granted for this agent in January 2020 in the United States with the indication of "adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection". Also, in June of the same year, the accelerated approval was granted for this agent with the indication of "adult relapsed / refractory follicular lymphoma who had at least 2 regimens of prior treatment and whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test", and of "adult relapsed / refractory follicular lymphoma for which there are no satisfactory alternative treatment options".

2. About epigenetics

Epigenetics is a branch of science that studies the mechanism for the acquired activation/inactivation of gene function and seeks to determine how gene function is inherited through cell division, irrespective of DNA base sequence alteration. Examples of modification that lead to the regulation of gene expression include methylation of DNA and modifications of histone (methylation, acetylation, phosphorylation, etc.).

3. About EZH2

EZH2 is one of the histone methyltransferases within a larger class of epigenetics-related proteins, and specifically catalyzes the methylation of histone H3 at lysine 27 (H3K27), thus controlling expression of various genes. It is indicated that an increase in methylation of H3K27 caused by EZH2 gain-of-function mutation, overexpression, or the dysfunction of EZH2 suppressive factors plays an important role in carcinogenesis.

1 Shinya Rai, et al. Phase 2 Study of Tazemetostat in Japanese patients with Relapsed or Refractory EZH2 mutation-positive B-cell Non-Hodgkin’s Lymphoma. AACR (Free AACR Whitepaper) Meet. 2021, CT176.

2 Franck Morschhauser, et al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. The Lancet Oncology. 2020 Nov; 21(11):1433-1442.

3 Sarah K. Knutson, Satoshi Kawano, Yukinori Minoshima, et al. Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent Antitumor Activity in EZH2-Mutant Non-Hodgkin Lymphoma. Molecular Cancer Therapeutics. 2014 Apr; 13(4):842–854.

4 Csaba Bödör, et al. EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood, 2013 Oct; 122(18), 3165-3168.

5 Ryan D. Morin, et al. Somatic mutation of EZH2 (Y641) in Follicular and Diffuse Large B-cell Lymphomas of Germinal Center Origin. Nat Genet. 2010 February; 42(2): 181–185.

Innovent Announces Sintilimab in Combination with Chemotherapy Meets the Primary Endpoint of Overall Survival in the Phase 3 ORIENT-16 Study for the First-Line Treatment of Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

On August 15, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported that the sintilimab Phase 3 ORIENT-16 study met its predefined primary endpoint of overall survival (OS) (Press release, Innovent Biologics, AUG 15, 2021, View Source [SID1234586587]). ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical trial evaluating sintilimab in combination with chemotherapy (oxaliplatin and capecitabine) compared to chemotherapy alone in the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

In an interim analysis, sintilimab in combination with chemotherapy demonstrated a statistically significant improvement in the primary endpoint of OS compared to placebo plus chemotherapy, in both the intention-to-treat (ITT) group and PD-L1 positive group. The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy. These results will be presented at an upcoming medical meeting.

Based on the study’s Independent Data Monitoring Committee (IDMC) recommendation, Innovent plans to review these results and file a supplemental new drug application (sNDA) of sintilimab with the Drug Evaluation Center (CDE) of the National Medical Products Administration (NMPA) in China.

The principal investigator of the ORIENT-16 study, Prof. Jianming Xu from the Fifth Medical Center of People’s Liberation Army General Hospital, stated, "ORIENT-16 is the first Phase 3 clinical trial in China to demonstrate an anti-PD-1 antibody in combination with chemotherapy significantly prolonged overall survival in the first-line treatment of advanced gastric cancer. Gastric cancer is one of the most common malignant tumor types globally and nearly half of all cases are diagnosed in China. The prognosis of advanced gastric cancer is very poor. Currently, chemotherapy is the primary treatment option and targeted agents have offered limited benefit. The results of the ORIENT-16 study have the potential to bring a new and more effective treatment option to people with gastric cancer."

Dr. Zhou Hui, Senior Vice President of Clinical Development of Innovent, stated, "While immunotherapy has greatly changed the treatment paradigm for many malignancies, it has not yet in gastric cancer. The treatment options for advanced gastric cancer are very limited and the ORIENT-16 study aimed to help address this unmet medical need. These results are very encouraging and confirmed the clinical value of sintilimab plus chemotherapy in the first-line treatment of advanced gastric cancer. We are grateful for all the contributions made by every investigator and patient in this study, and we hope that sintilimab can become a treatment option for people with gastric cancer. Today, sintilimab is one of a few PD-1 inhibitors that has shown to be efficacious in the first-line treatment of five major types of cancer – nonsquamous non-small cell lung cancer, squamous non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer."

About the ORIENT-16 Study

ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (oxaliplatin and capecitabine), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (ClinicalTrials.gov, NCT03745170). The primary endpoint was overall survival, in all randomized and in PD-L1 positive patients.

About Gastric Cancer

Gastric cancer is one of the most common malignant tumor types worldwide. According to GLOBOCAN estimates, there were approximately one million new cases and 769,000 new deaths of gastric cancer in 2020, making it the fifth most common cancer and third leading cause of cancer death globally. About half of all gastric cancer cases occurred in East Asia, mainly in China. Platinum-based chemotherapy is still the primary option in the first-line treatment of advanced gastric cancer. Currently, the 5-year survival rate of advanced or metastatic gastric cancer ranges from 5 to 20 percent, and the median overall survival is approximately one year.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has three clinical studies of sintilimab that have met their primary endpoints:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
In combination with oxaliplatin and capecitabine for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
The second-line treatment of esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.