On October 5, 2020 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, reported that it has entered into a strategic collaboration with Angel Pharmaceuticals that will enable the development and commercialization of its pipeline of precisely targeted investigational medicines in China (Press release, Corvus Pharmaceuticals, OCT 5, 2020, View Source [SID1234568105]).

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Angel Pharmaceuticals is a new China-based biopharmaceutical company with a mission to bring innovative quality medicines to Chinese patients for treatment of serious diseases including cancer, autoimmune diseases and infectious diseases. It was formed as a Corvus wholly-owned subsidiary and was launched with a post-money valuation of $106 million, based on a $41 million cash investment from a Chinese investor group that includes funds associated with Tigermed and Betta Pharmaceuticals, Hisun Pharmaceuticals and Zhejiang Puissance Capital, which investments are subject to the satisfaction of certain customary conditions. Contemporaneously with the financing, Angel Pharmaceuticals licensed the rights to develop and commercialize Corvus’ three clinical-stage candidates – ciforadenant, CPI-006 and CPI-818 – in greater China and obtained global rights to Corvus’ BTK inhibitor preclinical programs. Under the collaboration, Corvus will initially retain a 49.7% equity stake in Angel Pharmaceuticals and will be entitled to designate three individuals on Angel’s five-person Board of Directors.

"The formation and launch of Angel Pharmaceuticals to develop our product pipeline in greater China opens a significant new opportunity for Corvus," said Richard A. Miller, M.D., president and chief executive officer of Corvus. "We expect Corvus shareholders will benefit from this collaboration in two main ways: our ownership position in Angel in the rapidly growing Chinese biotech market, and the acceleration of our product development capabilities through the participation of patients in China. We believe Angel is positioned for success as a science-based Chinese biopharmaceutical company backed by an impressive group of investors with financial resources, and significant regulatory, drug development and commercialization experience. Their investment is strong validation of Corvus’ pipeline and its importance in addressing unmet needs in the Chinese and global markets. We have already begun working with the Angel leadership to initiate clinical trials in China with ciforadenant, CPI-006 and CPI-818 in cancer, autoimmune diseases and infectious diseases within the next 12 to 18 months. We believe that the expertise and development capabilities at Angel will accelerate and enhance Corvus’ global development capabilities."

"Dr. Miller is a world-renowned drug developer and he has built a first class management team at Corvus. The Angel team is fortunate to partner with Dr. Miller and his team on their novel product portfolio, which has demonstrated impressive results to date in the clinic," said Dr. Ted Wang, managing partner of Puissance Capital, co-founder and board member of Angel Pharmaceuticals. "Angel is launching at an opportune time, benefiting from China’s explosive growth in demand for innovative medicines, reform in drug regulation and approvals, and change in IPO listing requirements specifically designed to encourage drug innovation."

"Our goal in launching Angel is to build a company that will have a long-term, positive impact on society. We have brought together a local team that is aligned with this mission and that is very experienced in the Chinese market, including expertise in research and development, clinical operations and regulatory affairs, business development, and intellectual property protection. By standing on the shoulders of Corvus, Angel can accelerate drug development and bring innovative medicines, including internally developed programs, to patients in China and globally faster."

Strategic Rationale for Corvus

Establishes 49.7% ownership in a uniquely positioned biopharmaceutical company in the rapidly growing Chinese market.
Clinical study synergies and accelerated timelines, whereby data from patients enrolled in China studies could potentially be used as part of U.S. regulatory submissions as part of a global pivotal study protocol.
Research and development synergies, whereby Corvus will benefit from Angel’s research and development efforts and China’s deep pool of talented researchers.
Establishes collaboration with leading Chinese investors, biopharmaceutical companies and scientists with experience in regulatory affairs, clinical development, manufacturing and commercialization.
Launching with a Uniquely Positioned and Validated Oncology Pipeline
Angel Pharmaceuticals will be responsible for the clinical development and commercialization, including all related expenses, of the licensed pipeline programs in China, and for the pre-clinical BTK program globally. It plans to initiate clinical trials in China for ciforadenant, CPI-006 and CPI-818 in the next 12 to 18 months. In the United States, Corvus is planning to meet with the U.S. Food & Drug Administration (FDA) in December 2020 to discuss the study design and plans for a pivotal ciforadenant study in advanced refractory renal cell cancer (RCC) using the Adenosine Gene Signature as a biomarker. Angel Pharmaceuticals’ clinical trial activity in China is expected to be part of this global pivotal study. Angel Pharmaceuticals’ cash position at launch is expected to provide runway beyond its first two years. Such cash will not be available for uses by Corvus.

Strong Leadership Team, and Board of Directors
Angel Pharmaceuticals will have well-known, experienced local pharmaceutical executives with management experience in multinational companies in clinical, regulatory and research. At launch, the senior team includes seven leaders that hold a medical degree or Ph.D., and the company plans to expand its team with leading scientific talent in China. In addition, Dr. Miller, a co-founder of Angel, will serve as Chairman of the Board and interim chief executive officer, working closely with the founding leadership team.

The Angel Pharmaceuticals Board of Directors will initially be comprised of:

Richard Miller, chairman and chief executive officer of Corvus Pharmaceuticals
Leiv Lea, chief financial officer of Corvus Pharmaceuticals
Peter Thompson, Private Equity Partner with OrbiMed Advisors and co-founder and board member of Corvus Pharmaceuticals
Ted Wang, chief investment officer of Puissance Capital
Conference Call Details
Corvus will host a conference call and webcast today, Monday, October 5, 2020, at 8:30 a.m. ET (5:30 a.m. PT), to discuss the launch of Angel Pharmaceuticals. The conference call can be accessed by dialing 1-877-407-0784 (toll-free domestic) or 1-201-689-8560 (international) and using the conference ID 13711371. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.

On October 5, 2020 CARsgen Therapeutics Co., Ltd., a clinical-stage biopharmaceutical company, reported that the United States (US) Food and Drug Administration (FDA) has granted orphan drug designation to one of CARsgen’s first-in-class drug candidates, CT041, for the treatment of gastric and gastroesophageal junction adenocarcinoma (Press release, Carsgen Therapeutics, OCT 5, 2020, View Source [SID1234568104]). CT041 is a humanized anti-claudin18.2 autologous chimeric antigen receptor (CAR) T-cell product and is targeted to treat patients with claudin18.2-positive tumors.

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CT041 is the first claudin18.2-targeted CAR T-cell therapy that has received Investigational New Drug (IND) clearance by the US FDA and the first to receive IND clearance by the National Medical Products Administration (NMPA) in China. The initiation of an open label, multicenter, Phase 1b clinical trial (NCT04404595) to evaluate the safety and efficacy of autologous CT041 cell therapy in patients with advanced gastric, gastroesophageal, or pancreatic adenocarcinoma is currently underway.

"The orphan drug designation of CT041 by the FDA is of great significance to patients with advanced gastric cancer," said Dr. Zonghai Li, founder, CEO and CSO of CARsgen. "According to the World Health Organization, about 1,030,000 new cases of gastric adenocarcinoma are expected each year [1]. Despite the development of novel therapies, gastric cancer is still a disease with one of the highest unmet medical needs. Our goal is to continue the development of novel, safe and effective immunotherapies. This is our long-standing commitment to cancer patients worldwide."

Orphan drug designation is granted by the FDA Office of Orphan Products Development to investigational treatments that are intended for the treatment of rare diseases affecting fewer than 200,000 people in the US. Under the Orphan Drug Act, the CT041 anti-claudin18.2 product would be eligible for certain benefits including FDA support for clinical studies, special fee exemptions and reductions, and seven years of market exclusivity in the United States following marketing approval by the FDA.

References:

[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.

On October 5, 2020, Corvus Pharmaceuticals, Inc. ("Corvus" or the "Company"), reported that it entered into, and consummated certain transactions contemplated by, a Framework Agreement (the "Framework Agreement") by and among Corvus Hong Kong Limited, a wholly-owned subsidiary of Corvus Cayman (as defined below) ("Corvus HK"), Angel Pharmaceuticals Co., Ltd., a wholly-owned subsidiary of Corvus HK ("Angel Pharmaceuticals"), Jiaxng Puissance Angel Equity Investment Partnership (Limited Partnership) (the "Investment Entity") and AP BIOTECH DEVELOPMENT CORP. ("AP BIOTECH"), pursuant to which, and on the terms and subject to the conditions thereof, Corvus will grant a license to Angel Pharmaceuticals for certain of its intellectual property and dispose of certain assets comprised of the share capital of certain of its wholly-owned subsidiaries (Filing, 8-K, Corvus Pharmaceuticals, OCT 5, 2020, View Source [SID1234568103]). In particular, pursuant to the Framework Agreement and the agreements contemplated therein:

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i.Corvus, Corvus Biopharma International Ltd., a wholly-owned subsidiary of Corvus ("Corvus Cayman") and Corvus HK will grant Angel Pharmaceuticals the right to develop and commercialize Corvus’ three clinical-stage candidates, ciforadenant, CPI-006 and CPI-818, in greater China and global rights with respect to Corvus’ BTK inhibitor preclinical programs;

ii.the Investment Entity will invest RMB 235 million in Angel Pharmaceuticals in exchange for registered capital in the amount of $56,400 (representing an equity interest of approximately 35.0% in Angel Pharmaceuticals) and AP BIOTECH will receive registered capital in the amount of $13,900 (representing an equity interest of approximately 8.6% in Angel Pharmaceuticals) (collectively, the "Initial Capital Increase");

iii.upon completion of the Initial Capital Increase, Corvus HK will issue warrants to purchase its ordinary shares to the Investment Entity and AP BIOTECH and will enter into a related equity transfer agreement with such parties to provide them with an ownership interest in Corvus HK that shall be equal to but replace their ownership interest in Angel Pharmaceuticals following any determination by the board of directors of Angel Pharmaceuticals to list the shares of Angel Pharmaceuticals publicly; and

iv.following the Initial Capital Increase, Angel Pharmaceuticals will enable Hangzhou Betta Investment Management Co., Ltd. ("Betta") to subscribe for increased registered capital of Angel Pharmaceuticals in an amount of $6,000 (representing an equity interest of approximately 3.5% in Angel Pharmaceuticals) in exchange for investments of RMB 25 million and Hangzhou Tiger Equity Investment Partnership LP ("Tigermed") to subscribe for increased registered capital of Angel Pharmaceuticals in an amount of $4,800 (representing an equity interest of approximately 2.8% in Angel Pharmaceuticals) in exchange for investments of RMB 20 million (the "Second Capital Increase" and, together with the Initial Capital Increase, the "Capital Increases").

Following the consummation of the foregoing transactions, it is expected that Corvus HK will hold a 49.7% equity interest in Angel Pharmaceuticals and that Angel Pharmaceuticals will have received aggregate proceeds from the Capital Increases of approximately $41.0 million, indicative of a post-money valuation of approximately $106.0 million. Corvus expects Angel Pharmaceuticals to use the proceeds from the Capital Increases for development of Corvus’ product candidate pipeline and no amount of the proceeds will be available for use by Corvus.

In connection with and subject to the consummation of the foregoing transactions, each of Corvus HK, the Investment Entity, AP BIOTECH, Betta and Tigermed will enter into a shareholders agreement relating to shareholder rights, governance and management of Angel Pharmaceuticals, and pursuant to which Corvus will be entitled to designate three individuals on Angel Pharmaceuticals’ five-person board of directors. It is currently contemplated that the board of directors of Angel Pharmaceuticals will initially be comprised of Richard Miller, chairman and chief executive officer of Corvus, Leiv Lea, chief financial officer of Corvus, Peter Thompson, co-founder and board member of Corvus, and Ted Wang, chief investment officer of Puissance Capital. In addition, Dr. Miller will serve as Angel Pharmaceutical’s interim chief executive officer.

On October 5, 2020 Quanterix Corporation (NASDAQ: QTRX), a company digitizing biomarker analysis to advance the science of precision health, reported it has entered into a non-exclusive royalty-bearing license agreement with Abbott Laboratories (NYSE: ABT), the global healthcare company (Press release, Quanterix, OCT 5, 2020, View Source [SID1234568102]). The non-exclusive license grants Abbott access to Quanterix’s portfolio of bead-based technology patents for use in in vitro diagnostic (IVD) applications.

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Under the terms of the agreement, Quanterix will receive an initial license fee, milestone fees subject to the achievement by Abbott of future development, regulatory, and launch milestones and royalties on the sale of licensed products. To learn more about Quanterix click here

On October 5, 2020 Researchers at The University of Texas MD Anderson Cancer Center reported that have identified molecular and cellular characteristics of anti-CD19 CAR T cell infusion products associated with how patients with large B-cell lymphoma (LBCL) respond to treatment and develop side effects (Press release, MD Anderson, OCT 5, 2020, View Source [SID1234568101]).

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The research team also found that early changes in circulating tumor DNA one week after CAR T cell therapy may be predictive of treatment response in a particular patient. The paper was published online today in Nature Medicine.

"CAR T cell therapy is highly effective against LBCL," said corresponding author Michael Green, Ph.D., associate professor of Lymphoma and Myeloma. "However, we experience two main clinical challenges: achieving long-term remission and managing treatment-associated adverse events."

This study suggests that, within the first week of therapy, clinicians may be able to identify a subset of patients who may experience more poor outcomes or adverse treatment reactions, said Green. This would allow the care team to adjust therapy to improve efficacy or to act to mitigate toxicity.

CAR T cell signature, early molecular response may predict long-term outcomes

For this study, researchers performed single-cell analysis on CAR T cells to study gene expression profiles in the infused cells. CAR T cells were collected from those remaining in infusion bags following treatment of 24 patients with LBCL. These genetic profiles were compared to treatment responses, determined at three months post-infusion by PET/CT scan.

"When we look at the characteristics of the infused CAR T cells, we found that samples from patients who were less responsive to treatment had exhausted T cells, whereas those who experienced complete responses had T cells expressing ‘memory’ signatures," said co-corresponding author Sattva Neelapu, M.D., professor of Lymphoma and Myeloma. "Additionally, one cellular signature of T cell exhaustion was more commonly found in patients who exhibited a poor molecular response, and poor molecular response is generally associated with less-positive, long-term outcomes."

Further, the researchers analyzed early molecular responses in the patients by monitoring changes in circulating tumor DNA from treatment to one week post-infusion. The magnitude of change in tumor-associated DNA corresponded with response, suggesting that patients who displayed an early molecular response were more likely to experience a clinical response to treatment.

CAR T cell features predict likelihood of severe side effects

Adverse side effects of CAR T cell therapy can include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS). These adverse events can delay patients’ recovery and can lead to increased need for hospitalization and intensive care.

"When we examined the infusion product, we found that a cell population with characteristics similar to myeloid cells, with a monocyte-like transcriptional signature, was associated with development of high-grade neurotoxicity," said Green. "Detecting these cells may subsequently lead us to identify patients who would be at higher risk of developing neurotoxicity, allowing us to provide prophylactic treatment with agents that target the specific cellular features."

Further examination may lead to insights into the types and attributes of the cells present within the CAR T infusion product.

"This study also tells us that some rare and unexpected cells identified by single-cell analysis could be biologically important," said co-corresponding author Linghua Wang, M.D., assistant professor of Genomic Medicine. "Going forward, we plan to functionally characterize these monocyte-like cells to better understand their specific biological mechanisms driving these clinical results."

These findings will help researchers develop clinical interventions that can block or target these cells. They also plan to validate the capacity of circulating tumor DNA to accurately predict patients’ long-term outcomes.

This research was supported in part by the B-cell Lymphoma Moon Shot, part of MD Anderson’s Moon Shots Program. With support from the Moon Shot and the Cancer Prevention & Research Institute of Texas (CPRIT), the research team plans to utilize PDX models of disease that relapsed following anti-CD19 CAR T cell therapy to preclinically test interventions that could lead to better treatment responses or to prevention of adverse side effects.

Other research support came from the Schweitzer Family Fund, the National Cancer Institute (P30 CA016672) and start-up research funds from MD Anderson. A full list of co-authors and their disclosures can be found here.