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.

On October 5, 2020 Oasmia Pharmaceutical AB, an innovation-focused specialty pharmaceutical company, reported that Elevar Therapeutics, Inc. and Taiba Middle East FZ LLC have entered into an exclusive agreement under which Taiba will commercialize and distribute Apealea (micellar paclitaxel) in certain countries throughout the Middle East and North African (MENA) region (Press release, Oasmia, OCT 5, 2020, View Source [SID1234568100]). Under the terms of the agreement, Taiba will also be responsible for managing named-patient requests through which physicians can legally and ethically prescribe Apealea for patients prior to commercial availability.

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Apealea is a patented formulation of paclitaxel in combination with Oasmia’s proprietary XR-17 technology which encapsulates individual active pharmaceutical ingredients (APIs) in a layer of micelles, making the API and micelle formulation water soluble and therefore usable in water based intravenous injections.

Apealea has been approved by the European regulatory authorities for use in combination with carboplatin for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer.

In March 2020, Oasmia signed a global strategic partnership with Elevar Therapeutics for the commercialization of Apealea, making Oasmia eligible for potential milestone payments of up to USD 678 million- and double-digit royalties on sales.

François Martelet, M.D., CEO of Oasmia, commented: "It is great to see Elevar secure a quality regional partner for the MENA region which will initiate the process of obtaining regulatory approvals and commercialization. If regulatory approval is obtained, Apealea will be the first Cremophor-free formulation of paclitaxel approved for use in ovarian cancer in the Middle East and North Africa region and offer many cancer patients a therapeutic option with far less side effects."

Alex Kim, CEO of Elevar Therapeutics, added: "Partnering with Taiba in the Middle East and North Africa is an important milestone in our global registration and commercialization strategy for Apealea. This is the first regional partnership deal for Apealea, we are in active discussions with a number of other potential partners for other regions around the world and look forward to updating the public as these deals are executed."