On January 18, 2022 Cosette Pharmaceuticals, Inc., a New Jersey-based specialty pharmaceutical company, reported that it has closed a transaction to acquire the US sales and distribution rights to eight branded commercial products from leading Japanese pharmaceutical company, Daiichi Sankyo Company, Ltd (4568:JP) and affiliates (Press release, Cosette Pharmaceuticals, 18 18, 2022, https://www.businesswire.com/news/home/20220118005370/en/%C2%A0Cosette-Pharmaceuticals-Acquires-Rights-to-Eight-Branded-Products-from-Daiichi-Sankyo [SID1234605656]). The transaction adds eight prescription products focused on cardiovascular indications to Cosette’s current portfolio of over forty-five commercial products:

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BENICAR (olmesartan medoxomil)
BENICAR HCT (olmesartan medoxomil/hydrochlorothiazide)
WELCHOL (colesevelam HCL) tablets
WELCHOL (colesevelam HCL) Oral Suspension
AZOR (amlodipine/olmesartan medoxomil)
TRIBENZOR (olmesartan medoxomil/amlodipine/hydrochlorothiazide)
EFFIENT (prasugrel)
EVOXAC (cevimeline HCL)
"This transformative acquisition represents a significant expansion and diversification of Cosette’s portfolio and business," said Apurva Saraf, Cosette’s President and CEO. "We look forward to build on this transaction and successfully acquire and integrate important product portfolios in the future, and to continue to make these critical medications available for patients and prescribers."

"As part of our 2030 vision of becoming a global top 10 leader in oncology, we are shifting our structure to focus on our oncology portfolio in the U.S., while ensuring these legacy medicines continue to be available to the patients who rely on them," said Ken Keller, President & CEO, Daiichi Sankyo, Inc. "We are proud and thankful of the effort by our teams at Daiichi Sankyo for their dedication to patients and their providers and look forward to a smooth transition with Cosette."

The agreement outlines a 30-month transition period during which Daiichi Sankyo and Cosette Pharmaceuticals will transfer responsibilities for the manufacture, supply and commercialization of these products, including quality assurance, pharmacovigilance and regulatory matters.

According to IQVIA, U.S. annual sales for the acquired products for the 12 months ended November 2021 were approximately $123 million. No financial details will be disclosed.

Products:

Please see Package Insert (PI) for full prescribing information including complete safety information:

BENICAR (olmesartan medoxomil) See full prescribing information including boxed warning regarding fetal toxicity
BENICAR HCT (olmesartan medoxomil/hydrochlorothiazide) See full prescribing information including boxed warning regarding fetal toxicity
WELCHOL (colesevelam HCI) Tablets See full prescribing information
WELCHOL (colesevelam HCI) Oral Suspension See full prescribing information
AZOR (amlodipine/olmesartan medoxomil) See full prescribing information including boxed warning regarding fetal toxicity
TRIBENZOR (olmesartan medoxomil/amlodipine/hydrochlorothiazide) See full prescribing Information including boxed warning regarding fetal toxicity
EFFIENT (prasugrel) See full prescribing Information, including boxed warning regarding bleeding risk, and medication guide.
EVOXAC (cevimeline HCI) See full prescribing Information
Advisors

Morgan Lewis & Bockius LLP served as legal counsel and BofA Securities served as exclusive financial advisor to Cosette Pharmaceuticals. Goldman Sachs & Co. LLC served as exclusive financial advisor to Daiichi Sankyo.

On January 18, 2021 City of Hope, a world-renowned cancer research and treatment organization, and CytoImmune Therapeutics, a clinical-stage immunotherapy company that is developing a novel class of natural killer (NK) cell-based cancer therapies, reported a study published in the high-impact journal Gastroenterology that demonstrates off-the-shelf anti-prostate stem cell antigen (PSCA) chimeric antigen receptor (CAR) NK cells significantly suppressed pancreatic cancer in vitro and in vivo using a method known as freeze-thaw (Press release, City of Hope, 18 18, 2022, View Source [SID1234605655]).

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The therapy — PSCA CAR_s15 NK cells, also known as CYTO NK-203 — persisted more than 90 days after infusion and significantly prolonged the survival of mice with pancreatic cancer, showing that the freeze-thaw method works. For the study, PSCA CAR_s15 NK cells were produced and then frozen. The cells were then thawed and used in preclinical studies at City of Hope.

"Our patients need additional ways to attack their pancreatic cancer. The work presented by City of Hope’s team is distinctive and promising for two reasons: First of all, it is based on a precision medicine approach that is a special target in the patient’s pancreatic cancer — PSCA. Secondly, it is an immunologic approach, using human natural killer cells, which are specifically engineered to attack the patient’s cancer. These findings should be accelerated to a clinical trial as rapidly as possible," said Daniel D. Von Hoff, M.D., a distinguished professor in the Molecular Medicine Division of the Translational Genomics Research Institute (TGen), an affiliate of City of Hope. He also is senior consultant-clinical investigator at City of Hope and is one of the nation’s leading authorities on the treatment and care of pancreatic cancer patients.

"City of Hope is committed to finding more effective and innovative treatments for difficult-to-treat solid cancers, and pancreatic cancer is clearly one of them," said Saul Priceman, Ph.D., assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope and a study author. "These new PSCA CAR_s15 NK cell preclinical studies provide tremendous support for the anticipated upcoming clinical trials to evaluate efficacy and safety of this novel CAR-engineered NK cell therapy in patients with pancreatic cancer, which is a promising expansion of our existing clinical programs that target PSCA in solid cancers using CAR-engineered T cell therapy."

Pancreatic cancer is the third leading cause of cancer-related death in the United States with a five-year survival rate of approximately 10%. The cancer is typically detected when it is at a late stage and incurable. Chemotherapy or other therapies provide modest benefit. Therefore, the development of new therapies for pancreatic cancer is crucial. The therapy can also be used for other PSCA+ cancers, such as stomach and prostate.

NK cell technology works by using natural killer cells from a patient or donor. NK cells are then engineered so they express a receptor — a CAR — that is specific for a protein expressed by cancerous cells, along with the secretion of IL-15, which sustains the survival of the NK cells.

Christina Coughlin, M.D., CEO of CytoImmune Therapeutics, said, "We are excited to share this data on our CAR NK candidate for pancreatic cancer. This foundational data supports robust anti-tumor activity with CYTO NK-203, making us confident our innovative and off-the-shelf NK cell therapy approach has the potential to deliver more accessible, safe and effective cell-based treatment options to cancer patients. We are encouraged by these findings and look forward to continuing our work with City of Hope in order to move this initiative to the clinic."

This immunotherapy is revolutionizing the treatment of some blood cancers; however, its use in the treatment of solid tumors has been limited, in part because most of the proteins currently used to target CAR cells to solid tumors are present in low levels on other normal tissues, leading to toxic side effects.

Based on research by Michael Caligiuri, M.D., president of City of Hope National Medical Center and the Deana and Steve Campbell Physician-in-Chief Distinguished Chair, and Jianhua Yu, Ph.D., professor and director of the Natural Killer Cell Biology Research Program, who have nearly 55 years of collective laboratory investigation of NK cells, CytoImmune is developing an NK cell platform designed to overcome the limitations and challenges of current technologies for engineering NK cells. The platform is designed to generate an abundant supply of CAR NK cells from a single umbilical cord donor, engineered with the CAR for effective recognition of tumor targets, and secreting IL-15 to improve the persistence of CAR NK cells for sustained activity in the body. The process enables scientists to freeze, transport and store engineered CAR NK cells for off-the-shelf use for the treatment of cancer.

The study titled "Off-the-shelf PSCA-directed chimeric antigen receptor natural killer cell therapy to treat pancreatic cancer" can be found here.

On January 18, 2022 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm,’ reported a peer-reviewed publication in the Journal of Medical Economics (View Source) citing the clinical and associated health economic benefits of lenzilumab (Press release, Humanigen, JAN 18, 2022, View Source [SID1234605654]). The publication demonstrated, in all cases, lenzilumab plus SOC improved all specified clinical outcomes compared with SOC alone. Lenzilumab plus SOC, resulted in an estimated cost savings of $13,190 per patient (net savings of $3,190, after an assumed price of $10,000 for lenzilumab) in those receiving remdesivir with baseline C-Reactive Protein (CRP) levels <150 mg/L, and aged <85 years, the primary analysis population in the fully enrolled ACTIV-5/BET-B study. In other subpopulations, per-patient savings were also observed, including those aged <85 years with baseline CRP <150mg/L with or without remdesivir (cost savings = $11,858, net cost savings = $1,858) and within the subpopulation of Black/African American patients with baseline CRP <150mg/L (cost savings = $23,154, net cost savings = $13,154).

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"This publication demonstrates the opportunity to realise significant cost savings for healthcare systems, while also improving outcomes for patients," said Dr. Adrian Kilcoyne, Chief Medical Officer, Humanigen. "With the current omicron surge, the importance of variant-agnostic and both clinically effective and cost-effective therapies is paramount."

This peer-reviewed publication highlights the significant costs of treating hospitalized COVID-19 patients and the economic benefits of potentially improving survival without ventilation, ventilator use, time to recovery, mortality, time in the ICU, and time to invasive mechanical ventilation, which may be associated with adding lenzilumab to standard of care from the US hospital perspective.

"During these unprecedented and challenging times, we are preparing to commercialize lenzilumab as a single day treatment which is variant-agnostic and, if authorized, a driver of clinical and economic value to patients and healthcare systems," said Edward P. Jordan, Chief Commercial Officer, Humanigen.

On January 18, 2022 A2 Biotherapeutics reported the Tmod system exploits irreversible genetic changes in cancer cells called loss of heterozygosity (LOH) (Press release, A2 Biotherapeutics, JAN 18, 2022, View Source [SID1234605600]). A2 Bio will be presenting on Saturday, January 22nd at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium taking place virtually and in-person on January 20–22, 2022, at the Moscone Center in San Francisco, CA.

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A2 Bio in partnership with Tempus, a leader in artificial intelligence and precision medicine, analyzed the Tempus xT NGS assay database that has over 21,000 samples with HLA locus LOH data and over 10,000 of which are from patients with advanced disease stage ≥ 3; 3,000 of these samples are from GI cancer patients. These results demonstrate clonal frequency of HLA LOH in advanced GI solid tumor cancers of 16.3%, with a range of 15.6%-20.8% among colorectal, pancreatic, and gastroesophageal tumors. In addition, these frequencies are similar to primary tumors from The Cancer Genome Atlas (TCGA) database. Thus, HLA LOH is a well-defined discriminator between tumor and normal cells and can be exploited for NOT logic-gated Tmod CAR T to reduce on-target off-tumor toxicity. These results expand knowledge about HLA LOH in these tumors and pave the way for the use of Tempus xT NGS in screening patients for future Tmod CAR T cell therapy.

"A2 Bio has developed Tmod CAR T, which targets clonal HLA LOH as a clear differentiator between normal versus tumor cells," said William Go, MD, PhD, Chief Medical Officer at A2 Bio. "The Tempus xT next generation sequencing assay will be utilized in BASECAMP-1. BASECAMP-1 is a study to identify HLA LOH solid tumor cancer patients and obtain their T cells earlier in their treatment paradigm who may benefit from future carcinoembryonic antigen (CEA) and mesothelin (MSLN) Tmod CAR T therapy. Novel therapies are sorely needed in GI malignancies, especially in pancreatic cancer, where limited therapeutic advances have been made in over two decades."

Lead author J. Randolph Hecht, MD, Professor of Clinical Medicine, Director of the UCLA Gastrointestinal Oncology Program and principal investigator of the BASECAMP-1 trial, stated: "Tmod CAR T is an elegant and truly novel therapeutic utilizing a NOT logic gate to distinguish between normal and tumor cells. While other T cell therapies have failed in GI cancers due to toxicity or lack of efficacy, targeting HLA LOH with Tmod may provide the therapeutic safety window necessary for clinically significant outcomes. In addition, patients who might benefit from this approach can be identified using the widely used Tempus xT NGS assay early in the course of their disease."

ASCO GI Poster Information

Title: Next generation sequencing (NGS) to identify relapsed gastrointestinal (GI) solid tumor patients with human leukocyte antigen (HLA) loss of heterozygosity (LOH) for future logic-gated CAR T therapy to reduce on target off tumor toxicity

Presenter: J. Randolph Hecht, MD, Director of the UCLA Gastrointestinal Oncology Program

Session: Poster Session C: Cancers of the Colon, Rectum, and Anus.

Date/Time: Saturday, January 22 at 6:30 am to 7:55 am and 12:30 pm to 2:00 pm PT

Location: Abstract 190 – Level 1, West Hall; Moscone Center, San Francisco, CA

A2 Bio’s posters presented can be viewed on the company’s website at www.a2bio.com/science/abstracts-and-publications.

On January 18, 2022 Akeso reported that Ligufalimab combined with Ivonescimab has obtained approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the People’s Republic of China (”China”) to initiate a Phase Ib/II clinical trial with or without chemotherapy for the treatment of advanced malignant tumors, with an aim to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity of Ligufalimab combined with Ivonescimab combined with or without chemotherapy for the treatment of advanced malignant tumors (Press release, Akeso Biopharma, JAN 18, 2022, View Source [SID1234605606]).

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The main target subjects of the phase II clinical trial were patients with gastrointestinal tumors. Previously, a phase Ib/II clinical trial of Ligufalimab combined with Ivonescimab has been initiated with main target subjects of patients with head and neck malignant tumors.

Related statistics have shown that malignant tumors have become the major cause of death in the population of China, where deaths from malignant tumors account for approximatelyn23.91% of deaths from all causes of the population. The five-year relative survival rate of malignant tumors in China is approximately 40.5%, which is still far from developed countries. In addition, gastrointestinal tumors account for six out of the top ten death rate of advanced malignant tumors. Among which, treatments for advanced gastric cancer, biliary malignant tumors, pancreatic cancer and other common gastrointestinal tumors are limited and the efficacy is not high, resulting in a huge gap of clinical demand.

Related studies have shown that Ivonescimab can simultaneously stimulate anti-tumor immune response and inhibit tumor angiogenesis through activation of T cells. Since the over-expression of VEGF in the tumor microenvironment has immunosuppressive effects, the use of a bi-specific antibody that blocks both PD-1 and VEGF can achieve synergistic anti-tumor effects of PD-1/PD-L1 antibodies and anti-VEGF antibodies. It is expected to achieve good clinical efficacy and safety. Currently, anti-PD-1/PD-L1 antibody drugs on the market or under research combined with chemotherapy has shown certain clinical benefits for gastrointestinal tumors. For non-small cell lung cancer and hepatocellular carcinoma, the combination of anti-PD-1/PD-L1 antibodies with anti-VEGF antibodies has shown notable synergistic effects.

Related studies have also shown that combination therapy with anti-PD-1 drugs and targeted CD47 drugs yields synergistic antitumor effect through activation of both innate and adaptive immune response, and has demonstrated satisfactory anti-tumor effect in some of the patients with solid tumors with no additional safety risk. CD47 up-regulation can inhibit the phagocytosis of macrophages and the anti-tumor effect of VEGF/VEGFR inhibitors. At the same time, anti-VEGF/VEGFR treatment can also induce CD47 up-regulation, thereby inhibiting the anti-tumor function of macrophages. Therefore, blocking both VEGF and CD47 can effectively inhibit the immunosuppressive pathway induced by anti-angiogenesis therapy (CD47 up-regulation) while enhancing the phagocytosis of macrophages to improve the anti-tumor efficacy.

Therefore, the combination therapy of Ligufalimab and Ivonescimab is expected to activate both innate and adaptive immune pathways, so to achieve the synergistic effect of inhibiting the three tumor immune targets of PD-1, VEGF and CD47 through the combination of the two drugs, thus achieving better anti-tumor effects as compared with existing therapies. Furthermore, based on the statistics of the in vitro and in vivo pharmacodynamics and toxicology studies of Ligufalimab and Ivonescimab, the anti-tumor activity and the controlled safety profile in several clinical trials of different types of tumors, it is expected that the combination of Ivonescimab and Ligufalimab and/or chemotherapy will have a positive effect for the treatment of gastrointestinal tumors.

Currently, Ivonescimab has taken the lead in entering the phase III clinical trial globally, and Ligufalimab is also one of the world’s leading CD47 monoclonal antibodies in clinical research and development progress. The clinical trial of Ligufalimab combined with Ivonescimab in the treatment of head and neck malignant tumors and gastrointestinal tumors is another embodiment of the Company’s continuous exploration of the clinical and commercial value of its rich drug pipeline.