An ACS agreement

“Cardiovascular and metabolic disease (CVMD) is a core therapeutic area for MedImmune, and Shionogi’s biologic program will be a valuable and strategic complement to our existing cardiovascular program,” Cristina Rondinone, vice president and head of the MedImmune CVMD Innovative Medicines Unit, said in a news release. “We are committed to sourcing the best scientific research across the globe. We were pleased to identify this early-stage program and will work to advance its research and development as quickly as possible to hopefully bring an important new medicine to ACS patients.”

The American Heart Association describes ACS as “an umbrella term for situations where the blood supplied to the heart muscle is suddenly blocked.” Heart attacks and unstable angina are both examples of ACS.

Per the terms of the deal, MedImmune will acquire exclusive rights to Shionogi’s cardiovascular biologic program and will assume responsibility for all future research, development and manufacturing. AstraZeneca will assume responsibility for any future commercialization, and Shionogi will have an option to co-market in Japan. No financial details were disclosed for this agreement.

“Shionogi and AstraZeneca have been working together to bring Crestor to patients for nearly two decades. Such a positive relationship created the foundation for this agreement with MedImmune,” Dr. Kohji Hanasaki, senior vice president of Shionogi’s Pharmaceutical Research Division, commented in a statement. “Shionogi is now pursuing research and development in the therapeutic areas to which we should devote resources in the new medium-term business plan. We think that this biologic program gets the best chance of success by joining our promising research with MedImmune’s proven capabilities for advancing biologic research as well as AstraZeneca’s commercial capabilities in marketing cardiovascular therapies.”

Contrary to the approach of most cholesterol medications, this biologic program seeks to target high-density lipoprotein (HDL) levels, or good cholesterol, rather than trying to lower low-density lipoprotein (LDL) levels. The program acts on a biological mechanism that plays a physiological role in the metabolism of HDL. In the body, HDL works to move cholesterol out of blood vessels and plaques, and higher HDL levels have the potential to decrease individuals’ residual risk of cardiovascular disease.

“Maybe action against LDL is not enough for some patients,” Rondinone explains. “You will need to raise HDL for those patients who have really low HDL and actually cannot take cholesterol from the tissues and eliminate that bad cholesterol. So this approach, and some of the approaches that we are having at MedImmune, is mainly to strive to modify the metabolism of the good HDL and try to make the HDL functional.”

“We have internal assets, but also we are looking at innovation in every place: in companies, in academic institutions, in collaborations. So when we believe that there is some interesting target program, we are willing to collaborate,” Rondinone tells DDNews. “Collaborations such as the one we have entered with Shionogi actually support the drive to deliver new medicines to patients and are shaping the way we treat this condition.”

In other recent partnering news, MedImmune, together with AstraZeneca, announced four new collaborations with the University of Cambridge in mid-October, building on the organizations’ existing strategic partnership. The four agreements include a three-year collaboration centered on neurodegenerative diseases, a material transfer agreement granting access to select AstraZeneca compounds, a Ph.D. program and an entrepreneur-in-residence program.

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OSAKA, Japan—Shionogi & Co. Ltd. thinks it may have a new soldier in the war against multidrug-resistant (MDR) pathogens, in the form of S-649266, a new parenteral siderophore cephalosporin antibiotic discovered by the company. According to recent preclinical studies, S-649266 exhibits marked potency against Gram-negative bacteria, including MDR pathogens, and has demonstrated active penetration into bacteria and stability to beta-lactamases that hydrolyze carbapenem antibiotics.

S-649266 has unique structural features that exploit the way Gram-negative bacteria acquire iron necessary for growth. S-649266 binds to free iron and is actively transported across the outer membrane with the iron. This “Trojan horse” strategy allows S-649266 to enter the periplasmic space where it binds to penicillin-binding proteins and disrupts cell wall synthesis.

“Multidrug-resistant bacteria continue to increase, and with these difficult-to-treat infections come increased morbidity, mortality and costs not just in dollars but in an overall societal cost due to the impact of these problematic infections,” said Richard P. Wenzel, professor of medicine at Virginia Commonwealth University and former president of the International Society for Infectious Diseases, in a news release about the preclinical findings. “S-649266 has many of the criteria needed to be of value in this ongoing fight; we await clinical results with anticipation.”

Among some of the findings reported in the past few months, data indicated that compared with other cephalosporins and carbapenems, S-649266 showed robust in-vitro activity against Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae, including MDR strains. Against carbapenemase producers, S-649266 was said to be more active than meropenem and cefepime. In addition, S-649266 was reportedly shown to be 10 to 1,000 times more stable to carbapenemase than ceftazidime, cefepime and meropenem.

“Opinion leaders we've been working with in the U.S., Europe and Japan believe the efficient use of the iron uptake system may allow S-649266 to be an effective approach to treat Gram-negative bacterial infections that are not able to be treated by available antibiotics,” said Dr. Tsutae Den Nagata, chief medical officer for Shionogi. “S-649266 is the most advanced product in our anti-infective development portfolio. We are looking forward to the next stage of its development.”