NIH Awards Grant to Battle Sepsis to San Diego's Allele Biotechnology and Pharmaceuticals
National Institutes of Health, Bethesda, MD. Credit: bakdc / Shutterstock.com
The National Institute of General Medical Sciences, part of the National Institutes of Health (NIH), awarded Allele Biotechnology and Pharmaceuticals a Small Business Innovative Research grant to develop therapies for sepsis.
Allele, based in San Diego, focuses on non-integrating cellular reprogramming methods to discover new drugs and cell therapies. Within that context, they work to develop human and non-human primate induced Pluripotent Stem Cells (iPS) cells.
The NIH grant is for Allele to develop new single-domain nanoantibody (nAb) therapies to treat sepsis. Sepsis and septic shock have been increasing worldwide and the mortality rate can reach over 60 percent for septic shock.
Allele has been working in recent years on ways of intervening in what are called “cytokine storms.” The so-called cytokine storm is one of the bigger problems observed in immuno-oncology therapeutics, such as CAR-T. In a more general population, they are dramatic and potentially deadly responses to bacterial infections. These are severe inflammatory responses. In sepsis, the cytokine storm is seen early and causes vascular endothelial barrier dysfunction.
Some companies have attempted to develop interventions using monoclonal antibodies that target upstream cytokines. But they haven’t shown meaningful improvement in mortality rate.
Allele states that it “has engineered novel multi-valent and multi-specific nAbs, originally identified from an immunized llama, to combat cytokine storms. These nAbs have superior therapeutic efficacy over conventional antibody drugs in animal models of sepsis because of their unique structural and functional properties.”
nAbs are also called VHH domains. They are small fragments of antibodies that are stable and easy to manufacture. Allele claims this class of antibodies show significant capacity to penetrate tissues and tumors.
The first approved nAb-based drug is Belgian company Ablynx’s Cablivi (caplacizumab) for von Willebrand factor (vWF). Sanofi acquired Ablynx for $4.8 billion early this year. The drug was approved by the European Commission for adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), a rare blood-clotting disorder, on September 3, 2018.
The drug is under priority review by the U.S. Food and Drug Administration (FDA) for aTTP and has a target action date of February 6, 2019.
Allele began working on nAbs in 2008. It has been funded by the NIH since 2011 and private investments since 2013. The company states, “These funds strengthened Allele’s platform, allowing Allele to drastically enhance its capacity of internal research and outside collaboration. Allele now generates high quality nAbs targeting the most devastating diseases including cancers, inflammation, neurological and ophthalmological diseases, and possesses dozens of exciting nAb drug candidates in its pipeline.”
According to the Centers for Disease Control and Prevention (CDC), sepsis occurs most often in individuals 65 years or older or younger than 1 year. Other at-risk populations include people with weakened immune systems or who have chronic medical conditions such as diabetes. The most common infections associated with sepsis are lung, urinary tract, skin and gut. The most common pathogens associated with sepsis are Staphylococcus aureus, Escherichia coli, and some strains of Streptococcus.
From one study, in the U.S. in 2014, there were 173,690 cases of sepsis. Of those, 26,061 died in the hospital and 10,731 were discharged to hospice. The study concluded, “In clinical data from 409 hospitals, sepsis was present in 6 percent of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014.”