Specific Funding To Support COVID-19 Clinical Trial

July 21, 2020. New Haven, CT. - Today, the Office of Cooperative Research (OCR) at Yale University announced the 2020 Blavatnik Award recipients, which is made possible by a generous grant from the Blavatnik Family Foundation. The Blavatnik Fund for Innovation at Yale (the fund) supports Yale faculty in the commercialization of applied research and technology in the life sciences. A significant obstacle to the development of early-stage university discoveries is the lack of funding for the proof-of-concept and validation studies needed to demonstrate commercial potential. To overcome this barrier, the fund provides monetary and business development support to help validate nascent technologies and identify potential industry partners to advance these technologies to the marketplace.

Naftali Kaminski, MD, a past recipient, received additional funding this year toward an existing project with possible COVID-19 response applications. The new funds will help support a human clinical trial for a new drug called sobetirome. The drug addresses lung fibrosis and Kaminski, along with his research team, believes it shows promise for treating certain life-threatening effects of COVID-19.

“Yale has launched a multifaceted response to the COVID-19 pandemic, and we are thrilled the fund is helping the upcoming launch of a clinical trial for sobetirome. We are hopeful Dr. Kaminski’s research will help move the needle”, explained Bill Wiesler, PhD, MBA, director of The Blavatnik Fund for Innovation at Yale.

Twelve awards were made this year, the largest number given in a single year since the fund began in 2017. This year also marks the highest amount of money awarded, a total of $2.6M. Each of the finalists was selected from among the top presenters at Yale Venture’s PitchFest in December of 2019.

“The additional grant generously given to Yale will enable us to continue a high level of support and funding for the many promising faculty innovations for the next three years. We are incredibly grateful to the Blavatnik Family Foundation for its partnership.” said Michael C. Crair, PhD, Vice Provost for Research, Yale University.

This year’s new Blavatnik awardees include Choukri Ben Mamoun, PhD for EliV5, first-in-class antifungal agents. Fungal infections are responsible for more than one billion clinical cases worldwide each year resulting in more than 1.5 million deaths. New classes of anti-fungals are desperately needed, particularly with the emergence of multidrug resistant strains. To address this need, EliV5 Therapeutics is developing new classes of anti-fungals that disrupt the first and essential step in CoA biosynthesis catalyzed by the pantothenate kinase, PanK. They have completed a screen of ~160,000 small molecules against Aspergillus PanK and identified several lead and selective inhibitors. The primary focus of this application is to evaluate the efficacy, pharmacological properties and safety of these compounds.

Ranjit S. Bindra, MD, PhD was awarded funding for Athena Therapeutics. Bindra and his team recently discovered that tumor-associated mutations in several key genes induce defects in NAD metabolism, a key pathway required for cancer proliferation. They found that NAD defects confer sensitivity to a class of drugs which also target NAD metabolism, called NAMPT inhibitors (NAMPTi’s). Numerous NAMPTi’s have made it to clinical trials, but most have been shelved after demonstrating limited efficacy along with dose-limiting toxicity. Those trials were performed without biomarkers; and toxicities likely arose from escalating doses on patients who were not likely to respond.

Peter M. Glazer, MD, PhD received funding for his work with antibody-mediated gene delivery and editing. 3E10 is a cell-penetrating antibody that binds DNA and transports the donor DNA into cells, where it binds to RAD51 to alter the function of the RAD51 DNA repair pathway to promote gene editing. The antibody/donor DNA combination can be given by IV injection and could be applied to genetic disorders such as sickle cell disease.

Sidi Chen, PhD will use his award for MAEGI Medicine, a new paradigm of immune gene therapy. Unlike all existing immunotherapy such as checkpoint blockade, cell therapy, cancer vaccine, oncolytic virus or broadly acting recombinant proteins, MAEGI is based on direct multiplexed activation of endogenous genes. While MAEGI showed strong pre-clinical efficacy as a single agent, its distinct molecular mechanism of action provides an orthogonal approach to combo with various other modalities. This project will perform optimization of an off-the-shelf version of MAEGI, further validate its efficacy and test its potential toxicity, in order to bridge the current develop to the advanced stage of pre-IND.

Akiko Iwasaki, PhD has received monetary support for CynAxis, an immunological approach to provide drug access to the central nervous system (CNS). The vast majority of drugs and biologics fail to enter the brain for treatment of brain cancers and neurological diseases. Iwasaki’s discovery has yielded key insights into how the immune system naturally overcomes the blood brain barrier to fight infections. She intends to leverage this knowledge to enable safe and transient drug access to the CNS using a simple intranasal peptide delivery approach.

Jonathan Bogan, MD will utilize his funding to combat obesity through a novel mechanism. Bogan’s work has led, unexpectedly, to the identification of a novel mechanism that controls the production of body heat. This mechanism is impaired in obesity, which may contribute to an imbalance between calories consumed and expended, promoting further obesity. His aim is to target this pathway therapeutically by developing compounds that slow the degradation of a proteolytic cleavage product.  Clinical application of this therapeutic approach can be guided by pharmacogenetics, and it may be enhanced by combination treatment using approved drugs.

Barbara Ehrlich, PhD has found a new target for the rare Wolfram syndrome. Center Pharm is focused on developing therapies for rare and deadly genetically defined disorders, and is focusing on Wolfram syndrome as a proof-of-concept therapeutic indication. They have generated knowledge involving neuronal calcium sensor-1 (NCS1) as an important modulator of pathogenesis and propose screening strategies to identify new drugs targeting NCS1 stabilization in Wolfram syndrome patients.  Using preliminary results, they have identified a lead molecule that will stabilize cell function in WFS1 KO backgrounds. This molecule will be a first in class drug to slow Wolfram Syndrome disease progression

Ya Ha, PhD is targeting p53 mutation in human cancer. There is currently no treatment that specifically targets p53 mutation, the most common genetic abnormality associated with human cancer. Loss of p53 tumor suppressor function provides cells with a proliferative advantage but renders them susceptible to metabolic stress. He has developed potent and selective inhibitors for PIP4K2A and PIP4K2B, lipid kinases that regulate cell metabolism and are essential for the growth of p53-deficient tumors.

Mark A Lemmon, PhD, FRS will use his funding to further his research for drugging fibrodysplasia ossificans progressiva (FOP). Inspired by the mode of action of natural products such as rapamycin, cyclosporine-A, and FK-506, Lemmon and his team have developed a computational platform for de novo designing of dual inhibitors that can simultaneously engage their targets and—most important— augment protein-protein interactions. Employing this strategy and iterative modifications, they have designed and synthesized a mutant selective inhibitor (Kd 230 nM) for Alk2(R206H), depicting a proof-of-concept for this platform towards the treatment of FOP and diffuse intrinsic pontine glioma.

Three Blavatnik Award recipients received additional funding for projects the fund has already supported. Those recipients are Jeffrey Bender, MD for an enhancing miRNA target-based oligonucleotide therapy for the treatment of uveitis and other inflammatory disorders, John Deacon, PhD to support his company, Cytosolix, who is developing novel small molecule oncology drugs that target a universal biomarker of solid tumors: acidity, and Andrew Miranker, PhD, for Pangolin Therapeutics’ work in breaking toxin propagation in multiple system atrophy.