The blood-brain barrier is a major obstacle for treatment efficacy in the treatment of both primary CNS cancers and brain metastases, as most drugs are not CNS permeable and systemic toxicities are dose-limiting. BrainStorm Therapeutics seeks to leverage proprietary nanoparticle formulations and novel delivery strategies developed in the Saltzman laboratory, combined with brain tumor biomarkers identified in the Bindra Laboratory, to overcome this major problem. We will develop an entirely new therapeutic strategy for the treatment of CNS tumors, with great potential for rapid translation into the clinic.

OCR Business Development Lead: John Puziss

There are no drugs approved to treat core symptoms of autism, the costliest pediatric disease in the US (estimated $250 billion/year). Oxytocin, the drug with the most-promising clinical data, has successful, placebo-controlled trials on four continents, but some results are weak.

The laboratory of Steve Chang at Yale has discovered, published and filed for patent on the amplification of oxytocin’s effect through combination with naloxone. The Chang patent is being combined with oxytocin formulation and delivery patents owned by the NYC-based biotech Pastorus. The Blavatnik award would fund a proof-of-concept clinical trial of the [oxytocin + naloxone] product.

OCR Business Development Lead: Lolahon Kadiri

The etiology of age-related macular degeneration (AMD) is caused by many factors including oxidative stress/mitochondrial dysfunction, resulting in retinal pigment epithelial (RPE) cell dysfunction and eventual cell death or what is known as geographic atrophy AMD in late stage “dry” AMD. We developed a high-throughput assay that mimics the effects of oxidative stress and identified three protective chemotypes, which are novel, drug-like and represent excellent starting structures for further development. Secondary analysis of the identified show efficacy in human RPE cells in in vitro and in vivo models of oxidative stress, blue light-induced damage, and aged Bruch’s membrane.

OCR Business Development Lead: Lolahon Kadiri

Reprogramming a patient’s own cytotoxic T cells with a Chimeric Antigen Receptor (CAR) to attack B cell leukemias is remarkably successful. In contrast, T cell lymphomas are highly aggressive and remain incurable. Here, we develop a novel CAR to target a subset of T cell lymphomas, while avoiding self killing and employing strategies for synergistic combination therapies.

OCR Business Development Lead: Chris Unsworth

There is a pressing need for antiviral compounds that target SARS-CoV-2 replication enzymes, not only to combat the current pandemic, but for future coronavirus outbreaks. A key impediment is the lack of a robust high-throughput viral replication assay with low biosafety requirements. We have developed SARS-CoV-2 replicons – fragments of the viral genome that replicate in cells but do not make infectious virus particles – and shown that they are useful for drug screening, dose titration, and drug synergy studies. We will complete optimization of second-generation replicons, conduct pilot screens, and validate assay scalability and robustness for large-scale screening.

OCR Business Development Lead: Chris Unsworth

Triple-negative breast cancer (TNBC) lacks targeted therapies and therefore rely on chemotherapy with its associated side effects. TNBC is an aggressive disease with high metabolic rewiring. We have identified PCK2 as a TNBC-specific metabolic target by comparing RNA sequencing data from patient-matched clinical samples. PCK2 is a novel target and lacks an inhibitor, a protein model, and an enzyme assay. To this end, we have created a homology model, a high throughput enzyme assay, and identified an active hit. Using the Blavatnik fund, we propose to perform lead optimization, PK/PD, and in vivo validation.

OCR Business Development Lead: David Lewin

COVID-19 is causing untold global harm to human health. There is no anti-viral treatment for early COVID-19 infection. A drug to prevent SARS-CoV-2 infection and transmission would have global importance including virus eradication. Camostat, a repurposed serine protease inhibitor in Phase II clinical trial at Yale for early, outpatient, treatment of COVID-19, requires molecular optimization. The goal of this project is to develop a more potent and selective TMPRSS2 inhibitor with robust anti-COVID-19 efficacy and pharmacokinetics sufficient to enable once-daily oral dosing in humans. Such a drug might be active against other coronaviruses given known mechanism of action.

OCR Business Development Lead: David Lewin