Aeromics is a clinical stage drug development company developing the world’s first drug targeting a molecular water channel for the treatment of cerebral edema (brain swelling) in stroke. Each year almost 900,000 Americans and an additional 900,000 Europeans suffer a new or recurrent stroke, 85% of which are ischemic. Stroke is the third leading cause of death in the USA and the leading cause of disability. The annual medical costs are estimated at ~$70B in the U.S. and are expected to double by 2025. Cerebral edema is predictive of patient outcome in ischemic strokes, and yet there are no approved therapeutics that effectively target and treat cerebral edema as a causal driver of stroke severity.
A paradigm shift in our understanding of water physiology was the discovery aquaporins, proteins that form water channels to allow water into and out of cells, by Peter Agre (2003 Nobel Prize in Chemistry). Despite the vital role of aquaporins in maintaining water homeostasis and its implications in various disease states, therapeutic agents targeting aquaporins have remained elusive until now. Aeromics’ drug candidate, AER-271, targets aquaporin-4 (AQP4), the primary water channel in the brain, and has best-in-class credentials for acute intravenous therapy for stroke-related cerebral edema. AER-271 has proven pharmacology demonstrating control of cerebral edema in models for ischemic stroke, cardiac arrest, and water toxicity.
Basking Biosciences, Inc. is developing the first reversible thrombolytic therapy for Acute Ischemic Stroke (AIS). The company was founded in 2019 by Bruce Sullenger, PhD of Duke University and Shahid Nimjee, MD, PhD of The Ohio State University. Basking is focused on exploiting the properties of RNA biology to develop aptamers with high affinity and specificity against proteins involved in coagulation and hemostasis. DTRI-031 is an RNA aptamer that binds to von Willebrand Factor (vWF) and has demonstrated potent vessel recanalization ability across multiple murine and canine preclinical models. DTRI-025 is a sequence specific reversal oligonucleotide that rapidly and durably neutralizes the pharmacologic effect of DTRI-031.
Ischemia Care is a commercial-stage diagnostic company developing a platform of RNA expression blood tests to determine the cause of ischemic stroke and TIA. ISC’s first test, ISCDX, launched upon the completion of the BASE clinical trial (NCT02014896) which enrolled over 1,700 subjects at 20 major hospitals in the US. ISCDX seeks to characterize the underlying cause of the roughly 35% of incident strokes known as cryptogenic, enabling physicians to better care for their patients and more effectively prevent recurrent strokes. ISCDX was launched commercially in 2019.
Remedy Pharmaceuticals, Inc. is a privately-held, late clinical stage pharmaceutical company focused on developing and bringing lifesaving treatment to people affected by acute central nervous system edema. Remedy is developing CIRARA for the improvement of functional outcomes by reducing the formation of cerebral edema in patients following Large Hemispheric Infarction (massive ischemic stroke affecting the total or sub-total territory of the middle cerebral artery). There are currently no therapeutic approaches targeted at reducing the development of edema early after Large Hemispheric Infarction, and CIRARA is now in Phase 3 trials with the aim of meaningfully reducing the high mortality and morbidity of this disease.
Remedy Pharmaceutical’s CIRARA program was acquired by Biogen in 2017.
ZZ Biotech LLC is a clinical stage company developing innovative biologic treatments for ischemic stroke. ZZ Biotech was formed in 2006 to focus on the development of 3K3A-APC, a novel second-generation variant of a naturally occurring human protein, activated Protein C (APC). The major unwanted side effect of APC is bleeding, which limits its pharmacologic dosing in man. 3K3A-APC has markedly reduced anticoagulant activity, but preserved cell-protective and anti-inflammatory activities compared to wild-type APC. In animal models of stroke 3K3A-APC has shown an advantage over wild-type APC in enhanced efficacy and reduced risk for bleeding. Additionally, the combination of 3K3A-APC and tissue Plasminogen Activator (tPA) provides benefits well beyond those found with either agent alone.
ZZ Biotech has completed a multicenter Phase 2 clinical trial (RHAPSODY) of 3K3A-APC in moderate to severe acute ischemic stroke patients treated with intravenous tPA, intra-arterial thrombectomy, or both. The study was supported by the National Institutes of Health through a pair of NeuroNEXT grants. RHAPSODY established the maximally-tolerated dose (MTD) of 3K3A-APC in ischemic stroke patients and demonstrated substantial reduction in both total hemorrhage volume and hemorrhage incidence among patients treated with 3K3A-3PC vs. those treated with placebo.