Azome is developing first in class drugs to revolutionize the treatment of severe inflammatory diseases and injuries including bronchopulmonary dysplasia (BPD), acute respiratory distress syndrome (ARDS), exacerbations in idiopathic lung fibrosis (ILF), acute lung injury, acute kidney injury, and sepsis for which there are currently no preventative and a limited set of therapeutic options.
Azome Therapeutics was founded by the University of Florida’s Chair of Pediatrics, Dr. Rashmin Savani, and former pharmaceutical executives with a mission to revolutionize the treatment of inflammatory diseases. Azome’s patented technology is based on a significant body of research, some of which was published in Nature Communications.
We are focused on severe inflammatory diseases that share a common biological mechanism: the NLRP3 Inflammasome. These diseases include acute respiratory distress syndrome (ARDS) and bronchopulmonary dysplasia (BPD), for which there are no therapeutic options. Azome’s technology is a novel platform approach for addressing these severe unmet clinical needs, targeting the earliest activation signal for inflammasome activation. Tissue injury results in the elaboration of endogenous danger signals recognized by Toll-like receptors to activate inflammation, mechanisms that require the Receptor for Hyaluronan-Mediated Motility (RHAMM).
We designed Azome’s lead product (AZM-152) that antagonizes RHAMM and blocks inflammation and fibrosis in animal models after a single SubQ microgram per kg dose without apparent toxicity. To develop RHAMM antagonists for chronic inflammation and as orally administered drugs, Azome also identified two small molecule series, designated AZM-12 and AZM-39, that are non-cytotoxic and inhibit inflammasome activation at micromolar concentrations. Collectively, our in vitro and in vivo data demonstrate that Azome’s RHAMM inhibitors act by a threat-agnostic mechanism to block both the priming and activation phases of the NLRP3 inflammasome and are effective in multiple models of injury, including sepsis, pneumonia, and acute lung injury.
Azome's leadership team has executed preclinical and clinical development programs, submitted INDs and NDAs, resulting in numerous drug approvals in a variety of therapeutic areas.
- Elliott Gruskin, PhD, Co-Founder & CEO is a global pharmaceutical operating executive. Following the acquisition of Synthes by JnJ, Dr. Gruskin served as an Operating Company President in JnJ’s orthopedics division, where he led a $350 million global biomaterials business.
- Steven Romano, MD, Non-Executive Chairman of the Board, serves as Chief Medical Officer and Head of R&D at Silence Therapeutics. Dr. Romano’s C-Suite experience will be leveraged to ensure efficient execution of Azome's R&D.
- Rashmin C. Savani, MBChB, Co-Founder & Head of Scientific Advisory Board, is Professor, Nemours Eminent Scholar, and Chair of Pediatrics at the University of Florida College of Medicine in Gainesville. Dr. Savani’s laboratory discovered AZM-152. Dr. Savani's scientific and clinical expertise will contribute to Azome’s development of its lead asset and technology platform.
Azome will partner with a major global pharmaceutical company for market access. A partner with a significant presence in the hospital critical care environment will be required. Non-confidential discussions are underway with several potential commercial partners.
Azome will derive revenue from licensing its intellectual property to a larger pharmaceutical or biotech company. Anticipated licensing agreements will involve upfront, and milestone payments based on the achievement of specific development or regulatory milestones. There will also be royalties on future product sales.
Azome is seeking $10 M to launch IND-Enabling studies for AZM-152 for ARDS, support the NCATS CRADA for BPD and expand the small molecule pipeline of RHAMM inhibitors. Under the NCATS CRADA, Azome is responsible for AZM-152 drug supply. Consequently, $1M is targeted to transfer AZM-152 production to a contract manufacturer. Azome is currently in discussions with Corden Pharma to provide peptide synthesis. Additional use of proceeds include:
- $3-4 million to execute the IND-Enabling studies for AZM-152 to file an IND for ARDS. This project will take 18 months to complete. Azome is currently in discussions with LabCorp for toxicology studies.
- Small molecule hit to lead program to develop orally available small molecule RHAMM inhibitors to treat chronic inflammatory diseases. Azome is currently in discussions with Eurofins to screen additional libraries and develop the structure activity relationship data necessary to nominate a lead small molecule for development.
- Meet obligations under the University of Florida and Lawson licenses.
- Regulatory consulting to file Orphan Drug and Rare Pediatric Disease Designations for AZM-152 for BPD (the latter designation will make Azome eligible for a FDA Expedited Review Voucher)
Azome designed a potent peptide-based RHAMM inhibitor, AZM-152, that shows no sign of dose limiting toxicity in animal models including a bleomycin injury model of ARDS and lung fibrosis, a neonatal hyperoxia model of bronchopulmonary dysplasia, and an intraperitoneal LPS model of sepsis. All the data were consistent with a marked reduction of inflammation and biomarker analysis was consistent with a reduction in NLRP3 inflammasome activation. Thus, the overall mechanism of action for AZM-152 includes a reduction of the transcription of NLRP3 monomers, which prevents to formation and maintenance of NLRP3 inflammasomes and the reduction in transcription of the key precursor forms of the pro-inflammatory cytokines IL1beta and IL18, which are the substrates for caspase-associated inflammasome processing to mature cytokines. In an acute inflammatory scenario, AZM-152 will prevent the assembly of NLRP3 inflammasomes. In a chronic inflammatory setting AZM-152 will not only prevent the assembly of additional inflammasomes, but it will also deprive existing inflammasomes of the pro-inflammatory cytokine substrates. Collectively, these data provided the basis for the NCATS CRADA to advance AZM-152 for an IND to treat BPD, a project that will take 36 months. In addition, Azome plans to advance AZM-152 for an IND to treat acute ARDS in 18 months. Azome has also identified two small molecule series, designated AZM-12 and AZM-39, that are non-cytotoxic and inhibit inflammasome activation at micromolar concentrations. These small molecules are the basis for a hit to lead program to develop orally available drugs to treat chronic inflammatory diseases.
Azome has executed a $3-5 million dollar Cooperative Research and Development Agreement (CRADA) with the National Center for Advancing Translational Sciences (NCATS) to investigate AZM-152, the company’s novel inflammasome antagonist, in bronchopulmonary dysplasia (BPD). Under the terms of the agreement, NCATS will collaborate with Azome and perform preclinical development studies of AZM-152 to enable Azome to submit an Investigational New Drug (IND) application for the prevention of BPD in preterm infants.
