Precision Medicine
Development Approach
Our highly targeted therapeutics are founded on a strong scientific and clinical rationale that enables accelerated clinical development and increased probability of success.
Our highly targeted therapeutics are founded on a strong scientific and clinical rationale that enables accelerated clinical development and increased probability of success.
Identify accessible molecular targets that have strong associations to diseases with substantial unmet need
Verify the role of the potential target in disease pathology and establish its utility as a biomarker
Investigate novel therapeutics aimed at altering the identified molecular targets, and validate the clinical hypothesis
Progress these targeted therapeutics through a proof-of-concept study to demonstrate efficacy and safety, accelerating the time to clinical development
AVTX-002 is a novel, first-in-class, fully human anti-LIGHT monoclonal antibody in development for acute respiratory distress syndrome (ARDS), inflammatory bowel disease (IBD), and non-eosinophilic asthma (NEA). Compelling support for the involvement of LIGHT in IBD, along with demonstrated proof-of-concept, resulted in Avalo’s exclusive licensing rights for the development and commercialization of AVTX-002.
Data indicate a strong association between a mutation in the gene encoding for the immunomodulator decoy receptor 3 (DcR3) and Crohn’s disease. Our research on the functional consequences of DcR3 mutations identified the cytokine LIGHT as a potential primary target. We built upon this research by engaging experts from academic research institutions, including the Children’s Hospital of Philadelphia (CHOP), before investing in this hypothesis.
We proceeded to assess LIGHT levels in pediatric patients with active Crohn’s disease compared with age- and sex-matched healthy controls and showed that plasma LIGHT levels were significantly elevated in 83% of the patients with Crohn’s disease. These data, along with data from preclinical experimental models, established LIGHT as a credible biomarker for Crohn’s disease and a promising molecular target for treatment.
*Determined by Mann-Whitney U test. Plasma samples from CHOP Biobank.
We initiated a phase 1, open-label, proof-of-concept study of AVTX-002 in patients with moderate to severe Crohn’s disease in whom treatment with an approved anti–tumor necrosis alpha (TNFα) monoclonal antibody had failed. Preliminary results show that treatment with AVTX-002 resulted in a rapid decrease in LIGHT levels and improvement in symptoms, including clinically meaningful endoscopic healing. AVTX-002 was well tolerated, with no serious adverse events.
*SES-CD, Simple Endoscopic Score for Crohn’s Disease.
In 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, resulting in the COVID-19 (coronavirus infectious disease 2019) pandemic. Two separate research publications had established the critical role of LIGHT in the progression of ARDS, a primary cause of death from COVID-19 infection. With research into AVTX-002 already underway for treatment of IBD, we evaluated the potential of LIGHT as a treatment target for COVID-19–induced ARDS to address this worldwide public health crisis.
Assessment of LIGHT levels in patients hospitalized with COVID-19 ARDS compared with healthy controls showed that elevated LIGHT levels were associated with COVID-19 ARDS, with a significant association between elevated LIGHT and mortality in patients ≥60 years of age. These data confirmed LIGHT as a central driver of COVID-19–related cytokine storm and a credible biomarker for COVID-19 ARDS.
We quickly mobilized to establish proof-of-concept for AVTX-002 in the treatment of cytokine storm–induced COVID-19 ARDS. In a phase 2 study of patients hospitalized with COVID-19 ARDS, treatment with AVTX-002 in addition to standard of care at the treatment site resulted in a rapid decrease in LIGHT levels and reduced risk of respiratory failure and mortality. AVTX-002 was well tolerated, with no serious adverse events.
Efficacy was greatest in patients aged ≥60 years, the population most vulnerable to severe complications and death from COVID-19 infection.