Adverum is advancing a robust pipeline of gene therapy product candidates targeting unmet medical needs in serious rare and ocular diseases.
- Product Candidate, Indication
- ADVM-043 (Rare Disease)
For the treatment of alpha-1 antitrypsin (A1AT) deficiency, we are advancing our gene therapy candidate ADVM-043 (AAVrh.10-A1AT) in the Phase 1/2 ADVANCE clinical trial. The ADVANCE trial is a multi-center, open-label, dose-escalation study. The primary endpoint is safety and tolerability and secondary endpoints include changes in plasma concentrations of both total and M-specific A1AT levels. The study will include up to 20 patients across up to four dosing cohorts of up to 5 patients each. Additional information about the ADVANCE clinical trial can be found at ClinicalTrials.gov under trial identifier number NCT02168686.
ADVM-043 is designed as a potential single-administration treatment to induce stable, long-term A1AT protein. In a preclinical proof-of-concept study, ADVM-043 demonstrated robust protein expression above therapeutic levels in mice following either intravenous (IV) or intrapleural (IP) administration. In another study in non-human primates, evidence of stable long-term expression of hA1AT mRNA was observed out to one year following IP administration of ADVM-043.
- ADVM-053 (Rare Disease)
For the treatment of hereditary angioedema (HAE), we are advancing our preclinical gene therapy product candidate ADVM-053 (AAVrh10-C1EI). ADVM-053 is designed as a potential single-administration treatment to provide sustained release of the C1 esterase inhibitor (“C1EI”) protein to eliminate protein level variability and prevent breakthrough attacks. In preclinical studies, a single intravenous administration of ADVM-053 increased C1EI protein expression above therapeutic levels.
For wet AMD, we are advancing our preclinical gene therapy product candidate ADVM-022 (AAV.7m8-aflibercept). With a proprietary vector capsid (AAV.7m8) and a proprietary expression cassette, ADMV-022 is administered as a single intravitreal injection and is designed to minimize the treatment burden of frequent injections. In preclinical studies, a single intravitreal injection of ADVM-022 showed efficacy that was comparable to the anti-VEGF standard of care.
- Product Candidate, Indication
- Up to 5 Undisclosed Targets²
IndicationInherited Retinal Disease
- AVA-311 (Ocular Disease)¹
AVA-311 is being developed for the treatment of Juvenile X-linked Retinoschisis (XLRS), an inherited retinal disease caused by mutations in the RS1 gene located on the X chromosome, therefore occurring almost exclusively in males. AVA-311 is comprised of an optimized AAV vector to deliver the RS1 gene into the eye via intravitreal injection.
In May 2014, Adverum signed a collaboration agreement with Regeneron that includes the development of AVA-311.
¹ Collaboration agreement with Regeneron Pharmaceuticals to research, develop, and commercialize gene therapy products (AVA-311 and up to 3 undisclosed targets) for ophthalmic diseases
² Collaboration agreement with Editas Medicines to explore the delivery of genome editing medicines for the treatment of inherited retinal diseases
Through directed evolution, we generate a diverse library of millions of AAV variants and subsequently screen the variants in multiple in vitro and in vivo tests to identify the optimal variant for a specific disease. Our directed evolution technology allows us to create proprietary vectors and optimize them to target cells in tissues such as different layers of the retina. Each of these cell layers constitutes a potential therapeutic target for currently unmet medical needs, providing us with multiple opportunities to apply our directed evolution technology.
Our seasoned pharmaceutical development team has decades of gene therapy manufacturing experience. Adverum’s industrialized manufacturing process—based on our proprietary baculovirus expression system—is highly efficient and scalable, with production yields up to one hundred times greater than those obtained using conventional AAV production systems.
Our process enables us to manufacture commercial grade material for diseases with large patient populations. We have performed multiple single use bioreactor production / purification runs and have the ability to make highly concentrated purified vector.
Adverum collaborates with leading biopharmaceutical companies and academic institutions to advance the potential of gene therapy for treating patients.
Our collaboration agreements with Editas leverage our AAV expertise and technologies in ophthalmic vector development and product delivery. With Editas, we are providing our AAV vectors for use with Editas’ CRISPR-based genome editing technologies to treat inherited retinal diseases. Our agreement with Regeneron provides for the development of up to eight distinct ocular therapeutic targets, four of which are already identified, including AVA-311 for the treatment of juvenile XLRS.
Our current collaborators include:
We are open to exploring additional collaboration opportunities and encourage you to contact us for more information.
- High Levels of Persistent Expression of A1-Antitrypsin Mediated by the Nonhuman Primate Serotype rh.10 Adeno-associated Virus Despite Preexisting Immunity to Common Human Adeno-associated Viruses, Mol Ther Vol. 13, No. 1, January 2006,De et al.
- Intrapleural Administration of an AAVrh.10 Vector Coding for Human a1-Antitrypsin for the Treatment of a1-Antitrypsin Deficiency, HUMAN GENE THERAPY CLINICAL DEVELOPMENT 24:161–173 (December 2013), Chiuchiolo et al.
- Perdomini, M., (2014) Prevention and Reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich’s ataxia Nature Medicine Volume 20 (Number 5, May) 542-549
- Sharpe LT, Stockman A, Jagle H, Nathans J. Opsin genes, photopigments, color vision and color blindness. In: Gegenfurtner KR, Sharpe LT (eds.) Color Vision. Cambridge UP: Cambridge, 1999.
- Perdomini et al. Nature Med, April 2014 Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich’s Ataxia