Avrobio has filed for an $86.25 million IPO. The offering would give the Atlas Venture-backed startup the means to run clinical trials of gene therapies designed to supplant enzyme replacement therapies from Sanofi, Shire and Pfizer.
Cambridge, Massachusetts-based Avrobio’s approach entails taking hematopoietic stem cells from patients and using lentiviral vectors to insert a copy of the gene that is defective in the target disease. Patients then undergo a conditioning regimen—which Avrobio thinks is milder than that used by other ex vivo lentiviral-based gene therapies—before receiving a shot of the gene therapy to induce lasting production of the enzyme behind their condition.
Avrobio is using the approach to treat lysosomal storage diseases, a group of indications in which the efficacy of replacing missing enzymes is proven. Today, patients with Fabry disease—Avrobio’s top target—receive frequent, multi-hour infusions of enzyme replacement therapies made by Sanofi and Shire. Avrobio wants to replace these infusions with a one-time gene therapy that equips the body to make the missing enzyme.
The startup is still some way from showing it can deliver on this potential and unseat the incumbents. Two patients have received AVR-RD-01, the Fabry disease gene therapy. Levels of the enzyme alpha-galactosidase A began to rise days after receiving the therapy and remain elevated as much as 12 months later. The AGA level of the patient with 12 months of follow-up has fallen over the past six months but is still above that seen in men with classic Fabry disease.
With the trial yet to see any serious adverse events linked to the treatment, Avrobio is preparing to move the lead candidate into a larger phase 2 trial. The multinational study will enroll eight to 12 treatment-naïve patients, give them a single dose of AVR-RD-01 and track them for 48 weeks. Avrobio will transition to a new lentiviral vector designed to boost efficacy during the phase 2 trial.
Avrobio expects to get the phase 2 trial underway around the middle of this year. Beyond that, the biotech is eyeing phase 1/2 trials of gene therapies against Gaucher disease and cystinosis. Dosing of the first patients in those trials is penciled in for next year.
Private investments from Atlas, Clarius Life Sciences, SV Life Sciences and others left Avrobio with $58 million in cash and equivalents as of the end of March. The addition of IPO monies would set Avrobio up to initiate the aforementioned trials while also moving a Pompe disease prospect through preclinical development.
In turning to public investors to fund the work, Avrobio has joined a clutch of gene therapy startups seeking to ride the wave of positive sentiment sparked by Novartis’ $8.7 billion takeover of Avexis and Spark Therapeutics’ landmark approval. This year, Homology Medicine, Rocket Pharmaceuticals and Solid Biosciences have bolstered the ranks of public gene therapy biotechs. MeiraGTx and Avrobio have filed the paperwork to join them.