OUR VIEWS Ideas & Insights

2021 Annual Report: CEO Geoff MacKay on how gene therapy’s promise propels us forward

Former President & CEO

Geoff MacKay | Former President & CEO

2021 challenged us all in many ways. As successive waves of SARS-CoV2 variants swept around the globe, we saw a monumental scientific achievement in our industry – the development and distribution of a completely new vaccine – accompanied by various failures and missteps that undermined progress against the pandemic. It was an imperfect and at times messy path, but as a society in 2022, we’re taking our first tentative steps into the post-pandemic era.

The gene therapy industry overall similarly faced challenges in 2021, touching on safety, manufacturing, regulatory and commercialization issues. AVROBIO has not been immune; we recently deprioritized our Fabry disease program due to several factors, including emerging clinical data suggesting variable engraftment coupled with challenging market and regulatory dynamics. While a very difficult decision because of its impact on the patients and families we aim to serve, we believe it was the right step forward for AVROBIO and our stockholders. We have reduced our headcount and streamlined our operations as we aim to extend our cash runway into the first quarter of 2024 to support development of multiple important, and what we believe will be value-driving, clinical programs.

While we have faced headwinds recently, we remain excited about the fundamental promise of our gene therapy. With the steady progress we’ve made across our clinical programs in cystinosis and Gaucher disease type 1, and the path we’ve charted in 2022 as we seek to move multiple programs into late-stage trials, we see great opportunities to move toward our goal of helping free people with lysosomal disorders from disease progression, painful and debilitating symptoms and the burden of chronic treatment regimens. Additionally, in 2021, we received Rare Pediatric Disease Designation for AVR-RD-05, our gene therapy for the treatment of mucopolysaccharidosis type II (MPSII) or Hunter syndrome, a rare and seriously debilitating lysosomal disorder that primarily affects young boys; as well as received Fast Track Designation from the  U.S. Food and Drug Administration and Orphan Drug Designation from the European Commission (EC) for AVR-RD-04, the company’s investigational gene therapy for the treatment of cystinosis. Both of AVROBIO’s investigational gene therapies in the clinic have received Orphan Disease Designations from FDA and EC.

We were also proud to see our industry-leading gene therapy platform, plato®, recognized as the 2021 Technology Innovation winner of the Fierce Innovation Awards: Life Sciences Edition.

So far this year, we reported interim data from the collaborator-sponsored, ongoing Phase 1/2 clinical trial[i] of AVR-RD-04, an investigational gene therapy for cystinosis at the WORLDSymposium® 2022 held in February. This devastating disease causes severe visual impairment, a dramatically shortened lifespan and a kidney transplant in 90% of patients – even on today’s standard of care. The first three patients infused with AVR-RD-04 remain off oral cysteamine, with follow-up durations ranging between 12- and 26-months post-gene therapy infusion. Sustained engraftment, demonstrated by stable vector copy number (VCN) levels, has been observed in each of these patients. A fourth patient was infused in November 2021. No adverse events related to the drug product have been reported in the four patients infused through the most recent safety cut-off date of Dec. 1, 2021.

We strengthened our crew at AVROBIO, including the appointment of three new leaders, including

  • Essra Ridha, M.D., MRCP, FFPM, was named chief medical officer in October 2021. She was previously clinical development lead at AVROBIO and has extensive experience in cell and gene therapy development gained at Sangamo Therapeutics and GlaxoSmithKline.
  • Azadeh Golipour, Ph.D., was named chief technology officer in January 2022. She has filled multiple roles with increasing responsibility during her five-year career at AVROBIO.
  • Sean O’Bryan, was named chief regulatory officer in February 2022. He brings a wealth of experience in regulatory strategy and product development for cell and gene therapies.

Later this year, we anticipate providing a clinical update for our Gaucher disease type 1 program, including data on the first patient who is now more than 18 months post-infusion. We intend to engage with regulatory agencies on the initiation of clinical trials for cystinosis and Gaucher disease type 3 planned to commence in 2023. Additionally, we expect to advance our preclinical programs for Hunter syndrome and Pompe disease by initiating clinical trials in 2023 and to strengthen our industry-leading gene therapy platform, plato®, to ensure that our manufacturing, delivery and analytics are Phase 3 ready.

We’re excited about the many catalysts ahead, and confident that we can meet the various challenges of delivering an investigational therapy to the people who need it. The needs of the lysosomal disorder community we aim to serve are pressing, and the AVROBIO crew works with urgency every day to advance our work and move closer to realizing our vision of freeing people from a lifetime of genetic disease.

Read more about our 2021 performance in the Annual Report. We look forward to updating you on our progress as 2022 unfolds.

[i] Collaborator-sponsored Phase 1/2 clinical trial of AVR-RD-04 is funded in part by grants to University of California San Diego from the California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation (CRF) and National Institutes of Health (NIH)