Developing gene therapies for rare diseases: an interview with Geoff MacKay

gene therapy

Geoff MacKay is currently the president and CEO of AVROBIO, a clinical-stage lentiviral gene therapy company that treats lysosomal disorders, and a board member of Talaris Therapeutics and Satellos Bioscience. He is also the founding CEO of eGenesis, a biotech that applies CRISPR-Cas9 gene editing to xenotransplantation and the former president and CEO of Organogenesis, a world-leading cell therapy company. Earlier in his career, MacKay spent 11 years at Novartis in senior leadership positions within the global transplantation and immunology franchise.

In this interview, Geoff MacKay (AVROBIO, MA, USA), discusses his extensive work in the area of clinical-stage lentiviral gene therapy to treat lysosomal disorders and what inspired him to dedicate his career to the area of cell and gene therapy. In addition to this, we hear more about the role of AVROBIO in the field and his predictions for how he envisions gene therapy technology to evolve in the future.

What first brought you to the area of cell & gene therapy?

As a consultant early in my career, I found myself with an unusual pair of assignments: half my week with the cheese division of Kraft General Foods and half with Merck. You can guess which of these I found the most inspiring! I was drawn to the potential for transforming the lives of patients through science, and that interest drove my next career move – to Sandoz, a Swiss pharma company that eventually morphed into Novartis.

Over more than a decade, I gained experience within the global Novartis organization across functions ranging from marketing to clinical research, finally taking the role of vice president of immunology and transplantation. During my tenure, we were very early pioneers in the nascent area of cell and gene therapy. Unfortunately, it was too early for Novartis, and they eventually withdrew from the space altogether. For me, however, there was no turning back. Having been exposed to the edge of innovation, I was incredibly excited about the potential I had seen and decided to persevere. I elected to orient my career toward pushing the limits of what we could accomplish for patients. I have been fortunate to have that opportunity.

You have achieved so much in your career, including your tenure at Novartis, chairman of both MassBio & The Alliance of Regenerative Medicine, the founding CEO of eGenesis & the CEO of Organogenesis. What led to your move to AVROBIO & what was your vision for the company?

I am proud of all these stops in my career and am thrilled to be at AVROBIO now.

To take you along on my journey: during my 11 years leading Organogenesis, we achieved the first regulatory approvals for cell therapy and the first commercial model for a mass-producing living cell therapy. Even today, with more than a million patients dosed, Organogenesis has treated more patients with living cell therapy than the rest of the field combined. It taught me a lot about scaling up and the commercialization of technologies using living cells.

Toward the end of my stint at Organogenesis, gene therapy was starting to deliver a critical mass of clinical validation. Multiple companies, in multiple diseases, with multiple approaches were showing potentially curative results in devastating diseases. I knew I wanted to be part of what I saw as the next major revolution in medicine. Surrounding myself with a few leading industry luminaries, we decided to build AVROBIO.

By then, I had the experience to know that manufacturing at scale was going to be a huge challenge for the field, so I made that a priority for my team from the outset. I also made sure we were focusing from day 1 on viable development programs, not just science projects. Our goal was to get medicines to patients as quickly as we could. This guided our decision to in-license-proven programs where we could take the baton from academics and move quickly into the clinic, and that is what we have done.

Our vision for AVROBIO is to bring personalized gene therapy to the world. With multiple programs potentially slated to enter registration trials next year, we are excited to be moving towards that goal.

How would you summarize the role of AVROBIO in the field of cell & gene therapy?

AVROBIO is a leader in lentiviral gene therapy. It is a proven approach with broad utility across the industry and is further supported by our growing clinical dataset.

We have been champions of lentiviral gene therapy because we believe it is the most effective way to provide durable, ‘head-to-toe’ treatment for patients, as lentiviral gene therapy is expected to integrate and deliver the therapeutic gene to both the body and the brain. Our focus has been on a family of diseases – lysosomal disorders – that frequently have a devastating breadth of impact across both the CNS and organs throughout the body. These are patients who need that ‘head-to-toe’ approach.

We believe we have the largest pipeline of investigational gene therapies for lysosomal disorders. We are developing the first gene therapies in the world for Fabry disease, cystinosis and Gaucher disease type 1, all of which are in the clinic. We are planning to have the first lentiviral gene therapies in the clinic for several other indications next year.

As I mentioned, one of the things we have been most focused on has been developing the ability to scale worldwide. To advance that goal, we have pioneered an industry-leading gene therapy platform called plato® that incorporates several advanced technologies, including automated manufacturing.

We know that a single gene can change someone’s life dramatically, for better or for worse. We are working to bring therapeutic genes to people living with lysosomal disorders around the world so we can change their lives for the better.

How do you envision gene therapy technology will evolve in the future?

From a clinical perspective, I think we will generally see gene therapy moving into younger patients, with the goal of addressing genetic disease as early as possible to prevent long-term damage. This will be particularly urgent in diseases with a major neurological component, as protecting the developing brain may be key to enhancing long-term outcomes. Advances in newborn genetic screening certainly help to enable this to become a reality.

We are also already witnessing multiple development programs moving into larger populations targeting areas such as cardiovascular disease. From a technology perspective, polygenic disease will be the next frontier to tackle. This modality has enormous potential that we are just starting to realize. When I entered this field, gene therapy conferences felt like support groups for a handful of true believers. Now, big pharma, biotech and investors alike are aligned around driving this field forward. In a few short years, I believe gene therapy could be mainstream medicine for the many people who need it – and that is the most exciting thought of all.

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The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of RegMedNet or Future Science Group.