Most of our Retina Conversations to date have been with doctors and researchers, but future advances in therapy for retinal diseases largely depend on the efforts of the numerous companies pursuing novel investigational concepts that entail large financial requirements and great execution risk.

Leone Patterson, BS, MBA, is CEO and president of Adverum Biopharmaceuticals, a US gene-therapy company advancing the concept of producing continuous gene-derived anti-VEGF therapy in the eye itself. The company’s investigational gene therapy, ADVM-022 has now moved into the phase 1 OPTIC trial for wet AMD.

Ms. Patterson took time to sit down with Retinal Physician to discuss the all-important and challenging business and management responsibilities of leading an investigational drug company that can spell the difference between success and failure.

Q. Can you give us some insight into your education and business background?

A. I grew up in New Zealand and moved to the United States where I attended Chapman University in Southern California for my undergrad. I later decided to pursue my Executive MBA at St. Mary’s College to be better prepared for more senior management opportunities that I was starting to encounter. The earlier part of my career was at global professional services firm KPMG, where I had the opportunity to work with multiple public health care companies.

After partnering externally with these firms and building an understanding of the industry, I became inspired to take on more active internal roles within public companies in health care that were developing novel medicines to more directly help patients and eventually lead teams of dedicated professionals with my similar passion.

I have been fortunate to work with some prominent pharma and biotech companies, including Novartis, Chiron, Exelixis, and now Adverum. I joined Adverum in 2016 as I saw the field of gene therapy gaining significant traction, and it has been exciting to work with some of the best in this field.

Q. Many of our readers may remember Adverum from its early Avalanche days. Since then, there’s been a major merger and an exciting new drug development initiative that’s about to enter clinical trials. Could you bring us up to date on company developments?

A. Adverum was established following the merger of Avalanche with Annapurna in 2016, creating a strong combined company. Avalanche brought industry-leading AAV vector development, including design and clinical applications. They also brought process development and manufacturing capabilities as well as ocular gene-therapy expertise. Annapurna brought a diverse pipeline of gene therapy product candidates in rare diseases. The combination provides the potential for what we believe is a meaningful and robust pipeline that can address multiple patient needs, including multiple novel gene therapy programs targeting wet AMD, A1AT deficiency, and hereditary angioedema (HAE), as well as other programs.

Q. Have you had any important mentors in your business career? How have they helped you be a better leader?

A. I believe my mentors from both business and sports have helped me become a better leader. In business, I have worked alongside some inspiring leaders who have served as my mentors over the years. At Novartis, Joerg Reinhardt (now chairman of Novartis), and George Scangos at Exelixis really were great role models for leadership.

I’ve also had mentors in sports, as I used to play basketball and was part of New Zealand’s national team in the 2000 Summer Olympics. Through practice and competition, I learned valuable lessons from coaches and teammates that I can apply to my professional career. First, I think it is important to lead by example and lead with intent. I also look for team players who can challenge the status quo with a natural curiosity and have a positive attitude. I will work just as hard as the rest of the team to execute our plans to succeed and bring solutions to patients. I am unfazed by unexpected challenges and I seize the opportunity to celebrate the team’s success.

Q. What are the major challenges for Adverum on the business side?

A. I think for most companies developing gene therapies, manufacturing can present a challenge as the therapies advance into larger, late-stage clinical trials. We like to think ahead at Adverum and want to be prepared in advance to conduct pivotal phase 3 clinical trials as well as to launch commercial product once approved. To do this, we have recently signed a 10-year lease on a new facility based in Redwood City, California, which we plan to occupy in the second half of 2019. This facility expands our manufacturing capabilities, enabling us to scale up our manufacturing process at the 2000-liter scale, as well as offering us the opportunity for future cGMP manufacturing of our clinical trial material.

Q. What steps have you taken to ensure adequate financing for your business initiatives?

A. Having a strong cash position is critical for a biotechnology company to execute clinical and regulatory plans for new therapies. Our most recently reported cash position was approximately $235 million at June 30, 2018, which included a $64 million equity raise in February 2018. Our cash is expected to be sufficient to fund our 3 lead programs into 2020, including preliminary clinical data for at least 2 of these programs, and through the initial stage of scaling up manufacturing capabilities.

Q. For a relatively small drug development company, what criteria do you use in prioritizing potential drug development initiatives?

A. In prioritizing our gene-therapy development initiatives, we first assess whether it has the potential to improve a patient’s quality of life, then a few examples of other factors may be to look at the set of preclinical data generated to date, the clinical and regulatory path to support FDA approval, and the current and future potential competitive landscape for disease treatment and whether or not we can be differentiated. We are focusing our efforts on our 3 lead gene therapy programs, in wet AMD, A1AT deficiency, and HAE. These are the programs that, to date, have generated the most compelling set of preclinical data and have defined clinical development paths that our team can execute to bring a novel gene therapy approach to patients.

Q. Long-term efficacy data on ADVM-022 in nonhuman primates were presented in 2018. What do you believe are the most interesting data from these studies? What feedback did you receive from physicians following the presentation of these data?

A. We presented the data at the American Society of Gene & Cell Therapy annual meeting in May 2018. Physicians called the new data “unprecedented” and were very excited by the long-term efficacy following a single intravitreal injection of ADVM-022. To summarize, the long-term efficacy of ADVM-022 at 13 months following a single intravitreal injection was consistent with earlier reported data, showing this gene therapy was safe and statistically significant (P<.0001) in preventing the development of grade 4 lesions compared to the vehicle control group.

This therapy induced long-term efficacy at 13 months that was comparable/identical to aflibercept, an anti-VEGF standard-of-care therapy, delivered at time of lasering. The intraocular expression of aflibercept was sustained for up to 16 months. Robust levels of aflibercept protein were detected up to 16 months in aqueous and vitreous humor and, more importantly, in retina and choroid tissues, where neovascularization occurs in wet AMD. For safety, ADVM-022 was well tolerated, with no serious adverse events.

Q. What are the next steps for the ADVM-022 gene therapy program?

A. We recently announced an active Investigational New Drug (IND) for ADVM-022 and a Fast Track designation. We are excited to be moving this program toward clinical development in patients, and we expect to initiate the phase 1 in the fourth quarter of 2018. ADVM-022 is designed to provide sustained expression of those same anti-VEGF proteins after just a single intravitreal injection, which would eliminate the need for frequent injections and burdensome office visits.

Q. Given the cost of developing and commercializing a new drug concept, would Adverum be open to having a partner on ADVM-022?

A. While our wet AMD program is generating more partnering interest given the recently presented long-term efficacy and safety data from ADVM-022 and the market opportunity, we have the expertise and cash to advance our gene therapy programs ourselves and we are currently focused on executing our development plans.

Q. What do you see as the long-term prospects for gene therapy in the ophthalmic arena?

A. Gene therapy is a promising treatment for ocular disease in particular because of structural and functional properties of the eye. Because the eye is a relatively self-limiting organ, gene therapy can be delivered locally to the eye, reducing systemic exposure. Recently, we saw the approval of the first gene therapy for a genetic disease and first AAV-based gene therapy approved in the United States. We hope to see many more successful applications of gene therapies to come, where restoration of gene or protein expression leads to significant improvement in symptoms for patients living with ophthalmic disease. RP