re: Generation

March 17, 2021

Toward a new paradigm in treatment for hemophilia A

A CONVERSATION WITH OUR CHIEF MEDICAL OFFICER DOUG KERR, MD, PHD, MBA

In March we recognize Bleeding Disorders Awareness Month and the communities affected by these conditions, including hemophilia. As we continue to advance our efforts toward a durable, redosable gene therapy for hemophilia A, we reflect on how we hope to serve these communities.

As part of this, we spoke with Doug Kerr, chief medical officer of Generation Bio, about his vision of a new paradigm in treatment for hemophilia.

What brought you to Generation Bio?

As a clinician and scientist, my whole career has been centered around genetic disease. I was working in this space, including working on AAV gene therapy programs, and increasingly began to see the limitations of current approaches, like the inability to deliver large genes or redose, to name a few. I knew there needed to be a better way.

At Generation Bio I saw the opportunity to invent that new way. I really saw this as an opportunity to build upon AAV gene therapy and impact more patients more completely. Generation Bio is working towards a platform with so much potential: You could re-dose at the outset of therapy to calibrate the expression level for each patient, re-dose with the same medicine in the future if needed, and scale up to treat not just rare, but also common diseases all around the world. I joined the team as one of the earliest employees to help advance the science so we could move toward treating people.

Our work aims to change the way we treat genetic disease entirely. It’s a revolutionary vision for people living with hemophilia and those living with many other rare and prevalent genetic diseases.

My own role at the company has evolved as our research has advanced. I joined as chief scientific officer, moved to chief development officer when our programs matured into the translational phase, and recently took on role of chief medical officer as we prepare to enter the clinic.

What do you think are some of the biggest challenges in the current hemophilia treatment landscape?

I have to first say that the field has come a long way towards developing a disease-modifying treatment, and the outlook for hemophilia patients is far better than it used to be – but there is a long road ahead.

Individuals with hemophilia are burdened with the need for regular infusions. There are now long-acting factors, but they still have to be administered two to three times a week, which means that people with hemophilia can never forget about their disease. It’s always on their minds.

I’ve also heard feedback from the community that there’s a lot of frustration about the one-size-fits-all nature of current gene therapy approaches. Every patient has a different need, based on his or her activity level, tolerance for risk and other factors. Yet you can’t customize the current treatments to individual needs.

Another challenge is getting treatment to those who need it. In fact, approximately 75% of hemophilia A patients worldwide still receive inadequate treatment or have no access to treatment at all.

This is a major reason why hemophilia A is our lead program. We believe this is an opportunity to really make a difference in the lives of patients. Our goals are to free them from a lifetime of chronic treatment and to deliver a lifetime of protection from bleeds.

How does Generation Bio aim to overcome these challenges in hemophilia treatment?

Our goal is to develop a treatment that will allow patients to live their lives and forget about the disease in a way that they currently cannot.

To do this, we’re developing a non-viral gene therapy for hemophilia A that is designed to be titratable, durable and redosable, if needed. Our platform uses a construct called closed-ended DNA, or ceDNA, to hold a functional factor VIII gene, and we plan to deliver this to a patient’s cells using cell targeted lipid nanoparticles, or ctLNPs.

Because our delivery system is non-viral, we believe we will be able to titrate patients to the most effective dose for them, based on the level that they and their doctor think is appropriate. We also believe we will be able to treat very young children at the onset of disease, and redose if needed years later. And the non-viral approach means we don’t have to exclude people with pre-existing antibodies to AAV vectors. This means more people can receive the care they need, even if they have previously been treated with an AAV gene therapy.

On a larger scale, our platform is able to be manufactured using existing biologics infrastructure – requiring significantly fewer resources than are needed to produce AAV gene therapy. Our hope is that this scalable manufacturing process will enable broader access to these potentially life-changing therapies.

What do you want the hemophilia community to know about Generation Bio’s efforts to develop a treatment?

I would say that the community should know that we want to partner with them, learn from them and make sure their voice is present in everything we do in the field.

As chief medical officer, what I most look forward to is learning directly from the hemophilia community – individuals, families, advocacy groups and physicians – and ensuring these perspectives inform our work.

We’ve begun these important conversations with the patient community and their insights are shaping our next generation of therapies. What we’ve learned so far is that individualization, safety and predictable, long-lasting protection are some of the most important areas of focus. We believe it’s important for patients to be able to maintain their factor VIII at the levels they feel most comfortable with to best fit their lifestyle.

Above all, safety is key – the community needs to know how seriously we take safety as well as transparency in our information about our potential therapies.

I would also highlight that we’ve made important and exciting progress toward bringing a potential therapy into the clinic. In January, we announced two milestone achievements for non-viral gene therapy: target levels of factor VIII expression in mouse models of hemophilia A and translation of expression to non-human primates. These data show us we’re on the right track. Our hope is to begin clinical trials in 2022.

We are working hard to create a future without fear of bleeds, without chronic treatment and without the shadow of the disease hanging over every family living with hemophilia. Someday in the near future, I hope to recognize Bleeding Disorders Awareness Month at a time when there are treatments available to families around the world that allow them to forget, for years on end, that they have hemophilia.

 

Safe Harbor Statement: Any statements in this Blog about our future expectations, plans and prospects, including statements relating to about our strategic plans or objectives, our technology platforms, our research and clinical development plans, and other statements containing the words “believes,” “anticipates,” “plans,” “expects,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the conduct of research activities; the initiation and completion of preclinical studies and clinical trials and clinical development of any product candidates; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; expectations for regulatory approvals to conduct trials or to market products; challenges in the manufacture of genetic medicine products; our ability to obtain sufficient cash resources to fund our foreseeable and unforeseeable operating expenses and capital expenditure requirements; and the impact of the COVID-19 pandemic on our business and operations; as well as the other risks and uncertainties set forth in the “Risk Factors” section of our annual report on Form 10-K, as updated by our most recent quarterly report on Form 10-Q, which are on file with the Securities and Exchange Commission, and in any subsequent filings we may make with the Securities and Exchange Commission. In addition, the forward-looking statements included in this Blog represent our views as of the date hereof. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date on which they were made.

Take a seat at the table.

We are always looking for those who are ready to share their vision, talent, and tenacity—who believe in our mission and themselves.

Imagine a world without genetic disease.

What do you see? More health? Fewer doctor appointments? More bike riding? More peanut butter and jelly sandwiches? More life?
See our shared vision.
cross