Excision BioTherapeutics’ founding scientists found a way to use gene editing CRISPR technology to remove the source of viral infections – the DNA – with the potential for a one-time administration cure for infectious diseases.
For decades, researchers have tried to inactivate viral DNA without success. A primary reason for these failures is that when researchers made only a single cut in viral DNA, the viral genes mutated to overcome the edits. Once Jennifer Doudna published the first paper on CRISPR biology, which eventually earned her the Nobel Prize in Chemistry, Kamel Khalili and his team applied the technology to target viral DNA with multiple cuts to remove large sections of viral genomes. Deleting these large sections of DNA, or “excisions”, were the essential innovation to successfully inactivate the viral DNA.
Since these discoveries, Excision scientists evolved the original discoveries, maximized the safety and efficacy of the approach, advanced the pipeline through preclinical development, and progressed the lead candidate into FDA-cleared human clinical trial. Excision researchers and bioinformaticians further developed novel approaches and unique software to design therapeutics that are highly efficient at cutting viral DNA only, without detecting any cuts in human DNA. Fundamentally, this approach of targeting viral DNA while protecting and preserving human DNA allowed Excision’s development scientists to produce therapeutic candidates which have been shown to be safe and effective in preclinical studies.
Excision’s most advanced product candidate is EBT-101, a potential one-time therapy to cure HIV.
In addition, Excision is developing therapeutics to potentially cure Hepatitis B, Herpes Virus, and JC Virus, which is the cause of the rare, fatal, brain disorder PML. The incidence and prevalence of these indications are atypical for gene therapeutics. Hepatitis B, as an example, has infected approximately one million individuals in the United States, more than 1.2 million in Europe, and as many as 350 million worldwide.
As the company grows, our team looks forward to using the Excision platform to expand the pipeline to treat additional viral infections.
Our vision for Excision hasn't changed. Our original vision was to cure people of viral infectious diseases by meeting two challenges.
The first is to apply aspects of biology and technology which were not commonly connected, bringing together biotech and pharmaceutical research with the diverse experience and expertise of multiple individuals at the tops of their fields. I have assembled a diverse team that is collaborating to advance therapies through development, manufacturing, clinical development, and commercialization.
This is truly one of my favorite aspects about biotech and pharmaceutical research - the diversity of expertise required to bring a product to patients. Put simply, no one can do it alone. Multiple individuals, at the tops of their fields, with highly diverse experience and expertise, need to closely collaborate to advance therapies through development, manufacturing, clinical development, and commercialization.
And second, we knew there would be a fundamentally important patient and physician aspect to successful development. This is one of the reasons Excision has proactively connected with and sought feedback from HIV/AIDS community advocates. Their engagement, partnership, and thoughtful guidance has been invaluable.
What has evolved is how we are building the pipeline and the tools to develop new therapeutics. Excision’s team has developed and continues to advance approaches and a platform in multiple areas. For example, the innovations in therapeutic designs, testing (assay) technologies, informatics approaches, proprietary software, manufacturing approaches, and others - all facilitate and enable the other areas. It’s a thrilling scientific network effect that is helping to speed Excision’s products to market.
The entire team at Excision shares a passion for work which is larger than any one of us or even the company itself. Our focus is on the millions of people around the world who deserve cures for their diseases.
I have always had a passion for both science and how scientific management can either facilitate or hinder innovation. After receiving degrees in genetics and English from Cornell, and a masters in Medical and Health Communication at Tufts University School of Medicine and Emerson College, I sought out and wanted to work for Genzyme. I was lucky enough to join the company as Henri Termeer was building such a special organization. I was able to work with multiple divisions including those advancing novel approaches and delivery technologies for gene and cell therapies.
Following my MBA at Harvard, I joined Genentech to help develop their commercial oncology portfolio. I then spent time in commercial strategy, led sales teams, and business development at smaller biotechnology companies. I later joined Novartis and led commercial sales in the Western US and Latin America for infectious disease products including HIV, Hepatitis C, and Hepatitis B.
I feel very fortunate that I have been able to assemble a team at Excision where we get to combine experience in the sciences of gene therapy, infectious disease therapy, and building successful companies.
My inspiration is derived from people. I am lucky to have the chance to hopefully help individuals living with debilitating diseases. At Excision, similar to companies I worked with previously, we have received letters from patients explaining the devastation of their ailments and thanking us for developing therapeutics which might cure them. We often de-identify these letters and discuss them as a team. These first-person accounts serve as monuments of inspiration to guide the long work hours into evenings and weekends. I think the entire team here at Excision shares a passion for work which is larger than any one of us or even the company itself. Our focus is on the millions of people around the world who deserve cures for their diseases.
In addition, I am inspired by the incredible team at Excision. We are a group with highly diverse backgrounds, ethnicities, home countries, interests, and expertise (we sometimes joke that the only thing we all agree on is the importance of good food). While we may vehemently challenge opinions and assumptions, we know that the data-driven conclusions improve outcomes beyond what we could have developed as individuals.
One exciting and challenging aspect at Excision (as with many startups) is that we are focused on – and are steadily accomplishing – things that have not been achieved before. This focus on the unprecedented is both a challenge and an inspiration. When Excision’s technology became the first to remove HIV genomes from animals and generate cures, almost by definition, there were people skeptical that we could achieve our goals of translating this to humans. Evidence-based scientists and physicians rightly demand rigorous science and we’ve been fortunate to have the team, investors, and resources to prove our technology.
Three lessons have been particularly useful to what we have achieved at Excision and might translate to other startup leaders. First, build a team and a support network who are deeply passionate about your vision and take the time to understand the business. Our best partners – employees, investors, research collaborators, or others – are those who have studied our business in significant detail to assess what can be possible and how we can prove each remaining technical or commercial question. I believe everyone involved with Excision has come together because we want to do something groundbreaking that can benefit so many.
Second, there are many elements to finding creative solutions to challenges. The key is to identify each one, then prioritize them. Although it's important to clarify each one, not all are equally important. Focus on the most critical.
And third, be patient and pragmatic as you work through the chain of critical elements. It is a daily balance to achieve a step-wise approach to successfully turn new ideas into products.
Investors are an invaluable part of early-stage companies in many ways that are not purely financial. Those that have a genuine passion for the promise of success and are willing to help in different ways are some of the most powerful elements supporting companies.
Some investors primarily help with significant financial support. Others are instrumental in making introductions and connections to key individuals. Others have brought invaluable insights from other disciplines and companies to help shape domestic and international strategies. Others add patient perspectives to help refine product or development strategies. Just as our management team values diversity of background and opinions, we also value diversity from our investors.
We often say that in biotech, companies can never have enough “friends.” What we mean is that the more diverse and experienced the network of individuals involved, the more successful a company will be. Small companies have very limited resources and therefore are unable to hire as many people as might be necessary to achieve all of their objectives. However, diverse investor networks can often contribute key ideas and leads to opportunities. Such connections can identify new development partnerships, funding opportunities, government collaborations, manufacturing options and sites, commercial opportunities, or other solutions to development challenges - any of which can lead to successful products and enhance enterprise value. Just as we value a diversity of background and opinions in our management and technical team, a similar diversity can be useful among our investors.