Sarah, you have a long and successful career in the life sciences industry. What specifically led you to Avidity in 2019?
I was drawn to Avidity in 2019 primarily because it presented a unique confluence of my expertise in RNA technologies, company-building experience, and a deep-rooted passion for addressing rare diseases. The opportunity to contribute to the development of potentially transformative treatments for patients with rare diseases, many of whom had never been treated before, was compelling. My first interaction with the Avidity team, particularly the Chief Scientific Officer, Dr. Art Levin, deepened my interest as we discussed the scientific possibilities. I was all-in after understanding the innovative science and realizing the broad potential of our proprietary Antibody Oligonucleotide Conjugates (AOC) technology platform.
Can you explain what makes your new class of RNA therapeutics, the Antibody Oligonucleotide Conjugates (AOC), so special?
Our AOC technology is a groundbreaking advancement for the RNA field developed by our team in San Diego. It addresses a significant challenge: delivering RNA therapeutics to tissues and cells beyond the liver, a feat previously thought to be unachievable. We were the first to demonstrate the targeted delivery of RNA to muscle – a revolutionary advancement in the field of RNA therapeutics. Our AOC platform has significant potential to target a variety of diseases at their root cause, including those affecting the heart and immune cells, which have previously been untreatable. By conjugating siRNA to an antibody that serves as a delivery vehicle, we have pioneered a method to target muscle cells and beyond with precision. Which positions us at the forefront of the RNA field.
RNA acts as the crucial messenger between DNA and the protein production process in our bodies, serving a role analogous to a postal service. Our approach involves intervening in this 'postal service' to prevent the production of proteins that should not be produced, without altering the DNA itself. This method effectively cuts off the faulty instructions at their source. We utilize AOCs where we attach our therapeutic RNA to an antibody. This antibody then targets specific receptors on cells, akin to the muscle cells with transferrin receptors, ensuring the precise delivery of RNA into the cells. The process can be likened to passengers boarding a "magic school bus" — the antibody — which then transports them directly to their required destination within the body, illustrating our biological approach's logical and targeted nature.
What prompted Avidity to focus on muscle-related and rare diseases?
Our focus on muscle-related diseases stems from our discovery that the transferrin receptor type 1 is highly effective in targeting muscle cells, including in the heart. As for our emphasis on rare diseases, it is driven by our ability to precisely target the genetic roots of these conditions using our RNA technology. This area represents a realm of high unmet need, with our efforts concentrated on diseases that currently have limited or no approved therapies available. We are committed to pioneering treatments for people living with devastating diseases who have had no alternatives, aiming to profoundly improve their lives.
We currently have three clinical-stage programs in three distinct rare muscle diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy amenable to exon 44 skipping (DMD44) and facioscapulohumeral muscular dystrophy (FSHD). We are also advancing preclinical programs to address additional DMD, rare skeletal muscle, and rare precision cardiology programs. We continue to broaden our reach of AOCs in other indications including cardiology and immunology through partnerships.
What is the place for partnership in your strategy of addressing these diseases?
We are intent on developing and commercializing treatments for rare diseases independently while collaborating with partners like Eli Lilly and Bristol Myers Squibb for broader patient populations, including cardiology and immunology. Our partnership with BMS in cardiology, underscores our dedication to leveraging our platform across a spectrum of diseases. Our blended approach of in-house discovery and key partnerships enables us to maintain a focus on rare diseases, where the need is greatest, while also exploring opportunities to address more common conditions through strategic collaborations.
How does Avidity manage to overcome the inherent challenges that are associated with rare disease therapeutics when it comes to business viability?
Despite the inherent business challenges of focusing on rare diseases, my extensive global leadership experience in launching therapies in this space has proven that it is not only viable but also profoundly impactful. The key is developing treatments that offer significant benefits, thereby creating a strong health economic argument for their value.
Our strategy revolves around making a substantial difference in the lives of people living with rare diseases, which, in turn, supports a solid business rationale for our focus.
What can we expect from Avidity in the coming year, and what underpinned last year’s success for the company?
This year is pivotal for Avidity. In March of this year, we reported positive long-term data from our MARINA open-label extension (MARINA-OLE) study showing reversal of disease progression in people living with myotonic dystrophy type 1 (DM1) across multiple endpoints including vHOT, muscle strength and activities of daily living when compared to END-DM1 natural history data. These endpoints are the same key endpoints that will be used in the global Phase 3 HARBOR trial for DM1 that we are planning to initiate in the second quarter of 2024.
We are also planning to share data from significant clinical readouts from our DMD44 and FSHD clinical programs.
Launching a Phase 3 trial in a rare disease setting, especially for myotonic dystrophy, is undeniably a significant milestone, accompanied by its own set of challenges, notably in patient recruitment on a global scale. However, our confidence in moving forward at full steam is bolstered by extensive preparatory work, including site selection and deep regulatory engagements regarding the trial design. The myotonic dystrophy patient community's strong organization and eagerness, combined with the fact that we are the only company initiating Phase 3 studies in the US for this disease, further amplify our optimism.
Last year, despite industry-wide challenges, our success was driven by our robust financial position, strategic partnerships, and breakthroughs in our lead program in DM1, which demonstrated promising functional changes early in clinical trials. These achievements, coupled with investor recognition of our potential to create value in rare diseases, contributed to our success. We are in a strong financial position, which includes a recent financing of approximately $400 million, providing a cash runway into late 2026.
What is your outlook on the biotech sector? Is this a promising time for investors to bet on the industry?
The biotech sector is on the cusp of a recovery, fueled by continuous innovation and positive developments across the industry, including M&A activities and breakthrough clinical results. The challenges of the past few years, accentuated by the COVID-19 pandemic, have led to a more discerning investment landscape, yet the advances in targeting previously untreatable diseases signal an exciting era for biotech. This context, combined with our achievements and strategic direction, underscores the potential for significant advancements and investment opportunities in the sector.
Where do you see Avidity five years from now?
Looking ahead, I envision Avidity as a transformative force in the lives of people affected by rare and previously untreatable diseases. Our aim is to achieve significant milestones in the skeletal muscle space and pioneer precision cardiology programs as well as expand the possibilities of our AOC technology platform to broader indications. We are committed to pushing the boundaries of RNA delivery technology further, addressing a broader range of diseases and continuing to lead in the development of groundbreaking therapies. Our goal is to profoundly impact healthcare and patient lives, marking a new era in the treatment of rare diseases.
