Cytokinetics is a  biopharma company developing therapies for muscle-related diseases.

Robert, what made you join Cytokinetics in 1998 and, importantly, what made you stay for so long?

When I joined Cytokinetics, the company was an abstract concept without committed funding, employees, or operations. The founders, leading scientists in their fields, admittedly lacked business experience but had an extraordinary vision for the biology, which is where I came in. My role was to bring business acumen and planning, raise capital, and operationalize their vision, marking the true beginnings of the company. My decision to join was profoundly influenced by the founders' foresight for the science and their collaborative spirit. They aimed to advance their more basic science through pharmaceutical applications at the company, focusing on industrializing their academic achievements without competing interests. Their approach, envisioning the company as a vehicle for scientific progress, and their continued collaborative involvement as advisors, greatly contributed to my long-term commitment.

What were the initial goals of the company? How have they evolved over time?

Initially, our science was rooted more broadly around the cytoskeleton, leading us into anti-cancer research. However, we discovered new methods for modulating muscle bio-machinery, mechanics and contractility, which catalyzed a more heightened focus towards muscle biology, particularly targeting diseases associated with muscle dysfunction and weakness. This strategic pivot prioritized muscle biology over oncology. Our pioneering focus to muscle biology was unique, as no other company then had made muscle its anchor biological platform. We aimed to be at the forefront of developing novel therapies for muscle-related diseases, driven by the aging demographic trends.

Despite a broader interest in muscle disease from other companies focusing on diabetes and metabolic syndromes, none had explicitly targeted muscle as a primary area for innovative therapeutic development.

Our early dedication to muscle biology positioned us as leaders in this emerging pharmacology. Our strategic focus enabled us to be well positioned as a partner of choice to companies focused to clinical indications adjacent to our own commitments.

Has the current focus on cardiac muscle been a constant for Cytokinetics?

While our pipeline focus is predominantly on cardiac muscle enabling foundation for our specialty cardiology business ambitions, our research extends beyond the heart to also include skeletal muscle. Our journey into cardiology is both a part of our history and a commitment to our future, but has been accompanied by flexible pivots over the years between cardiology and neuromuscular research as flexed with scientific discoveries and challenges we encountered, particularly with developing a potential new medicine for ALS. Our strategy involves balancing groundbreaking activities and leadership in areas of high unmet medical needs, not strictly dictated by business strategy but by where our scientific discoveries lead us to the benefit of patients and their caregivers who depend on us.

Can you discuss what follows after aficamten’s good Phase 3 results for the treatment of obstructive hypertrophic cardiomyopathy? Relatedly, what is aficamten’s position relative to Bristol Myers Squibb’s treatment?

Aficamten demonstrated significant improvements in patients with obstructive hypertrophic cardiomyopathy across all endpoints in a Phase 3 clinical trial, including measures of exercise capacity and quality of life. These results, planned to be presented at a medical conference in Lisbon in May, represents a pivotal moment for us, showcasing aficamten’s potential impact on patient outcomes and reinforcing our commitment to transforming scientific discoveries into therapeutic advancements. We are planning for direct commercial go to market activities in 2025, following our expected regulatory submissions in the US and Europe in 2024. This timeline is pivotal for us as we aim to transition from the corporate development phase to directly impacting patients' lives with our therapies.

Aficamten’s development follows the success of mavacamten, commercialized by BMS, which originated from our research and was further developed by MyoKardia, a spin-off from Cytokinetics. This narrative underscores our capacity for innovation and contribution to the field of cardiac myosin inhibition. Our goal is not to compete directly with BMS but to advance the field and the category, offering new therapeutic options based on our continuous innovation and scientific discoveries.

You also have another drug with Phase 3 trial results…

Indeed, besides aficamten, we have another potential drug, omecamtiv mecarbil for the potential treatment of heart failure that faced a setback with the FDA despite a positive Phase 3 trial, necessitating a second confirmatory trial for heart failure treatment. This additional opportunity delineates our broader focus on myosin modulation, with one drug, omecamtiv mecarbil,aiming to activate cardiac muscle contractility for heart failure treatment and another, aficamten, aiming to inhibit it for hypertrophic cardiomyopathy. These developments highlight our dual strategic approach in cardiac muscle modulation, showcasing our versatility in addressing different facets of severe cardiovascular disease.

How did Cytokinetics navigate the economic challenges during the pandemic and the period that followed?

During the pandemic period, our strong balance sheet and R&D pipeline insulated us from the widespread challenges, although it did present operational hurdles. The biotech sector's fluctuations, amplified by COVID, did not sway our strategic course. Our approach has always been cautious, leveraging diverse capital sources beyond equity markets, ensuring steady progress amidst industry ebbs and flows. This disciplined approach, irrespective of prevailing  stock price and access to equity capital underscores our commitment to sustainable growth and prudent capital deployment and efficiencies.

What role do partnerships play in your strategy?

Partnerships have been crucial in our journey, enabling advancements we could not have achieved alone. Early alliances with GSK, Astellas, and Amgen provided essential capital and access to expertise. However, as we have grown, our dependency on partnerships has evolved. We now possess the capability to advance independently in many areas, though strategic collaborations, especially in certain geographies like China, Japan, and Latin America, remain valuable. Our approach to partnerships now also considers opportunities for inorganic growth, potentially incorporating complementary modalities like gene-directed and cell therapies into our more organic muscle biology focus. This strategic evolution reflects our ambition to remain at the forefront of pioneering muscle biology research and therapy development.

Will next year be an important one for Cytokinetics?

Yes, I do anticipate next year to be a landmark year for Cytokinetics, marking the first time a patient may receive a medicine entirely discovered and developed by our team. This achievement, while immensely satisfying, represents just the beginning of our journey. The true challenge and our commitment extend to ensuring equitable access to our medicine for all potential beneficiaries, irrespective of their geographical location, ethnicity, or financial capacity. This ethos of inclusivity and equity forms the cornerstone of our mission as we move forward.

Looking ahead, our ambition is to not only successfully launch this groundbreaking medicine but also to initiate new projects and development opportunities that further cement our enduring role in scientific innovation and patient care. A year from now, I hope to share progress not just in terms of commercial success but in our continued efforts to push the boundaries of research and development. This vision includes expanding our portfolio and resources to tackle new challenges, thereby opening a new chapter in our commitment to advancing human health.