January 23, 2025 / The Clinical Trial Vanguard Executive Interviews
In this interview, we engage with David Craig from Sarcomatrix Therapeutics to discuss the development of S-969, a novel oral small molecule targeting the Hippo-YAP pathway. Our conversation covers regulatory challenges, clinical trial design, manufacturing scale-up, intellectual property protection, and strategic partnerships, offering insights into Sarcomatrix’s approach to addressing muscle wasting diseases.
Moe: What regulatory challenges do you foresee for S-969, and how will you address them?
The integrins are crucial structural proteins involved in cell signaling. Our research team has found a way to increase the expression of the muscle-specific α7β1 integrin through a kinase on the Hippo-YAP pathway. This integrin is vital for muscle fiber rebuilding and myogenesis. For instance, in healthy individuals, after exercise, this integrin’s expression can increase by 200-300%, and in elite athletes, it can go up to 500%. From a regulatory perspective, we are leveraging the accelerated approval pathway based on
biomarkers, as established by companies like Sarepta. This approach, combined with patient advocacy, potentially positions us to enter the market by 2029. We are making sure to follow proven paths to market, learning from the experiences of others in the field.
Moe: How are you designing trials to measure S-969’s efficacy and safety across diverse populations?
We plan to use the increased expression of α7β1integrin as a biomarker for accelerated approval. The agency and NIH recommend this as a favorable biomarker. Additionally, we’ll employ the North Star Scale, which is crucial for our trials despite being considered somewhat subjective. This scale involves a series of exercises to assess muscle function. We’ll also conduct pre and post-treatment muscle biopsies to determine muscle fiber count and myogenic expression signals, such as MyoD. These comprehensive measures will help us evaluate the drug’s impact across diverse patient populations.
Moe: What strategies are in place to scale manufacturing and ensure quality control?
I’ve been fortunate to gain experience from several biotech companies, learning the importance of manufacturing and quality control. For example, at Portola, we learned that most complete response letters are due to manufacturing and quality issues. We’ve brought on Al Swarz, an expert in protein and small molecules, to refine our RFP for CDMO and CRO partnerships. Additionally, Vikas, a colleague with a boutique IT group, is helping us implement quality and clinical trial management systems. Our molecule is relatively simple to manufacture, and we are confident in our ability to maintain high purity levels, as demonstrated in our preclinical studies with mice, rats, and dogs.
Moe: How are you safeguarding your intellectual property to maintain a competitive edge?
The University of Nevada’s tech transfer group has successfully filed method and utility patents for our small molecules targeting α7β1integrin. They provide IP filings and deferred payments with milestones and licensing. We have robust IP protection in the U.S., Europe, Asia, and other regions. Our second program, a protein replacement therapy, also has strong IP protection, ensuring our competitive edge. This comprehensive IP strategy covers a broad class of muscle diseases, including muscle wasting.
Moe: How do you differentiate yourself scientifically and strategically from competitors?
We are unique in focusing on small molecules that upregulate α7β1integrin expression, leveraging natural myogenic pathways. This holistic approach addresses multiple pathways, unlike competitors targeting individual pathways. Our small molecules also support skeletal and cardiac muscle, potentially impacting cardiac and respiratory failure, the leading causes of death in these patients. This comprehensive approach offers a more effective solution for muscle wasting conditions, setting us apart from other companies in the field.
Moe: How do you evaluate and select strategic partners to enhance R&D capabilities?
We are fortunate to collaborate with the Burkin lab at the University of Nevada, Reno, a leader in integrins and laminins research. Our Chief Science Officer, Ryan Wuebbles, PhD, is well-connected with patient advocacy groups, and my connections have helped us engage with the patient community. For example, my niece, who lived with muscular dystrophy, inspired our commitment to this field. We prioritize cutting-edge science and the depth of knowledge when evaluating potential partners, ensuring we work with the best researchers and engage with the patient community effectively.
Moe: How are you allocating resources to balance research, trial preparation, and financial sustainability?
We have a $2 million Phase 2B grant supporting our preclinical research. This includes a small nonhuman primate study for PKPD and a study using the Duchenne muscular dystrophy dog model at Texas A&M. Our $5 million seed round will cover operational costs until our IND filing. In comparison, a $65 million Series A round will advance us through Phase 1 and potentially to market by 2029. This strategic allocation ensures we can sustain operations while advancing our research and clinical trials.
Moe: What steps are you taking to ensure diversity and inclusion in patient recruitment?
We leverage patient registries and collaborate with groups like the Muscular Dystrophy Association to access diverse patient populations. While the disease predominantly affects males and has been supported by the Caucasian community, we are actively seeking to address recruitment disparities and engage with minority groups. We have conducted incidence and prevalence analyses worldwide, identifying opportunities to capture untreated patients in Europe and Asia, ensuring a diverse and inclusive approach to patient recruitment.
Moe: How will you incorporate patient feedback or real-world data into your studies?
Using standard tools and validated motion detection monitoring, we aim to incorporate patient feedback and quality measures. These insights will supplement the North Star Scale and help us better understand patient needs, particularly in improving quality-of-life aspects like gut motility. For example, validated motion detection can track steps and gait, providing valuable data to enhance our understanding of the drug’s impact on patients’ daily lives.
