Welcome to Partnology’s Biotech Leader Spotlight Series, where we highlight the remarkable accomplishments and visionary leadership of biotech industry pioneers. This series is about showcasing the groundbreaking strides made by exceptional leaders who have transformed scientific possibilities into tangible realities. Through insightful interviews, we invite you to join us in following the inspiring journeys of these executives who continue to shape the landscape of the biotech industry. This week we are recognizing:
Dr. Samuel Collins brings nearly 20 years of experience spanning academia and industry, with a focus in rare disease and pediatrics. He is currently serving as Consultant Chief Medical Officer at Mahzi Therapeutics, a biotech company focused on treating under-served rare genetic neurodevelopmental disorders. He previously served as the CMO of Actio Biosciences, where he oversaw all aspects of clinical development, as well as medical and regulatory affairs, for the company’s pipeline of precision medicines. Prior to Actio he served as VP, Clinical Development at Edgewise Therapeutics, and was key to advancing their lead asset from Phase 1 to pivotal studies.
Prior to Edgewise, Dr. Collins spent several years at Pfizer, serving as Senior Director, Clinical Research within the company’s rare disease division. He served as Medical Director of Therachon AG, prior to its 2019 acquisition by Pfizer, and before that, was Medical Director at Premier Research. Before entering the industry, he held a number of clinical and academic positions in London, Southampton and Melbourne, Australia. Dr. Collins holds an MBBS from the University College, London, a Ph.D. from the University of Southampton and an MBA from Durham University. He is a published author on nearly 20 peer-reviewed publications.
You’ve transitioned from pediatric respiratory medicine and academic research into biotech leadership roles across both Europe and the U.S. — what initially drew you to industry, and what has kept you passionate about drug development in rare diseases?
Many people don’t think about making the jump from academia to industry, because when you’re in academia, you don’t always understand things from the industry perspective. I was conducting research in rare and orphan lung diseases, working closely with patients and seeing firsthand the real unmet needs in those conditions. However, over time, I became frustrated with the pace of change—the difficulty in securing funding, actually getting the work started, and translating research into meaningful therapies. It’s really challenging in academia.
That led me to start looking elsewhere, and I realized that industry offered the resources and structure to truly move things forward. In industry, you can actually develop and deliver therapies that make a real impact for patients. I came to see that this was where I could make the greatest difference.
Staying in rare diseases has continued to fuel my passion. You’re always working in areas where patients and their families are desperately in need of help—highly engaged, motivated, and searching for ways to improve their lives. Rare disease research allows you to serve underserved populations and see the tangible impact of new treatments and therapies in real time—something you don’t always get to witness in academia.
You’ve held senior roles at both emerging startups and large pharma. How do you adapt your leadership and decision-making approach between those two environments?
It’s interesting, because they’re very different environments, and how you navigate them can vary quite a bit. At the core, though, you still have to maintain your role as both a physician and a scientist. You want to ground everything in solid science, conduct clinical trials that are safe, and design studies with the best chance of showing efficacy and ultimately reaching patients. So the fundamental goals remain the same.
The difference between the two lies in how defined your role is and where you spend your time. In large pharma, my experience has been that the environment is quite inward-looking. You spend a lot of time working with internal teams—people who are incredibly knowledgeable within their specific areas so you can learn a huge amount from them, and they’re great resources, but much of your effort goes into navigating the internal structure to advance programs.
In contrast, in small biotech—the environment I personally prefer—you’re constantly crossing the boundaries of your job title and doing whatever’s necessary to move the program forward. It’s a much more externally focused role: working directly with investigators, key opinion leaders, patient groups, regulators, and investors. In startups and smaller biotechs, the focus is on advancing the program and forging the path ahead, whereas in large pharma, it’s often more about justifying that path internally to secure support and investment.
Mahzi Therapeutics is tackling ultra-rare neurodevelopmental disorders — areas that often lack precedent for trial design or regulatory guidance. How do you approach building clinical programs when there’s limited natural history data or established endpoints?
This is definitely a bit of a double-edged sword. It’s one of the aspects of rare disease and biotech that I find both exciting and, at times, the most frustrating. The path isn’t clearly defined—the endpoints aren’t always established, and you’re often working with imperfect data.
But it ties back to what I mentioned earlier: in these areas, you have to be very outward-looking. I had a boss many years ago who used to say that in these environments, you need “big ears and a small mouth.” You go out, listen to everyone—patient groups, regulators, investigators—and then carefully chart your path forward.
Sometimes that means gathering natural history data or it means conducting patient-focused drug development to determine what truly matters to patients. From there, you build what you believe is the best approach. Often, that can be very successful, because you can go to regulators and say, “Here’s what this disease looks like.” You can educate them, show them what’s important to patients, and demonstrate that your proposed path forward is both reasonable and scientifically sound.
It’s incredibly rewarding when all those pieces come together and you start seeing real progress toward advancing a therapy. So while it’s exciting, it’s also one of the most challenging parts—laying those early building blocks from the ground up.
Tell me more about Mahzi Therapeutics and what you’re currently working on:
Mahzi is quite a unique company in that close collaboration with patient groups is absolutely central to its mission. Many companies work well with patient organizations, but Mahzi was essentially founded by Yael Weiss, the CEO, to specifically help patient groups that may not be as well-versed in drug development. These groups often have some promising science they’ve funded or initial ideas they’re eager to advance, and Mahzi’s purpose is to guide them through the process of moving from early research into the clinic and ultimately into clinical trials.
What’s really interesting and commendable about Yael and the team at Mahzi is that their support often extends to organizations whose assets Mahzi may never directly develop or benefit from. There’s a genuine desire to share knowledge, help them get organized, and fund the underlying science—whether or not it ultimately becomes a Mahzi program. That spirit of collaboration and selflessness is rare and has been one of the most rewarding aspects of working there.
The company’s lead program focuses on Pitt-Hopkins syndrome, developed in close partnership with the Pitt-Hopkins Research Foundation in the U.S. We’re hoping to dose the first patients in our Phase 1/2 study early in the new year, following FDA clearance of our IND about six weeks ago.
It’s been a fantastic experience—one where I’ve been able to help lay the foundational building blocks of a program that has a real chance to progress through the clinic and, hopefully, become a transformative treatment for patients living with a disease that, until now, has had no therapeutic options.
You’ve led multiple successful interactions with regulators across the U.S., EU, and Asia. Can you share an example where creative regulatory strategy or proactive engagement changed the trajectory of a program?
I would say that our goal is always to be creative without being overly aggressive in how we approach these programs. It truly is a collaboration. If you view regulators as adversaries or roadblocks, you won’t make progress. The people who work in these agencies do so because they want to ensure that treatments are safe and that science continues to advance.
The foundation of any productive interaction with regulators is collaboration—coming to the table with solid science, robust data, and a well-thought-out plan. You want to demonstrate that you’re committed to advancing the program responsibly, while also being mindful of patient safety and the appropriate pace of investigation. When regulators have confidence in you and in your approach, they’re often open and flexible. But you have to present them with a path forward rather than asking, “What should we do next?”
A great example of this was my time at Edgewise Therapeutics, which has become a real success story. The company, headquartered in Boulder, Colorado, focuses on cardiovascular and neuromuscular diseases, including Duchenne and Becker muscular dystrophy. When I joined, Edgewise was a Phase 1 startup with a single program, and it’s been remarkable to see how far they’ve come.
One of the most successful aspects was the Becker muscular dystrophy program. We included patients early on, collected safety and efficacy data, and worked to deeply understand the natural history of the disease. Once we began to see promising efficacy signals and had identified a safe, potentially effective dose, we approached the regulators with a proposal: to adapt the ongoing Phase 2 study by adding a separate, encapsulated cohort that could serve as a pivotal or registrational cohort.
The regulators supported this approach because we had the data and a solid, evidence-based plan—complete with statistical analyses, enrollment strategy, and operational details. This flexibility fundamentally changed the trajectory of the program. It allowed us to move forward without waiting for a full Phase 3 trial, which is especially important in rare diseases where patient populations are small and time is critical.
By adapting the Phase 2 design based on emerging data and engaging regulators in a transparent, science-driven way—both in the U.S. and Europe—we were able to accelerate the path toward a potential treatment for the Becker community. It was a great example of how thoughtful planning, data-driven collaboration, and mutual trust with regulators can truly make a difference.
Looking ahead, what emerging technologies or trends — scientific, operational, or regulatory — do you think will most reshape the future of rare disease development?
There are a few key trends emerging. The first—and the one everyone’s talking about—is AI. It’s interesting because “AI” has become such a catch-all term. Many of the things now branded as AI are actually approaches that have been part of drug development for years—like in silico molecular modeling, structural analysis, or computational safety assessments that predict off-target effects and receptor binding. These methods are all variations of machine learning and large-scale data processing.
So, while AI is indeed transforming the field, in many ways it’s been here all along. What’s changing now is the scale, sophistication, and accessibility of these tools. I think AI will continue to enhance how we select drug candidates and indications, optimize molecular design to minimize off-target effects, and improve early-stage precision. We’re already seeing this reflected in biotech startups and acquisitions—particularly in technologies like antibody engineering and next-generation molecular design platforms.
Another important impact of AI is its potential to reduce the burden of preclinical testing. I’m a strong proponent of minimizing animal testing wherever possible, and I think computational approaches can help achieve that. For example, some toxicology testing is unnecessarily repeated, even when viral capsids or other vectors have been used safely many times before. Better modeling and computational toxicology could meaningfully reduce redundant studies, streamline early development, and make it easier to launch programs—especially in rare diseases where resources and patient populations are limited.
The other major trend is on the regulatory side. We’ve seen a temporary shift away from rare disease investment—many VCs have become more cautious—but I think that will rebound. I expect to see renewed incentives and the return of programs like priority review vouchers, which can make ultra-rare development more viable. These mechanisms help ensure that patients with very small populations—sometimes only a few hundred in the U.S.—still have a path to treatment.
Ultimately, I’m optimistic about the future of rare disease development. With smarter computational tools, evolving regulatory flexibility, and renewed incentives, I think we’ll see continued progress in getting transformative therapies to patients—and doing so in more efficient and innovative ways.
