How Biotech Leaders Keep Pace With The Next Wave Of Genetic Therapies

By Amber Salzman, CEO, Epicrispr Biotechnologies

Recently, the first patient in history was treated with an epigenetic editing therapy for facioscapulohumeral muscular dystrophy (FSHD). It was an extraordinary scientific milestone, but more importantly, it underscored a critical challenge facing every biotech leader today: how do we keep pace with scientific breakthroughs that are outstripping the regulatory, clinical, and operational frameworks designed to evaluate them?

This is not just a story about one trial, one company, or one disease. It is a case study for the entire biotech community about what it takes to responsibly advance transformative therapies. The lessons extend beyond gene and epigenetic editing to any novel modality that challenges conventional thinking.

A Personal Perspective On Urgency

My perspective is rooted in personal experience. Decades ago, when my son and nephew were both diagnosed with adrenoleukodystrophy (ALD), a devastating genetic disease that robs young boys of neurological function, I was working at GSK. My nephew, Oliver, was diagnosed first. His prognosis was tragically short. Months later, tests revealed my son carried the same ticking time bomb.

Through the mentorship of the late physician-scientist Tachi Yamada, I connected with pioneers like Jim Wilson in Philadelphia and Patrick Aubourg in Paris. Together, against deep skepticism and at a time when the entire field of gene therapy was under regulatory siege, we helped advance what became eli-cel (Skysona), the first gene therapy for ALD. The published data showed halted disease progression in two boys — a life-saving breakthrough.

But for my family, it came too late. My son had to undergo a stem cell transplant instead. He survived, and today he is 25, working as a behavioral therapist and pursuing graduate school. That experience imprinted a lesson I carry into every leadership decision: patients cannot wait for perfect consensus or ideal conditions. Time lost is function lost — or life lost.

What Epigenetic Editing Teaches Us

The emergence of epigenetic editing is a reminder that innovation doesn’t always fit neatly into the frameworks we know. Unlike traditional CRISPR, which cuts DNA, epigenetic editing alters gene expression without breaking the sequence itself. Think of it as turning the volume up or down on a gene instead of taking a hammer to the instrument.

For biotech executives, this raises immediate questions: How do you design trials when functional outcomes may take years, but molecular signals of change emerge earlier? How do you balance safety and urgency when delivery vectors carry both risk and promise? And how do you build evidence that regulators, investors, and — most importantly — patients can trust?

From our journey into the clinic, four imperatives stand out for leaders across the industry.

1. Don’t Let Limitations Become Roadblocks

Cas9 is the most widely used CRISPR enzyme. But because it is bacterial in origin, it can trigger immune responses and limit in vivo delivery. Its large size also constrains payload engineering, often forcing trade-offs that reduce efficacy. Many executives would see those limitations and wait for someone else to solve them.

Instead, our field has to innovate past them. In our case, we developed CasONYX, a variant of CasMINI, which is non-bacterial, highly active in mammalian cells, and small enough to allow more efficient delivery. The broader point is this: when a technology presents obstacles, don’t accept them as permanent. Push your teams to engineer around the barriers, not work within them.

2. Don’t Confuse Failures With Dead Ends

Roughly 1,000 patients have been dosed with therapies delivered by AAVrh74, a viral vector targeting skeletal muscle. The record includes both tragic failures and striking successes. The temptation, especially in today’s risk-sensitive environment, is to treat setbacks as reasons to stop.

Leaders must resist this. Failures should trigger rigorous investigation, not abandonment. For novel modalities, data must be dissected, contextualized, and learned from. Sometimes the answer is that a specific design or dose is unsafe. But more often, the truth is more nuanced. For executives, the mandate is to keep asking: what does the data actually tell us, and what opportunities remain if we read it carefully?

3. Build Better Translational Models

One of the most dangerous traps in biotech is assuming in vitro results will predict in vivo outcomes. For epigenetic editing in FSHD, we knew that was insufficient. So we started with patient-derived myoblasts, but quickly expanded to xenograft mice whose muscle had been replaced with tissue from patients. That provided critical insights into dosing and vector levels.

Still, that wasn’t enough. To test whether functional improvements were possible, we collaborated to build human 3D FSHD muscle organoids, allowing us to measure contractility. In these models, we observed a dose-dependent rescue of muscle force following treatment.

The lesson for executives: don’t stop at the easiest model or the one that has “always been used.” Ask whether your models reflect the human biology you are targeting. The more faithfully they do, the more confidence you — and regulators — can have when moving into patients.

4. Treat Patients As Co-Developers

Perhaps the most profound shift in drug development is the recognition that patients are not just trial participants; they are collaborators. Their lived experience should shape trial design, endpoint selection, and definitions of acceptable risk.

For FSHD, that meant considering measures of disease progression that traditional trials might miss. A timed walk might not capture loss of upper-body function, and vice versa. By working with patient communities and technology partners, we identified imaging biomarkers that track fat fraction and muscle mass across the whole body. These not only provide regulators with objective data, but also shorten the time patients must wait to learn if a therapy is helping.

For biotech leaders, involving patients early isn’t just ethical — it’s strategic. It leads to better science, clearer regulatory dialogue, and more sustainable trust.

A Shared Responsibility

The first patient dosed with an epigenetic editing therapy should not be remembered as an isolated achievement. It marks the dawn of a new era in medicine — one where scientific possibility is no longer the bottleneck. The bottlenecks now lie in how quickly and responsibly we can translate discovery into delivery.

For executives across the industry, the call to action is clear:

• Push past technological limitations.
• Learn deeply from failures instead of retreating.
• Demand translational models that truly reflect human disease.
• And above all, make patients true partners in the process.

The science is ready. Patients are waiting. Whether genetic medicine becomes a series of disconnected breakthroughs or a reliable engine for cures depends on the choices leaders make today.

The future of health is being written right now. The only question is whether we, as an industry, will move quickly and boldly enough to deliver it.

Editor’s note: Click here to view a Business of Biotech podcast discussion with Amber Salzman, Ph.D., recorded live in Boston during the BIO conference in June 2025.  

About The Author:

Amber Salzman, Ph.D., is Epicrispr Biotechnologies’ CEO and director. Dr. Salzman is a leader with more than 30 years of experience in the pharmaceuticals industry. Before joining Epicrispr, Dr. Salzman served as the president and CEO of Ohana Biosciences, pioneering the industry’s first sperm biology platform. Before Ohana, she served as the president and CEO of Adverum Biotechnologies and was a cofounder of Annapurna, SAS, where she served as president and CEO before its merger with Avalanche Biotechnologies to become Adverum. In that role, she saw the company’s stock price double. Dr. Salzman began her career as a member of the GlaxoSmithKline (GSK) research and development executive team, where she was responsible for operations in drug development across multiple therapeutic areas, overseeing global clinical trials with over 30,000 enrolled patients, managing 1,600 employees and a $1.25B budget. Following her time at GSK, Dr. Salzman served as the CEO of Cardiokine, a pharmaceutical company that developed treatments for the prevention of cardiovascular diseases and saw the successful sale of the company to Cornerstone Therapeutics. Dr. Salzman currently serves on the Osler Diagnostics (UK) and AviadoBio (UK) Boards. Dr. Salzman received her bachelor’s degree from Temple University and holds a Ph.D. in mathematics from Bryn Mawr College. In addition to advocating for patients living with rare diseases, Dr. Salzman leads the Stop ALD Foundation, a nonprofit medical research foundation focused on developing novel gene therapies for adrenoleukodystrophy (ALD).