Five Lessons For Biotech CEOs Pioneering A New Therapeutic Modality

By Weiyi Zhang, Ph.D.

Developing an entirely new therapeutic modality requires more than scientific innovation. It requires conviction, perseverance, and a willingness to challenge established thinking. Throughout biotechnology's history, transformative advances from monoclonal antibodies to gene therapies and mRNA vaccines, have often faced skepticism before achieving clinical validation.

At RiboX Therapeutics, we have experienced this firsthand as we work to pioneer circular RNA (circRNA), an emerging class of RNA medicines with the potential to overcome some of the limitations of conventional mRNA therapeutics.

When developing a technology that has limited clinical precedent, skepticism is inevitable, and often warranted. Scientists, investors, regulators, and potential partners naturally want to understand whether a new approach can deliver on its promise. Questions about stability, delivery, durability, safety, and therapeutic efficacy are all essential to advancing responsible innovation.

But skepticism should not discourage scientific ambition. It should motivate us to generate better evidence.

Our recent publication in The New England Journal of Medicine represents an important milestone in that journey. The research letter, published in October 2026, reported first-in-human Phase 1 findings for RXRG001, our investigational circular RNA therapy for radiation-induced xerostomia, a debilitating condition that can develop following radiation treatment for head and neck cancer.

In six patients, researchers observed improvements in salivary flow following treatment, with treatment-related adverse events reported as mild or moderate and transient. Although these early findings require confirmation in larger, controlled studies, they represent an encouraging step toward establishing the clinical potential of circular RNA medicines.

For our team, this milestone reinforces a principle that applies to any biotechnology company pioneering a new therapeutic modality: the most compelling response to scientific skepticism is credible, reproducible data. Below are five critical lessons for biotech leaders working to bring new drug modalities to patients:

1) Have The Conviction To Pursue Science That Challenges Conventional Thinking

Every major therapeutic breakthrough begins with a willingness to explore possibilities that others may consider too uncertain or technically challenging.

Circular RNA is a compelling example. Unlike conventional linear mRNA, circular RNA has a covalently closed structure that may provide greater resistance to degradation and enable sustained protein expression. These properties offer opportunities to expand how RNA medicines are designed and delivered.

However, translating these theoretical advantages into viable medicines requires overcoming significant scientific and technical challenges. When we began advancing circular RNA therapeutics, there were important unanswered questions about engineering, manufacturing, delivery, and clinical activity.

As a CEO, it is essential to maintain confidence in the underlying scientific rationale while remaining open to evidence that challenges your assumptions.

Conviction should never mean ignoring criticism. It means having a clear scientific hypothesis, surrounding yourself with talented researchers, and committing to the experiments needed to test it.

2) Embrace Scientific Skepticism As An Opportunity To Strengthen Your Technology

When developing a new modality, skepticism is part of the process.

We have encountered questions about whether circular RNA could achieve sufficient protein expression, whether it could be delivered effectively to specific tissues, and whether its theoretical advantages would translate into clinically meaningful outcomes.

These questions are not obstacles to innovation. They are opportunities to refine the technology and generate stronger evidence.

Rather than focusing on convincing skeptics through ambitious promises, biotech leaders should identify the most important unanswered questions and systematically address them through experiments and clinical development.

For circular RNA, that means demonstrating not only that the molecules can be engineered and manufactured, but also that they can produce meaningful biological effects in patients while maintaining an acceptable safety profile.

Over time, the conversation can begin to shift from whether a technology is scientifically feasible to understanding where it may offer the greatest clinical benefit.

3) Let Clinical Data Speak For Themselves

For companies pioneering a new modality, there is no substitute for human clinical data.

Preclinical research provides the foundation for drug development, but clinical studies ultimately determine whether a scientific concept can become a meaningful therapeutic intervention.

Our recent NEJM publication marks an important step in this process.

RXRG001 is designed to deliver circular RNA encoding aquaporin-1, a protein involved in water transport, to help restore salivary function in patients experiencing radiation-induced xerostomia.

In our initial six patients, the study demonstrated improvements in salivary flow following administration, alongside encouraging early safety and tolerability findings.

These results do not establish definitive clinical efficacy, nor do they validate every potential application of circular RNA. However, they provide important early human evidence that an engineered circular RNA therapeutic can produce measurable biological activity.

For our team, that represents progress toward answering some of the foundational questions surrounding this emerging modality.

It also illustrates why scientific leaders must resist the temptation to overstate early findings. Being transparent about what the data demonstrate — and what remains to be established — is essential to building long-term credibility.

4) Keep Advancing The Science While Building Trust With Stakeholders

Biotechnology development is a marathon, not a sprint. This is particularly true when companies are creating an entirely new therapeutic modality.

There will inevitably be periods when external skepticism, competitive developments, or shifting investor sentiment create uncertainty about a company's prospects.

During these moments, CEOs must remain focused on the long-term objective: advancing the science and developing medicines that can meaningfully improve patients' lives.

At the same time, scientific progress should be accompanied by transparent communication.

Publishing research, presenting findings at scientific conferences, engaging with regulators, and maintaining open dialogue with investors and patient communities are all essential components of building credibility.

The recent NEJM publication illustrates the value of sharing emerging clinical evidence with the broader medical community, where the findings can be evaluated, challenged, and built upon.

Trust is not established through a single announcement. It develops over time through consistent scientific execution, transparent disclosure, and a willingness to acknowledge uncertainty.

5) Think Beyond A Single Program To The Broader Potential Of The Modality

When pioneering a new therapeutic platform, the ultimate opportunity often extends beyond the first clinical indication.

Our initial clinical work with RXRG001 focuses on radiation-induced xerostomia, but we believe engineered circular RNA could support a much broader range of therapeutic applications.

For example, RiboX is also advancing circular RNA-based approaches for in vivo cell engineering, including an investigational in vivo CAR-T program targeting autoimmune cytopenias.

These programs involve different biological applications and delivery considerations, underscoring the importance of continuing to refine the platform as our understanding evolves.

The broader vision is not simply to develop an individual drug. It is to establish circular RNA as a potentially versatile therapeutic modality capable of addressing diseases through multiple mechanisms.

However, platform potential must be demonstrated one program at a time. Success in one indication does not guarantee success in another, and every application requires its own rigorous preclinical and clinical validation.

For CEOs, the challenge is balancing enthusiasm for the long-term platform opportunity with disciplined execution against near-term clinical milestones.

The Future Belongs To Companies Willing To Challenge What's Possible

Biotechnology has made extraordinary progress because generations of scientists and entrepreneurs were willing to challenge conventional thinking.

New therapeutic modalities rarely achieve widespread acceptance overnight. They evolve through years of experimentation, setbacks, refinements, and incremental discoveries.

For those of us pioneering circular RNA therapeutics, the journey is still in its early stages. There are important questions to answer about delivery, durability, manufacturing, safety, and the full range of diseases that may benefit from this approach.

But the progress we are beginning to observe in human studies gives us reason for optimism.

The publication of our first-in-human findings in The New England Journal of Medicine is not the culmination of this journey. It is an early milestone that underscores why we began pursuing circular RNA medicines in the first place.

My advice to fellow biotech CEOs developing new therapeutic modalities is simple: pursue bold scientific ideas, welcome constructive skepticism, stay focused on patients, and remain committed to generating rigorous evidence.

Scientific breakthroughs are rarely achieved by following established expectations. They emerge when teams have the courage to pursue new possibilities and the discipline to test them.

At the end of the day, the data speak for themselves. And ultimately, it is the patients who stand to benefit from our willingness to keep pushing the boundaries of what medicine can achieve.

About The Author:

Dr. Weiyi Zhang is the CEO and CoFounder of RiboX Therapeutics, a biotechnology company pioneering circular RNA-based medicines. Previously, she served as Vice President and Head of External Innovation Hub China at Boehringer Ingelheim, overseeing research collaborations, business development, licensing and venture investments across Asia. She led investments in and served on the boards of Delonix Bioworks, Nuevocor Therapeutics and RiboX Therapeutics. Earlier, she held innovation and partnering roles at Bayer Healthcare. Dr. Zhang holds a Ph.D. in Cell Biology from Ruhr University Bochum and completed postdoctoral research at the National Institute of Biological Sciences in Beijing and the University of Hong Kong.