From Bench to BLA: Why Japan’s Ryuichi Morishita Believes AI Could Fix Gene Therapy’s Cost Crisis

For decades, gene therapy was the “perpetual future” of medicine—a field of immense promise that seemed perpetually stalled by safety concerns and delivery failures. But for Dr. Ryuichi Morishita, Endowed Chair Professor at Osaka University and a pivotal figure in Japan’s regulatory evolution, the field has finally crossed its Rubicon.

The transition hasn’t just been scientific; it has been industrial and political. From the early days of cardiovascular research in 1987 to obtaining conditional approvals for critical limb ischemia in 2015, Dr. Morishita has seen the modality move from a high-risk experiment to a widely accepted pillar of modern healthcare. He recalls a time when the government was “severely nervous” about the very concept of altering genetic material. Today, that nervousness has been replaced by a pragmatic race to scale.

“The target of gene therapy has been widely accepted now,” Dr. Morishita notes, citing the global impact of the COVID-19 pandemic as the unexpected catalyst that normalized genetic medicine for millions. Now, as his company, AnGes, prepares for a Biologics License Application (BLA) in the United States, the focus is shifting toward what he calls the “Second Generation”—where AI, stem cells, and high-throughput manufacturing finally solve the bottlenecks of cost and scale.

The Regulatory Pivot: Why Japan Set the Global Tone

One of the most successful aspects of Dr. Morishita’s strategy has been his dual role as a scientist and a policy architect. Working within the heart of the Japanese government under the Abe cabinet, he wasn’t just following laws; he was helping to write them. This “insider” perspective revealed that the greatest barrier to innovation wasn’t a lack of brilliance in the lab, but a rigid legal system that didn’t know how to categorize “living” medicines.

He points to the dramatic shift in public perception following 2020. Before the pandemic, a gene therapy trial was a rare, scrutinized event. Post-COVID, the infrastructure for mRNA and DNA production has been tested on billions. This global “stress test” proved that genetic delivery could be safe, reliable, and—most importantly—manufacturable at a scale previously thought impossible.

• The Conditional Approval Model: Japan’s breakthrough “Fast Track” system allows for approval once safety is confirmed, letting patients access life-saving treatments while long-term efficacy data is still being gathered.
• The Economic Reality: Despite his roots in Osaka, Morishita is clear-eyed about the U.S. market. With higher pharmaceutical pricing and a robust Phase 3 infrastructure, the U.S. remains the essential destination for turning a scientific success into a sustainable business.

Solving the “Disconnect”: Why Promising Lab Science Fails in Humans

A recurring theme in Dr. Morishita’s career is the frustrating “disconnect” between a successful lab result and a durable patient outcome. He identifies the primary culprit not as a failure of biology, but as a failure of endpoint strategy. In the lab, a scientist looks for any sign of improvement; in a Phase 3 trial, a regulator looks for a specific, high-bar victory—such as the complete healing of a chronic ulcer.

This gap is where many biotechs bleed out. Dr. Morishita explains that as the trial progresses from Phase 1 to Phase 3, the “primary endpoint” must become a laser-focused political and scientific target. If you don’t know exactly what the government wants to see 10 years before you finish, you are likely to fail. He also highlights the “Money Gap”: the cost of production for plasmid DNA skyrocketed after the pandemic, making the transition from small-scale academic research to large-scale industrial manufacturing a “fight of the wars” for resources.

The AI Revolution: Engineering the Next Generation

Dr. Morishita is a vocal advocate for the integration of Artificial Intelligence to solve the heterogeneous challenges of cardiovascular disease. Unlike rare diseases, which often involve a single genetic “fix,” heart disease is messy and influenced by a thousand variables. Humans, he argues, are no longer capable of processing the sheer volume of data required to design these trials effectively.

Instead of traditional, multi-year double-blind studies that cost hundreds of millions, he envisions a “Speed-of-Model” approach. By using AI to build a “Natural Course” of a disease—essentially a digital twin of how a patient’s condition would worsen without treatment—researchers can run smaller, more efficient trials.

• The “Homing Missile” Delivery: Moving beyond simple direct injections, Morishita’s team is engineering EX-vivo designer cells. These are stem cells modified with specific genes and adhesion molecules that allow them to circulate and “home in” on damaged tissue. This is relevant because it solves the “localization” problem; instead of hoping an injection hits the right spot, the cells actively seek out stroke or heart failure sites.
• The LLM Advisor: In a refreshingly candid moment, he admits to using tools like ChatGPT to interrogate his own strategies. “Sometimes we miss a big operational disease because we are focused on our own specialty. AI covers the mass of applications we might overlook.”

The Morishita Methodology for Lasting Impact

Professor Morishita’s career suggests that scientific discovery is only the first step. To move from a breakthrough to a backbone of medical care, leaders must master several overlooked factors:

• Adopt the “One-Arm” AI Trial Design: Use AI-generated historical data to simulate natural disease courses. This allows for smaller trials where every patient receives the treatment, significantly reducing costs and increasing the “successful relate” of Phase 3 studies.
• The “Second Gen” Delivery Strategy: Move away from localized injections toward EX-vivo designer cells. By engineering stem cells to seek out target areas, you expand the reach of gene therapy to complex, widespread conditions like chronic heart failure and stroke where precise manual targeting is difficult.
• Bridge the Academic-Industrial Divide: Ensure that the research team includes experts in manufacturing (CMC) from day one. Scientific brilliance is useless if the therapy cannot be scaled up or if the “production scale” costs make the final price tag impossible for the healthcare system to absorb.
• Proactive Global Alignment: Don’t wait for your local government to set the pace. Understand the pricing and regulatory differences between the U.S. (FDA), Europe (EMA), and Japan (PMDA) early to ensure your product has a viable path to reimbursement in the world’s most expensive markets.

A Roadmap for the Third Generation

Reflecting on his tenure as a leader in the Japan Society of Gene Therapy, Dr. Morishita emphasizes that the “blueprint” for the next generation must be built on open-hearted collaboration. He worries that academia has become too siloed, with brilliant researchers who have no understanding of CMC (Chemistry, Manufacturing, and Controls) or the gritty realities of a clinical trial.

To succeed in this new era, he encourages young scientists to be “global nomads”—attending conferences in the U.S. and Europe, meeting manufacturers face-to-face, and learning the language of the regulators. He believes that the “Second Generation” of gene therapy will be defined by those who can bridge the gap between the bench and the bedside by being as comfortable with a spreadsheet or a legal brief as they are with a pipette.

“Conditions have been changed year by year,” Dr. Morishita concludes. The goal is no longer just to prove that the biology works—we know it does. The mission now is to build the industrial, regulatory, and AI-driven systems that can actually deliver that biology to the 10 million patients waiting for a cure. As the field looks toward a “Third Generation,” the legacy of Morishita’s work serves as a reminder: the most effective therapy is the one that actually reaches the patient.

Author

Bernice Lottering

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