“About 20 years ago, giants like GSK, Novartis, and Roche all set up R&D centers in China to focus on neurological drugs — but later they all withdrew,” Dr. Guo began, highlighting this shared industry memory.

The reason for the retreat was simple: CNS drug development is extraordinarily difficult. A lack of effective biomarkers and high clinical failure rates deterred numerous pharmaceutical companies.

Two decades later, however, Dr. Guo sees a vastly different landscape. “We have entered an excellent era.” This optimism is built on multiple technological breakthroughs — modern analytical techniques, AI-driven phenotypic analysis, novel delivery technologies, and brain delivery solutions for peptide and nucleic acid drugs.

“The biggest future explosion may come in neurodegenerative diseases, especially Alzheimer’s disease (AD) and Parkinson’s disease (PD),” Dr. Guo predicted. Behind this judgment are relatively well-defined biomarkers for these diseases — Aβ, tau, and α‑synuclein — as well as new methods for crossing the blood-brain barrier.

Nevertheless, psychiatric disorders still face major challenges. “Depression, schizophrenia, anxiety, and other conditions still lack clear biomarkers, and their pathological mechanisms require further research,” Dr. Guo acknowledged.

“But I believe great progress will be made and blockbuster drugs will launch within the next decade. Look back 20 years: oncology also faced huge problems — no good biomarkers, limited understanding of gene mutations. Yet over those 20 years, oncology advanced rapidly, yielding many targeted therapies, including small molecules, peptides, antibodies, and cell therapies represented by CAR-T, bringing huge benefits to patients.”

The high failure rate in CNS drug development stems largely from ambiguity in evaluation systems.

“In oncology, you can visualize solid tumors via imaging and identify mutations through genetic testing. But neuropsychiatric diseases? They can’t be seen under a microscope or detected in a blood test,” Dr. Guo explained, pointing to the field’s fundamental dilemma: a lack of biomarkers.

This gap creates enormous obstacles in preclinical research. “Many people question: Do mice get depressed? Do they have schizophrenia?” Dr. Guo’s answer is yes. “Mice definitely experience depression and schizophrenia-like states. The difficulty is — mice can’t tell you, ‘I’m depressed.’”

Unable to “speak,” animals force researchers to pursue more objective assessment methods. Dr. Guo noted that after years of effort, Honshu Bio has identified promising biomarkers, such as electrophysiological signatures and biochemical indicators. Cross-species consistency may serve as a bridge between preclinical and clinical research.

Meanwhile, AI-driven behavioral analysis is emerging as a new breakthrough. Using video analysis, AI can precisely detect subtle changes in animal posture, facial expressions, and other behaviors, identifying phenotypic signatures linked to different psychiatric disorders.

“We aim to minimize human intervention and use big data to uncover phenotypic differences invisible to the naked eye,” Dr. Guo emphasized.

In April 2025, the FDA announced it would gradually phase out mandatory animal testing for drugs including monoclonal antibodies, encouraging instead “New Approach Methodologies” (NAMs) such as organoids, organ chips, and AI computational models. What does this regulatory revolution — hailed as a “century-long paradigm shift” — mean for CNS R&D?

Dr. Guo offered a calm and rational perspective: “Complete replacement is impossible. Animal testing remains an irreplaceable component of in vivo systemic research.”

Yet he also recognizes the strategic value of NAMs. Organ chips and organoids can solve targeted problems in the CNS field. For example, “using organ chips to simulate whether a drug can cross the blood-brain barrier is a highly effective application.”

Advances in organoid and organ-chip technology are driving innovation in drug discovery and evaluation. Honshu Bio is also developing these technologies for early drug discovery and blood-brain barrier penetration assessment. But Dr. Guo stressed that these techniques and animal models should coexist and complement each other, rather than simply replace one another.

“The FDA’s ISTAND program and the Context of Use (COU) framework are establishing validation pathways for these new technologies. But widespread application still has a long way to go.”

Compared with Europe and the U.S., China’s CNS drug development features a unique industrial ecosystem.

“In drug discovery, Europe and the U.S. indeed lead in de novo target identification from 0 to 1. But in engineering, China has already surpassed overseas players,” Dr. Guo noted. In recent years, numerous Chinese CNS pipelines have gone global through BD transactions, proving the strength of domestic R&D.

The biggest challenge facing China’s CNS sector is insufficient original innovation capacity. “We publish numerous papers in Nature, Science, and Cell every day, but too few mechanistic discoveries are truly translated into first-in-class drugs,” Dr. Guo argued. This requires deep integration between academia and industry: “Drug developers need basic research to drive progress; otherwise, there is no source of innovation.”

China’s market, however, holds unique advantages:

• A large population means even rare diseases can have substantial patient groups.
• A rapidly aging society (with average life expectancy in Shanghai approaching 87) has made neurodegenerative diseases an urgent social issue.
• Government-led investment in biomedicine provides strong industrial support.

“We can clearly see Japan’s aging process. Brain health will become an increasingly prominent issue in China. Leveraging our population and engineering advantages, combined with solid basic research, is the key to localization.”

In its six years since founding, Honshu Bio has accumulated hundreds of clients: 60% large pharma and 30% biotech. Dr. Guo summarized three key reasons clients choose Honshu:

1. Extreme pursuit of clinical translation“We don’t just run animal studies — we seek certainty amid uncertainty. We have developed cutting-edge stem cell and organoid models, electrophysiological biomarkers, and AI analysis tools so preclinical data can truly predict clinical outcomes.”

2. Deep vertical expertiseHonshu’s core team has 8–10 years of dedicated experience in neuroscience, enabling rigorous phenotypic and pathological analysis.

3. Balancing high efficiency and qualityAs BD overseas becomes common, Dr. Guo warned: “Don’t chase only upfront payments — build a strong reputation. Recent program terminations show that efficiency and quality are the greatest challenges for innovative pharma.”

To innovative drug companies looking to partner with Honshu in the future, Dr. Guo offered three key words:

• CollaborationMulti-level cooperation: enterprise-to-enterprise, enterprise-to-academia, enterprise-to-regulator, and China-to-global.

• Innovation“0-to-1 innovation is painful and requires massive foundational investment. CROs must also innovate. Without new analytical tools, it’s hard to stand out in competition.”

• Efficiency & Quality“Don’t just take the first step — plan for Phase II and Phase III success. This mindset must always be front and center.”

Alzheimer’s patients gradually lose memories of time and family, and self-care abilities. Depression traps people in prolonged sorrow and despair, often accompanied by sleep disorders and physical symptoms. Epilepsy patients endure repeated seizures… CNS diseases affect countless Chinese families.

The ultimate meaning of CNS drug development may lie in these intimate human experiences. As technological light pierces the fog of the blood-brain barrier, as AI algorithms capture tiny behavioral changes in animals, as organoids simulate drug effects in the human brain, and as organ chips replicate neuronal firing — we move one step closer to that “certain” answer.

“I believe the future will be better,” said Dr. Guo. This conviction comes from both rational judgment of technological progress and reverence for the essence of life sciences.

In the face of CNS — often called “the hardest nut to crack” — Chinese forces are writing a new narrative. And companies like Honshu Bio aim to be the translation hub connecting basic research and clinical value — perhaps the true meaning behind the name “Honshu”.