Returning To Nature: Discovering The Next Generation Of Medicines

A conversation with Eric Brown, Ph.D., CEO and CSO, Kapoose Creek Bio

Nature has been used in drug discovery to make antibiotics, anti-inflammatories, cancer therapies, and more. But due to cost and time, there has been less focus placed on pursuing nature’s chemistry. Researchers at Kapoose Creek Bio are now looking to use nature, specifically fungi, to treat mental health and neurodegenerative disorders.

In this Q&A, Life Science Connect’s Morgan Kohler caught up with Eric Brown, Ph.D., chief executive officer and chief scientific officer of Kapoose Creek Bio, to discuss the company’s discovery of drugs from nature.

Why are we seeing a resurgent interest in drug development from nature?

The truth is that nature always has been a gold mine for drug discovery. It provided us with some of the most transformative medicines of our time — from penicillin to cholesterol-lowering statins, cancer-fighting taxol, and more. But mining drugs from nature has traditionally been labor-intensive and expensive. As a result, researchers had largely abandoned nature’s pharmacy in recent years, favoring synthetic libraries that are easier and more cost-effective to produce, modify, and screen.

Now, advances in technology, and particularly artificial intelligence (AI), have given important new life to the field, enabling researchers to utilize nature faster and far more efficiently than ever before. Today, the opportunity to discover and develop new drugs from nature is enormous, and it also couldn’t come at a better time. The world is battling rising healthcare challenges ranging from antibiotic resistance to treatment-resistant depression, emerging infectious diseases, and more. We need to find new therapies to treat a growing list of complex conditions, and nature’s chemistry offers exciting potential to meet this goal.

Can you tell us about the untapped potential of fungi in drug discovery and preclinical development for treating neurodegenerative disorders and mental health?

Fungi represent an extraordinary, yet largely untapped, source of bioactive compounds with significant promise for drug discovery — especially in the realm of neurodegenerative and mental health disorders. Fungi are known to produce remarkably diverse secondary metabolites, many with significant effects on the human nervous system, including the ability to cross the blood-brain barrier and act directly on central nervous system targets. This potential is especially exciting in the context of finding new treatments for neurological disorders, such as depression and Alzheimer’s and Parkinson’s diseases.

Our lead compound for depression, now advancing toward clinical development, is an example of the therapeutic potential of fungi. KCB-100 is sourced from a fungus with a long history of use in brain health. Advanced AI and metabolomic technologies helped us characterize its mechanism and demonstrate robust preclinical data within months. In addition to being able to cross the blood-brain barrier and potentially enhance neuroplasticity, the compound is non-hallucinogenic — a key differentiator from psychedelic and ketamine-based therapies that risk undesirable psychoactive side effects in patients.

It’s important to note that less than 1% of fungal metabolites have been explored for therapeutic applications, leaving vast reserves of potential medicines undiscovered. This presents a huge opportunity for modern medicine, and it’s imperative that researchers re-invest in its potential.

Can you share details about how new technology is helping to advance your drug discovery efforts?

Artificial intelligence and modern omics technologies are helping to revolutionize drug discovery from nature at every stage — from identifying promising bioactive molecules to deciphering their mechanism of action and advancing them through scaled production and optimization into drugs.

Drug discovery used to rely on labor-intensive screening methods, which required thousands of hours of manual work. Now, advanced automation, image analysis, and AI-guided technologies allow scientists to create and analyze vast amounts of data in record time, helping us to very quickly recognize patterns in chemistry and phenotype that facilitate the creation of large functional maps of bioactive molecules. These maps essentially act as powerful search tools, quickly offering clues about the compounds’ potential targets and generating predictions for therapeutic applications. Historically, these steps took years of experimental work.  

With these new technologies, it is now possible for us to identify potential drug candidates within months, which is significantly faster than previous approaches that take up to five times longer. They also can help overcome another traditional hurdle: translating molecules into viable therapeutics with unprecedented speed by optimizing chemistry and predicting toxicity prior to initiating costly clinical trials. This not only helps increase the likelihood of success but truly represents a game-changing opportunity for those of us mining nature for the next generation of medicines.

What is the biggest challenge in preclinical development that you’ve encountered and how have you approached addressing that challenge?

One of the biggest challenges when working with rare or structurally complex natural products in preclinical development is ensuring we have a reliable supply of promising compounds. Many molecules that show therapeutic potential exist only in very small quantities in nature, which makes traditional extraction methods impractical. To overcome this hurdle, we take a pragmatic approach to scaling production and powering downstream development. Where we can, we use total chemical synthesis, and when necessary, we turn to fermentation, where fungi often have substantial yield advantages over other natural sources.

We also have a significant research effort in synthetic biology aimed at engineering microbes for production. The goal of scaled production is to support both downstream development and provide abundant chemical scaffold for semi-synthetic modification of lead natural products. The latter is nearly always required to improve properties, such as the pharmacology of nature’s chemistry, and to provide composition of matter intellectual property.

What is your advice for drug discovery scientists researching nature-based drugs?

My advice would be to approach the drug discovery process with a balance of ambition and humility, and to never lose sight of patient needs. While today’s technology has entirely transformed what was once considered a tedious, resource-intensive process, I would also say that developing drugs from nature is still very much a nonlinear and unpredictable process.

So, working in this field requires a resilient mindset, a talented interdisciplinary team, endless curiosity and patience, and a willingness to embrace complexity and the unknown. It is essential to view the work through the critical lens of whether the science you’re developing will translate to addressing an unmet need impacting patients in the clinic.

The ultimate reward in our work is translating nature’s ingenuity into therapies that improve lives, and I am confident that remembering these fundamentals can help us make that happen.

About The Author

Eric Brown, Ph.D., is the chief executive officer and chief science officer of Kapoose Creek Bio. He is also a Distinguished University Professor in the Department of Biochemistry and Biomedical Sciences at McMaster University. He has more than 30 years of drug discovery experience, spanning the pharmaceutical industry and academia. He is internationally recognized for research in antibiotic discovery and for pioneering innovations across diverse areas of drug discovery, applying tools from chemical and systems biology to explore the complexity underlying disease.