Strategic case for a Sarawak Drug Discovery Centre

SOME readers of this article may well be taking Lipitor (atorvastatin). Marketed in 1997 for high blood cholesterol, it became the highest-earning prescription drug in history. Developed at a cost of less than US$300 million during the 1980s and 1990s, it has since earned a cumulative US$165 billion.

Imagine if you owned the patent for this drug and received a 3 per cent royalty on its sales—you would have earned US$5 billion from your discovery. Although most drugs are not this lucrative, this highlights the enormous returns that can arise from discovering and patenting a prescription drug for a major global health condition.

For common ailments like fever or pain, we often turn to paracetamol for quick relief. But if we suffer a stroke, there is still no approved drug to promote survival of the damaged brain cells that are slowly dying over several days. For Parkinson’s disease, current drugs can ease movement difficulties, but they cannot stop the underlying disease from progressing.

For certain other illnesses, the drugs available may lose their effectiveness over time, or give rise to additional problems. Billions of people worldwide are waiting for the breakthrough drugs that will rewrite the future of medicine.

Since prehistoric times, plants have stood as humanity’s ultimate medicine cabinet. Long before modern prescriptions, healing began in the garden, where families fought illness with home-brewed teas, healing spices, and herbal concentrates. Yet in developed countries, government funding for drug discovery from natural products has dropped or ceased. Most large pharmaceutical companies screen synthetic chemical libraries for potential drugs, while few investigate natural products.

Between 1981 and 2019, 56 per cent of drugs approved by the US Food and Drug Administration (FDA) were natural products or their derivatives. Of the anticancer drugs approved during that period, almost two-thirds (64.9 per cent) fell into this category. Remarkably, 84 per cent of approved central nervous system drugs were natural products or synthetic versions of them.

Natural products are biologically more active due to a greater diversity of chemical structure and they produce less toxicity. Data shows that when new drugs enter human testing, the natural product-derived ones have a clear advantage because they navigate these clinical trials far more successfully than man-made synthetics.

Borneo, the third largest island in the world, straddles the equator. As a result, the region escaped the glacial freeze of the last Ice Age, giving rise to one of the Earth’s oldest tropical rainforest ecosystems, home to the highest plant and mammal diversity in Southeast Asia.

Borneo boasts an astonishing 15,000 plant species, a third of which are found nowhere else on Earth—a level of biodiversity that makes its lowlands the most plant-rich terrestrial ecoregion on earth. In 2018, forests covered 62 per cent of Sarawak. However, the true epicentres for unique plant diversity are strictly the lowland rainforests. Consequently, scientists are left with a narrower frontier, as these crucial lowlands currently cover just 32 per cent of the state.

Given our strategic location, we seek returns from our bioresources. If we market nutraceuticals and cosmeceuticals, consumers will face plenty of competing choices at the supermarket, and some may simply not buy because these products are not a necessity. However, our rainforest is a reservoir of compounds that may become not just better drugs, but the only treatments for global diseases.

We need a paradigm shift towards intentionally discovering such compounds, because securing patent rights to a successful drug can create substantial long-term value when that drug is prescribed worldwide, particularly for conditions requiring treatment for months or even decades.

Our major obstacle is the long, costly and risky path from discovering a promising compound to obtaining regulatory approval in major markets such as the US or Europe. On average, it may take 12-15 years to complete development, and many compounds drop out along the way due to toxicity or because they are inferior to existing treatment options. Factoring in the cost of failed candidates, pharmaceutical companies spend in the order of US$1 billion to develop a new therapeutic agent through to regulatory approval—a feat no national company has yet accomplished.

A better strategy is to out-license the patent rights to a capable partner able to move the compound efficiently through to regulatory approval. As the patent owner and licensor, we would typically receive an upfront payment and milestone payments as development progresses, together with royalties on future sales if the drug ultimately reaches the market. The capabilities we need include the ability to manage the safety and efficacy studies required to maximise the value of our patent. We then identify prospective licensees, pitch the compound, negotiate terms and conclude the best licensing deal.

Thus far, the only compound from Borneo to receive US FDA approval is the well-known antibiotic vancomycin, which was approved in 1958. It arose from a central Kalimantan soil sample sent to the US pharmaceutical company Eli Lilly, who subsequently owned the patent.

There is still no drug or botanical product from Malaysia that has progressed through human testing to approval by a major regulatory authority. Two Sarawak compounds discovered as far back as 1987 and 2004, and owned or co-owned by the state, have yet to advance beyond the early stages of human testing.

Globally, over 90 per cent of plant species remain unscreened for bioactive compounds, representing a massive, untapped resource for drug discovery.

A study on medicinal plants used in Sabah from 1922 to 2024 identified 696 plant species. Of these, 156 species used by local Sabahan indigenous groups remain unstudied for their chemical constituents and potential medicinal effects. The lowland forest area of Sarawak is roughly double that of Sabah. According to the Sarawak Forest Department, our local ethnic communities use approximately 1,300 plant species as herbal remedies.

The Sarawak Biodiversity Centre (SBC) maintains a repository of natural products from our rainforest and preserves indigenous knowledge of medicinal plants. Among its other functions, it monitors and licenses bioprospectors. It is the first institution in Malaysia to sign and implement the Nagoya Protocol on Access and Benefit Sharing—an international regulatory framework for the sustainable and equitable sharing of benefits arising from the use of genetic resources. I initiated a joint research programme with SBC, during which they transferred some of their compounds to us.

While at Universiti Malaysia Sarawak, my lab optimised a specific type of neuron for modelling complex brain diseases. Today, we are among the global leaders in its application, fulfilling requests from researchers as far away as Korea and the US. We used this platform to model global conditions in urgent need of better drugs, including stroke, Parkinson’s disease, and neuropsychiatric illnesses like depression and schizophrenia.

At my lab, we put the SBC compounds through our disease models and identified one particularly active compound from a plant found in Ba Kelalan. We found the compound could activate not one but two members of the largest family of cell surface proteins in humans. This protein family mediates a wide range of normal bodily functions, but disease can disrupt the way these proteins work. This class of proteins is of exceptional interest to the pharmaceutical industry because it is the target of 36 per cent of drugs approved by the US FDA, representing a quarter of the global therapeutic drug market.

Drugs that act on more than one cellular target are increasingly being viewed as a promising approach to treating complex diseases driven by multiple interacting factors. In these diseases, single-target drugs may relieve symptoms without slowing or halting disease progression. By acting on several disease pathways and physiological systems, a multitarget drug may produce synergistic effects offering greater therapeutic benefit than a single-target drug.

The compound that demonstrated activity in our neurological disease models had a novel chemical structure. We have jointly filed a composition-of-matter patent application which, if granted, would give us the right to exclude others from making, using or selling the patented compound and any variants covered by the claims. If further animal studies provide convincing evidence of efficacy, the compound could attract an out-licensing deal with a pharmaceutical company involving an upfront payment in the millions of US dollars.

The important takeaway is that we are located in one of the world’s richest and still largely untapped reservoirs of potential new drugs. With the right facilities and expertise, we can select diseases of interest and screen for compounds that can counter their effects in cells, tissues, organs or whole-animal models. If we can find one such compound, we can find more. We will own the intellectual property and decide how best to make it available to a waiting world.

Over the years, scientists at several institutions in the state have pursued independent projects involving different aspects of drug discovery. Without specialised support, these investigators may not advance their discoveries into patented compounds with drug-development potential. The state should seize this opportunity by establishing its own dedicated Drug Discovery Centre, equipped to generate, develop and patent promising drug candidates while also supporting other players in the sector.

Such a centre should have the equipment and expertise to undertake plant extraction, drug screening, structural elucidation and molecular mechanism studies, as well as to manage intellectual property protection, animal studies and monetisation through an out-licensing model. There are state-owned natural-product drug discovery centres worldwide, but few, if any, sit at the doorstep of megabiodiversity with direct access to its resources.

The drug industry is highly lucrative and natural product-derived drugs have a greater success to reach regulatory approval. Located at the most plant-diverse ecoregion on the planet, we are living alongside the next medical breakthroughs.

With studies reporting an annual decline in Sarawak’s forest cover of around 0.6 per cent, this is the time to fund our dedicated centre and bring new drugs to the market. The initial investment may be substantial, but a successful Drug Discovery Centre can generate scientific, economic and societal value far beyond the cost of establishing it.

*Dr William Lim Kiong Seng is Associate Research Fellow of the Therapeutic Research Centre, Universiti Malaysia Sarawak