Singapore set out on a journey to become a biotech hub back in 2000 when the local government made biomedical research the “fourth pillar” of the city state’s economy in what’s known as the National Biomedical Science Strategy. Under that initiative, Singapore in 2003 established Biopolis, a custom-built biomedical R&D hub.
Billions of dollars were pumped into the life sciences sector over the next 20 years, new research institutes and government agencies were formed, and biopharma companies large and small set up shops. But biotech is still hardly the first thing that comes to mind when people think about Singapore.
Singapore still needs a big success story, said Christopher Tan, a biotech investor who has experience in both the U.S. and Singapore. Tan is a partner at Outram Bio, an emerging venture capital firm in Singapore.
“We’ve invested in the long haul, we have seen some early green shoots, some small wins,” Tan said. “Still waiting for the big ones. No Modernas yet. But I think it’s a journey.”
Litmus paper of interest
The Singapore government has been “banging the drum,” while private investment in the country took a long time to understand drug development, said Guy Heathers, a serial entrepreneur in Singapore. And success is becoming what he called the “litmus paper of interest.”
Singapore came so close to a major breakthrough several times, but its biotech pH kept falling off balance. Nasdaq-listed Aslan Pharmaceuticals appeared to be the wunderkind with the chops to do it—until its lead drug, a pan-HER inhibitor called varlitinib, failed in a midstage trial in 2019.
Cell therapy specialist Tessa Therapeutics was once on the rise, with a lead CD30-targeted candidate in phase 3 development. But the company surprisingly shut down a few weeks ago after raising more than $200 million in funding, far more than many other Singapore-based biotechs have managed. No cost-cutting plan, no strategic pivot. The dramatic shutdown inevitably creates a negative sentiment in Singapore’s local biotech ecosystem, said Heathers, who previously served a few years as vice president of business development at Tessa. Heathers is currently chief business officer of a preclinical-stage biotech called Albatroz Therapeutics, which is funded by Tan’s Outram.
In another setback that could put a damper on Singapore’s biotech scene, Aum Biosciences, a midstage company working on cancer therapeutics, in June terminated a SPAC deal with Nasdaq-listed Mountain Crest Acquisition Corp V.
Heathers is now concerned that private investors, who tend to be generalists in Singapore, might back away from biotech before new sparks of success can rekindle their interest. “When you get examples of companies making money for investors—being bought out by pharma or being exited on Nasdaq—it’s becoming real for a lot of investors,” he said.
If a major success is defined as having a drug approved in the U.S., then Singapore boasts one such case. Last year, CTI Biopharma won FDA approval for JAK inhibitor Vonjo as a myelofibrosis treatment. The molecule was originally developed by S*BIO, a Singapore biotech that has long ceased to exist.
But if Big Pharma recognition is considered the bar to meet, Singapore had that, too. Last year, Boehringer Ingelheim signed a broad licensing deal to develop tumor-specific agents such as antibody-drug conjugates and T-cell engagers based on a panel of antibodies by Singapore’s Agency for Science, Technology and Research (A*STAR).
We’re very focused on doing really good science, but we are kind of unwilling to pound the table and say, ‘Look at me.’” — Christopher Tan
It may not be that Singapore lacks quality innovation. As in Vonjo’s case, people simply didn’t remember Singapore’s contribution.
“We need to do a better job of surfacing good signs in front of the decision-makers […] who have the power of the pen to say, ‘Look, that’s really interesting,’” Tan said. “Culturally, I think we’ve been a bit more reticent. We’re very focused on doing really good science, but we are kind of unwilling to pound the table and say, ‘Look at me.’”
“When somebody sees, ‘oh, my god, here’s something that’s come out of Singapore that’s been approved, that’s really having that global impact,’ I think that will change the attention,” said Damian O’Connell, CEO of A*STAR’s Experimental Drug Development Centre (EDDC).
But one-offs won’t move the needle. Singapore needs to be a “serial winner” with a “critical mass” of similarly positive news to make people really recognize its place in the whole drug ecosystem, O’Connell said. He believes that the country has put together the necessary components, and it’s only time before more successes come out.
“I’m convinced that we’re on the right trajectory,” O’Connell said. “I’m convinced that in the next five years or so, that we will have an emergence of good stories coming out of the [Singapore] biotech ecosystem.”
The baton for the most promising Singapore biotech seems to have passed to Hummingbird Bioscience, which made a splash in 2021 by raising $125 million in a series C round led by Novo Holdings. Developing antibody drugs for cancer and autoimmune disease, Hummingbird has only reached phase 1 in the clinic. Aslan also remains in the game with eczema candidate eblasakimab having just posted some mixed phase 2 results.
Evolving biotech hub
Singapore has accrued plenty of experience for early-stage studies, but the country’s maturation as a biotech hub will require more late-stage experience and business networks, Tessa’s then-CEO Thomas Willemsen said during an interview in May.
Compared with more established biotech hubs like Boston, Singapore still lacks the cluster effect where one could just walk down the street and talk collaborations, Willemsen said.
Heathers could still remember Singapore’s lack of experience in the biotech business model when he arrived in 2000. With an economy built on trading, Singapore at that time was unfamiliar with the idea of an innovation-driven industry that’s reliant on intellectual properties. A lot of scientists were also only thinking about publications, Benjamin Toh, executive director for A*STAR’s biomedical research council, recalled.
Besides, a thriving real estate market didn’t make waiting for 10 years to develop a drug that appealing an investment. So, despite some initial interest, biotech startups built with government funding during the first 10 years of the initiative largely just did more science and died, Heathers recalled.
“But they learn,” Heathers said of the Singapore government. “Now I think it’s very much really focused on that economic goal.”
There’s been a mindset shift among scientists to start thinking about translating science into products and into biotech spinouts, Toh said. Over time, people started to appreciate the value of biotech companies, and investors also started looking for alternative investments as the economy matured and the real estate market cooled.
Not counting large pharma companies’ local offices, the number of Singapore-based biotechs has increased from just seven in 2012 to 52 in 2022, according to a recent report by SGInnovate and L.E.K. Consulting. But only three companies were at commercial stage, including one focused on biosimilars; and two were in clinical phase 3, including Tessa. The scale is simply no match to the Boston area, where over 1,000 biopharma companies call home.
Perhaps Singapore shouldn’t be compared side by side with Boston. The island country is only about 280 square miles with less than 5.5 million people. The Greater Boston region itself has about 5 million people residing in an area that’s five times as large as Singapore.
To Heathers, 20 successful biotechs would be a good count for the size of the island to have a successful ecosystem. But Singapore still needs to establish itself among biotech hubs in the global ecosystem. Singapore is trying very hard to find the right niche to play; after all, as Heathers sees it, areas such as small-molecule chemistry can be difficult to catch up.
“What I appreciate about the Singapore spirit is that we’re always learning, and we’re always adapting, because you recognize we will never be a Boston, we will never be a San Francisco,” Irene Cheong, executive director of A*STAR’s innovation and enterprise group, said. Cheong compared Singapore to chili padi, a very small type of chili with a very high concentration of capsaicin.
“We can never be the scope that we see in other international biotech hubs,” Cheong said. “And I think that forces our hand to choose, very carefully.”
Right now, nucleic acid therapeutics, bioprocessing and cell and gene therapies are among the areas that Singapore has chosen to double down on, Cheong said.
“It’s very difficult for Singapore to suddenly create a medicinal chemistry industry,” Heathers said. “But cell therapy is brand new, and everybody is still figuring this out.”
Heavy government involvement
A*STAR, a unit under Singapore’s Ministry of Trade and Industry (MTI), is spearheading Singapore’s big biotech ambition.
“There is a concerted effort to say, what can we be doing to capture more of the value chain to create more companies here so that people invest in Singapore,” Outram’s Tan said.
“There’s a lot of political will behind” Singapore’s biotech plan, said Stephen Sunderland, head of L.E.K.’s Southeast Asia healthcare and life science practice based in Singapore. “Ultimately, governments are very good at creating environments in which corporates can operate, including imperative by taxes.”
Back in 2000, the Singapore government laid out $2 billion over five years as part of the initial push to catapult into a biotech hub. Between 2006 and 2015, the state poured around 7.3 billion Singapore dollars ($5.5 billion) into the biomedical science sector, according to the MTI. Another 4 billion Singapore dollars ($3 billion) was laid out in 2016 under a five-year R&D expenditure plan. The country’s new Research, Innovation and Enterprise 2025 scheme includes a record 25 billion Singapore dollars ($19 billion) of funding from 2021 to 2025, with an expanded human health sector as one of the four pillars.
Under the biomedical sciences initiative launched in 2000, the Singapore government realized the need for a research-intensive medical school. So in 2005, it facilitated a collaboration between Duke University and the National University of Singapore to form the Duke-NUS Medical School and invested heavily in the first seven years to get the ball rolling.
To foster Singapore’s research capabilities, the government formed Create, a national project that brings in top global universities and research institutes. Massachusetts Institute of Technology, the University of California, Berkeley and ETH Zurich are among those that have established footprints.
There’s also Temasek, the large investment firm owned by the Singapore government, for which biotech is a key interest area. The firm previously backed Tessa, although the fund doesn’t limit its financing target to domestic entities.
At A*STAR, Toh’s biomedical research council brings early research through target validation and into early clinical trials, while Cheong’s group focuses on helping scientists identify commercial opportunities. And O’Connell’s EDDC is basically a publicly funded biotech company that turns research into drugs to either spin into new companies or out-license to other biopharma companies. And a separate MTI unit known as the Economic Development Board works to bring investment into Singapore.
“We have all these different pots, from clinical trials development, manufacturing, you name it, we’ve got some form of funding to support you with it,” Cheong said. “But more and more, we’re finding it’s about enabling them to ask the right questions to the right people.”
For each project A*STAR funds, a program manager will be assigned to help innovators navigate the entire process. These include linking them up with mentors or advisers and guiding them through the development pathway. Toh sees A*STAR’s role as “generating a pipeline of knowledge” to help grow Singapore’s biotech ecosystem. In a setup that may look problematic in the U.S., A*STAR staffers regularly rotate into existing biotech companies. They can both support the company and bring back new learnings from the industry.
“I think that kind of porosity and flexibility is important because we need to see all aspects of our ecosystem, not just in the public sector, but also from the private sector,” Cheong said.
A crystallization process
While the government can train young professionals or lure industry veterans, Singapore’s biotech talent pool is simply not that deep, L.E.K.’s Sunderland said. Without many success stories, Singapore has historically lacked experienced biotech leaders and experts in late-stage drug development.
Willemsen also acknowledged that as Tessa’s work started to weigh more heavily toward late-stage clinical development and commercialization, a second headquarters in Boston would make sense. But if any biotechs targeting a global impact simply move out of Singapore once they reach a certain stage, it could mean that the country never builds that late-stage knowledge.
“There is a bit of a risk of a vicious cycle around that,” Sunderland said, “because you miss the later stages of commercialization, and that expertise, that talent, still sits offshore somewhere. Even if for headquarters tax purposes, IP still resides in Singapore, the actual people who know how to do that do not.”
The talent gap may only get worse as more Singapore biotechs move up the development ladder. By L.E.K. and SGInnovate’s estimate, the number of clinical-stage biotech companies in Singapore will swell from 14 in 2022 to 36 in 2032. That will create a 41% talent shortage in clinical roles, or more than 120 positions out of a total demand of nearly 300, according to the pair’s “Bridging the Talent Gaps in Singapore’s Biotech Sector” report.
“If I had a magic wand, and I could wave it and like, give me this, it would be the experienced biotech managers, meaning people who have run and taken assets, services through regulatory, delivered into the marketplace and cycled a few times,” Cheong said. “I think that experience is what’s missing in Singapore right now.”
The country is working to fill the gap either by migrating talent from abroad—like it did 20 years ago—or by putting training programs in place. A few years ago, the Singapore government collaborated with Stanford University to bring its innovation fellowship program, called Stanford Byers Center for Biodesign, to Singapore. The chapter became independent of Stanford in 2018. Now housed under A*STAR, Singapore Biodesign has trained over 800 people.
SGInnovate has created the Helix immersion program, which offers a one-year, full-time, on-the-job training for biomedical professionals. Functions the program covers span therapeutic project management, regulatory affairs, manufacturing controls and early drug metabolism and pharmacokinetics analytics.
Singapore has lured many renowned scientists and biopharma insiders over the past two decades to lay the foundation of the country’s biotech industry. And it’s resorting to that strategy again to further boost the sector. For example, John Connolly, Ph.D., who later became chief scientific officer of the Parker Institute for Cancer Immunotherapy, joined A*STAR in 2010 to lead its translational immunology efforts. He also previously served as Tessa’s chief scientific officer until 2020.
“Our recognition is that scientists like scientists of the same quality,” Cheong said. “It’s almost like a crystallization process—if your center crystal is of a certain quality, then theoretically, they kind of attract.”
A tightrope between East and West
One way that Singapore could attract more seasoned biopharma veterans is through Big Pharma. For example, Willemsen was Takeda’s Asia-Pacific head based in Singapore before jumping over to Tessa last year.
Foreign pharmas have a long history in Singapore. In 1972, Beecham, a legacy GSK company, decided to invest in a chemical facility in Singapore, which marked the birth of the biomedical industry in the country. In 2003, Novartis established the Novartis Institute for Tropical Diseases at the then newly built Biopolis research hub.
Singapore historically became an economic success partly because of its strategic location in the busy trade path of the Malacca Strait. Today, Singapore stands at the crossroads of the West and the East. Rising geopolitical tension between China and the U.S. appears to be fueling a fresh boom of pharma investment in Singapore.
In 2021, Sanofi unveiled a plan to invest 400 million euros ($440 million) to build a new vaccine production site in Singapore. The same year, BioNTech pledged to set up a Southeast Asia regional headquarters and has bought a legacy Novartis plant for mRNA vaccine manufacturing. The next year, Merck opened a secondary packaging facility in Singapore to churn out vaccines and other biologics, just as the New Jersey pharma broke ground on an inhaler facility in the country. Even Chinese CDMO giant WuXi Biologics is plotting heavy investment in Singapore by laying out $1.4 billion over a 10-year span to beef up R&D, plus large-scale drug substance and drug product manufacturing.
“There are some wider market factors … that could be triggers or facilitators in the growth of that [biotech] ecosystem within Singapore,” L.E.K.’s Sunderland said, “part of which is clearly some nervousness around China as an origin for product or destination market for talent.”
Singapore itself isn’t a large commercial market—or at least not a destination for the launch of a drug. But Singapore as a biopharma manufacturing hub makes sense because of the large market surrounding it, Sunderland said.
Singapore has largely sat out the U.S.-China power struggle. As Albatroz’s Heathers put it, “the whole existence of Singapore is really much on treading that tightrope between the West and the East.” That political stance has made the country a good spot for companies pointing at China and investors looking to exit in the U.S.
Scientists have lately become collateral damage of the deteriorating U.S.-China relationship. Scholars with ties to China faced—sometimes wrongfully—increased scrutiny as U.S. authorities crack down on China’s influence in the scientific community.
“With the situation globally, I think a lot of top talent are also looking for a safe haven that appreciates their talent, that nurtures their science,” Cheong said.
“Are we leveraging this to benefit our biotech industry? My response would be we’ve always been welcoming. If the case is that the external factors have made it more compelling for Singapore to be considered, then we welcome that too.”