Singapore venture capitalist XQ Lin has long had his finger on the pulse of cutting-edge cancer therapies. For more than two years, he tracked the progress of a team of Duke-NUS cancer scientists as they made inroads into a new way of using the immune system to fight cancers, a field known as cancer immunotherapy. When the field of engineered T cells used to treat cancer achieved initial clinical validation, Lin knew that it was time to enter the fray.

“So when the field got hot earlier this year, we had a case of 天時地利人和 (tiān shí, dì lì, rén hé),” said Lin, using the Chinese phrase meaning ‘the right person in the right place at the right time’.

By August, Lin’s Esco Ventures X, along with another local investor, Jeffrey Lu from Avendesora, teamed up with David Epstein, former Duke-NUS Vice-Dean for Innovation and Entrepreneurship and now an associate professor with the School’s Cancer and Stem Cell Biology Programme, and Dr Raymond Lee, a research fellow in his lab, to establish PairXBio. 

It all started when Lee and Epstein, then an associate professor at the School, had a eureka moment back in 2017. At the time, they were deciphering what the changes in protein structure caused by defects in RNA splicing could teach them about how cancer — gastric cancer, in particular — develops and spreads. Healthy cells cut, or splice,  individual segments of genes from large chunks of messenger RNA to make essential proteins required for human health. In cancerous cells, these cuts are executed incorrectly and at different locations, creating large changes in the protein sequence.

“But unlike cancer-induced changes in DNA, which are now known to be unique to individual patients, we found that the splicing patterns we had observed were shared across groups of cancer patients,” said Epstein, a discovery that he believes was a first of its kind.

To turn his science into a computer algorithm, Dr Raymond Lee had help from different teams from across the medical school

Lee and Epstein’s discovery suddenly opened an opportunity to develop a new approach to developing cancer immunotherapies designed to help larger numbers of patients. As a molecular biologist, Lee focused first on writing a computer algorithm that would allow the team to identify which particular part, or antigen, from the pattern of spliced proteins was associated with cancer. Using the data from the algorithm, he worked with colleagues to develop the necessary screens to search for the antigen and prove that these types of antigenic regions trigger an immune response in cancer patients.

“I still remember the email our collaborator sent at about midnight saying we had a possible hit,” said Lee, reliving the excitement of the moment.

Further research revealed that this ‘hit’ was shared by a significant group of gastric cancer patients in Singapore.

“We found that this novel cancer antigen appears to be shared by approximately ten per cent of gastric cancer patients,” said Epstein.

This discovery set off a chain of events that would take more than a year before the science could be reproduced and expanded to a level where the team felt their invention could be commercialised.

With the guidance of Epstein and assistance from the team from Duke-NUS’ Centre for Technology and Development (CTeD), Lee collaborated with clinicians from across Singapore to expand their study to other cancers common in Asia, focusing on head and neck, liver and colorectal cancers. 

“CTeD not only protects inventions made by Duke-NUS scientists but also helps matchmake and road-test discoveries to a point where the right investor will take them on,” said Associate Professor Chris Laing, who has since taken over from Epstein as Senior Associate Dean for Innovation and Entrepreneurship.

A scientist at heart, Lee was grateful for the support from the team at CTeD. They supported him with drafting and negotiating the necessary agreements and also coached him on how to navigate the biotech sector and pitch to potential investors.

“At the time, I was looking at a huge black box,” said Lee. “I had no idea how to go about it, but I was curious to see how far I could go with it.”  

In January 2020, Esco Ventures X, a global biotech venture capital firm affiliated with Singapore-grown life sciences giant Esco Lifesciences Group, agreed to seed finance the project to obtain more data for validation.

For Lin, investing in a platform technology that addresses one or more bottlenecks in the development of therapeutics was an attractive proposition.

“PairXBio has the potential to generate multiple therapeutic candidates against multiple cancer types and showed promising results in terms of patient samples,” said Lin, whose Esco Ventures X focuses exclusively on creating and investing in biotech companies, developing next-generation therapeutics.

Looking back at the journey so far, Lee and Epstein (who has since stepped down from the role of Vice-Dean to helm his own Boston-based start-up in precision oncology), are the scientific founders of PairXBio, say that starting a biotech company is like “venturing into the great unknown”.

“I’m thankful to have met a capable and trusted team who brings their diverse skillsets and strengths to the table,” Lee added.