Tackling the blood-brain barrier: Duke-NUS discovery leads to startup Travecta

BIOWORLD, MARCH 2018,  Volume 29, No. 56

By David Ho, Staff Writer

HONG KONG – Travecta Therapeutics Pte Ltd. is the latest startup to join Singapore’s biotech block. The newly formed drug discovery company is based on intellectual property derived from discoveries made at Duke-NUS Medical School (Duke-NUS).

Travecta is based on the findings of its scientific founder, David Silver, who published research in 2014 that established a path and transport system that specifically takes lipids such as the omega-3 fatty acid – docosahexaenoic acid (DHA) – to the brain. Silver discovered that a transporter protein called Mfsd2a carries DHA in the chemical form of lysophosphatidylcholine (LPC) to the brain.

“The challenge of delivering central nervous system drugs lies in the blood-brain barrier, which prevents 98 percent of smallmolecule drugs from entering the brain,” said Silver, who is also deputy director of the cardiovascular and metabolic diseases program at Duke-NUS. “MSfd2a is a lysolipid transporter that is highly expressed at the blood-brain barrier and enables the exploitation of its natural transport mechanism to deliver therapeutics conjugated to lysolipid scaffolds for delivery across the blood-brain barrier. “The pathway we found can be exploited to deliver new or existing drugs which have proven ineffective due to their lack of transport across the blood-brain barrier,” he told BioWorld.

“This offers many opportunities, including the revitalization of dormant candidates, the repurposing of existing drugs and the development of new therapies for currently untreatable diseases.”

Travecta now plans to use the Duke-NUS technology to develop therapeutic agents that can be selectively delivered across the blood-brain barrier through a Mfsd2a-directed drug delivery platform for treatment of diseases of the brain, eye and central nervous system, with the aim of providing improved treatment with reduced side effects.

Michael Shleifer, a co-founder of Travecta, told BioWorld the team has found “key indications and targets that have promising outcomes, based on the characteristics of the MFSD2a transporter,” though he declined to divulge any specific indications.

However, Shleifer did say that the clinical studies of proprietary compounds will be conducted in the U.S. As Travecta is based in Singapore, it will additionally work on clearing China’s regulatory path.

“The prioritization of the pipeline is based on many factors, including the regulatory path, which will depend on some specific aspect of each molecule. The platform aims at accelerating drug development by integrating a multidisciplinary approach, which means that we will be careful with drug candidates that bear a high regulatory risk,” said Shleifer.

Laurent Benissan, another co-founder of Travecta, said their conversations with industry partners “show a significant interest due to Travecta’s innovation and the large portfolio of drug candidates which could benefit from it.”

“We can work on direct conjugation of existing molecules by designing synthetics and execute synthesis,” Benissan told BioWorld. “As an alternative, in situations where direct conjugation is not optimal, we offer suitable analogues and work with our partners’ teams to explore the right candidates.”

Once the platform is developed, Travecta plans to develop both an internal pipeline and partnerships with the industry.

Developing a platform around the LPC and Mfsd2a transport system for targeted drug delivery represents among the best of our bench-to-bedside innovations.” – David M. Epstein, Duke-NUS

“Our programs are usually based on risk-sharing models where we receive funding and resources, while offering know-how and support of the clinical plans. Our strengths derive from the partnership with Duke-NUS, a world class research institution, and the agility of being a well-funded early stage company,” said Benissan, who also works at Sprim, a global health research and information consulting firm that will provides insights for clinical and regulatory development to Travecta.

“This model supports the effective translation of R&D and preclinical research to commercial discussions with industry partners,” added Benissan.

The license agreement between Duke-NUS and Travecta was facilitated by the Duke-NUS’ Centre for Technology and Development (CTeD), which is part of an innovation and entrepreneurship initiative focused on commercializing research carried out at Duke-NUS.

CTeD and Silver have worked together for the past several years to develop and commercialize that discovery. That includes the founding of Vanteres (formerly known as Babynostics US, Inc.) that is also based on the same research by Silver.

Travecta is backed by TKS I, a health care and life sciencefocused venture fund by Tikehau Investment Management in Singapore. It is the strategic investment arm of Tikehau Capital, which manages around €12.6 billion (US$16 billion) in assets.

David M. Epstein, Duke-NUS’ vice dean of innovation and entrepreneurship, said that “developing a platform around the LPC and Mfsd2a transport system for targeted drug delivery represents among the best of our bench-to-bedside innovations.”