PureTech seeks a CNS success repeat in Seaport
10 Apr 2024
Phase 2AcquisitionDrug ApprovalLicense out/in
Fresh off the success of schizophrenia-focused Karuna Therapeutics, which Bristol Myers Squibb recently acquired for $14 billion, PureTech Health made another neurology bet on Tuesday, launching Seaport Therapeutics with a $100-million oversubscribed series A.
Both were founded by PureTech to address a massive unmet need in central nervous system (CNS) disorders, and some of the investors in Seaport’s A round – including co-lead investors ARCH Venture Partners and Sofinnova Investments – were early backers of Karuna.
The two companies also were created with a similar goal, according to Chen. Take a compound with known efficacy – and known drawbacks – and solve the existing problems “to get the optimal profile for patients.”
For Karuna, it was about fixing the tolerability issues with xanomeline, which had previously demonstrated antipsychotic benefits in a schizophrenia study run by Eli Lilly, but ultimately was dropped due to a high rate of gastrointestinal side effects. The result of Karuna’s efforts, KarXT (xanomeline-trospium), recently posted positive long-term safety and efficacy data and is awaiting an FDA decision in September.
From the outset, Seaport’s mission is a bit broader: to use its Glyph platform to improve known mood disorder treatments in varied ways, such as creating an oral version or avoiding liver toxicities.
Going the lymphatic route
Seaport holds an exclusive licence to the Glyph platform from the lab of Chris Porter at Monash University. The technology exploits the lymphatic system to allow bypassing of the liver. By attaching a fat molecule, a therapeutic compound is treated as a dietary fat and absorbed directly into the bloodstream, avoiding first-pass metabolism.
To Chen’s knowledge, no other group is pursuing drug delivery using the lymphatic system, which he called a “dark area of biology.”
“No one really ever talks about how olive oil is absorbed,” he explained. “But in this case, we’re able to use this proprietary chemistry platform to take advantage of the way the body absorbs things like olive oil and actually solve a really important problem, which is that a lot of these CNS drugs are effective or potent or active and have, in some cases, clinical data showing that they work, but they are held back by some key flaw or deficit.”
Seaport’s lead candidate, SPT-300, is a prodrug of allopregnanolone in Phase II testing. The neurosteroid has been shown to be effective for postpartum depression, but required a 60-hour IV infusion, Chen said. SPT-300 is given as a pill and has already demonstrated proof-of-concept in a clinical model of anxiety in healthy volunteers.
The biotech’s preclinical pipeline includes SPT-320, a prodrug of agomelatine for generalised anxiety disorder, and SPT-348, a prodrug of non-hallucinogenic neuroplastogen for mood and other neuropsychiatric disorders.
Agomelatine is approved in Europe and Australia for anxiety, Chen said, but because much of the drug is broken down in the liver before it reaches the bloodstream, it can cause transient adaptive increases in liver enzymes. Patients on the drug are required to undergo frequent liver function tests to monitor the liver side effects.
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