NorthSea Therapeutics initiates Phase 1 trial of SEFA-6179, targeting the orphan indication of liver disease associated with intestinal failure
Preclinical studies have demonstrated the beneficial effects of SEFA-6179 in preventing the development of parenteral nutrition-induced cholestasis and liver damage associated with intestinal failure-associated liver failure (IFALD)
SEFA-6179 is NST’s third program to enter the clinic
NST strengthens its position as a multi-asset clinical development company targeting the first orphan indication with high unmet medical need
AMSTERDAM, February 02, 2022–(BUSINESS WIRE)–NorthSea Therapeutics BV, (“NST”), a biotechnology company developing new and innovative strategies for the treatment of NASH and other metabolic diseases, today announces that it has launched a phase 1 study with SEFA-6179 in adult subjects, targeting the initial orphan indication for the treatment of IFALD.
IFALD is a multifactorial condition characterized by the development of hepatic inflammation, cholestasis and steatosis in patients with intestinal failure and/or short bowel syndrome. It occurs after prolonged use of total parenteral (intravenous) nutrition. The development of liver fibrosis, which can progress to cirrhosis and liver failure, is a major concern for patients with this disease. No approved drug treatment exists for this population.
The SEFA-6179 Phase 1 clinical trial is being conducted in the UK and is expected to enroll approximately 90 healthy participants. The study is a randomized, placebo-controlled, single dose and multiple ascending dose trial evaluating the safety, tolerability and pharmacokinetics of SEFA-6179. Final results are expected in the third quarter of 2022 and will support the initiation of a global phase 2 study in patients with IFALD, which is expected to start in the first quarter of 2023.
Professor Palle Bekker JeppesenHead of the Department of Intestinal Insufficiency and Liver Diseases at Rigshospitalet Copenhagen, said: “SEFA-6179 showed a broad therapeutic effect on key biomarkers of liver injury as well as improvements in liver histology in several preclinical models. The availability of oral therapy could optimize the management of this hepatic disease with a high medical need. It could provide significant clinical benefit to patients on long-term parenteral nutrition at high risk of IFALD.
NST has a library of structurally modified fatty acids (SEFAs) which are all new chemical entities with unique and differentiated physicochemical properties and biological targets.
Rob de Ree, CEO of NST, commented: “The initiation of this trial is a key step in NST’s journey to becoming a multi-asset company with a strong clinical SEFA pipeline. We are delighted to develop our first candidate for an orphan indication, in particular for an indication where patients currently have no therapeutics. choices available.”
SEFA-6179 is a novel, highly potent, orally administered, synthetic medium-chain fatty acid analog. The molecule directly targets the liver and has demonstrated robust treatment of cholestasis, steatosis and fibrosis in several preclinical models. The unique pharmacological properties of SEFA-6179 facilitate intestinal absorption, which is essential to ensure optimal drug absorption in patients with intestinal failure and short bowel syndrome. Unlike natural fatty acids, NST’s SEFAs are designed to prevent rapid utilization as an energy source, allowing for optimal drug exposure.
NST also has two other SEFA programs in the clinic:
The company’s lead product icosabutate recently completed enrollment in its Phase 2b study in NASH. Last year, NST released strong interim results, and first results are expected in the first quarter of 2023.
SEFA-1024 is being developed for dyslipidemia. The phase 1 study is expected to be completed in the second quarter of 2022.
About Intestinal Failure Associated Liver Disease (IFALD)
IFALD is a multifactorial condition in patients with bowel failure and/or major resection. It is characterized by the development of hepatic inflammation, cholestasis and steatosis. It has been shown to be associated with prolonged administration of parenteral nutrition. Patients with IFALD are often asymptomatic in the early stages, but progress to increased liver biochemistries, steatosis, and fibrosis. This can eventually lead to liver failure, transplant, and death if left untreated. There is a clear medical need for treatment options for patients and there are currently no approved treatments for IFALD.
SEFA-6179 is a novel, highly potent synthetic medium-chain fatty acid (MCFA) analog. MCFAs are rapidly taken up by passive diffusion rather than receptor-mediated transport, but are rapidly metabolized. SEFA-6179 was designed to maintain the ease of transport to the liver and into cells that is characteristic of unmodified MCFAs, while providing enhanced pharmacological effects by avoiding rapid metabolism.
SEFA-6179 treatment completely prevented severe cholestasis and the development of fibrosis in piglets with liver damage due to intravenous (parenteral) nutrition (NP). SEFA-6179 also prevented the pronounced increase in liver injury markers in mice receiving parenteral nutrition in combination with an inflammatory stimulus (endotoxin). Additionally, SEFA-6179 significantly reduced the number of myofibroblasts, the main collagen-producing cell in the liver, in addition to liver inflammation and steatosis in mice with established fibrosis.
The ability of SEFA-6179 to target multiple pathogenic components of IFALD, in addition to its oral dosing potential, highlights its potential to become a highly effective drug for the treatment of NP-induced liver disease as well as other indications of potential liver disease.
About NorthSea Therapeutics
NorthSea Therapeutics BV (NST) is a Dutch biotechnology company specializing in the development of structurally modified fatty acids (SEFAs) for the treatment of non-alcoholic steatohepatitis (NASH) and other metabolic disorders.
NST licensed the rights to its lead compound, icosabutate, and a SEFA library from Pronova BioPharma Norge AS (now part of BASF), which developed Lovaza® (American brand, Omacor brand® in Europe), a successful cardiovascular drug. Icosabutate has been shown to be safe and effective in two previous Phase 2 clinical studies for the treatment of hypertriglyceridemia and mixed dyslipidemia and is currently in clinical development for NASH. The ICONA Phase 2b trial of icosabutate in patients with biopsy-confirmed NASH is expected to complete in the first quarter of 2023.
Two additional SEFAs are in clinical development: SEFA-1024 is in phase 1 to be developed for patients with severe hypertriglyceridemia, and SEFA-6179 is in phase 1 development for the orphan indication IFALD (Intestinal Failure Associated Liver Disease) .
NST is headquartered in the Netherlands with a presence in Norway and the United States and is backed by Ysios Capital, Forbion Growth, Forbion Ventures, venBio partners, Novo Seeds, Sofinnova Investments, BGV, NSV and Hercules Capital.
To learn more about us, visit: www.northseatherapeutics.com
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NorthSea Therapeutics BV
Rob de Ree (CEO)
Email: [email protected]hseatherapeutics.com
Tel: +31 356993000
Instinctive Partners (Media)
Melanie Toyne-Sewell / Agnes Stephens / Katie Duffell / Grace Rutter
Email: [email protected]
Tel: +44 20 7457 2020