ARO-HSD

AbbVie is teaming up with ADARx Pharmaceuticals to develop siRNA therapeutics, committing $335 million upfront and potentially "several billion dollars" in additional milestone payments. The deal, announced Wednesday, is AbbVie's latest effort to diversify its therapeutic modalities across neuroscience, immunology and oncology.The partnership will combine the pharma's expertise in antibody engineering, antibody-drug conjugates, and tissue delivery approaches with ADARx's proprietary RNA technology platform.While siRNA is seen as a promising genetic medicine approach for silencing disease-causing genes, Jonathon Sedgwick, global head of discovery research at AbbVie, says "challenges still remain in targeting and delivering siRNA effectively."Silencing and deliveryADARx says its siRNA programmes are unique in two aspects — silencing and delivery. Specifically, the company's proprietary mRNA silencing technology allows for fine-tuned sequence design and optimisation, while on the delivery front, its cell-targeted delivery system uses engineered ligands to guide RNA therapeutics directly to specific cell types via receptor-mediated internalisation."Our approach has the potential for selective cellular uptake to minimise off target effects and maximal therapeutic effects," CEO Zhen Li told FirstWord in an email.The siRNA space has been garnering attention. Eli Lilly recently unveiled Phase II data for its siRNA lepodisiran in patients with high levels of lipoprotein(a), a risk factor for heart disease. In addition, Boehringer Ingelheim last year partnered with Chinese biotech Suzhou Ribo Life Science for up to $2 billion to develop siRNA therapies against metabolic dysfunction-associated steatohepatitis.Meanwhile, GSK struck a deal Wednesday to acquire Boston Pharmaceuticals' steatotic liver disease treatment efimosfermin alfa, highlighting a possible combo with the UK drugmaker's siRNA therapeutic GSK4532990.

Looking to broaden its hepatology portfolio, GSK inked a deal with Boston Pharmaceuticals potentially worth up to $2 billion, securing rights to the Phase III-ready steatotic liver disease (SLD) treatment efimosfermin alfa. Boston Pharma previously in-licensed the FGF21 analogue — also known as BOS-580 — from Novartis in 2020.Under the terms of the transaction announced Wednesday, GSK will pay $1.2 billion upfront to acquire efimosfermin alfa, with Boston Pharma eligible to receive additional milestone payments totalling $800 million. Additionally, GSK will also be responsible for milestone and tiered royalty payments on the asset to Novartis."The FGF21 class has shown some of the most exciting data" in metabolic dysfunction-associated steatohepatitis (MASH), remarked Tony Wood, chief scientific officer at GSK. He added that efimosfermin "has the potential to define a new standard-of-care with its monthly dosing and tolerability profile," with a potential first launch in 2029. The deal with GSK comes six months after Boston Pharma presented top-line data from a Phase II study of efimosfermin in patients with F2–F3 MASH showing significant and rapid fibrosis reversal, arrested progression, with benefits independent of GLP-1 therapy, alongside improved triglycerides and glycaemic control.GSK also highlighted efimosfermin's potential in other SLD indications, such as alcohol-related liver disease, and in combination with its experimental siRNA therapeutic GSK4532990 in certain SLD sub-populations.Other investigational FGF21 drugs under development include Akero Therapeutics’ efruxifermin and 89bio's pegozafermin, with the latter undergoing late-stage testing to potentially support an accelerated approval filing in the US and conditional approval in Europe.Speaking to FirstWord earlier this year, Jörn Schattenberg — a hepatologist and professor of medicine at the University Medical Center Homburg and University of the Saarland — said that "there are some significant differences" between the various FGF21 therapies, including in pharmacokinetics. Read more on his take here.