Yesterday’s first part of this two-part series surveyed bispecific antibodies for immunological and inflammatory (I&I) disease. Apart from bispecifics, Leerink analyst Thomas Smith lately has proven interested in I&I overall, unveiling his “five for 2025” in a January report that listed five indications with “potential for disruption” in the year ahead.

Boehringer Ingelheim GmbH terminated its second metabolic dysfunction-associated steatohepatitis (MASH) alliance on March 6, ending an $870 million license agreement inked with Yuhan Corp. for dual GLP-1/FGF21 agonist, BI-3006337 (YH-25724). Yuhan said March 7 that Boehringer, of Ingelheim, Germany, returned rights to YH-25724, a dual-acting glucagon-like peptide-1 and fibroblast growth factor 21 receptor agonist, based on the counterparty’s “strategic judgement” on developing MASH therapeutics.

Olix Pharmaceuticals Inc. walked the talk in realizing a new $630 million licensing deal with Eli Lilly and Co. for its cardiovascular and metabolic disease asset, OLX-702A (OLX-75016), rallying stock by 30% after it had largely recovered from a terminated deal with France’s Théa Open Innovation last year.

Olix Pharmaceuticals Inc. walked the talk in realizing a new $630 million licensing deal with Eli Lilly and Co. for its cardiovascular and metabolic disease asset, OLX-702A (OLX-75016), rallying stock by 30% after it had largely recovered from a terminated deal with France’s Théa Open Innovation last year.

Hypoxia-inducible factors (HIFs) are crucial to maintain oxygen homeostasis by regulating cellular metabolic adaptation under hypoxia conditions. Depletion of factor inhibiting HIF (FIH), an enzyme that negatively regulates the activity of the HIF-1α isoform, has been associated with reductions in hepatic steatosis and body mass in mice.

What a difference 60 weeks can make. That’s the lesson Akero Therapeutics Inc. shared with the rollout of what executives called “unprecedented” data from the phase IIb Symmetry trial testing efruxifermin (EFX), its FGF21 receptor agonist, in patients with compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). While earlier findings had shown only a trend in improvement at 36 weeks, full 96-week results showed more than doubling of earlier effect size, hitting the primary endpoint and sending shares of Akero (NASDAQ:AKRO) up 97% to close Jan. 27 at $51.71.

Fatty acid synthase (FASN), an enzyme that drives de novo lipogenesis, plays a relevant role in metabolic disorders such as obesity, non-alcoholic fatty liver disease (NAFLD) or type 2 diabetes. Denifanstat (TVB-2640), a FASN inhibitor, has recently shown positive results in a phase II study in patients with metabolic dysfunction-associated steatohepatitis (MASH).