Abelacimab

iStock, Alona Horkova Flagship Pioneering’s ProFound Therapeutics will use its proprietary technology to mine the expanded proteome for novel cardiovascular therapeutics. Novartis has promised to pay up to $750 million per target, though it has not specified how many targets it will go after. Novartis entered into a four-year partnership with Flagship Pioneering’s ProFound Therapeutics to discover and develop novel protein therapies for cardiovascular conditions. The deal, announced Thursday, has Novartis promising $25 million in upfront and near-term milestone payments and will be on the hook for downstream milestones worth $750 million per target. ProFound will also be entitled to tiered royalties. The companies did not disclose how many targets they plan on going after, nor did they identify which specific indications they will focus on. Proteins are at the center of the ProFound partnership. The companies will leverage the startup’s ProFoundry platform , which looks for novel drug targets within the human proteome, the collection of all human proteins, aided by computational and predictive AI models to accelerate the process. Fiona Marshall, president of biomedical research at Novartis, said in a statement on Tuesday that through the ProFound collaboration, the pharma aims to “explore under-researched biology, uncover new mechanisms, and translate pioneering science into life-changing treatments.” With Thursday’s announcement, ProFound joins fellow Flagship startup Generate:Biomedicines, which inked a pact with Novartis in September 2024. The AI-focused deal involved a $65 million upfront commitment and carries the potential for hefty performance-based milestones, giving the arrangement an overall value of up to $1 billion. Generate will leverage its generative capabilities to discover and develop protein therapeutics for Novartis to study in the clinic. Novartis already has a strong presence in the cardiovascular space with its heart failure drug Entresto, which in 2024 surged 31% year-on-year to bring in more than $7.8 billion. Despite its double-digit growth, however, Entresto is currently under threat from generic competitors, which Novartis is trying hard to block . Beyond Entresto, Novartis also has the siRNA therapeutic Leqvio, approved in 2021 to lower cholesterol in patients with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia. In August last year, the pharma released Phase III data showing that Leqvio could strongly lower levels of low-density lipoprotein cholesterol in patients who were at low or moderate risk of developing ASCVD, potentially opening up avenues for label expansion. In February, Novartis dropped $925 million upfront and pledged up to $2.15 billion in regulatory and sales milestones to acquire Anthos Therapeutics and its blood thinner abelacimab. The investigational antibody targets Factor XI, a key clotting protein. In 2019, Novartis helped launch Anthos alongside Blackstone Life Sciences, in the process offloading abelacimab to the startup. The pharma is now studying abelacimab in three Phase III studies, including one in atrial fibrillation and two in cancer-associated thrombosis.

Taylor Tieden for BioSpace At the heart of the acquisition is Regulus’ farabursen, an miRNA-targeting oligonucleotide in early-stage development for rare autosomal dominant polycystic kidney disease. Novartis is buying Regulus Therapeutics for $800 million upfront , beefing up its oligonucleotide pipeline with the San Diego biotech’s miRNA-targeting assets, according to a press announcement on Wednesday. Under the terms of the acquisition agreement, Novartis will procure all of Regulus’ shares for $7 a pop—a purchase price that represents a 108% premium to the biotech’s closing price on Tuesday. Novartis is also offering Regulus’ shareholders a $7-per-share contingent value right, payable after hitting certain milestones. All told, the acquisition could be worth $1.7 billion. Boards of directors of both companies have unanimously approved the transaction, which is expected to close in the back half of the year, pending customary closing conditions. The centerpiece of Wednesday’s merger is Regulus’ farabursen—its regulatory approval is the trigger for Novartis’ contingent value right offer—an oligonucleotide being developed for autosomal dominant polycystic kidney disease (ADPKD), a rare, hereditary condition that affects around 160,000 patients in the U.S., according to Regulus. The disease is caused by mutations in the Pkd1 or Pkd2 gene, leading to the accumulation of fluid-filled cysts in and across the kidneys and worsening kidney function over time. When left unchecked, ADPKD can lead to kidney failure and eventually death. According to Regulus, Pkd1 or Pkd2 mutations are tied to the upregulation of miR-17, a microRNA molecule that “ directly leads ” to suppression of certain genes, ultimately dampening the production of the proteins encoded by those genes, polycystin 1 (PC1) and 2 (PC2). Farabursen binds to miR-17 to disrupt this pathway to “correct the underlying pathology of ADPKD,” according to Regulus. Through this mechanism of action, farabursen can restore PC1 and PC2 levels, in turn reducing the growth of cysts. Farabursen is in a Phase Ib study that is expected to complete later this year. Aside from farabursen, Regulus is also advancing another nephrology asset and is working on a program for an undisclosed central nervous system indication. The Regulus move is in line with Novartis’ business development philosophy this year. During the pharma’s year-end report for 2024, CEO Vas Narasimhan told reporters the company would “continue our strategy to look for primarily bolt-on acquisitions that we think will bolster our growth in the 2030 and beyond period.” A few days later, Novartis put $3.1 billion on the line to acquire Anthos Therapeutics and its anticoagulant antibody abelacimab.