Novartis Makes Potential $750M+ Bet Per Cardiovascular Disease Target in Another Flagship Pact

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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.

Tristan is an independent science writer based in Metro Manila, with more than eight years of experience writing about medicine, biotech and science. He can be reached at tristan.manalac@biospace.com, tristan@tristanmanalac.com or on LinkedIn.
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