Novo on the ‘ins and outs’ of its nucleic acid growthNovo on the ‘ins and outs’ of its nucleic acid growth

Novo Nordisk’s transformation from a small Danish company focused on insulin production to one of the biggest players in the pharma space is well-documented. The company’s current portfolio is being driven by blockbuster drugs Ozempic and Wegovy (both semuglatide) for diabetes and weight loss, which pulled in DKK 86.5 billion ($12 billion) and DKK 38.3 billion ($5.4 billion) for the first nine months of 2024. 

Semaglutide is a glucagon-like peptide-1 (GLP-1) drug, a receptor agonist designed to mimic the action of the naturally occurring hormone of the same name. The drug binds to GLP-1 receptors to promote insulin secretion, suppress glucagon release, and slow gastric emptying – an effect associated with weight loss. 

However, beneath the hood of Novo Nordisk’s drug development engine, the company’s ambitions go far beyond GLP-1s. Its research team has a wide breadth of modalities in its pipeline, including a host of nucleic acid-based therapies. “We are very much looking at established platforms within this field,” Karina Thorn, corporate VP and head of Research, Global Nucleic Acid Therapies (GNAT) at Novo Nordisk, said at TIDES Europe in November 2024. 

Collaboration catalyst 

Novo Nordisk has launched one RNAi product – Rivfloza (nedosiran) for rare genetic condition primary hyperoxaluria type 1 – and has more than five nucleic acid-based candidates in the clinic, Thorn told a packed room in Hamburg, Germany. Nearly 40 other programs, meanwhile, are in preclinical development targeting metabolic diseases, rare conditions, and multifactorial disorders. 

This pipeline grew from leveraging Novo Nordisk’s internal R&D network, comprising hubs in Boston (Massachusetts), Boulder (Colorado), and Copenhagen (Denmark), with external partnerships. Whether with biotech, pharma, academic institutions, or even service providers, these collaborations focus on “co-creation opportunities” rather than straight up dealmaking. 

“That is way more than making a financial transaction between different collaborators,” Thorn said. “We are leaning into marrying the scientific stronghold from the collaborators with what we may build internally.”  

Thorn spoke of five major investments and collaborations that demonstrate this approach and have helped grow Novo Nordisk into an RNA powerhouse. “Each of them has a brilliant story, but also a different story.” 

Cardior and non-coding RNA 

In March, Novo Nordisk acquired Cardior Pharmaceuticals for €1.03 billion ($1.08 billion) adding a non-coding RNA (ncRNA) technology and CDR132L, an antisense oligonucleotide candidate for the treatment of heart failure, based on the platform. While not translated into proteins, ncRNA does regulate critical cellular processes and acts on key disease pathways simultaneously, triggering a concerted therapeutic effect against key hallmarks of heart disease. 

This “example of a nucleic acid-driven external engagement” brought Novo Nordisk “a mature technology,” said Thorn. “It represented a clinical asset in Phase II for the investigation of heart function. This was really an acquisition driven by an interesting asset and the results that it had, but also a reflection that the RNA platform could be something that could inspire us earlier in the pipeline.” 

2seventy and AAV 

Acquiring a nearly ready-made asset differs from the journey Novo Nordisk took with adeno-associated virus (AAV) vector-based gene therapy developer 2seventy Bio. 

In October 2019, Novo and bluebird bio inked a three-year collaboration to develop a hemophilia A gene therapy. This partnership also gave Novo Nordisk access to in vivo genome editing platform megaTAL: single-chain fusion enzymes that combines the natural DNA cleaving processes of Homing Endonucleases (HEs) with the DNA binding region of transcription activator-like (TAL) effectors. 

“It was a true scientific cooperation. There was one component where the 2seventy team based in Boston were in charge and had that proprietary megaTAL nuclease technology for doing precise genomics. We at the Novo Nordisk side had a lot of knowledge about AAV and factor VIII – that was the antigen being applied.” 

2seventy spun out from bluebird in 2021, and in 2024, Novo Nordisk acquired the candidate and gene editing tech in full. 

Dicerna’s GalXC 

Novo Nordisk’s dealings with Lexington, Massachusetts-based Dicerna Pharmaceuticals represented a similar model of partnership that went from a feasibility study collaboration to a full-out acquisition in the RNA space. 

In 2019, Novo Nordisk paid $175 million upfront to collaborate with Dicerna in the discovery and development of RNAi therapies for liver-related cardiometabolic diseases. The deal leveraged Dicerna’s suite of GalXC technologies, which targeted specific genes to maximize pharmaceutical acceptability by enabling access to intracellular disease targets across hepatic and extrahepatic cell and tissue types. 

“This was an agreement that was based on the stronghold of what Dicerna had established with their GalXC platform targeting applications in the liver. This was a large investment going back to how we could apply our novel targets into the platform that had been developed within the GalXC RNAi space.” 

Two years into the collaboration, Novo Nordisk upped its interest in the platform and acquired Dicerna for $3.3 billion in what Thorn described as “marrying the internal investment with tissue targeting binders and what has been developed on the RNAi side.” 

She continued: “This is one of the main reasons that we went from the research collaboration working quite well to now creating a win-win situation, both for Novo Nordisk and for Dicerna, of how we can impact the portfolio even more broadly when we are together and not just collaborators.” 

Gene therapy expansion 

The last two examples Thorn gave of Novo Nordisk’s oligo-focused dealmaking sit in the gene therapy space. 

In May 2023, the firm inked a $225-335 million R&D collaboration with ElevateBio subsidiary Life Edit Therapeutics, with the aim of developing therapies for both rare genetic disorders and more prevalent cardiometabolic diseases. The deal gave access to Life Edit’s CRISPR base editing technology – a method of genome editing that converts one nucleotide base into another without cutting both strands of DNA.  

Meanwhile in September 2024, Novo Nordisk entered a collaboration with NanoVation, accessing the firm’s long-circulating lipid nanoparticle (lcLNP) technology. The firm says lcLNPs have the ability to deliver RNA to cells outside of the liver by aiding functional nucleic acid delivery to extrahepatic cell types. 

Both of these deals are focused on multiple targets, “one of them being more cargo-focused, the other one more delivery-focused.” Like its other deals in the space, Novo Nordisk’s targets and expertise in biology complement the third-party tech platforms, Thorn said, with the question of how to “move that forward in the maturation into clinical candidates” as a permanent horizon.