Genius Equation: Novo, Evotec Launch Accelerator, Evoking Einstein

By Alex Philippidis

Novo Nordisk and Evotec are evoking Albert Einstein in partnering to launch a translational drug discovery accelerator designed to advance early research from academic institutions into novel therapies.

The companies have named their accelerator LAB eN²—a takeoff on Einstein’s famous equation E=MC²—energy equals mass times the speed of light squared. The “e” in eN² stands for Evotec, while the “N” stands for Novo Nordisk.

LAB eN² will be based in Cambridge, MA, part of the Greater Boston region where Novo has anchored—and earlier this year announced plans to expand—its U.S. R&D operations. The company also has facilities in the Boston suburbs of Lexington, MA, and Watertown, MA.

The accelerator aims to work with biotechs, academic institutions, and venture capital firms partnering on startups that focus on therapies for cardiometabolic diseases as well as rare blood and rare endocrine disorders, Uli Stilz, head of Novo Nordisk’s Bio Innovation Hub, told GEN Edge.

“We want to help accelerate academic discoveries in a unique way,” Stilz said. “How can we help these very early ideas coming out of academia, which often can be transformational? How can we help those early ideas to start the translation journey, and bring all the capabilities and resources it takes to actually bring those ideas to different inflection points—and of course, with a vision to test those concepts in humans?”

Four academic institutions have signed up to participate in LAB eN²: Harvard University, Mass General Brigham, Yale University, and Beth Israel Deaconess Medical Center.

Tractable and transformative

Investigators at those institutions can apply for Discovery Awards of between $1 million and $4 million per project to fund concepts deemed to have “tractable” and “transformative” drug discovery potential. The funding will support joint development of the concepts by the academic investigators, as well as Evotec and the Bio Innovation Hub.

In addition to the funding, the Discovery Awards include:

• Support from the collaboration lead in identifying the most suitable projects and developing a drug discovery workplace
• Drug discovery and development expertise
• Resources to design a drug discovery program and identify a therapeutic candidate
• Access to platforms for a range of therapeutic modalities
• Disease area expertise to achieve preclinical proof of concept
• Regulatory and commercial advice

Projects selected for Discovery Awards are initially funded to reach key preclinical milestones. Projects that achieve their value-inflection points are eligible for additional funding up to the IND application stage.

Among examples of projects Novo Nordisk and Evotec said are likely to receive support: Target validation efforts; screening and hit identification; medicinal chemistry; antibody development; RNA, cell, and gene therapy; structural biology; in vitro validation; and in vivo validation.

Stilz said LAB eN² will provide funding, scientific expertise, and technology to help advance product concepts through preclinical proof of concept. At that point, Novo Nordisk may select from among the successful therapeutic product candidates for further investment and development.

Novo Nordisk has an option to in-license the technology and associated intellectual property—though Novo could instead join with Evotec and the originating academic institution to launch a new start-up company to further pursue the technology being funded.

While the first investigators arrived in Cambridge in 2020—no small feat given travel restrictions associated with the pandemic—the Bio Innovation Hub was formally launched in 2021 as an R&D unit designed to partner with academic institutions, emerging biotechs, and established companies. The Hub was designed to connect startups with Novo Nordisk’s deep knowledge of disease and a century of translational and drug development capabilities, with the goal of accelerating development of new therapies based on innovative ideas.

“It’s a cross-functional team of physician scientists, disease biologists, molecular scientists who think about next-generation modalities,” Stilz said.

Modalities of interest

Among modalities of interest, he said, are programmable medicines that can complement small molecule drugs—the focus of an employment ad in which the Bio Innovation Hub was seeking an “innovation lead” to engage with external partners on potential opportunities to partner on programmable breakthrough therapies.

“We have a keen interest in programmable medicines, how they could complement what we can do today with small molecules,” Stilz said. “I’m scientifically and personally very excited about this area because I think it can help us on this journey to precision medicine to make to make very precise interventions.”

Key to achieving precision therapies is addressing the delivery of those new treatments within the body. That’s the focus of an ongoing Novo Nordisk collaboration involving the Hub with RNA-based drug developer Eleven Therapeutics. In July, the companies launched a research collaboration designed to identify novel molecules that promote precise delivery of nucleic acid.

The collaboration combines Eleven’s DELiveri platform, designed to advance precision in nucleic acid medicine for cardiometabolic diseases. DELiveri uses DNA-encoded libraries or “DELs” to discover conjugates that effectively deliver therapeutic molecules and thus have potential in numerous potential therapeutic areas. Through the collaboration—whose value has not been disclosed—Novo Nordisk obtained exclusivity in stages for specific cell types and applications associated with Eleven’s DELiveri platform.

“We have an interest really to invest in how we can deliver to different cell types, how we can complement siRNAs [small interfering RNAs], which primarily allows you to down-regulate all the modalities, which would allow us to achieve gain of function biological readouts,” Stilz said. “I’m very optimistic about programmable medicines and the impact that they can have on chronic cardiometabolic diseases.”

Earlier this month, Novo Nordisk said the Bio Innovation Hub would join the Broad Institute of MIT and Harvard in a research alliance intended to advance three programs in diabetes and cardiometabolic disease over the next three years. Two programs will work to identify drug targets for clinically important subtypes of type 2 diabetes, while the third will strive to unravel genetic causes of cardiac fibrosis.

The Broad-Novo Nordisk collaboration plans to interrogate genetic subtypes of diabetes and, through the Broad’s Center for the Development of Therapeutics, apply large-scale cell screens to examine the relationships between genes and pathways that could serve as therapeutic targets. Investigators will also work to identify and validate genes that could serve as therapeutic targets to inhibit or possibly reverse fibrosis.

Up-to-$2.76B collaboration

Another modality of apparent interest to Novo Nordisk is AI. Recently, Novo Nordisk joined Valo Health to announce an up-to-$2.76 billion-plus partnership to discover and develop novel treatments for cardiometabolic diseases based on Valo’s large human dataset and AI-based computation.

The Novo-Valo partnership combines Novo Nordisk’s expertise with Valo’s Opal Computational Platform including access to real-world patient data, AI-enabled small molecule discovery and Biowire^® human tissue modeling platform. Novo Nordisk agreed to pay Valo $60 million upfront, up to $2.7 billion in payments tied to achieving milestones for up to 11 programs, plus an undisclosed amount of R&D funding and potential royalty payments.

Five collaborations

Over the past two years, the Bio Innovation Hub launched five collaborations with partners that include:

• Dewpoint Therapeutics: The Boston startup and Novo Nordisk are exploring how modulating biomolecular condensates with condensate-modifying drugs or “c-mods” can reverse the course of insulin resistance and diabetes.
• Flagship Pioneering: Novo Nordisk is working with startups being funded and nurtured by the venture capital giant that aim to develop “breakthrough transformative” treatments for cardiometabolic and rare diseases.
• Kojin Therapeutics: The Boston startup and Novo Nordisk are researching how cardiometabolic disease can be targeted through ferroptosis, an intracellular iron-dependent form of cell death.
• Mellicell: The Newton, MA, developer of treatments for diabetes and other metabolic diseases is partnering with Novo Nordisk to test an in vitro 3D human adipocyte model for higher translatability when screening therapeutics designed to treat cardiometabolic disease.
• Octagon Therapeutics: Novo Nordisk and the Boston autoimmune disease drug developer are partnering to develop a novel platform technology targeting specific lymphocyte populations driving disease progression in non-alcoholic steatohepatitis (NASH).

Some 15 people work at the Bio Innovation Hub, which occupies 10,000 square feet within Novo Nordisk’s R&D site in Cambridge. Most of them are researchers, with some staffers focused on business development.

“The Hub is an integral part of the overall innovation strategy at Novo Nordisk, with a unique approach to tap into innovation in a co-creation model with partners, and so in a very flexible way tap into new ways of thinking, tap into frontiers of science, and really try to find new clues, scientific clues, and starting points to untangle these complex cardiometabolic diseases and find new, next-generation treatment options to help improve life for people living with cardiometabolic diseases,” Stilz said.

Pipeline challenge

LAB eN2 could also help Novo Nordisk address another challenge—that of replenishing its pipeline as some of its most successfully marketed drugs face a loss of exclusivity following the expiration of patents.

By year’s end, primary patents on the active ingredient will expire in the United States and Europe for two Novo Nordisk liraglutide injection blockbusters, the first-generation GLP-1 obesity drug Saxenda® and the GLP-1 therapy for type 2 diabetes Victoza®.

During the first half of this year, sales of Saxenda jumped 36%, from DKK 4.46 billion (about $632.7 billion) to DKK 6.067 billion ($860.5 million), after climbing 52% last year, to DKK 10.676 billion ($1.514 billion) from DKK 7.014 billion (about $994.8 million) in 2021. Saxenda is among drugs enjoying sales jumps as patients flock to obesity treatments.

Victoza sales, however, tumbled 23% in January–June, to DKK 4.651 billion ($659.6 million) from DKK 6.032 billion ($855.5 million), following an 18% year-over-year decline in 2022, to DKK 12.322 billion ($1.748 billion) from DKK 15.054 billion ($2.135 billion) in 2021. Novo Nordisk said North America drove the sales decline, which it attributed to a change in patient preference for less frequent dosing: “The GLP-1 market is moving towards once-weekly and tablet-based treatments.”

By June 2024, Novo Nordisk expects Victoza to face competition from generic versions set to be launched by Teva, Pfizer, and Viatris. Most of Victoza’s patents will have expired by November 2024, although its U.S. formulation patent will not expire until February 2026.

Alex Philippidis is senior business editor of GEN.

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