Neomorph and Novo Nordisk Strike $1.46B Deal to Develop Molecular Glue Degraders for Cardiometabolic and Rare Diseases

On February 26, Neomorph announced that it had entered into a collaboration and license agreement with Novo Nordisk to discover, develop, and commercialize multiple molecular glue degraders. Neomorph will lead the discovery and preclinical activities for specific targeted drugs, while Novo Nordisk has obtained exclusive rights for further clinical development and commercialization of the collaboration projects.

According to the terms of the agreement, Neomorph will receive an upfront payment and near-term milestone payments, as well as R&D funding. Neomorph is also expected to receive future clinical, commercial, and sales milestone payments, bringing the potential total value of the deal across multiple targets to up to $1.46 billion (approximately RMB 10.5 billion), along with tiered royalties.

Novo Nordisk's Senior Vice President of Global Research Technology, Brian Vandahl, stated in a release that he is pleased to collaborate with Neomorph and looks forward to advancing research on Neomorph's novel molecular glue degraders, aiding Novo Nordisk in progressing "new treatment options for patients with serious chronic diseases."

Phil Chamberlain, Ph.D., Co-founder, President, and CEO of Neomorph, stated: "By combining Neomorph's proprietary molecular glue discovery platform with Novo Nordisk's extensive expertise in cardiometabolic and rare diseases, we are well-positioned to develop transformative treatments in these areas. Through this collaboration, our platform will expand into new therapeutic fields, complementing our current research efforts in oncology."

For MNC giants, a deal worth $1.46 billion may not seem particularly large. However, for Novo Nordisk, which has always been "cautious," such a rare and bold move undoubtedly reveals the underlying strategic significance.

Looking back at Novo Nordisk's recent transactions, it only paid more than 1 billion US dollars in cash at one time when acquiring Inversago to obtain the oral CB1 reverse agonist weight loss synergy pipeline.

Notably, this transaction also marks Novo Nordisk's first foray into the protein degradation drug sector, which is related to its strategic plan for 2025. Novo Nordisk has been heavily investing in metabolic diseases, and in recent years, its intentions to expand into new areas have become increasingly clear.

On the one hand, Novo Nordisk intends to expand its presence in other metabolic disease areas, including cardiovascular diseases and non-alcoholic fatty liver disease. On the other hand, in 2022, Novo Nordisk renamed its biopharmaceutical division as the Rare Disease Division, further expanding its existing hemophilia and growth disorder businesses.

According to Novo Nordisk's 2023 annual report, the revenue from its two major indication segments—diabetes and obesity (insulin, GLP-1)—reached DKK 215.098 billion (approximately USD 32.175 billion), accounting for 92.61% of the total annual revenue. The remaining revenue from the rare disease segment was only DKK 17.163 billion (approximately USD 2.496 billion).

From the collaboration content between Novo Nordisk and Neomorph, the two parties have reached a multi-target cooperation to develop novel molecular glue degraders for cardiometabolic and rare diseases. This transaction is clearly an important step for Novo Nordisk to accelerate its layout in rare diseases and metabolic disorders.

Although the field of molecular glue is relatively new, it has recently attracted increasing attention from the biopharmaceutical industry.

Compared with PROTAC, molecular glues have a lower molecular weight due to the absence of a Linker, which increases oral bioavailability and improves cell membrane permeability, demonstrating better drug-like properties. However, the discovery of molecular glues is somewhat accidental, lacking systematic discovery methods and rational design strategies, making it impossible to obtain them through large-scale screening of components like PROTAC. Thus, only a handful of molecular glue degraders have been discovered to date.

Currently, three molecular glue drugs—thalidomide, lenalidomide, and pomalidomide—have been approved by the FDA. These drugs have similar structures and function by recruiting the E3 ubiquitin ligase CRBN to degrade target proteins, including transcription factors IKZF1/3. Their core indication is multiple myeloma (MM).

In 2019, BMS acquired Celgene for a staggering $74 billion, gaining three marketed "amide" products and a pipeline including CC-92480, CC-99282, and CC-220, solidifying its leading position in the molecular glue field. Correspondingly, sales performance was impressive, with lenalidomide reaching $12.89 billion in sales in 2021, and pomalidomide peaking at $3.332 billion in sales the same year.

Moreover, just two weeks ago on February 14, BMS reached a $674 million deal with VantAI, under which the former will use the latter’s AI platform to develop molecular glues.

While BMS continues to solidify its barriers in the molecular glue field, several MNCs such as Merck, Roche, and Merck KGaA are also stepping up their investments in this area. In April 2023, Merck entered into a $2.55 billion molecular glue collaboration with Vienna-based biotech company Proxygen. In September 2023, Genentech paid $47 million upfront for Orionis Biosciences' molecular glue platform to apply the technology to oncology and neurodegenerative disease targets. Genentech has committed up to $2 billion in funding for this deal.

Based on the molecular glues that have currently entered the clinical stage, their indications are typically cancer. In fields outside of cancer, the application of molecular glues is generally still in the early stages of development. However, due to their ability to target difficult-to-drug targets through ternary complex structures, molecular glues inherently possess the potential to develop targets across almost all fields. Therefore, this transaction between Novo Nordisk and Neomorph can be said to open up new possibilities for the application of molecular glues.

As a rising star in the field of molecular glue, Neomorph was founded in 2020. The company's founding team consists of leading experts in the fields of protein degradation and molecular glue, and maintains a significant and close relationship with the Center for Protein Degradation at the Dana Farber Cancer Institute.

Phil Chamberlain, Ph.D., the current President and CEO of Neomorph, led the establishment of Celgene's cereblon modulation platform. Eric Fischer and Benjamin Ebert both contributed to uncovering the degradation mechanisms of thalidomide and its analogs. Leveraging their expertise and achievements in this field, in December 2020, Neomorph announced a $109 million Series A financing round to advance its proprietary targeted protein degradation platform and specific program development.

The core of this licensing agreement is Neomorph's targeted protein degradation platform.

For Neomorph, the collaboration with Novo Nordisk will help expand its platform into new therapeutic areas. For Novo Nordisk, choosing Neomorph, a rising star in the molecular glue field, not only reinforces its core strategy of focusing on rare diseases but also represents a significant step in comprehensively covering the metabolic field. In the next phase, Novo Nordisk will collaborate with Neomorph on multiple targets within the core areas of cardiometabolism and rare diseases, opening up new possibilities for the application of molecular glue degraders in the future.

References:

A Rare Move by the Metabolic Giant —— Gazelle Society