Protein Degradation Therapeutics Surpasses $3.6 Billion in Deals: Amgen, BMS Accelerate Adoption of AI and DEL Technologies

In the 20 years since the publication of the first PROTAC molecule paper on protein degradation drugs, this technology has transitioned from academia to preclinical and clinical new drug development projects, achieving clinical proof of concept in oncology for the first time in 2019. Targeted protein degradation is a hot area in current new drug research and development, capable of targeting previously "undruggable" targets. By degrading disease-related proteins, it can treat various diseases and address challenges that traditional small molecules or biologics cannot solve.

As of March this year, there are 24 protein degradation drugs in clinical stages globally, with 141 in preclinical stages (33 in China and 108 outside China). These therapies under research target more than 55 different targets. The field of targeted protein degradation is entering a crucial stage of development, with transaction and collaboration events rapidly increasing. According to incomplete statistics from publicly available information as of June 7, 2022, there were 12 global transactions for targeted protein degradation therapies (including R&D or licensing collaborations and acquisitions) in 2022. Five of these disclosed total transaction amounts exceeding $3.6 billion, including companies such as Amphista and Plexium engaging in collaborations with multiple well-known pharmaceutical enterprises through their unique technologies. Compared to the same period last year, major pharmaceutical companies have accelerated their strategic moves in this space.

This article will provide a detailed introduction to the transaction events of targeted protein degradation therapy in 2022 in chronological order based on publicly available information for readers' reference.

1. Salarius Pharmaceuticals Acquires DeuteRx’s Oral Protein Degradation Drug Portfolio

On January 13, 2022, Salarius Pharmaceuticals, a developer of targeted oncology therapies, announced the acquisition of a portfolio of oral small-molecule targeted protein degradation drugs from DeuteRx to expand its oncology pipeline. The acquisition includes DeuteRx's lead candidate DRX-164 (now renamed SP-3164 by Salarius Pharmaceuticals), a related patent portfolio, and a series of undisclosed anti-cancer products developed in the field of targeted protein degradation.

According to the terms of the agreement, the total transaction amount could reach up to $274.5 million. DeuteRx will receive an upfront payment from Salarius Pharmaceuticals, including a cash payment of $1.5 million and a restricted stock investment of $1 million. As part of the agreement, Salarius Pharmaceuticals and DeuteRx will collaborate to complete the development activities for SP-3164 as well as future research and development activities for subsequent products. Upon the successful development of SP-3164, DeuteRx is entitled to receive future clinical and regulatory milestone payments of up to $53 million for SP-3164, sales milestone payments of up to $135 million, and royalties on net sales. Additionally, DeuteRx is eligible to receive clinical, regulatory, and sales milestone payments for two future products, along with royalties on net sales, totaling up to $84 million.

2. Newray Collaborates with Israel's Weizmann Institute of Science to Accelerate Development of Novel Covalent Molecular Glue Degraders

On January 25, 2022, Monte Rosa Therapeutics, a company specializing in the development of tumor protein degradation therapies, announced a collaboration with Yeda Research and Development Company, the commercial arm of Israel's Weizmann Institute of Science, and Dr. Nir London. The partnership aims to leverage Covalent Ligand Directed Release (CoLDR) technology to accelerate the discovery and development of novel covalent molecular glue degrader drugs.

Monte Rosa Therapeutics is a tumor protein degradation therapy research and development company headquartered in Massachusetts, USA. The company's drug discovery platform combines a proprietary small molecule protein degradation drug compound library with proteomics, structural biology, machine learning-based target screening technology, and computational chemistry, which can be used to predict and obtain protein degradation drug profiles.

$350 Million Boosts Development of New Molecular Glue, Amgen Forges R&D Collaboration

On February 4, 2022, Amgen and Plexium announced a multi-year research and development collaboration to discover novel molecular glue therapies for targeted protein degradation aimed at historically challenging drug targets. This collaboration will focus on expanding targeted protein degradation opportunities by identifying previously unknown molecular glues or monovalent degrader drugs.

This collaboration combines Plexium's cell-based high-throughput screening technology to drive the discovery of innovative molecular glue candidate therapies.

Under the terms of the agreement, the collaboration will initially focus on two programs, with Amgen having the option to add additional programs. Plexium is eligible to receive milestone payments based on research and development, regulatory, and commercial progress, with a total amount potentially exceeding $500 million. Amgen will hold the commercialization license for each program advanced to a pre-defined preclinical development stage and will be responsible for global development and commercialization.

4. AI Boosts Protein Degradation Drug Development, Merck KGaA Germany Forges R&D Collaboration

On February 9, 2022, CelerisTx announced a research collaboration agreement with Merck KGaA of Germany to discover and design novel small molecule binders and bifunctional protein degrader drugs using CelerisTx's graph-based artificial intelligence (AI) technology platform.

CelerisTx, founded in 2020, is dedicated to filling the knowledge gap in the rational design of these compounds. The company's developed Celeris One platform is a closed-loop discovery engine capable of predicting biomolecular interactions. It generates new chemical entities that meet the success criteria for relevant degradation drugs and extends this knowledge to synthesis and biochemical validation. The application of this discovery engine is expected to streamline the discovery process of potent degradation drugs while enhancing the productivity of upstream R&D.

5. AI Helps Develop Protein Degradation Therapy, Newcomer Secures Over $600 Million Collaboration

On February 28, 2022, Blueprint Medicines announced a strategic collaboration with Proteovant Therapeutics, a subsidiary of Roivant Sciences, to discover and develop novel targeted protein degradation therapies aimed at addressing unmet medical needs in the fields of oncology and hematology. Targeted protein degradation leverages the body's natural protein disposal system, offering the potential to develop innovative targeted drugs for previously "undruggable" protein targets. Under the terms of the agreement, Proteovant will receive an upfront payment of $20 million and is eligible for additional potential research, development, regulatory, and commercialization milestone payments of up to $632 million, as well as tiered royalties on net sales of future products from the first two programs.

This collaboration will combine Proteovant's AI-based Targeted Protein Degradation (TPD) technology platform with Blueprint Medicines' expertise in precision medicine to discover novel targeted protein degradation drugs. The two companies will jointly research key targets and advance up to two novel protein degrader drugs into the development candidate stage. As a core part of the collaboration, VantAI, the exclusive partner of Proteovant’s TPD platform, will utilize advanced AI technologies for the generation and optimization of protein degradation drugs. After identifying clinical development candidates, Blueprint Medicines holds an exclusive option to develop and commercialize the collaboration products.

6. Collaborated with Janssen on R&D, AI to Aid in Developing New Molecular Glue and Other Drugs

On April 13, 2022, VantAI, an AI-driven drug design company, announced a multi-year collaboration agreement with Janssen. According to the agreement, both parties will leverage VantAI’s deep learning platform to develop novel molecular glues and heterobifunctional protein degradation drugs targeting key disease targets. Under the terms of the agreement, the collaboration will focus on the development of two targeted protein degradation drugs and a novel E3 ubiquitin ligase platform. Additionally, Janssen will obtain exclusive commercial licenses for all products arising from the collaboration and will be responsible for global development and commercialization.

VantAI, a subsidiary of Roivant Sciences, is dedicated to using machine learning to design and optimize induced proximity drugs. The company's evolutionary scoring system draws on naturally occurring protein interaction interfaces, enabling generative models to design smaller molecular weight molecular glues that form highly cooperative ternary complexes. VantAI has partnered with numerous biopharmaceutical collaborators to initiate exciting new development programs through its unique "Protein-Contact-First" strategy, requiring only a fraction of the time and cost of traditional methods.

7. Research collaboration with Boehringer Ingelheim reached, AI to boost development of innovative protein degradation drugs

On April 22, 2022, VantAI and Boehringer Ingelheim jointly announced that they had reached an early-stage drug discovery research collaboration, focusing on discovering innovative degrader drugs for traditionally "undruggable" targets.

This collaboration will initially focus on a degrader program that combines multiple unique E3 ligase platforms. Scientists from both companies will leverage VantAI's geometric deep learning platform to optimize the design of new molecules for each E3 ligase platform. By utilizing the unique interaction interfaces between targets and different E3 ligases, new avenues for enhancing drug potency and selectivity will be created.

8. Molecular Glue Start-up Collaborates with AbbVie to Tackle Neurological Diseases

On April 29, 2022, Plexium announced that it had entered into a research and development agreement with AbbVie to jointly develop innovative targeted protein degradation therapies for neurological diseases. This collaboration will combine AbbVie's extensive capabilities in neuroscience with Plexium's comprehensive targeted protein degradation platform to develop innovative therapies for historically challenging targets.

Plexium Focuses on Developing Monovalent Degraders. Plexium's targeted protein degradation platform uses phenotypic screening of DNA-encoded libraries to identify and evaluate degrader candidates with cellular activity in disease-relevant cellular contexts. As a drug discovery engine, it aims to identify novel small molecules that bind to E3 ligases. These small molecules can bind individually to the target protein or the E3 ligase, inducing conformational changes that ultimately lead to degradation of the target protein. Additionally, the platform is well-suited for studying E3 ligases and the impact of modulating E3 ligase activity on cellular phenotypes, and can be used to identify novel small molecules that bind to E3 ligases, optimizing the small molecules for specific activity profiles.

9. Newray and Germany-based Merck Reach €893.5 Million Collaboration to Advance Next-Generation Targeted Protein Degradation Therapy Development

On May 4, 2022, Amphista Therapeutics, a company specializing in the development of tumor protein degradation therapies, entered into a collaboration with Merck Healthcare, a subsidiary of Merck KGaA (Germany). The two companies will leverage Amphista Therapeutics' proprietary protein degradation drug discovery platform, Eclipsys, to develop small-molecule protein degraders targeting three specific sites within the fields of oncology and immunology, advancing the development of next-generation targeted protein degradation therapies. According to the terms of the agreement, Amphista Therapeutics is entitled to receive upfront payments, research and development funding, and milestone payments, amounting to a total of up to 893.5 million euros.

Amphista Therapeutics is a cancer protein degradation therapy development company headquartered in Scotland and founded by Advent Life Sciences. It is advancing the development of a series of drug candidates, initially focused on oncology to address many difficult-to-treat types of cancer. The company leverages the body's natural processes to selectively and efficiently degrade and remove disease-causing proteins. Its product pipeline, based on a novel targeted protein degradation platform, primarily focuses on diseases including cancer.

10. Newray and Bristol-Myers Squibb Reach $1.28 Billion Collaboration to Advance Novel Targeted Protein Degradation Therapy Development

On May 5, 2022, Amphista Therapeutics, a developer of tumor protein degradation therapies, reached a collaboration with Bristol Myers Squibb. The partnership aims to utilize Amphista Therapeutics' proprietary protein degradation drug discovery platform, Eclipsys, to develop novel targeted protein degradation therapies.

Under the terms of the agreement, the two parties will collaborate to discover and develop small molecule protein degraders. Bristol-Myers Squibb will obtain the global exclusive license for the developed degraders and be responsible for further development and commercialization activities. Amphista Therapeutics will receive a $30 million upfront payment and is eligible to receive potential payments of up to $1.25 billion, including milestone payments, limited expansion collaboration payments, and royalties based on global net product sales.

11. "Targeted Protein Degradation + Proteomics" Strategic Cooperation Reached to Jointly Develop Targeted Protein Degradation Drugs

On May 7, 2022, Hengrui Pharmaceuticals, a company specializing in the development of drugs for protein homeostasis regulation, and Jingjie Biotechnology, a company focused on the application and development of proteomics technology, reached a strategic cooperation agreement. Both parties will establish a long-term and comprehensive strategic partnership in areas such as target discovery and drug development within the targeted protein degradation field. Through this collaboration, Hengrui Pharmaceuticals and Jingjie Biotechnology will fully utilize their respective proprietary small molecule DaMLib libraries, DaTProD platforms, and "Integrated Proteomics Platforms" to jointly lead breakthroughs in targeted protein degradation technology.

Hezheng Pharmaceuticals has independently developed the DaMLib drug-like fragment library and the protein degradation/rescue drug DaTProD and DaTProSTM technology platforms, supporting the efficient output of new drug candidate molecules. The company has built a project pipeline with more than 10 Class 1 new drugs, of which 3 molecules have entered clinical research, and 2 protein degradation molecules have entered preclinical research.

PTM Bio is committed to the application and development of proteomics technology. With the scientific background of "proteomics-precision medicine" frontier research, it has formed a business model that integrates R&D, production, and services. It has now built an "integrated proteomics platform," which includes a proteomics technology platform, an epigenetics technology platform, a biomarker discovery platform, a high-quality antibody development platform, a diagnostic kit platform, and a big data analysis platform.

12. AI Assists in Developing Protein Degradation Therapies, Targeting "Undruggable" Drug Targets

On May 10, 2022, ETERN Therapeutics, which focuses on developing "undruggable" drug targets, and Insilico Medicine, an AI-driven end-to-end clinical stage drug discovery company, announced a collaboration agreement. The two parties will discover and design potential new mechanism drugs for several undisclosed targets.

This collaboration aims to combine Insilico Medicine's end-to-end AI-driven drug discovery platform, Pharma.AI, with Itera Biotech's Dynamic Structure Platform to develop small molecule drugs targeting selected sites. According to the cooperation agreement, both parties will leverage Insilico Medicine’s proprietary generative AI technology platform and molecular design methods such as computer simulation, along with Itera Biotech’s Dynamic Structure Platform and biological screening system, to jointly discover, design, and screen PROTAC small molecule candidate drugs for oncology targets, promoting the development and subsequent translation of innovative drugs.

Original Title: Protein Degradation Therapy Deals Break $3.6 Billion in 2022! Amgen, AbbVie, Merck KGaA, BMS Accelerate AI and DEL Technology Applications

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