BeiGene Strikes $1.33 Billion Deal for Ensem's CDK2 Inhibitor ETX-197, Marking Its Second Major Licensing Agreement Within Four Months

On November 21, BeOne Medicines announced a collaboration with Ensem Therapeutics to obtain the global exclusive license for the latter's differentiated CDK2 inhibitor ETX-197. Ensem Therapeutics will receive an undisclosed upfront payment and subsequent milestone payments, totaling up to $1.33 billion.

This is the second project introduction cooperation transaction completed by BeOne Medicines this year.

Ensem Therapeutics, which has reached a cooperation with BeOne Medicines,Incubated by CBC Group,It is an innovative pharmaceutical company established in May 2021, with its headquarters located in Boston, USA.

In April last year, Ensem completed a $67 million Series A financing round led by GGV Capital, with participation from Pavilion Capital, Cenova Capital, Mitsui & Co. Global Investment, Inc., and CBC Group. In October 2023, it completed a nearly $10 million Series A+ financing round.

Ensem Therapeutics Focuses on Undruggable Targets to Develop Novel Cancer Drugs, Utilizing Its Unique Kinetic Technology Platform to Develop Innovative Small Molecule Drugs Based on Protein/RNA Dynamic Conformational Changes. Its Platform: Kinetic Ensemble^TMIntegrates molecular simulation, artificial intelligence deep learning, and macromolecular dynamics technologies to identify cryptic binding pockets and accelerate structure-based drug design, developing high-value and difficult-to-drug precision medicine therapies.

Ensem's CDK2 inhibitor ETX-197 was born under this platform. In addition, there are two pipelines in the preclinical stage.

Behind the advanced drug discovery platform is the support of an excellent founding team. Ensem's team consists of experienced drug hunters with extensive expertise in advancing new drugs into clinical trials and regulatory approval. Dr. Shengfang Jin, President and Chief Scientific Officer, is a co-founder of gene-editing pioneer Editas Medicine and formerly served as Vice President of Discovery Biology. Earlier in her career, Dr. Jin also served as Senior Director of Biology at Agios Pharmaceuticals, a pharmaceutical company specializing in genetic diseases, where she led the development of small-molecule cancer metabolism and rare genetic disease portfolios.

Even though it was a newcomer, Ensem Therapeutics still won the favor of BeOne Medicines with its solid strength.

Regarding this collaboration, Wang Lai, Chief Research Officer of BeOne Medicines, stated: "This collaboration complements the company's internally discovered Phase 1 CDK4 inhibitor, which has the potential to enhance current CDK4/6 inhibitors for some breast cancer patients and strengthen our early-stage development pipeline in breast cancer and other solid tumors."

The collaboration between BeOne Medicines and Ensem Therapeutics not only strengthens its own layout in solid tumor tracks such as breast cancer, but also secures a position in the popular CDK2 inhibitor field.

Studies show that CDK2 is associated with breast cancer, ovarian cancer, uterine cancer, gastric cancer, and esophageal cancer. It is involved in the changes that lead to breast cancer resistance to CDK4/6 inhibitors.

Currently, CDK2 has become a popular target for treating solid tumors. Despite ongoing efforts to develop CDK2 inhibitors, no related drugs have been approved for marketing yet.

This is related to the difficulty of its drug development. In fact, CDK2 was identified as a target for anti-tumor drug research and development early on, but initial efforts were stalled, largely due to off-target effects of early candidate compounds, which led to unresolved drug toxicity issues.

However, the industry has not abandoned the development of CDK2 inhibitors. Bayer, Pfizer, Incyte Corporation, and Blueprint Medicines are all focusing on this track for drug development. Recently, Incyte Corporation's INCN123667 has reignited industry interest in inhibiting CDK2, with its product currently in Phase 1 clinical trials for the treatment of triple-negative breast cancer (TNBC).

PF-07104091, developed by Pfizer, is currently undergoing two Phase 1/2 clinical trials overseas to explore its efficacy and safety as a monotherapy or in combination for treating various tumors, including non-small cell lung cancer and breast cancer. In July 2022, the PF-07104091 tablet received clinical approval in China and is being developed for the treatment of advanced solid tumors. Current clinical research results indicate that PF-07104091 as a monotherapy demonstrates good tolerability and shows promising efficacy in HR+/HER2- metastatic breast cancer (MBC) resistant to CDK4/6 inhibitors.

Compared with the progress of other CDK2 inhibitors, Ensem's ETX-197 is currently in the preclinical stage, not taking the lead in competition but also not falling far behind. However, Ensem claims it to be the best-in-class candidate drug. They believe this molecule has the potential to treat patients with cyclin E-amplified tumors and those who have developed resistance to standard treatments due to CDK2 activity dysregulation.

BeOne Medicines' introduction of Ensem Therapeutics' ETX-197 has the potential to cover CDK4/6 inhibitor-resistant patients, forming a complementary relationship with its own products, demonstrating its determination in breast cancer strategy.

Thus, despite the challenge of drug toxicity, CDK2 inhibitors still hold a series of potentials in the treatment of solid tumors.

The collaboration deal with Ensem Therapeutics marks BeOne Medicines' second partnership transaction in 2023, coming four months after its previous move.

In July 2023, BeOne Medicines reached a cooperation agreement with Duality Biologics to obtain global rights to a preclinical ADC drug for the treatment of specific solid tumor patients. This transaction is worth up to $1.3 billion.

As a benchmark for innovative pharmaceutical companies in China, BeOne Medicines' external cooperation strategy is becoming increasingly flexible and mature.

In terms of project introduction, BeOne Medicines has a unique perspective. Whether it's the collaboration with ImmuneOnco Biopharmaceuticals or Ensem Therapeutics, they have strengthened their own product pipelines by focusing on technological and pipeline differentiation. Meanwhile, BeOne Medicines is not afraid of risks, as all collaborations involve preclinical products. They have made significant investments to secure a position in popular therapeutic areas.

In terms of licensing cooperation, in September this year, BeOne Medicines and Novartis signed the "Mutual Termination and Release Agreement" regarding the collaboration on Tislelizumab, mutually terminating the licensing agreement. After more than two and a half years of partnership, BeOne Medicines has regained full global rights to develop, manufacture, and commercialize Tislelizumab.

The maturity of BeOne Medicines' commercialization is evident. On one hand, its global clinical registration and commercialization capabilities are gradually strengthening, allowing it to either independently or with new partners continue advancing products globally even after the termination of a collaboration. On the other hand, BeOne Medicines is leading China's innovative pharmaceutical companies in seeking new growth curves in recent years, providing broader growth opportunities for emerging Biotech firms.