Johnson & Johnson Terminates $915M Collaboration with Hanmi, Returns Global Rights to GLP-1/GCG Dual Agonist JNJ-6456511

On July 4, Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, announced the termination of its collaboration with Hanmi Pharmaceutical on the GLP-1/GCG dual receptor agonist antidiabetic drug JNJ-6456511 (HM12525A), returning the global development rights. Triggered by this news, Hanmi’s stock price plummeted by 27% on the same day.

Hanmi stated in public filings that Janssen terminated the collaboration primarily because, although JNJ-6456511 met the primary endpoint of weight reduction in two Phase II studies, it was inferior to Janssen’s existing drugs in lowering blood glucose levels. In fact, Johnson & Johnson had already suspended clinical development of JNJ-6456511 in 2018 due to drug manufacturing and supply issues.

Hanmi Pharmaceutical stunned the entire pharmaceutical industry in 2015 with several major license-out deals with pharmaceutical giants, including:

March 4, 2015: Eli Lilly and Hanmi Pharmaceutical entered into an agreement granting Eli Lilly exclusive global development rights (excluding South Korea) for the BTK inhibitor HM71224 for the treatment of autoimmune diseases. The deal included a $50 million upfront payment, with up to $640 million in subsequent R&D, regulatory, and sales milestones, bringing the total transaction value to $690 million.

On July 29, 2015, Boehringer Ingelheim and Hanmi Pharmaceutical signed an agreement granting Boehringer Ingelheim exclusive global development rights (excluding South Korea and China) to the third-generation EGFR inhibitor HM61713. The deal included a $50 million upfront payment, followed by $700 million in milestone payments and double-digit tiered sales royalties, bringing the total transaction value to $750 million.

On November 5, 2015, Sanofi entered into an agreement with Hanmi Pharmaceutical to acquire development rights for three of Hanmi’s investigational long-acting diabetes drug assets, including the long-acting GLP-1 receptor agonist efpeglenatide, a once-weekly insulin product, and a fixed-dose combination GLP-1 receptor/insulin product. Sanofi paid an upfront fee of €400 million, with additional milestone payments totaling €3.5 billion and double-digit sales royalties, bringing the total transaction value to €3.9 billion.

On November 10, 2015, Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, reached an agreement with Hanmi Pharmaceutical to obtain exclusive global development rights for the GLP-1/GCG dual receptor agonist HM12525A in regions outside South Korea and China. Janssen paid an upfront fee of $105 million to Hanmi, with additional milestone payments totaling $810 million for research and development, regulatory approval, and sales achievements, as well as double-digit post-launch sales royalties. The total value of the transaction amounted to $915 million. HM12525A was being developed for the treatment of diabetes and obesity and was poised to enter Phase II clinical trials at the time.

On November 23, 2015, Zai Lab entered into an agreement with Hanmi Pharmaceutical, securing exclusive development rights for the third-generation EGFR inhibitor HM61713 in China (including Hong Kong and Macau). According to some media reports, the total value of the transaction amounted to USD 85.28 million.

On September 29, 2016, Genentech, a member of the Roche Group, entered into an agreement with Hanmi Pharmaceutical to acquire exclusive global development rights (excluding South Korea) for HM95573, an oral pan-RAF inhibitor in Phase I clinical trials. The deal included an upfront payment of $80 million, potential milestone payments totaling $830 million, and tiered double-digit sales royalties, bringing the total transaction value to $910 million.

However, most of the aforementioned transactions have largely failed to stand the test of time; several have ended in unsuccessful collaborations, plunging Hanmi into controversy:

In October 2016, Boehringer Ingelheim terminated the clinical development of the third-generation EGFR inhibitor Olmutinib (HM61713) due to severe skin toxicity and ended its collaboration with Hanmi Pharmaceutical on this project.

In December 2016, the financial scope of the diabetes drug development collaboration between Sanofi and Hanmi Pharmaceutical was reduced. Sanofi returned the rights for the research, development, and commercialization of the novel combination therapy comprising efpeglenatide and LAPS insulin. Hanmi Pharmaceutical refunded the €190 million upfront payment received from Sanofi, and the milestone payments were reduced to €2.7 billion. Furthermore, the new agreement required Hanmi Pharmaceutical to provide partial financing and assume responsibility for the subsequent development of efpeglenatide.

In February 2018, Eli Lilly terminated the development of poseltinib due to insufficient efficacy demonstrated in its Phase II clinical trial for rheumatoid arthritis.

In April 2018, Zai Lab decided to terminate its collaboration with Hanmi Pharmaceutical on the third-generation EGFR inhibitor Olmutinib (HM61713).

In July 2019, Johnson & Johnson returned the global development rights for JNJ-6456511 (HM12525A), a GLP/GCR receptor dual agonist hypoglycemic agent.

Original Title: Hanmi Pharmaceutical Faces Another Return! Johnson & Johnson Terminates $900 Million Collaboration, Returns Global Rights to Novel GLP-1/GCGR Dual Agonist for Diabetes