Third-gen TKI for lung cancer

RIDGEFIELD, Conn.—Boehringer Ingelheim Pharmaceuticals Inc., the largest U.S. subsidiary of Germany’s Boehringer Ingelheim Corp., announced recently that it and Seoul, South Korea-based Hanmi Pharmaceutical Co. Ltd have sealed an exclusive license and collaboration agreement for the development and global commercialization rights—except South Korea, China and Hong Kong—of HM61713, a novel third-generation EGFR-targeted therapy for the treatment of non-small cell lung cancer.

 

Under the terms of the deal, Hanmi will receive an initial payment of $50 million and is entitled to potential milestone payments of $680 million, plus tiered double-digit royalties on future net sales. The agreement is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act, similar requirements outside the U.S. and other customary closing conditions.

 

Dr. Jörg Barth, corporate senior vice president and head of the oncology therapy area for Boehringer Ingelheim, said in the release announcing the agreement, “This exclusive license agreement with Hanmi Pharmaceutical is a significant step towards our vision of providing a wide range of lung cancer treatment options as we better understand the underlying drivers of this devastating disease. The in-licensing of a third-generation EGFR agent bolsters our existing lung cancer portfolio and reiterates our commitment towards improving the lives of people with cancer through innovation and tailored treatment options.”

 

HM61713 is a novel orally active, irreversible EGFR mutation-selective tyrosine kinase inhibitor (TKI). At this year’s annual meeting of the American Society of Clinical Oncology, interim results of the Phase 1/2 clinical trial were presented and showed strong efficacy signals, combined with a favorable safety profile. The compound is currently in Phase 2 clinical development for patients with non-small cell lung cancer with T790M mutations who have developed resistance to previous EGFR targeting agents. Preparations have begun for a broader Phase 3 trial program to be initiated in 2016.

 

The third generation of EGFR inhibitors is defined by their EGFR mutant-selective profile, a Boehringer Ingelheim spokesperson explains to DDNews. This means that they preferentially inhibit mutated forms of EGFR in the tumor while sparing the normal EGFR (wild-type) forms present in normal tissue. The inhibition of normal EGFR is associated with the main side effects (e.g., skin rashes and diarrhea) of first-generation (gefitinib, erlotinib) and second-generation (afatinib) EGFR TKIs. In addition to inhibiting tumors with common EGFR mutations (exon deletion 19/Del19 and exon 21/L858R), which are sensitive to first- and second-generation TKIs, the compounds like HM61713 (BI code BI1482694) display activity against T790M mutations—the most common resistance mechanism to TKIs.

 

Third-generation EGFR TKIs such as HM61713 have been specifically designed to inhibit this particular mutant of the EGF receptor. Therefore, if used in the first-line setting, third-generation TKIs may indeed avoid the emergence of the T790M mutation. If used in the second-line setting after a first- or second-generation EGFR targeting agent, where the T790M mutation is already present in the majority of progressing tumors, a third-generation TKI will be active and able to overcome the resistance against previous EGFR targeting agents. For example, the response rate observed in Phase 1/2 clinical trials with HM61713/BI1482694 in a T790M-positive population resistant to erlotinib or gefitinib was 55 percent.

 

Phase 1/2 data presented at ASCO 2015 were very encouraging, Boehringer Ingelheim notes, demonstrating a response rate of 54.8 percent and a disease control rate of 95.2 percent with a favorable safety profile, putting HM61713 in a competitive position vs. other third-generation TKIs.

 

HM61713 is another important pillar in Boehringer Ingelheim’s global lung cancer franchise, which builds on two products, Giotrif/Gilotrif (afatinib) and Vargatef (nintedanib). With the inclusion of HM61713, Boehringer Ingelheim now has more than 10 compounds in clinical development in a wide variety of oncology indications, including immuno-oncology approaches like an mRNA-based therapeutic vaccine under development in collaboration with CureVac.

 

Dr. Jeewoong Son, chief medical officer of Hanmi Pharmaceutical, said, “We are excited at the potential this license agreement with Boehringer Ingelheim will bring to the successful development of HM61713 and the possibilities this will offer to lung cancer patients. Boehringer Ingelheim has significant expertise in the field of lung cancer, specifically in EGFR-mutated disease. With Boehringer Ingelheim’s strong pipeline demonstrating its long-term commitment to successful development of cancer treatments, we are confident we have found the right partner to make the potential of HM61713 a reality.”

 

Building on scientific expertise and excellence in the fields of pulmonary and cardiovascular medicine, metabolic disease, neurology, virology and immunology, Boehringer Ingelheim has embarked on a major research program to discover and develop innovative cancer treatments. Working in close collaboration with the international scientific community and a number of the world’s leading cancer centers, Boehringer Ingelheim’s commitment to oncology is underpinned by using advances in science to develop a range of targeted therapies for various solid tumors and hematological cancers. The current focus of late-stage research includes compounds in three areas: signal transduction inhibition, angiogenesis inhibition and cell-cycle kinase inhibition. The company is also evaluating a robust and growing pipeline of early-stage oncology compounds in areas including growth/survival signaling, immunotherapy and epigenetics.