Boehringer Ingelheim will partner with Lupin on combination cancer therapies that combine Lupin’s lead MEK inhibitor compound LNP3794 with one of Boehringer Ingelheim’s KRAS inhibitors for gastrointestinal and lung cancer patients with a broad range of oncogenic KRAS mutations. The collaboration could generate more than $700 million for the Mumbai biotech, the companies said today.

Boehringer Ingelheim agreed to license, develop, and commercialize LNP3794 through a collaboration intended in part to expand its pipeline of KRAS inhibitors. The companies seek to build on preclinical research showing that the combination of Boehringer Ingelheim’s novel KRAS inhibitors with MEK inhibitors resulted in increased anti-tumor activity based on their complementary mechanisms of action in keeping KRAS-driven cancers in check.

According to the companies, KRAS mutations occur in 1 in 7 of all human metastatic cancers making it the most frequently mutated cancer-causing gene, with mutation rates of more than 90% in pancreatic cancers, more than 40% in colorectal cancers, and more than 30% in lung adenocarcinomas.

“We believe this collaboration will significantly strengthen our KRAS program,” Norbert Kraut, PhD, head of global cancer research at Boehringer Ingelheim, said in a statement. “We have developed comprehensive approaches to successfully tackle the oncogenic KRAS–RAF–MEK–ERK pathway from the ground up, and this partnership is another key building block in our long-term strategy to bring novel treatments to patients in our quest to defeat intractable cancer types.”

Growing interest in cancer treatments

Boehringer Ingelheim’s partnership with Lupin is the latest recent signal of the German biopharma’s growing interest in developing cancer treatments.

In an interview during the 2019 Biotechnology Innovation Organization (BIO) International Convention, held in June in Philadelphia, Ioannis Sapountzis, PhD, corporate senior vice president, business development & licensing with Boehringer Ingelheim, told GEN the company planned to advance into the clinic cancer-cell directed therapies designed to reach KRAS and three other molecular pathways recognized as key drivers of cancer, yet long considered undruggable—Wnt, Myc, and p53.

Last month, Boehringer Ingelheim and the University of Texas MD Anderson Cancer Center agreed to partner on collaborative research on cancer therapies by establishing a joint Virtual Research and Development Center designed to enable effective data sharing and analysis between the organizations. The center will focus on the development of potential new KRAS inhibitors as well as a TRAILR2 agonistic antibody with the potential to selectively induce apoptosis.

The alliance with MD Anderson came a month after Boehringer Ingelheim expanded its immuno-oncology pipeline by shelling out up to €325 million (about $358 million) to acquire Swiss-owned AMAL Therapeutics, a developer of first-in-class cancer vaccines based on its KISIMA® technology platform.

According to its website, Lupin has advanced two clinical studies in oncology: A completed Phase I study in Europe on terminally-ill lung cancer, melanoma, and colon cancer patients; and a Phase II study launched in India with the goal of treating a refractory type of lung cancer which has RAS mutations, for which no treatment exists worldwide.

Oncology is one of three therapeutic areas of focus for Lupin’s Novel Drug Discovery and Development (NDDD) program; the other two are immunology and metabolic disorders.

LNP3794 is a potential treatment for skin cancer, pancreatic cancer, non-small cell lung carcinoma, colorectal cancer, or thyroid cancer. The compound is designed to block MEK, a protein shown to be activated in solid tumors with mutations in the BRAF and RAS genes, which are involved in cancer cell growth.

Phase I U.K. trial

LNP3794 is the subject of a 17-patient Phase I trial in the U.K. (IRAS ID 157025) designed to determine the maximum tolerated dose of the drug when administered orally to adults with advanced solid tumors that have progressed despite standard therapy, or for which no standard therapy exists.

“Lupin’s MEK Inhibitor program successfully cleared early clinical stages, demonstrating our capabilities in delivering world-class innovation,” stated Nilesh Gupta, managing director at Lupin. “We are proud of the achievements of our team and the capabilities we have built which enable us to further our new drug discovery program. We are delighted to partner with Boehringer Ingelheim in developing treatments that will truly benefit patients in need.”

Boehringer Ingelheim has agreed to pay Lupin $20 million upfront, and the rest in payments tied to achieving clinical, regulatory, and commercial milestones.

The partnership with Boehringer Ingelheim is Lupin’s second with a global biopharma over the past year. In December 2018, Lupin and AbbVie launched an up-to-$977 million collaboration to develop and commercialize novel drugs for blood cancers. AbbVie agreed to pay Lupin $30 million upfront, and up to $947 million in payments tied to achieving regulatory, development, and commercial milestones.

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