BEIJING – After a deal with Abbvie Inc. last year, Mumbai, India-based Lupin Ltd. inked another one, this time with German pharma Boehringer Ingelheim GmbH, to deepen its drug research efforts in gastrointestinal and lung cancers. Under the new agreement, the companies will explore the potential of a combination therapy using Lupin's MEK inhibitor compound, LNP-3794, and Boehringer Ingelheim's KRAS inhibitor.

For Lupin, the financial terms are lucrative. It will receive $20 million up front and, if defined clinical, regulatory and commercial milestones are achieved, it could receive more than $700 million. Plus, Lupin would be entitled to double-digit royalties on the sales resulting from the deal.

This is not the first partnership for the two companies. In 2016, they agreed to co-market Boehringer's diabetes drug, empagliflozin, in India; they later expanded the collaboration to market two more diabetes drugs.

But for now, both companies have remained tight-lipped on the timelines and the set-up of the clinical trials under the new agreement. Boehringer's media representative, Sarah Soetbeer, told BioWorld the partnership aims to address "patients with gastrointestinal and lung cancers harboring a broad range of oncogenic KRAS mutations."

According to Boehringer, KRAS mutations occur in roughly one in seven of all human metastatic cancers, making it the most frequently mutated cancer-causing gene. It relates to more than 90% of mutations in pancreatic cancers, more than 40% in colorectal cancers and more than 30% in lung adenocarcinomas.

"Preclinical data has shown that the combination of Boehringer Ingelheim's novel KRAS inhibitors with MEK inhibitors results in increased antitumor activity based on their complementary mechanisms of action in keeping KRAS-driven cancers in check," Soetbeer said. That is why the German drugmaker has targeted Lupin's LNP-3794, which has shown preclinical activity as a single agent as well as in combination.

LNP-3974 is being developed to treat a variety of cancers such as skin cancer, pancreatic cancer, non-small-cell lung carcinoma, colorectal cancer and thyroid cancer. It has undergone a phase I study in patients with advanced solid tumors having RAS/BRAF mutations in the U.K. that enrolled 17 patients.

Lupin claimed it has shown early clinical benefit in that small subset of patients, but specific clinical data have yet to be disclosed.

From generics to novel drugs

The licensing deal with Boehringer followed the deal with U.S.-headquartered Abbvie for developing a novel oncology drug to treat hematological cancer. Under the terms, Abbvie agreed to pay Lupin $30 million up front and as much as $947 million in milestones for an exclusive license to a molecule designed to inhibit a protein involved in both T-cell and B-cell lymphocyte activation across a range of blood cancers. (See BioWorld, Dec. 27, 2018.)

Both agreements highlight Lupin's effort to develop novel oncology drugs, marking a shift in its focus from generic drugs and biosimilars.

The Indian firm has long been known as the third largest drugmaker in its country and the world's eighth largest generics company by revenue.

It is also known for developing a biosimilar version of Enbrel (etanercept, Amgen Inc.) and has nine other biosimilar drug candidates. (See BioWorld, April 30, 2014.)

Lupin has established units to work on biotech research, generic pharmaceutical and API research and advanced drug delivery systems. Lesser known is its novel drug discovery and development team, formed in 2010 to build a pipeline of new chemical entities for oncology, immunology and metabolic indications.

"With the success of our second new drug discovery program in oncology, we have made a significant mark in bringing novel treatments to patients," Nilesh Gupta, managing director at Lupin, said of the partnership with Boehringer.

It continues to keep its pipeline confidential. But in the oncology space, Lupin has completed a phase I study in Europe on terminally ill patients suffering from lung cancer, melanoma and colon cancer. A phase II study has also begun in India for treating a refractory type of lung cancer that has RAS mutations and lacks treatment worldwide.

Lupin did not respond to BioWorld's request for further comments.

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