3D Rendering of Antibody Drug Conjugate Molecules
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The Nasdaq-listed precision oncology firm Leap Therapeutics has merged with the private company Flame Biosciences to get hold of a pipeline of cancer drugs, including antibodies targeting the emerging biomarker Claudin18.2.

The combined company will continue as Leap Therapeutics, trade on the Nasdaq and be led by Leap’s existing management team. In the process, Leap acquired Flame’s net cash of $50 million to swell its reserves to $115 million—enough to fund the development of its pipeline until 2025.

One of the biggest prizes for Leap is Flame’s clinical-stage anti-Claudin18.2 antibody FL-301, which is being developed for the treatment of gastric, gastroesophageal junction (GEJ) and pancreatic cancer. Leap also gets hold of two preclinical-stage programs from Flame: the bispecific antibody FL-501 that targets Claudin18.2 and CD137, and an antibody blocking GDF15.

Claudin18.2 is a protein that helps gastric mucosal cells stick together. It is rare in normal tissue, as it is normally hidden within the tight junctions of gastric cells. However, this structure can be disrupted in cancer, allowing Claudin18.2 to be a selective target for potential antibody drugs like FL-301. The candidate is undergoing a Phase I trial in China, and drug development outside of China was licensed to Flame by NovaRock Biotherapeutics in 2021.

In addition to Flame’s pipeline, Leap will also continue the development of its own lead candidate antibody, DKN-01. This drug blocks the protein Dickkopf-1 (DKK1), which promotes tumor growth and suppression of the immune system near the tumor. DKN-01 is advancing to Phase II clinical trials in gastric cancer, endometrial cancer, and colorectal cancer patients, and could benefit patients with tumors expressing high levels of DKK1

“This is a transformative transaction for Leap. Acquiring FL-301 is a perfect fit with our vision of developing novel biomarker-targeted therapies for cancer patients, that is represented by our DKN-01 program,” said Douglas E. Onsi, president & CEO of Leap, in a public statement. “We believe that DKK1 and Claudin18.2 will become important patient selection biomarkers in gastric cancer, alongside HER-2 and PD-L1 expression, with the potential for delivering personalized medicines to patients who currently have poor survival outcomes.”

Until recently, Flame’s flagship program had been FL-101, an antibody drug for non-small cell lung cancer that blocks the inflammatory protein interleukin-1β. However, a drug with a similar mechanism to FL-101, Novartis’ approved autoinflammatory disease treatment canakinumab, has repeatedly failed to treat cancer in multiple Phase III trials in the last few years. This led Flame to change its strategy, and the firm underwent the merger with Leap. 

As part of the merger agreement, and assuming approval by the Leap stockholders, Flame shareholders will own around 58% of Leap’s outstanding shares, and can expect 80% of the proceeds from potential deals to out-license or sell Flame’s interleukin-1β programs.

“Flame conducted an extensive strategic process. It was clear that the Leap development team, with its expertise in developing DKN-01, was the ideal partner for FL-301, our preclinical assets, and the Flame shareholders,” said Patricia Martin, the co-chief executive officer of Flame.

Claudin18.2 is a cancer target sought out by many other biopharma companies. One of the most advanced programs is Astellas’ zolbetuximab, which aced a Phase III trial in November 2022 in combination with chemotherapy. According to the topline results, the therapy boosted progression-free survival in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.

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