DUBLIN – Lassen Therapeutics Inc. is following the Enleofen Bio Pte Ltd. playbook by targeting the interleukin-11 receptor (IL-11R) as a novel approach to combating both fibrosis and cancer. It’s a move that paid off handsomely earlier this year for Singapore-based Enleofen, which entered a broad alliance in fibrosis with Boehringer Ingelheim GmbH, which could generate up to $1 billion in milestones for each product emanating from the partnership. San Diego-based Lassen is now laying claim to that space as well and has just emerged from stealth mode, having closed but not previously disclosed a $31 million series A round.

“We’re funded through the completion of our initial clinical studies,” CEO and co-founder Mark Barrett told BioWorld. Unlike Enleofen, however, the new firm is targeting cancer as well as fibrosis.

Barrett established the firm during a stint as entrepreneur-in-residence at Frazier Healthcare Partners, which led the series A round. He was previously global head of strategy and business development at the Sanofi Genzyme arm of Paris-based Sanofi SA and also held business development roles at Johnson & Johnson Co., of New Brunswick, N.J. Lassen’s co-founder and chief scientific officer (CSO), David King, is an experienced antibody developer with a long track record in biotech. He was previously CSO of two San Diego biotechs, Atyr Pharma Inc., and Anaptys Bio Inc., before which he also worked at Medarex (now part of New York-based Bristol Myers Squibb Co.) and Celltech (now part of Brussels-based UCB SA).

Mark Barrett, CEO, Lassen

Lassen is not starting from scratch. In conjunction with its series A round, which it completed last year, it has in-licensed antibody assets and associated intellectual property from Melbourne, Australia-based CSL Ltd., which has in turn acquired an equity interest in Lassen. “They had generated anti-IL-11 receptor antibodies,” Barrett said. “They had done some nice work and had a patent estate around that.” Lassen has further built on that effort and is now looking to enter the clinic next year. It has yet to finalize a lead indication. “It’s the opportunity as well as the challenge,” Barrett said. “We’re thinking about lung. We’re thinking about liver – and other organs where there may be important potential applications for IL-11 inhibition.” The company is exploring the possibilities through a number of academic collaborations.

Boehringer, of Ingelheim, Germany, and Enleofen are also taking an antibody-based approach and have identified conditions such as nonalcoholic steatohepatitis (NASH) and interstitial lung disease as potential therapeutic areas for their alliance.

Up to quite recently, however, IL-11’s history as a drug target was not very dramatic. The Genetics Institute gained FDA approval in 1997 for a recombinant IL-11, Neumega (oprelvekin), for boosting platelet growth in cancer patients at risk of thrombocytopenia because of myelosuppressive chemotherapy. It never delivered much in terms of sales.

The field of fibrosis has given rise to a plenitude of possible targets. Not all are readily druggable, however. Targeting transforming growth factor-beta (TGF-beta), long considered a central mediator of fibrosis, is complicated by its pleiotropic effects. Nevertheless several firms – including Eli Lilly and Co., Pfizer Inc. and Merck KGaA in partnership with Glaxosmithkline plc – are targeting the cytokine in cancer. Fibrogen Inc., of San Francisco, has long straddled the divide between cancer and fibrosis – it is in phase III in both pancreatic cancer and idiopathic pulmonary fibrosis with pamrevlumab, which targets connective tissue growth factor.

Interest in inhibiting IL-11 signaling in fibrosis has been spurred by recent work from the lab of Stuart Cook at Duke-National University of Singapore Medical School, Singapore, who is Enleofen’s scientific founder. His group reported in the Dec. 7, 2017, issue of Nature (the study appeared online on Nov. 13, 2017) that TGF-beta boosts transcription of and exerts its effects through IL-11 in primary human fibroblasts. They also showed that IL-11 is the main cause of cardiovascular fibrosis. A subsequent study from Cook’s group, published online on Sept. 25, 2019, in Science Translational Medicine, established that IL-11 is also a player in the pathology of idiopathic pulmonary fibrosis.

Other “fibro-inflammatory” conditions in which it is up-regulated include systemic sclerosis, rheumatoid arthritis, inflammatory bowel disease, kidney disease, drug-induced liver injury and NASH, Cook and Sebastian Schafer noted in a recent review published in the 2020 Annual Review of Medicine. It acts both by inhibiting tissue regeneration and by triggering myofibroblast activation, dysfunction of parenchymal cells and inflammation.

There is, Barrett said, genetic in vivo and in vitro data pointing to a role for IL-11 in certain cancer types as well, particularly those characterized by stroma-rich tumors and by the presence of cancer-associated fibroblasts.

In addition to Seattle-based Frazier, Alta Partners, of San Francisco, and Boston-based Longwood Fund also participated in Lassen’s investment.

No Comments