5:24 PM
Apr 11, 2019
 |  BC Innovations  |  Product Development

NLRP3 early and often

The inflammasome space heats up as pharmas get in

Inflammasome inhibitors could offer a step change for a slew of inflammatory diseases and pharma is taking notice. Two acquisitions in six months show the first inflammasome target -- NLRP3 -- is gaining momentum, but the question is how fast drug developers can discern the best set of indications from the sea of possibilities.

As the myriad contributions of innate immunity to disease become increasingly apparent, the attraction of the inflammasome, and in particular NLPR3, its most well-characterized component, is its therapeutic versatility.

Inhibitors of NLRP3 offer one of the most compelling alternatives to antibodies against IL-1β and other cytokines, which until now have been the mainstay of anti-inflammatory drug development.

The inflammasome drives innate immunity in a variety of cell types, sitting atop an inflammatory cascade that triggers cytokine release and immune cell recruitment. Preclinical studies have tied it to indications that cytokine mAbs can’t address, spanning metabolic disease, autoimmunity, neurology and oncology. NLRP3 inhibition is also expected to have safety advantages over targeting cytokines.

At least four biotechs with NLRP3 inhibitors have been founded in the last four years, and in 2018, they raised a collective $117 million in venture capital.

Pharmas have been quick to join in.

Within one year of launching with a $31 million series A round, IFM Tre Inc. was acquired by Novartis AG, based on preclinical data. In the deal, announced April 1, the IFM Therapeutics LLC subsidiary received $310 million up front and up to $1.3 billion in milestones, and the pharma inherited one program, IFM-2427, that started Phase I trials in March, and two others in preclinical development.

Jecure Therapeutics Inc. was acquired by Roche’s Genentech Inc. unit, for its preclinical NLRP3 program in non-alcoholic steatohepatitis (NASH), less than two years after raising $20 million in a series A round. The start-up received an undisclosed, all-cash sum, though sole investor Versant Ventures told BioCentury at the time it received “venture-like returns.”

The two other NLRP3 inhibitor companies, NodThera Ltd. and Inflazome Ltd., also have preclinical programs.

Despite being preclinical, IFM Tre had multiple suitors, said Novartis.

Prakash Raman, VP and global head of BD&L at Novartis Institutes for BioMedical Research, told BioCentury the “breadth of applicability for this mechanism” was a key driver of the dollar amount of the acquisition.

A major part of the strategy for all four players will be gaining evidence that can narrow the funnel and help prioritize indications where NLRP3 can have the biggest impact.

“The issue is going to be teasing apart if the inflammasome is a driver of disease...

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