Caraway, AbbVie Ink Deal to Develop TMEM175-targeting Therapies

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by Margarida Maia |

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Mesdopetam agreement

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Caraway Therapeutics is partnering with AbbVie to develop and market Caraway’s small molecule therapies targeting TMEM175, a potassium ion channel implicated in Parkinson’s disease and other neurodegenerative disorders.

TMEM175 is present in lysosomes — tiny compartments in cells containing enzymes that break down unwanted cell parts, digesting and recycling different types of molecules. When lysosomes don’t work properly, waste accumulates inside cells instead of being degraded and cleared.

Rare genetic variations in the TMEM175 gene, which provides instructions for making the lysosomal potassium ion channel, have been linked to both an increased occurrence of Parkinson’s disease and an earlier age at disease onset. While poorer TMEM175 function reduces lysosomal function in neurons (nerve cells), higher-than-normal levels of TMEM175 promote neuronal health.

“Variants in TMEM175 that reduce lysosomal function are highly prevalent genetic risk factors for the development of PD [Parkinson’s disease] and evidence suggests that patients with reduced TMEM175 function tend to have earlier age of disease onset and increased risk of dementia,” Martin Williams, Caraway’s CEO, said in a press release.

“TMEM175 is a compelling genetically validated target for which Caraway has developed a promising drug discovery program,” said Eric Karran, PhD, vice president of AbbVie’s Neuroscience Discovery.

The two companies plan to jointly advance the development of small molecules that modulate the activity of TMEM175. They will use Caraway’s medicine discovery program and expertise in lysosomal biology and cellular clearance mechanisms. In turn, AbbVie will provide expertise in disease biology, clinical development, and in bringing new products, if approved, to the market worldwide.

“We are delighted to partner with AbbVie on Caraway’s TMEM175 pipeline program for Parkinson’s disease and other neurodegenerative disorders,” Williams said. “We are looking forward to collaborating with AbbVie to develop novel TMEM175 modulators and bring new hope to patients suffering from Parkinson’s and other neurodegenerative disorders.”

Under this exclusive collaboration and option agreement, Caraway — a portfolio company of AbbVie Ventures — will receive an upfront payment of $17 million.

Upon meeting certain preclinical research and development milestones, Caraway will grant AbbVie an option to license the program and proceed into investigational, new drug-enabling studies to assess whether TMEM175 modulators are reasonably safe for initial testing in people. Further activities include clinical development and potential commercialization.

In addition, Caraway stands to receive up to $267 million in upfront and future option payments, as well as development milestones.

Caraway is also eligible for additional regulatory and commercial milestones, tiered royalties on global commercial sales, and has the option to take part in the therapy’s development in exchange for higher royalties.