Nerve cell inflammation has long been linked to neurodegenerative disease, but as a byproduct rather than a cause. Over the years, scientists have debunked that theory, including Stanford Medicine's Edgar Engleman, M.D., whose work laid the groundwork for a new company, Tranquis Therapeutics.
(Tranquis Therapeutics)
The startup comes to life with $30 million to discover and develop new medicines for neurodegenerative and aging-related diseases that target neuroinflammation through a key metabolic pathway. The capital, drawn from Remiges Ventures, SR One, Vivo Capital, Hillsborough Venture and Correlation Ventures, will bankroll the preclinical development of Tranquis’ lead program and expand its platform and pipeline.
“We’re focused on a novel approach that targets myeloid immune cell dysfunction,” Tranquis CEO Sanjay Kakkar, M.D., told Fierce Biotech, referring to a type of immune cell found in the brain and the peripheral nervous system.
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“In the brain, we refer to them as microglia. Their normal physiological role is to ingest and metabolize anything from dead or decaying cells to foreign materials and toxic substances, like amyloid, cholesterol and iron,” he said, adding that in neurodegenerative disease, these immune cells were thought to be overwhelmed, become dysfunctional and inflamed, and then release tissue-damaging inflammatory molecules.
In the 1990s, Engleman’s lab realized the immune system “was not just a bystander” in neurodegenerative disease, but a central actor. The team’s work found that myeloid immune cell dysfunction underpins various disorders, from amyotrophic lateral sclerosis (ALS) to Parkinson’s disease, Alzheimer’s disease and frontotemporal dementia (FTD).
“We think it’s a common pathway across multiple disease states,” Kakkar said.
But why hadn’t anyone figured this out before Engleman? They were looking in the wrong place, Kakkar said.
“What Ed and his team sought to do was to identify pathways that were known to be downregulated in patients with neurodegenerative disease … Others had looked for the function of those downregulated genes in neurons and found nothing,” he said. The key was looking beyond the nerve cells themselves—at the microglia in the brain and in peripheral monocytes, or white blood cells.
Tranquis’ lead program, TQS-168, is designed to restore a metabolic pathway that is downregulated in myeloid cells and return them to their normal function.
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“We have data in challenging animal models of ALS, FTD, Parkinson’s and age-related neuropathologies,” Kakkar said. “We are able to show in those models that we can upregulate the target gene and restore normal function of the cell and, as a result of that, show dramatic improvement in both survival and function in those models.”
Tranquis plans to move TQS-168 into the clinic in 2021. It is starting with smaller disease populations such as ALS and FTD before developing other compounds that target the same pathway in more prevalent ailments like Alzheimer’s disease.
“With the series A, we will be able to bring those next-generation compounds further into preclinical development and bring candidate compounds into the clinic as well,” Kakkar said.