FDA clears way for Phase 1 study of PIPE-791 in healthy volunteers

Pipeline Therapeutics will soon launch a Phase 1 clinical study to test PIPE-791, one of its candidate treatments for multiple sclerosis (MS), in healthy volunteers.

The announcement follows a go-ahead from the U.S. Food and Drug Administration (FDA) for an investigational new drug (IND) application to initiate clinical testing of the treatment based on preclinical studies of PIPE-791.

The Phase 1 study, which could start enrollment in the second half of 2023, will investigate how safe and well tolerated different doses of PIPE-791 are versus a placebo in about 80 healthy volunteers.

“We are excited to initiate the Phase 1 study of PIPE-791, which is designed to assess the safety and tolerability of PIPE-791 compared to placebo in healthy volunteers,” Stephen Huhn, MD, Pipeline’s chief medical officer and senior vice president of clinical development, said in a company press release.

In MS, the immune system launches an inflammatory attack against the myelin sheath, a fatty covering that protects and helps nerve cells send electrical signals, causing damage to the brain and spinal cord.

In normal circumstances, the damaged myelin can be repaired by oligodendrocytes, the cells chiefly in charge of making myelin in the brain and spinal cord. But the ongoing inflammation in MS makes the remyelination process faulty, leading to permanent damage.

PIPE-791 is a small molecule designed to enter the brain and block the lysophosphatidic acid 1 (LPA1) receptor, which seems to contribute to the disease’s abnormal remyelination.

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This protein is present at the surface of oligodendrocytes and resident immune cells called microglia and binds to LPA, a proinflammatory molecule that’s found at high levels in the blood and spinal fluid of people with MS. This binding can contribute to local inflammation that limits myelin repair.

By blocking the LPA1 receptor, PIPE-791 should counteract disease progression by easing inflammation and helping to regrow the myelin sheath. Earlier studies in lab-grown cells showed the drug protects oligodendrocytes from death and helps them grow to fully mature myelin-making cells.

Preclinical studies using animal models showed PIPE-791 does indeed bind to the LPA1 receptor in the nervous system, where it eases inflammation and promotes remyelination.

“The FDA clearance of PIPE-791’s IND marks another significant milestone for Pipeline and demonstrates our team’s continued focus and commitment to bringing precision therapies to patients with neurological diseases,” said Carmine Stengone, Pipeline’s president and CEO.

The company’s other candidate for remyelination in MS, PIPE-307, was recently acquired by Janssen Pharmaceuticals and is expected to enter a clinical trial with people with relapsing-remitting MS.

“PIPE-791 is our second clinical program and our first to address both remyelination and neuroinflammation. We look forward to evaluating our first-in-class approach to LPA1 inhibition with PIPE-791, with the goal to deliver meaningful benefit to individuals with MS, as well as other neurological and systemic diseases,” Stengone said.