CSTI-500 poised for Phase 2 clinical testing after positive Phase 1 safety data

Therapy is designed to ease PWS symptoms of hyperphagia, emotional outbursts

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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CSTI-500, an experimental oral therapy that ConSynance Therapeutics is developing to ease symptoms of Prader-Willi syndrome (PWS), showed a favorable safety and pharmacological profile in people with the disease, according to data from a Phase 1 clinical trial.

“CSTI-500 has the potential to significantly improve the lives of PWS patients and their loved ones by addressing two of the most debilitating symptoms — hyperphagia [uncontrollable hunger] and temper outbursts,” Shuang Liu, CEO and founder of ConSynance, said in a company press release. “These encouraging results from PWS patients underscore CSTI-500’s potential as a promising therapeutic candidate, bringing us one step closer to fulfilling the substantial unmet medical needs in the PWS community.”

Based on these findings, “CSTI-500 is now poised to advance into a Phase 2 clinical trial,” according to ConSynance.

The therapy is designed to ease hunger and trouble regulating emotional responses by altering the signaling of serotonin, dopamine, and norepinephrine — three neurotransmitters involved in regulating mood, behavior, and sleep.

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How CSTI-500 works; Phase 1 safety results

Neurotransmitters are molecules in the brain that nerve cells use to send signals to each other. A nerve cell can increase the strength of a signal by secreting more neurotransmitters toward neighboring cells or it can reduce its strength by taking neurotransmitters back into itself in a process called re-uptake.

As a triple monoamine uptake inhibitor, CSTI-500 specifically works by blocking the reuptake of serotonin, dopamine, and norepinephrine. It’s designed to modulate the three neurotransmitters in an optimal ratio to help manage symptoms linked to neurotransmitter deficiencies and is expected to boost the strength of signals sent with these chemicals.

Previous Phase 1 trials that evaluated single and multiple ascending doses in healthy volunteers provided “valuable safety, pharmacokinetics, and brain target engagement data,” the company said. Pharmacokinetics refers to the therapy’s movement into, through, and out of the body.

ConSynance also launched a Phase 1 study (NCT05504395) to investigate CSTI-500’s safety and pharmacokinetics in up to 14 people, ages 13-50, with PWS. Participants, recruited at the Vanderbilt University Medical Center, Tennessee, were given a single 10 mg dose by mouth as a newly developed capsule formulation.

The therapy was generally safe and well tolerated, with no reports of severe side effects, results showed. Its pharmacokinetic profile in patients was similar to healthy volunteers, confirming the equivalence of the capsule, the company noted.

“The robust pharmacokinetic and safety data of CSTI-500 in PWS patients provide strong support to proceed to a Phase 2 study,” ConSynance said.