Damona Pharmaceuticals Announces FDA Clearance of IND Application for a Phase 1 Clinical Trial of DPX-101, a Positive Allosteric Modulator Targeting the α5-GABA-A Receptor Subtype Selectively, with Broad Therapeutic Potential to Treat Cognitive Deficits Across Brain Disorders

— In preclinical models, small molecule DPX-101 demonstrated highly selective target activation and expected electrophysiological effects as well as improved cognitive performance in behavioral tests of frontal cortex and hippocampal functions —

TORONTO, November 4, 2024— Damona Pharmaceuticals, a clinical-stage biopharmaceutical company focused on discovering and developing small molecules for the treatment and prevention of cognitive deficits associated with brain disorders, announced today that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for DPX-101, a positive allosteric modulator (PAM) that selectively augments the function of the α5-GABA-A receptor (α5-GABAAR) in the brain for the potential treatment of cognitive deficits in Major Depressive Disorder (MDD) and other brain disorders. The company has planned a Phase 1 clinical trial to evaluate safety, tolerability, and pharmacokinetic and pharmacodynamic characteristics of DPX-101 in healthy adults.

“The FDA clearance of the DPX-101 IND allows us to initiate the Phase 1 clinical study of our lead asset, which promises to establish a new standard of care for the treatment of cognitive deficits associated with brain disorders,” said John Reilly, CEO of Damona. “Based on data from our preclinical studies and the compound’s selectivity for α5-GABAAR, we believe that DPX-101 could benefit a broad range of patients suffering from diseases that cause cognitive impairment. We look forward to the planned initiation of our Phase 1 clinical trial later this year.”

The Phase 1 randomized, double-blind, placebo- and comparator-controlled, single- and multiple-ascending dose (SAD/MAD) clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single- and multiple-ascending doses of DPX-101 in healthy adult participants. Part 1, a single-ascending dose (SAD) study, will enroll participants randomized into one of five planned cohorts. A parallel, open-label, comparator cohort will be treated with the α1-GABA-A receptor agonist Zolpidem to provide additional evidence on DPX-101 α5-GABAAR selectivity. Part 2, a multiple-ascending dose (MAD) study, will involve participants randomized into three escalating dose cohorts, each to receive daily administrations of DPX-101 or placebo for seven days. The planned primary endpoints are safety and tolerability of single and multiple oral doses of DPX-101. Planned secondary endpoints will assess the PK profile of DPX-101. Exploratory endpoints include the effect of DPX-101 on functional target engagement and key differentiation measurements compared to the effects of Zolpidem. The planned Phase 1 trial will use quantitative electroencephalogram (qEEG) as a biomarker to assess target engagement.

About DPX-101
DPX-101 is an investigational positive allosteric modulator (PAM) that selectively targets the α5 subunit of the GABA-A receptor (α5-GABAAR) to enhance its function. The α5-GABAAR subtype is a promising target for reversing cognitive impairment due to its location in the hippocampus and frontal cortex regions of the brain and its unique role in somatostatin-containing GABAergic interneuron tonic inhibition within microcircuits critical for healthy cognition. In preclinical studies, DPX-101 demonstrated highly selective activation of the α5-GABAAR and a broad therapeutic window with no side effects. In preclinical models of stress, depression, aging, and Alzheimer’s disease, DPX-101 reversed memory deficits and restored connections between brain cells. In a preclinical model of schizophrenia, DPX-101 reversed hyperactivity of dopamine neurons, a hallmark of schizophrenia. DPX-101 is orally available, passes the blood-brain barrier, and achieves appropriate plasma and brain levels.

About Damona Pharmaceuticals
Damona is a clinical-stage biopharmaceutical company dedicated to discovering and developing transformational precision medicines for patients suffering from cognitive deficits associated with brain disorders based on deep neuroscience knowledge of cortical microcircuits in health and disease. The company’s founder and collaborators have made pioneering discoveries regarding the unique role of the α5-GABA-A receptor subtype in cognition and its potential for reversing cognitive deficits in models of various brain disorders. Damona’s lead clinical program, DPX-101, is designed to reverse cognitive impairment and restore connections between brain cells. Learn more at www.damonapharma.com.

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Mary Moynihan
M2Friend Biocommunications
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