IAMA-6 / IAMA Therap - LARVOL DELTA

Selective NKCC1 inhibition by IAMA-6 for the treatment of Autism and Fragile X (ECNP 2024) - "Interestingly, NKCC1 inhibition by the FDA-approved diuretic bumetanide rescues core symptoms of autism spectrum disorders in rodent models and several clinical trials. Altogether, these Results indicate IAMA-6 as an effective treatment for core symptoms of autism spectrum disorders characterized by an altered Cl homeostasis. Considering these and other (Down syndrome) promising efficacy Results and its preclinical safety and tolerability profile, IAMA-6 is currently being evaluated in a first-in-human Phase 1 clinical study for its safety and pharmacokinetic profile in healthy volunteers."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • SLC12A2

Selective NKCC1 inhibition by IAMA-6 for the treatment of Down syndrome (ECNP 2024) - "Interestingly, NKCC1 inhibition by the FDA-approved diuretic bumetanide rescues cognitive impairments in a DS mouse model and showed promising effects in a DS boy. Higher dosages or early treatment may be beneficial to rescue also co-morbidities like hyperactivity and seizures. Considering these and other (autism) promising efficacy Results together with its preclinical safety and tolerability profile, IAMA-6 is currently being tested in a first-in-human Phase 1 clinical study for its safety and pharmacokinetics in healthy volunteers."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • SLC12A2

Selective NKCC1 inhibition for the treatment of drug-resistant epilepsy (ECNP 2024) - "Interestingly, NKCC1 inhibition by the FDA-approved diuretic bumetanide reduced seizures in rodent models of refractory epilepsy and in subjects with TLE in a pilot study and a phase II clinical trial. We found that 1 µM IAMA-6 significantly rescued the reversal potential of GABA (EGABA) of TLE brain-tissue preparations to the control level.Altogether these Results indicate that IAMA-6 may represent an effective treatment in TLE patients. Further experiments assessing the efficacy of IAMA-6 in reducing seizures in other forms of refractory epilepsy are ongoing, to corroborate the potential of IAMA-6 to ameliorate seizures in epilepsy."

CNS Disorders • Epilepsy • SLC12A2

IAMA-6 Oral Dose Study in Healthy Adults (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Iama Therapeutics S.r.l.

New P1 trial • CNS Disorders • Developmental Disorders • Psychiatry

IAMA Therapeutics Announces Approval of Clinical Trial Application (CTA) by the Italian Medicines Agency (AIFA) to Initiate a Phase 1 Study of IAMA-6 for the Treatment of Autism and Epilepsy (Businesswire) - "IAMA Therapeutics...announced that the Italian Medicines Agency (AIFA) has accepted the Clinical Trial Application (CTA) to initiate a Phase 1 first-in-human (FIH), randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and food effect of IAMA’s lead program IAMA-6, an orally administered small molecule therapeutic targeting NKCC1 for the treatment of autism and epilepsy....The Company expects to begin dosing healthy adults in the Phase 1 study in January 2024."

New P1 trial • Autism Spectrum Disorder • CNS Disorders • Epilepsy

Selective NKCC1 Inhibitors for the Treatment of Refractory Epilepsy (AES 2023) - "In conclusion, IAMA-6 is a solid lead compound advancing toward clinical studies and may represent an effective therapeutic strategy to improve MTLE. To further increase the translational value of IAMA-6, we are currently investigating its efficacy in restoring neuronal [Cl-]i directly in brain tissues from patients with MTLE and FCD. In addition, ongoing evaluation of IAMA-6 efficacy in Dravet syndrome will further expand the types of drug-resistant epilepsy and epileptic syndromes that may benefit from IAMA-6 treatment."

Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Psychiatry • SLC12A2

Selective NKCC1 Inhibitors for the Treatment of Neurodevelopmental and Neurological Disorders with Defective NKCC1/KCC2 expression-ratio (AAN 2023) - "IAMA-6 efficacy in refractory epilepsy will expand our pipeline of therapeutic indications. Finally, the discovery of new classes of selective NKCC1 inhibitors with different properties will further increase the number of candidates to be tested in additional and diverse conditions characterized by NKCC1/KCC2 imbalance."

Neurodevelopmental • Autism Spectrum Disorder • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • SLC12A2

IAMA Therapeutics to Present Data on Its Epilepsy Program at American Academy of Neurology Annual Meeting (2023) (Businesswire) - "IAMA Therapeutics...announced that preclinical data supporting its IAMA-6 program in focal refractory epilepsy will be presented at the 75th American Academy of Neurology (AAN) Annual Meeting, taking place on April 22-27 in Boston, Massachusetts....'We anticipate a possible IND/CTA filing in 1H2023. Preclinical data demonstrate potential efficacy and safety of IAMA-6 at low, chronic dosing, in animal models of focal and pharmacoresistant epilepsies.'"

IND • Preclinical • CNS Disorders • Epilepsy

Preclinical Development of the Na-K-2Cl Co-transporter-1 (NKCC1) Inhibitor ARN23746 for the Treatment of Neurodevelopmental Disorders. (PubMed, ACS Pharmacol Transl Sci) - "Recently, we have reported the discovery of the selective NKCC1 inhibitor "compound ARN23746" for the treatment of Down syndrome and autism in mouse models...Notably, ARN23746 does not present signs of toxicity or diuresis even if administered up to 50 times the effective dose. These results further support ARN23746 as a solid candidate for clinical trial-enabling studies."

Journal • Preclinical • Alzheimer's Disease • Autism Spectrum Disorder • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders • Psychiatry

IAMA Therapeutics and Psychogenics Sign a Preclinical Study Agreement for Dravet Syndrome (Businesswire) - "IAMA Therapeutics...and PsychoGenics Inc...announced that the companies have entered into an additional services agreement to identify the efficacy of novel drug candidates in preclinical animal models of Dravet syndrome. Under the terms of this second agreement, PsychoGenics will evaluate the anti-seizure efficacy of first-in-class selective-NKCC1 inhibitors, which aim to reduce intracellular chloride concentration and restore the physiological hyperpolarizing and inhibitory GABAergic transmission in a preclinical model of Dravet syndrome."

Licensing / partnership • CNS Disorders • Epilepsy

IAMA Therapeutics Announces Initiation of Preclinical Development Studies in Drug-resistant Epilepsy Under a Service Agreement with Psychogenics (Businesswire) - "IAMA Therapeutics...announced that the companies have entered into a service agreement to identify the efficacy of novel drug candidates in drug-resistant epilepsy. Under the terms of the agreement, PsychoGenics will evaluate the preclinical anti-seizure efficacy of first-in-class selective-NKCC1 inhibitors, which aims to reduce intracellular chloride concentration and restore the physiological hyperpolarizing and inhibitory GABAergic transmission in an animal model of refractory epilepsy."

Licensing / partnership • CNS Disorders • Epilepsy