science

Pushing the boundaries of neuroscience drug discovery

At IAMA, we are working to unlock major breakthroughs in neuroscience drug discovery and precision medicine to develop personalized treatments for patients suffering from untreatable neurological conditions. We are advancing treatments to make an impact on individuals affected by neurological disorders and their families.

We are developing diverse classes of small molecules to selectively inhibit validated targets, including the sodium-potassium chloride cotransporter (NKCC1).

our approach

Targeting the master regulators of multiple CNS diseases

A signaling imbalance between excitation and inhibition in the brain causes some epilepsies and forms of autism.

NKCC1 is a member of the Cation Chloride Cotransporter family, which mediate chloride transport across the membrane.

Cation-coupled chloride cotransporters (CCCs) modulate the transport of sodium and/or potassium cations coupled with chloride anions across the cell membrane. CCCs thus help regulate intracellular ionic concentration and consequent cell volume homeostasis. This has been largely exploited to develop diuretic drugs that act on CCCs expressed in the kidneys. However, a growing wealth of evidence has demonstrated that CCCs are also critically involved in a great variety of other pathologies, motivating the most recent drug discovery programs targeting CCCs.

The role of NKCC1 is to mediate the coupled movement of chloride with potassium and sodium across the cell membrane. In this way, NKCC1 plays essential roles in physiological processes, including modulating neuronal excitability.

The activity of NKCC1 increases in several pathological conditions; this is why NKCC1 inhibition shows great potential in treating idiopathic and secondary forms of autism (autism spectrum disorder, or ASD), refractory epilepsy, and other neurological conditions.

our pipeline

Selective Cation Chloride Cotransporter Inhibitors


our pipeline

Selective Cation Chloride Cotransporter Inhibitors


Lead Program: IAMA-6 for autism spectrum disorders and drug-resistant epilepsy


IAMA-6 is designed to selectively inhibit NKCC1 and restore neuronal excitability.

IAMA-6 has shown efficacy in preclinical models of idiopathic and syndromic forms of autism and drug-resistant epilepsy. We are further expanding our pipeline by testing efficacy of IAMA-6 in other CNS indications with highly unmet medical need. CTA-enabling studies have demonstrated that the compound is safe and well tolerated.

We are conducting a first-in-human, Phase 1 clinical study evaluating the safety, tolerability, and pharmacokinetics of single and multiple doses of IAMA-6 (identifier NCT06300398).

IAMA-299 for cognitive impairment


We are also progressing a preclinical program on an undisclosed target with the potential to treat congnitive impairment characterizing diverse neurological conditions.

research collaborations


IAMA Therapeutics has an ongoing research partnership with the Istituto Italiano di Tecnologia - Italian institute of Technology (IIT). In January 2022, Iama therapeutics entered into a license agreement with IIT that granted iama therapeutics an exclusive, worldwide license to research, develop, manufacture, and commercialize a class of selective NKCC1-inhibitors. Iama therapeutics is exploring the potential benefits of this class of molecules in a number of neurological diseases.

selected publications

A. Savardi, A. P. Malizia, M. De Vivo, L. Cancedda, M. Borgogno
"Preclinical Development of the Na-K-2Cl Co-transporter-1 (NKCC1) Inhibitor ARN23746 for the Treatment of Neurodevelopmental Disorders"
ACS Pharmacol Transl Sci. 2023, 6(1):1-11

A. Savardi, M. Borgogno, M. De Vivo, L. Cancedda
"Pharmacological tools to target NKCC1 in brain disorders"
Trends in Pharmacological Sciences (Cell Press) 2021, 42, 12, 1009-1034

C. Portioli, M. J. Ruiz Munevar, M. De Vivo, L. Cancedda
"Cation-coupled chloride cotransporters: chemical insights and disease implications"
Trends in Chemistry (Cell Press), 2021, 3, 10, 832–849

M. Borgogno, A. Savardi, J. Manigrasso, A. Turci, C. Portioli, G. Ottonello, S. M. Bertozzi, A. Armirotti, A. Contestabile, L. Cancedda, M. De Vivo
"Design, synthesis, in vitro and in vivo characterization of selective NKCC1 inhibitors for the treatment of core symptoms in Down syndrome and other brain disorders”
Journal of Medicinal Chemistry 2021, 64, 14, 10203–10229

A. Savardi, M Borgogno, R. Narducci, G. La Sala, J. Ortega, M. Summa, A. Armirotti, R. Bertorelli, A. Contestabile, M. De Vivo, L Cancedda
"Discovery of a small molecule drug candidate for selective NKCC1 inhibition in brain disorders"
Chem (Cell Press) 2020, 6, 1–24

L. Riccardi, V. Genna, M. De Vivo
"Metal-ligand interactions in drug design"
Nature Reviews Chemistry, 2018, 2, 100–112

G. Deidda, M. Parrini, S. Naskar, I. F. Bozarth, A. Contestabile, L. Cancedda
"Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome”
Nature Medicine, 2015, 21, 318–326