Relmada Therapeutics, Inc.

REL-1017: new treatment patterns for tomorrow

Unlocking a new mechanism of disease

Impaired neural plasticity in MDD

We believe that targeting impaired neural plasticity is the key for shifting the paradigm of treatment for those living with major depressive disorder. Neural plasticity involves the brain reorganizing its connections and reshaping its structure by strengthening or weakening synaptic transmissions. Impaired neural plasticity is thought to play an important role in the cause of depression. The persistence of impaired neural plasticity may maintain depressive states, increase the probability of a depression relapse, and limit the efficacy of cognitive-behavioral psychotherapy. 

We believe it is possible to restore neural plasticity in areas and circuits relevant to MDD by selectively targeting NMDAR hyperactive channels through treatment with REL-1017, producing rapid and long-lasting remission of major depressive episodes and decreasing the occurrence of relapses.

Embracing esmethadone

REL-1017 is also known as esmethadone. Esmethadone is one of two components of a pain and substance use medication known as methadone. According to the U.S. Drug Enforcement Agency (DEA), esmethadone lacks significant abuse liability and respiratory depressant effects. REL-1017 has been shown to potentially increase plasma levels of BDNF, a mediator of neural plasticity in humans (De Martin 2021). Furthermore, in animal models, esmethadone relieves depressive-like behaviors by enhancing synaptic proteins necessary for neural plasticity (Foga├ža 2019).

Our phase 2 data showed rapid, robust, and sustained antidepressant effects with REL-1017 in patients with inadequate response to standard antidepressants.

REL-1017 mechanism of action

Excessive ambient glutamate in the synaptic cleft and positive allosteric modulators increase the probability of opening the NMDAR channel pore.

Calcium enters the postsynaptic neuron through NMDARs with downstream effects. If a subset of NMDARs remains open too long, excessive calcium impairs the availability of synaptic proteins.

When synaptic proteins are not available, neural plasticity is impaired, which we believe contributes to MDD.

When the NMDAR channel is in the open configuration and free of magnesium, REL-1017 can block excessive calcium entry.

REL-1017 effectively blocks excessive amounts of calcium by positioning itself in the center of the open channel.