Freedom Biosciences has received the US Food and Drug Administration (FDA) approval of an investigational new drug (IND) application for FREE001 in patients with treatment-resistant depression (TRD).
Yale spin-out Freedom Biosciences is a clinical-stage biotechnology firm. The company is developing next-generation neuropsychiatric therapeutics.
Freedom’s lead programme FREE001 is a ketamine-based combination therapy to treat TRD.
With the approval, the biotechnology firm will start its Phase 2a FREE001-TRD-201 clinical trial for FREE001 in the first half of this year.
FREE001, a combination product of ketamine and temsirolimus, is currently under investigation for its potential application in TRD patients.
The asset is undergoing Phase 2a dose-ranging evaluation as an adjunctive therapy for adults with TRD who have shown insufficient response to a minimum of two antidepressant treatments.
This study aims to assess the safety, tolerability, pharmacokinetics, and efficacy of TRD therapy in this patient population.
Yale psychiatry chair, co-founder, and chief scientific advisor John Krystal said: “FREE001 builds on new ideas about brain mechanisms that limit the duration of ketamine efficacy.
“Extending the duration and perhaps magnitude of ketamine efficacy could improve the safety, reduce patient burden of care, and expand access to this important treatment.”
Growing clinical evidence supports the antidepressant properties of ketamine. Several dose-response studies have demonstrated KET`s efficacy, safety, and good tolerability.
Furthermore, the FDA approved Janssen’s esketamine (SPRAVATO), the S(+) enantiomer of KET, in March 2019 for treating treatment-resistant depression.
KET is believed to induce antidepressant effects by activating the mammalian targets of rapamycin complex 1 (mTORC1), which leads to synaptogenesis and subsequent activation of brain-derived neurotrophic factors.
In a clinical trial, 20 patients with major depression were randomly assigned to receive pretreatment with oral sirolimus, an mTORC1 inhibitor, or placebo two hours before intravenous (IV) administration of KET.
The study followed a double-blind crossover design, with treatment days spaced at least two weeks apart.
Results showed a significant treatment-by-time interaction over the subsequent two weeks, suggesting that SIR extended the antidepressant effects of KET compared to placebo.
