Freedom Biosciences Announces FDA Approval of IND Application for FREE001 in Patients with Treatment-Resistant Depression

SAN FRANCISCO, April 25, 2024 /PRNewswire/ -- Freedom Biosciences, Inc. ("Freedom Bio" or the "Company"), a clinical-stage biotechnology platform focused on developing next-generation neuropsychiatric therapeutics, today announced that the U.S. Food and Drug Administration (FDA) has notified the Company that it may proceed with its FREE001-TRD-201 study for its lead program, FREE001, a ketamine-based combination therapy for the treatment of treatment-resistant depression (TRD). Freedom Bio will initiate its Phase 2a clinical trial (the "Study") in the first half of this year. This milestone marks a significant step forward in the development of FREE001, which has the potential to address a critical unmet medical need in patients suffering from TRD.

John Krystal, M.D., Co-founder and Chief Scientific Advisor and the Chair of Psychiatry at Yale, commented "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."

About the Phase 2a Clinical Trial

FREE001 is an investigational combination product of ketamine and temsirolimus which is being tested for use in patients with treatment-resistant depression (TRD).

FREE001 is being developed as an adjunctive treatment in adults with TRD who have an inadequate response to at least 2 antidepressant treatments. The main objectives of this Phase 2a dose-ranging evaluation study are to evaluate the safety/tolerability, PK, and efficacy of FREE001 in adults with TRD.

Major depressive disorder (MDD) is a debilitating and chronic condition with limited effective treatment options. MDD is one of the most common mental health disorders in the United States (US), with an estimated 21.0 million adults (8.3% of all adults) having at least 1 major depressive episode in 2020¹³. MDD also impacts physical health, worsens outcomes of other medical conditions, and, on average, results in a 10-year reduction in life expectancy¹⁴.

While a range of therapeutic options are available for major depressive disorder, at least a third of all patients with MDD do not achieve remission from their depressive symptoms even after multiple different treatment attempts⁵. Treatment-resistant depression is generally defined as the failure to respond to two or more antidepressant treatments that have been administered at an effective dose for an adequate duration^3,12. TRD is associated with increased morbidity, mortality, and societal costs compared to MDD in general^6,7, and is thus a major cause of depression-related burden and disability. While an approximate third of patients with MDD experience TRD, the burden of treatment is significantly disproportionate, with nearly half of medication-treated MDD among the US population being attributable to TRD, and over half of the MDD-related health care burden tied to TRD¹⁵.

Accumulating clinical evidence supports the antidepressant effects of ketamine (KET)⁸. Several dose-response studies have found KET to be efficacious, safe, and well tolerated^11,2,4. Additionally, the S (+) enantiomer of KET, esketamine (SPRAVATO^®), was approved by the FDA in March 2019 for treatment-resistant depression. KET is thought to exert antidepressant effects through a mechanism involving activation of mammalian target of rapamycin complex 1 (mTORC1), producing synaptogenesis and downstream activation of brain-derived neurotrophic factor (BDNF)¹⁰.

In a clinical study, 20 patients with major depression were randomized to pretreatment with oral sirolimus (SIR) (6 mg), an mTORC1 inhibitor, or placebo 2 hours prior to intravenous (IV) KET (0.5 mg/kg) administration in a double-blind cross-over design with treatment days separated by at least 2 weeks¹. Over the subsequent 2 weeks, a significant treatment by time interaction was determined, suggesting a prolongation of the antidepressant effects of KET by SIR compared to placebo. This observation provides preliminary evidence that mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus (TEM; prodrug of SIR), may extend the treatment effects of KET up to 2 to 3 weeks.

Extending the duration of treatment could have significant benefits for reduction of the cost and resource burden for KET treatment on the medical system, patient convenience and adherence, as well as potentially reduce adverse events (AEs) due to less frequent dosing (e.g., 2 doses vs 8 doses in the first month of treatment and thereafter longer intervals between doses).

About Freedom Bio

Freedom Biosciences is a Yale spin-out and clinical-stage biotechnology platform developing next-generation neuropsychiatric therapeutics. Co-founded by Dr. John Krystal, Chair of Psychiatry at Yale University, and Dina Burkitbayeva, founder of PsyMed Ventures, the company leverages the expertise of Dr. David Hough, Chief Medical Officer, who led Spravato® development at Janssen, and Dr. Rob Berman, Senior Medical Advisor and Head of the Scientific Advisory Board, with experience as Co-founder and founding CMO of Biohaven Pharmaceuticals. In the 1990s Dr. Krystal and Dr. Berman first demonstrated ketamine's rapid antidepressant effects, a pioneering discovery that directly contributed to the FDA approval of Jannsen's Spravato® Esketamine spray.

Forward Looking Statements

This press release contains projections and forward-looking statements that involve risks and uncertainties, including statements regarding the potential benefits and success of FREE001. Actual results could differ materially from those anticipated in these forward-looking statements due to various factors, including but not limited to the risks and uncertainties associated with drug development and regulatory approval processes.

For more information about Freedom Bio and FREE001, please visit us at www.freedombio.co and on LinkedIn and X.

Dina Burkitbayeva
Chief Executive Officer
Freedom Biosciences, Inc.
[email protected]

References:

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13. Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results from the 2021 National Survey on Drug Use and Health. US Dept of Health and Human Services; 2022. Publication Number PEP22-07-01-005.
14. Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis [published correction appears in JAMA Psychiatry. 2015 Jul;72(7):736] [published correction appears in JAMA Psychiatry. 2015 Dec;72(12):1259]. JAMA Psychiatry. 2015;72(4):334-341.
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SOURCE Freedom Biosciences