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.
FREE001 builds on new ideas about brain
mechanisms that limit the duration of ketamine efficacy.
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
duration3,12. TRD is associated with increased
morbidity, mortality, and societal costs compared to MDD in
general6,7, 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
tolerated11,2,4. 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.
hello@freedombio.co
References:
- Abdallah CG, Averill LA, Gueorguieva R, et al. Modulation of
the antidepressant effects of ketamine by the mTORC1 inhibitor
rapamycin. Neuropsychopharmacology. 2020;45(6):990-997.
- Berman RM, Cappiello A, Anand A, et al. Antidepressant effects
of ketamine in depressed patients. Biol Psychiatry.
2000;47(4):351-354
- Fava M. Diagnosis and definition of treatment-resistant
depression. Biol Psychiatry. 2003 Apr 15;53(8):649-59.
- Fava M, Freeman MP, Flynn M, et al. Double-blind,
placebo-controlled, dose-ranging trial of intravenous ketamine as
adjunctive therapy in treatment-resistant depression (TRD)
[published correction appears in Mol Psychiatry. 2019 Jan 7;]. Mol Psychiatry.
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AJ. What did STAR*D teach us? Results from a large-scale,
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Ketamine: A Paradigm Shift for Depression Research and Treatment.
Neuron. 2019;101(5):774-778.
- Krystal JH, Kaye AP, Jefferson S, et al.. Ketamine and the
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antidepressant treatments. Proc Natl Acad Sci U S A.
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- Singh JB, Fedgchin M, Daly EJ, et al. A Double-Blind,
Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous
Ketamine in Patients With Treatment-Resistant Depression. Am J
Psychiatry. 2016;173(8):816-826.
- Souery D, Papakostas GI, Trivedi MH. Treatment-resistant
depression. J Clin Psychiatry. 2006;67 Suppl 6:16-22
- 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.
- 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.
- Zhdanava M, Pilon D, Ghelerter I, Chow W, Joshi K, Lefebvre P,
Sheehan JJ. The Prevalence and National Burden of
Treatment-Resistant Depression and Major Depressive Disorder in
the United States. J Clin
Psychiatry. 2021 Mar 16;82(2):20m13699. doi: 10.4088/JCP.20m13699.
PMID: 33989464.
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