Dr. Ahmad Doroudian reports

BETTERLIFE PHARMA PRIORITIZES BETR-001 TO LEAD IN MIGRAINE AND HEADACHE DISORDERS, TARGETING A CLINICALLY VALIDATED, FDA-PRECEDENTED SEROTONERGIC MECHANISM

Betterlife Pharma Inc. is prioritizing its lead clinical-stage asset, BETR-001, to pursue migraine and other primary headache disorders as its lead indications. The strategic focus concentrates BETR-001's development on one of the largest, most disabling and most underserved areas of neurology and does so through a serotonin-receptor mechanism of action that is already clinically validated and approved by the U.S. Food and Drug Administration (FDA) in multiple marketed migraine therapies.

BETR-001 is the patented, active (6R,9R) stereoisomer of 2-bromo-LSD (2-Br-LSD) -- a fully non-hallucinogenic derivative of LSD that acts as a 5-HT2A partial agonist and potent "neuroplastogen." Prioritizing BETR-001 for migraine and headache aligns the asset's validated pharmacology, existing human clinical precedent and de-risked regulatory package with a market of more than one billion patients, while preserving optionality across psychiatry and neuropathic pain.

A migraine mechanism that is already validated -- and already approved

Serotonin (5-HT) receptor pharmacology is the foundation of modern migraine therapy. Unlike the psychiatric indications pursued by most serotonergic programs, migraine is a field where serotonergic mechanisms of action have been repeatedly proven in the clinic and approved by regulators for more than six decades.

BETR-001 sits squarely within this validated serotonergic -- and specifically lysergic-pharmacology but is engineered to remove the liabilities that constrained the earlier agents: the fibrotic toxicity that limited methysergide, the vasoconstriction and cardiovascular restrictions of ergots and triptans and the hallucinogenic activity of LSD. In short, BETR-001 pursues a mechanism the field already knows works, in a molecule designed to be safer and more patient-friendly.

Direct human precedent already exists. In a published clinical pilot study, 2-bromo-LSD (the racemic form) reduced both the frequency and intensity of attacks in cluster headache patients, with no hallucinations or distortions and no cardiopulmonary adverse events (Karst et al., Cephalalgia, 2010). This provides rare, mechanism-confirming clinical evidence for BETR-001's activity in a severe headache disorder.

5-HT2A-driven neuroplasticity may offer benefits beyond symptom relief

Beyond acute serotonergic signaling, BETR-001 is a potent neuroplastogen. Its 5-HT2A partial agonism promotes dendritic and synaptic (spine) growth -- "rewiring" of neural circuits -- as demonstrated in peer-reviewed preclinical work (Lewis et al., Cell Reports, 2023), which characterized 2-Br-LSD as a non-hallucinogenic LSD analog with therapeutic potential and confirmed its effects are dependent on 5-HT2A activation.

Migraine is increasingly understood as a disorder of central sensitization and maladaptive neural plasticity, in which repeated attacks drive chronification, interictal burden and comorbid mood symptoms. A therapy that engages neuroplasticity therefore has the potential to move beyond episodic symptom control toward durable, potentially disease-modifying benefit -- an attribute no existing migraine class provides. This positions BETR-001 to address not only acute and episodic migraine, but also the highest-need segments: chronic migraine, medication-overuse headache and patients with comorbid anxiety or depression.

A large, disabling and underserved patient population

Migraine affects an estimated 1.1 billion people worldwide and is the second leading cause of years lived-with disability globally -- and the single leading cause of disability in people under age 50.

Despite recent innovation, current preventives (topiramate, beta-blockers and the CGRP antibodies and gepants) leave a large share of patients inadequately controlled, intolerant of side effects, or facing significant cost and access barriers -- sustaining a multibillion-dollar unmet need that a well-tolerated, oral, at-home, non-scheduled therapy is well positioned to serve.

Development status and next steps

Betterlife has completed its FDA pre-IND meeting for BETR-001, has initiated the final the IND-enabling toxicity study and substantially completed GMP scale-up manufacturing (achieved without using LSD as a starting material). The company anticipates filing its investigational new drug (IND) application in the first quarter of 2027.

Management commentary

"Migraine is one of the world's largest and most disabling conditions and it is one of the few areas where serotonergic pharmacology is not experimental: It is already approved and prescribed every day. BETR-001 lets us pursue that validated mechanism with a molecule that is non-hallucinogenic, non-scheduled and taken as a simple oral pill at home. That combination is unique among 5-HT2A programs and we believe it gives BETR-001 a clear, differentiated path to patients who need better options," said Dr. Ahmad Doroudian, chief executive officer, Betterlife Pharma.

About BETR-001

BETR-001 is the active (6R,9R) stereoisomer of 2-bromo-LSD, a fully non-hallucinogenic derivative of LSD and a potent 5-HT2A neuroplastogen. It is designed as an oral, at-home therapy that is not restricted as a controlled substance. BETR-001 is protected by a granted U.S. composition-of-matter patent with coverage to 2042, with additional filings under way in other major markets.

About Betterlife Pharma Inc.

Betterlife Pharma is a biotechnology company engaged in the development of cutting-edge treatments for neuro-psychiatric and neurological disorders. Its lead asset, BETR-001, is a non-hallucinogenic, non-controlled 5-HT2A neuroplastogen.

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