deuterated psilocybin analog (HLP003) / Helus Pharma - LARVOL DELTA

Next-Generation Pharmacotherapies for Unipolar Mood Disorders: A Leading Article on Phase II/III Drug Development Across Diverse Mechanisms. (PubMed, CNS Drugs) - "Following the US Food and Drug Administration (FDA) approval of esketamine and brexanolone in 2019, industry investment in therapeutics with novel mechanisms for mood and anxiety disorders has expanded, catalyzing a new wave of innovative interventions...The drug names discussed are ALTO-100, ALTO-203, ALTO-207, ALTO-300, BHV-7000, BI-1569912, BPL-003, COMP360, DT120, ELE-101, GATE-251, GH001, GM-1020, GM-2505, HLP003, MK-1942, NBI-1065845, NBI-1070770, NV-5138, PIPE-307, SEP-363856, SPT-300, VLS-01, and XEN1101. The US Clinical Trials registry (clinicaltrials.gov), MEDLINE, conference proceedings, and company communications such as press releases were consulted to obtain up-to-date trial information and reported outcomes. Overall, the therapeutic landscape shows an expanding range of clinical compounds under active development; nonetheless, persistent challenges remain, including approaches to therapeutics where functional unblinding may occur, the ways in which to..."

Journal • P2/3 data • Review • CNS Disorders • Mood Disorders • Psychiatry

APPROACH: "A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder" (clinicaltrials.gov) - P3 | N=220 | Active, not recruiting | Sponsor: Cybin IRL Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Mechanistic Study to Assess a Single Dose of CYB003 in Participants With Depression and Anxiety (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Ohio State University | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2027 ➔ Nov 2028 | Trial primary completion date: Mar 2027 ➔ Sep 2028

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Helus Pharma…announced that enrollment in the APPROACH Phase 3 clinical trial of HLP003 for the adjunctive treatment of major depressive disorder (MDD) is progressing as planned and has surpassed 86% enrollment (The Manila Times) - "The trial is part of the Company's broader Phase 3 PARADIGM program, which also includes the EMBRACE study and the EXTEND long-term extension study, supporting the continued advancement of HLP003 toward potential commercialization...The Company remains on track for topline data readout in Q4 2026."

Enrollment status • P3 data: top line • Major Depressive Disorder

Phase III Long-term Extension Trial to Assess Safety and Efficacy of CYB003 in MDD (EXTEND) (clinicaltrials.gov) - P3 | N=468 | Enrolling by invitation | Sponsor: Cybin IRL Limited | Recruiting ➔ Enrolling by invitation

Enrollment status • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

CYB003-004: Phase III Long-term Extension Trial to Assess Safety and Efficacy of CYB003 in MDD (EXTEND) (clinicaltrialsregister.eu) - P2/3 | N=110 | Not yet recruiting | Sponsor: Cybin IRL Limited

New P2/3 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

EMBRACE: A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder (clinicaltrials.gov) - P3 | N=330 | Recruiting | Sponsor: Cybin IRL Limited | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

EMBRACE: A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder (clinicaltrials.gov) - P3 | N=330 | Not yet recruiting | Sponsor: Cybin IRL Limited | Initiation date: Jul 2025 ➔ Oct 2025

Trial initiation date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Phase III Long-term Extension Trial to Assess Safety and Efficacy of CYB003 in MDD (EXTEND) (clinicaltrials.gov) - P3 | N=468 | Recruiting | Sponsor: Cybin IRL Limited | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

APPROACH: "A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder" (clinicaltrials.gov) - P3 | N=220 | Recruiting | Sponsor: Cybin IRL Limited | Trial completion date: May 2026 ➔ Sep 2026 | Trial primary completion date: Mar 2026 ➔ Aug 2026

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Cybin Receives Australian Approval for EMBRACE, a Multinational Pivotal Study Evaluating CYB003 for the Adjunctive Treatment of Major Depressive Disorder (Businesswire) - "EMBRACE will enroll 330 patients with moderate to severe MDD (MADRS≥24) who are on a stable dose of antidepressant medication but are responding inadequately. Study participants will be randomized 1:1:1 to receive either CYB003 16 mg, CYB003 8 mg, or inactive placebo. Each study arm will evaluate two doses, administered three weeks apart."

Trial status • Major Depressive Disorder

The Phase 3 PARADIGM program is expected to enroll a total of 550 participants across three studies: two 12-week randomized, double-blind, placebo-controlled studies, APPROACH and EMBRACE, and a long-term extension study, EXTEND. (Businesswire) - "The first Phase 3 trial, APPROACH, is currently dosing and is taking place at approximately 45 clinical sites across the U.S. The second Phase 3 trial, EMBRACE, is expected to enroll participants at approximately 60 clinical sites across the U.S., Europe, and Australia. Participants from APPROACH and EMBRACE will have the opportunity to roll over into EXTEND after completing the 12-week, double-blind, placebo-controlled treatment periods."

Trial status • Major Depressive Disorder

CYB003: Deuterated psilocin program (Cybin Press Release) - "Phase 3 PARADIGM program is underway, with topline data from first pivotal study, APPROACH, expected in 2026."

P3 data: top line • Trial status • Major Depressive Disorder

Cybin Receives UK MHRA Approval to Commence EMBRACE, A Multinational Pivotal Study Evaluating CYB003 for the Adjunctive Treatment of Major Depressive Disorder (Businesswire) - "-Cybin Inc....announced that it has received approval from the UK Medical and Healthcare Products Regulatory Agency ('MHRA') to commence EMBRACE, the second pivotal study in PARADIGM, the Company’s Phase 3 multinational program evaluating CYB003, a proprietary deuterated psilocin analog. The Company previously received Breakthrough Therapy Designation from the U.S. Food and Drug Administration ('FDA') for CYB003 for the adjunctive treatment of Major Depressive Disorder ('MDD')...With expected enrollment of 330 participants suffering from moderate to severe MDD, the EMBRACE study aims to generate critical late-stage data that, ultimately, may lead to transforming the standard of care for patients in need."

Trial status • Major Depressive Disorder

Cybin Announces Additional Strategic Clinical Site Partnerships to Support PARADIGM, a Multinational Phase 3 Program Evaluating CYB003 (Businesswire) - "Second Phase 3 study, EMBRACE, is expected to begin mid-2025...Cybin Inc...announced additional strategic partnership agreements ('SPAs'), bringing the total to 18 clinical sites engaged to advance Cybin’s multinational Phase 3 program evaluating CYB003 for the adjunctive treatment of MDD. The APPROACH study is expected to include approximately 45 clinical sites."

Commercial • Trial status • Major Depressive Disorder

A Mechanistic Study to Assess a Single Dose of CYB003 in Participants With Depression and Anxiety (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Ohio State University | Initiation date: Mar 2025 ➔ Sep 2025

Trial initiation date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Cybin Engages Thermo Fisher Scientific to Provide U.S.-Based Manufacturing for its CYB003 Program for the Adjunctive Treatment of Major Depressive Disorder (Businesswire) - "Cybin Inc...announced that it has engaged Thermo Fisher Scientific ('Thermo Fishe'), the world leader in serving science, to support the Phase 3 clinical supply and potential commercial manufacturing of CYB003, the Company’s proprietary deuterated psilocin program in Phase 3 development for the adjunctive treatment of Major Depressive Disorder ('MDD')."

Commercial • Major Depressive Disorder

Cybin Announces Additional U.S. Patent Supporting its CYB003 Breakthrough Therapy Program in Phase 3 Development for Major Depressive Disorder (Businesswire) - "Cybin Inc...announced that the United States Patent and Trademark Office has granted U.S. patent 12,291,499 in support of its CYB003 program in MDD...The patent, which is expected to provide exclusivity until 2041, includes claims to pharmaceutical compositions and oral dosage forms within the Company’s proprietary deuterated psilocin analog program, CYB003."

Patent • Major Depressive Disorder

Phase III Long-term Extension Trial to Assess Safety and Efficacy of CYB003 in MDD (EXTEND) (clinicaltrials.gov) - P3 | N=468 | Not yet recruiting | Sponsor: Cybin IRL Limited | N=220 ➔ 468 | Trial completion date: Sep 2027 ➔ Jan 2028 | Trial primary completion date: Sep 2027 ➔ Jan 2028

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Mechanistic Study to Assess a Single Dose of CYB003 in Participants with Depression and Anxiety (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Ohio State University

New P2 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Cybin Reports Third Quarter Fiscal Year 2025 Financial Results and Recent Business Highlights (Businesswire) - P1/2 | N=57 | NCT05385783 | Sponsor: Cybin IRL Limited | "CYB003: Summary of Phase 2 12-Month Efficacy Data in MDD Patients...100% of participants receiving two doses of 16 mg were responders; 71% of participants receiving two doses of 16 mg were in remission; Mean change from baseline in MADRS was approximately -23 points after two doses of 16 mg."

P2 data • Major Depressive Disorder

Cybin Reports Third Quarter Fiscal Year 2025 Financial Results and Recent Business Highlights (Businesswire) - "Upcoming Clinical Milestones and Future Studies: CYB003 - Deuterated Psilocin Program...Initiate second pivotal study, EMBRACE, around mid-2025; Initiate long-term extension study, EXTEND, which is expected to begin 12 weeks after commencement of APPROACH and EMBRACE, respectively."

New trial • Trial status • CNS Disorders • Major Depressive Disorder

EMBRACE: A Phase 3 Trial to Assess CYB003 in Major Depressive Disorder (clinicaltrials.gov) - P3 | N=330 | Not yet recruiting | Sponsor: Cybin IRL Limited

New P3 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Cybin Launches Strategic Clinical Site Partnerships to Support PARADIGM, a Multinational Pivotal Phase 3 Program Evaluating CYB003 for the Adjunctive Treatment of Major Depressive Disorder (Businesswire) - "Cybin Inc...announced the launch of its first strategic partnership agreement ('SPA') with Segal Trials in furtherance of Cybin’s multinational pivotal Phase 3 program evaluating CYB003 for the adjunctive treatment of Major Depressive Disorder ('MDD')."

Commercial • Major Depressive Disorder

Facet Life Sciences Named Regulatory Partner for Cybin's Neuropsychiatry Therapeutics Development Pipeline (PRNewswire) - "Facet Life Sciences...has been named as the US regulatory partner for Cybin Inc. ('Cybin'), a late-stage breakthrough neuropsychiatry company committed to revolutionizing mental healthcare by developing new and innovative treatment options to address the large unmet need for people who suffer from mental health conditions. This collaboration will support Cybin's pioneering work in next generation therapeutics, particularly for conditions like Major Depressive Disorder, Generalized Anxiety Disorder, and Central Nervous System disorders....Facet Life Sciences' role will encompass strategic nonclinical, CMC, clinical, and procedural regulatory development guidance, tactical regulatory, medical writing support and submission management for Cybin's key therapies, including CYB003..."

Commercial • CNS Disorders • General Anxiety Disorder • Major Depressive Disorder