dimethyltryptamine (SPL026) / Cybin - LARVOL DELTA

Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial. (PubMed, Front Psychiatry) - P1/2 | "Using the analysis of the safety, tolerability, PD, PK results, doses of 21.5 mg SPL026 were the most likely to provide an intense, tolerated experience. Based on the data obtained from this part of the trial, a dose of 21.5 mg SPL026 given as a 2-phase IV infusion over 10 min (6 mg/5 min and 15.5 mg/5 min) was selected as the dose to be taken into patients in Part B (to be presented in a future manuscript).Clinical trial registration:www.clinicaltrials.gov, identifier NCT04673383; https://www.clinicaltrialsregister.eu, identifier 2020-000251-13; https://www.isrctn.com/, identifier ISRCTN63465876."

Clinical • Journal • P1 data • PK/PD data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Pharmacodynamics of SPL026 (N,N-Dimethyltryptamine fumarate) with supportive therapy in patients with major depressive disorder (ECNP 2023) - "The results of this study demonstrate that SPL026 with supportive therapy elicits a significant, psychedelic experience with both rapid-acting and long-term pharmacodynamic changes in MDD patients. Results highlight that insights into mechanism of action can be gained by including PD measures in Phase IIa studies."

Clinical • PK/PD data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Small Pharma Reports Positive Top-line Data from SPL026 (DMT)-SSRI Drug Interaction Study in Patients with Major Depressive Disorder (Businesswire) - P1b | N=18 | NCT05553691 | Sponsor: Small Pharma Ltd | "'Together, these results provide strong proof-of-concept and give us further reason to believe in the synergistic power of our combined programs, upon the closing of the transaction expected in the fourth quarter of 2023'...However, a marked improvement was observed between the antidepressant effect of SPL026 treatment in the SSRI Cohort compared to the Non-SSRI Cohort. While the efficacy observed in the Non-SSRI Cohort was comparable to the efficacy data previously observed in Small Pharma’s SPL026 Phase IIa clinical trial, the antidepressant effects observed in the SSRI Cohort were of a greater magnitude, suggesting a potentially enhanced efficacy effect when SPL026 is administered in combination with SSRIs."

M&A • P1 data • CNS Disorders • Depression • Major Depressive Disorder

Efficacy, safety and tolerability of spl026 (dmt fumarate) with support therapy in patients with major depressive disorder (ECNP 2023) - "SPL026 showed a favourable safety profile, with no drug-related SAEs reported. In conclusion, the results of this study demonstrate that SPL026 with supportive therapy elicits a significant, rapid onset and durable antidepressant effect in patients with MDD."

Clinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Discovery and In Vitro Characterization of SPL028: Deuterated N,N-Dimethyltryptamine. (PubMed, ACS Med Chem Lett) - "The in vitro receptor binding profile of D-DMT was comparable to that of DMT, with the highest affinity at the 5-HT, 5-HT, and 5-HT receptors. D-DMT was therefore the preferred candidate to consider for further evaluation."

Journal • Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

SPL026 With or Without SSRIs in Participants With MDD (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Small Pharma Ltd | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

SPL026 With or Without SSRIs in Participants With MDD (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Small Pharma Ltd | Recruiting ➔ Active, not recruiting | Trial primary completion date: May 2023 ➔ Aug 2023

Combination therapy • Enrollment closed • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

IM and IV SPL026 Drug Product in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Small Pharma Ltd | Active, not recruiting ➔ Completed

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

Efficacy, Safety And Tolerability Of Spl026 (dmt Fumarate) With Support Therapy In Patients With Major Depressive Disorder (CINP 2023) - "No significant difference in antidepressant effect was identified between one vs two doses (separated by two weeks) of SPL026; both dosing regimens demonstrated a rapid onset and durable antidepressant effect. SPL026 showed a favorable safety and tolerability profile, with no drug- related serious adverse events reported. All adverse events related to treatment were considered mild or moderate and most occurred and resolved during the dosing visit."

Clinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Small Pharma Announces Significant Developments In Intellectual Property Portfolio (GlobeNewswire) - "5 new patent grants, 3 expected upcoming patent grants, and 8 notices of allowance in key international jurisdictions. Small Pharma...today announces an update to its intellectual property ('IP') portfolio, demonstrating significant progress already made by the Company in 2023."

Patent • CNS Disorders • Depression • Major Depressive Disorder

Pharmacokinetics of N,N-dimethyltryptamine in Humans. (PubMed, Eur J Drug Metab Pharmacokinet) - P1/2 | "This is the first study to determine, in detail, the full pharmacokinetics profile of DMT following a slow IV infusion in humans, confirming rapid attainment of peak plasma concentrations followed by rapid clearance. These findings provide evidence which supports the development of novel DMT infusion regimens for the treatment of MDD."

Journal • PK/PD data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • CYP2C19 • CYP2D6

IM and IV SPL026 Drug Product in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: Small Pharma Ltd | Recruiting ➔ Active, not recruiting

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

IM and IV SPL026 Drug Product in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Small Pharma Ltd | Trial completion date: Mar 2023 ➔ Jun 2023 | Trial primary completion date: Mar 2023 ➔ Jun 2023

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

IM and IV SPL026 Drug Product in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Small Pharma Ltd | Not yet recruiting ➔ Recruiting

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

SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients (clinicaltrials.gov) - P1/2 | N=66 | Completed | Sponsor: Small Pharma Ltd | Active, not recruiting ➔ Completed

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

IM and IV SPL026 Drug Product in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: Small Pharma Ltd

New P1 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Psychedelics for Depression: Phase I results from Small Pharma’s Phase I/IIa clinical trial of DMT-assisted psychedelic therapy (ECNP 2022) - "Small Pharma is conducting the world’s first regulated Phase I/IIa clinical trial of SPL026 (DMT fumarate), in combination with psychotherapy, in Major Depressive Disorder (MDD)...Psychedelics, such as DMT, offer the potential of an alternative treatment paradigm to the traditional SSRI or psychotherapy models currently available to patients. The Phase IIa component – a randomised, placebo-controlled proof of concept study in MDD patients, is underway with Result s due in the coming months."

Clinical • P1/2 data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

SPL026 With or Without SSRIs in Participants With MDD (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Small Pharma Ltd

Combination therapy • New P1 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients (clinicaltrials.gov) - P1/2 | N=66 | Active, not recruiting | Sponsor: Small Pharma Ltd | Recruiting ➔ Active, not recruiting

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

Small Pharma Successfully Completes Phase I Clinical Trial of DMT in Combination with Supportive Psychotherapy (Yahoo Finance) - "Small Pharma Inc...today announced both the successful completion of the Phase I part of the combined Phase I/IIa clinical trial and the initiation of the Phase IIa part in combination with psychotherapy of its lead candidate, SPL026, for the treatment of Major Depressive Disorder ('MDD')....The Phase I study has generated a robust dataset on the pharmacokinetics of SPL026 using Good Laboratory Practices as well as on safety and tolerability....Topline results are anticipated in the first half of 2022."

P1/2 data • Trial status • CNS Disorders • Depression • Major Depressive Disorder

Small Pharma to Headline the 2021 DMT Conference: A Molecular Masterclass (Yahoo Finance) - "Small Pharma Inc...announces that it will headline Microdose’s virtual 2021 DMT Conference as one of the event’s lead sponsors. The conference, taking place on September 9 and 10, will bring together some of the world’s leading industry figures exploring the potential of N,N-dimethyltryptamine (DMT) at the intersection of drug development and safety, clinical care and applications, law and regulation, business and markets, science and research as well as history and culture....Small Pharma's lead candidate SPL026 is currently in a Phase I/IIa randomized-controlled clinical trial for Major Depressive Disorder in the UK."

Review • CNS Disorders • Depression • Major Depressive Disorder

Small Pharma Reports First Fiscal Quarter 2021 Highlights (GlobeNewswire) - "Small Pharma has initiated a blinded, two-part Phase I/IIa clinical trial....Small Pharma has successfully completed the administration of SPL026, DMT-assisted therapy to 32 psychedelic-naive healthy subjects in the Phase I component of the trial....Small Pharma had positive discussions with UK regulators on the preliminary protocol for the Company’s Phase IIb clinical trial, anticipated to commence in the second half of 2022. The MHRA endorsed minimal additional preclinical safety studies...Small Pharma received granted status under patent number GB2585978 for its UK patent application GB2008303.6....This patent covers composition of matter protection on a range of novel tryptamines that delivers an extended psychedelic experience for use in protocols for treating depression."

New P2b trial • Patent • Trial status • CNS Disorders • Depression • Major Depressive Disorder

Small Pharma Inc. Expands Phase I/IIa Clinical Trial With Additional Study Site (PRNewswire) - "Small Pharma...announces the expansion of its Phase I/IIa clinical trial for its lead product, SPL026, a N,N-dimethyltryptamine ('DMT') based treatment for major depressive disorder ('MDD')....This patient proof of concept phase will commence in Q3 2021 and, as a result of appointing MAC, timelines for this Phase I/IIa clinical trial are expected to accelerate with anticipated top-line results brought forward from the end of 2022 to the first half of 2022."

P1/2 data • Trial status • CNS Disorders • Depression • Major Depressive Disorder

SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients (clinicaltrials.gov) - P1/2; N=68; Recruiting; Sponsor: Small Pharma Ltd; Not yet recruiting ➔ Recruiting

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

SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients (clinicaltrials.gov) - P1/2; N=68; Not yet recruiting; Sponsor: Small Pharma Ltd

Clinical • New P1/2 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry