• Results suggest that SSRIs enhance the efficacy of SPL026 (DMT) when administered to MDD patients on a stable dose of SSRIs versus patients not on SSRIs

• At Week 4, 100% of patients in the SSRI cohort responded to SPL026 (DMT) with 92% of patients in remission from depression

• No apparent differences in the safety and tolerability profile of SPL026 (DMT) following administration to participants in the SSRI and non-SSRI patient cohorts

LONDON, Sept. 26, 2023 (GLOBE NEWSWIRE) -- Small Pharma Inc. (TSXV: DMT) (OTCQB: DMTTF) (the “Company” or “Small Pharma”), a biotechnology company focused on short-duration psychedelic-assisted therapies for mental health conditions, today announces positive safety, tolerability and efficacy data from its Phase Ib study exploring the interaction between selective serotonin reuptake inhibitors (“SSRIs”) and SPL026, native N, N-dimethyltryptamine (“DMT”), in patients with Major Depressive Disorder (“MDD”).

The purpose of this study was to build upon the previously reported Phase I/IIa safety and efficacy profile of SPL026 with support therapy, to assess whether SPL026 can be safely administered with or without SSRIs - the current standard of care for MDD. In the Phase I/IIa SPL026 study, patients were required to be withdrawn from SSRIs, which can be a disruptive experience. Through the SPL026-SSRI drug interaction study, Small Pharma aimed to address this requirement, which could enable broader patient recruitment on future large-scale studies, and potentially accelerate the clinical development pathway. Additionally, removing the requirement to be withdrawn from SSRIs may facilitate patient access to SPL026 earlier in the MDD treatment journey, if approved.

This open-label study investigated the safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy of a single 27.5 mg intravenous infusion of SPL026, alone or in combination with SSRIs, in 17¹ patients, together with support therapy. The test cohort (N=12) (the “SSRI Cohort”) consisted of patients currently on a stable treatment course of SSRIs, which have been ineffective in fully relieving their depression symptoms. The control cohort (N=5) (the “Non-SSRI Cohort”) consisted of patients not currently using any pharmacological treatment to treat their depression symptoms. Patients were recruited with moderate-severe MDD as defined by a Hamilton Depression Rating Scale (HAM-D) score of >14. Efficacy was assessed using the Montgomery-Asberg Depression Rating scale (MADRS) to measure any change in patients’ depression symptoms from baseline. Additional exploratory endpoints include the Beck Depression Inventory (BDI) to assess patients’ self-reported depression.

Key Results
Safety & Tolerability

• SPL026 was well-tolerated by all patients in both the SSRI Cohort and Non-SSRI Cohort, with no apparent differences between cohorts
• No drug-related serious adverse events reported
• A small number of drug-related adverse events (“AEs”) reported
  • 8 in SSRI Cohort
  • 3 in Non-SSRI Cohort
  • All deemed to be mild or moderate in severity
• Majority of drug-related AEs were resolved during the dosing visit
  

Exploratory Efficacy
The results reaffirmed the efficacy initially demonstrated in the Phase IIa SPL026 study. 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 the Company’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.

The following chart outlines the efficacy results in both cohorts at baseline and at Week 4 following the dose of SPL026 with support therapy:

Dr. Carol Routledge, Chief Medical and Scientific Officer of Small Pharma, said: “Our primary goal in conducting this Phase Ib study was to understand if SPL026 could be safely administered in conjunction with SSRIs to assess whether patients would need to be withdrawn from their SSRI medication in future trials. While we were very pleased that the study demonstrated that patients may not need to be withdrawn, we were not expecting to see such a marked difference in efficacy when administering SPL026 in combination with SSRIs compared to SPL026 alone. The potentially enhanced efficacy effect of a DMT-based treatment when administered with SSRIs could lead to greater therapeutic benefit for patients, and a compelling argument for positioning it earlier in the treatment pathway. This was a small study, but the findings are both interesting and encouraging and warrant further exploration.”

George Tziras, Chief Executive Officer of Small Pharma, said: “These positive safety and tolerability results further support the patient access strategy for our DMT programs. There may be potential in the future to safely deliver a DMT-based treatment to patients on SSRIs that do not adequately relieve their depression symptoms. Moreover, the marked antidepressant effect seen in the SSRI patient cohort indicates the potential for a combination treatment. We look forward to exploring these findings further as part of the integrated DMT program with Cybin, subject to completion of the proposed arrangement transaction.”

About Small Pharma
Small Pharma is a biotechnology company progressing a pipeline of short-duration psychedelic-assisted therapies for the treatment of mental health conditions. Small Pharma has a portfolio of clinical-stage DMT-based assets, SPL026 and SPL028. The Company was granted an Innovation Passport designation for SPL026 from the U.K. Medicines and Healthcare products Regulatory Agency (the “MHRA”) and has a pipeline of proprietary preclinical assets.

Footnotes:
¹ Total study sample of 18. However, 17 participants were evaluable.

Contact Information:
Small Pharma Inc. & Investor Relations:
George Tziras, Chief Executive Officer
Email: ir@smallpharma.co.uk
Tel: +44 (0)7456 915 968

Media Relations:
Jenny Maguire, Head of External Affairs
Email: jenny.maguire@smallpharma.co.uk

Cautionary Note Regarding Forward Looking Statements
This press release contains statements that constitute “forward-looking information” (“forward-looking information”) within the meaning of the applicable Canadian securities legislation. All statements, other than statements of historical fact, are forward-looking information and are based on expectations, estimates and projections as at the date of this news release. Any statement that discusses predictions, expectations, beliefs, plans, projections, objectives, assumptions, future events or performance (often but not always using phrases such as “expects”, or “does not expect”, “is expected”, “anticipates” or “does not anticipate”, “plans”, “budget”, “scheduled”, “forecasts”, “estimates”, “believes” or “intends” or variations of such words and phrases or stating that certain actions, events or results “may” or “could”, “would”, “might” or “will” be taken to occur or be achieved) are not statements of historical fact and may be forward-looking information.

Forward-looking statements in this news release include statements regarding impacts on the Company’s strategy as a result of the results of the Phase Ib study; the potential enhanced efficacy effect of a DMT-based treatment when administered with SSRIs, and the impact of same, including enabling broader patient recruitment on future large-scale studies, potentially accelerating the clinical development pathway, a greater therapeutic benefit for patients and facilitating patient access to SPL026 earlier in the MDD treatment journey; the potential approval to allow patients; the potential for a combination treatment with SSRIs and SPL026; completion of the proposed arrangement transaction with Cybin; and the Company’s ability to provide short-duration psychedelic-assisted therapies for the treatment of mental health conditions.

In disclosing the forward-looking information contained in this press release, the Company has made certain assumptions. Although the Company believes that the expectations reflected in such forward-looking information are reasonable, it can give no assurance that the expectations of any forward-looking information will prove to be correct. Known and unknown risks, uncertainties, and other factors which may cause the actual results and future events to differ materially from those expressed or implied by such forward-looking information. Such factors include, but are not limited to: compliance with extensive government regulations; domestic and foreign laws and regulations adversely affecting the Company’s business and results of operations; the impact of pandemics or other future disruptions; and general business, economic, competitive, political and social uncertainties, and the risk factors set out in each of the Company's management's discussion and analysis for the three months ended May 31, 2023, and the Company’s annual information form for the year ended February 28, 2023. Accordingly, readers should not place undue reliance on the forward-looking information contained in this press release. Except as required by law, the Company disclaims any intention and assumes no obligation to update or revise any forward-looking information to reflect actual results, whether as a result of new information, future events, changes in assumptions, changes in factors affecting such forward-looking information or otherwise.

Small Pharma makes no medical, treatment or health benefit claims about its proposed products. The MHRA or other similar regulatory authorities have not evaluated claims regarding DMT-assisted therapies and other next generation psychoactive compounds. The efficacy of such therapies has not been confirmed by MHRA-approved research. There is no assurance that such DMT-assisted therapies and other psychoactive compounds can diagnose, treat, cure or prevent any disease or condition. Vigorous scientific research and clinical trials are needed. Any references to quality, consistency, efficacy and safety of potential therapies do not imply that Small Pharma verified such in clinical trials or that Small Pharma will complete such trials. If Small Pharma cannot obtain the approvals or research necessary to commercialize its business, it may have a material adverse effect on Small Pharma’s performance and operations. 

The TSX Venture Exchange (“TSXV”) has neither approved nor disapproved the contents of this news release. Neither the TSXV nor its Regulation Services Provider (as that term is defined in the policies of the TSXV) accepts responsibility for the adequacy or accuracy of this release.

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/16e0c1a8-86b3-4d76-8a4f-184ce02fbe18