Small Pharma Announces Further Positive Data from SPL026 Phase IIa Trial in Major Depressive Disorder Strengthening Topline Efficacy Results

-Patients’ self-reported depression and wellbeing scores corroborate MADRS efficacy data
-Statistically significant improvement in anxiety symptoms offers potential in new indications beyond depression

LONDON, March 07, 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 further positive results from the Company’s Phase IIa trial of SPL026, the first placebo-controlled study of a short-duration psychedelic for the treatment of Major Depressive Disorder (“MDD”). The trial investigated the efficacy and safety of a 21.5mg intravenous (“IV”) dose of SPL026, N,N-Dimethyltryptamine (“DMT”), with supportive therapy in 34 patients with moderate/severe MDD. Analyses of additional secondary and exploratory endpoints, including effects on self-reported depression, anxiety and wellbeing, demonstrated that patients receiving at least a single dose of IV SPL026 with supportive therapy experienced clinically relevant improvements in function and mood, further supporting previously announced topline efficacy results.

The two-staged study included a two-week blinded, randomized, placebo-controlled phase followed by a 12-week open-label phase, in which all participants received a single dose of SPL026. In January 2023 the Company reported that the Phase IIa trial met its primary endpoint with a statistically significant and clinically relevant reduction in depression symptoms at two-weeks post-dose, compared to placebo. SPL026 with supportive therapy also demonstrated a rapid onset and durable antidepressant effect, as assessed by the Montgomery-Asberg Depression Rating Scale (“MADRS”).

Analysis of patient-reported depression scores corroborate the MADRS assessments conducted by independent clinical raters. Improvements in depression scores from baseline were observed across all study timepoints in patients receiving at least a single dose of SPL026, as measured by the Beck Depression Inventory (“BDI”), including a statistically significant improvement in depression symptoms compared to placebo at two-weeks post-dose (p=0.002). The efficacy outcomes on the BDI were consistent with MADRS, providing additional support for the rapid and sustained therapeutic profile of SPL026 for the treatment of MDD.

Measures assessing patients’ anxiety and wellbeing, areas which are often negatively impacted by depression, were also analyzed across the study. Following both one and two doses of IV SPL026 with supportive therapy, patients demonstrated a rapid and sustained improvement in anxiety symptoms as measured by the State-Trait Anxiety Inventory-Trait (“STAI-T”) scale. A statistically significant improvement in anxiety symptoms was observed compared to placebo at two-weeks post-dose (p=0.03). At 12-weeks following the open-label dose, a -14.2 mean change from baseline (“CFB”) was demonstrated in the patient group receiving the single dose regimen.

Further, a rapid and sustained improvement in wellbeing was observed following at least a single treatment of IV SPL026 with supportive therapy, as measured by the Warwick-Edinburgh Mental Wellbeing Scale (“WEMWBS”). The results at two-weeks following the blinded dose of SPL026 or placebo showed a 10.1 mean CFB in the SPL026 group compared to 0.9 in the placebo group.

Statistical analysis was conducted on the MADRS open-label data. A statistically significant difference in mean total MADRS score was observed for both the one and two dose regimen groups across all open-label study timepoints (p<0.05). Further analysis was conducted to assess the difference in total MADRS scores between the one and two dose regimen groups using a mixed model of repeated measures for all subjects across all timepoints. No statistical difference (p=ns) was demonstrated between these dose regimens across all time points to 12-weeks. This analysis provides further support that a single dose of SPL026 is sufficient to elicit a rapid and durable antidepressant effect.

Further analysis of the Phase IIa dataset is ongoing and full trial results will be submitted for publication in a peer-reviewed journal.

Dr. Carol Routledge, Chief Medical and Scientific Officer commented: “We are encouraged by the data from our additional analyses, which further strengthens our previously reported topline efficacy results. We are pleased that patient reported outcomes on depression symptoms and broader measures on wellbeing are reflective of the rapid and durable antidepressant effects demonstrated by independent rater assessment using MADRS. Importantly, the data suggests that SPL026 has the potential to offer symptom relief from elevated anxiety, providing an encouraging basis from which to further explore its potential as a treatment for anxiety-related disorders. This data will help inform our future clinical strategy as we think about the expansion of the SPL026 clinical program and broader pipeline.”

George Tziras, Chief Executive Officer, added: “Alongside our recent release of positive topline efficacy results from the Phase IIa study, this additional analysis demonstrates that a single treatment of SPL026 with therapy has the potential to lead not only to rapid and long-lasting relief from depression but provide improvements in anxiety symptoms and offer a broader benefit to patients’ wellbeing. With an estimated cost of $1 trillion in lost global economic productivity due to depression¹, the potential for a treatment to offer a more holistic improvement in patients’ mental health has the potential to reduce negative societal and economic impacts of MDD.”

About the SPL026 Phase I/IIa trial
The two-staged Phase IIa study included a blinded, randomized, placebo-controlled two-week phase where the primary endpoint was to assess the efficacy of a single dose of SPL026 with supportive therapy, versus placebo with therapy at two-weeks post-dose. All study participants were then enrolled into an open-label phase where they received a single dose of SPL026 with supportive therapy, and were followed-up for a further 12-weeks in study. Patients continue to be followed up with for up to six months out of study. The open-label trial design enabled the assessment of durability of effect, as well as the comparative efficacy and safety of a one versus two dose regimen of SPL026.

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. The Company’s current focus is on exploring new therapeutic approaches for depression. Small Pharma’s lead candidate, SPL026, is a proprietary synthetic formulation of DMT. The Company is advancing clinical programs of SPL026 and SPL028 with supportive therapy for the treatment of mental health conditions, and was granted an Innovation Passport designation from the U.K. Medicines and Healthcare products Regulatory Agency (the “MHRA”) for IV SPL026 with supportive therapy for MDD. In addition, Small Pharma has a pipeline of proprietary preclinical assets in development.

Source
¹ Mental health matters (2020), The Lancet Global Health

For further information contact:

Small Pharma Inc.
George Tziras, Chief Executive Officer
Email: [email protected]
Tel: +1 (646) 751-4363

Investor Relations Contacts:
Eric Ribner
LifeSci Advisors
Email: [email protected]
Tel: +1 (646) 889-1200

Media Relations Contacts:
Jaber Mohamed
MHP Communications
Email: [email protected]
Tel: +44 (0)7720 326 847 

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 the Company’s Phase IIa study of SPL026, including the anticipated impact on the application of SPL026 for the treatment of mental health conditions, including depression, anxiety and wellbeing; the ability for SPL026 to elicit a rapid and durable antidepressant effect on a consistent basis; the publishing of full trial trials in a peer-reviewed journal and the timing for release of such results; the Company’s further explorations of SPL-026 as a treatment for anxiety-related disorders; the impact of the data on the Company’s future clinical strategy and expansion of its clinical pipeline; the potential effect and impact of SPL026 on individuals suffering from MDD and additional mental health conditions, including the ability to lead to rapid and long-lasting relief from depression, improvements in anxiety symptoms, and provide a benefit to patients’ wellbeing; the Company continuing to follow-up with patients in the Phase IIa trial for up to six months out of study; the potential impact of holistic treatments for mental health on society, including the Company’s ability to provide such treatments; and the Company’s ability to progress 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 COVID-19; and general business, economic, competitive, political and social uncertainties. 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. 

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