A Multicenter, Randomized, Double-Blind, Vehicle-Controlled, Parallel-Group Clinical Trial to Demonstrate the Superiority of 0.3% and 1% OPA-15406 Ointment Versus Vehicle in Pediatric Subjects with Atopic Dermatitis

A multicenter, randomized, double-blind, vehicle-controlled, parallel group trial to demonstrate the superiority of 0.3% and 1% OPA-15406 ointment to vehicle in pediatric subjects with AD. This trial consists of the 0.3% OPA-15406 group, the 1% OPA-15406 group, and the vehicle group.

Start Date17 Feb 2023

Sponsor / Collaborator

Otsuka Beijing Research Institute

NCT05667623

/ CompletedPhase 3

A Multinational, Multicenter, Randomized, Double-blind, Vehicle-controlled, Parallel-group Comparison Trial to Demonstrate the Superiority of 1% OPA-15406 Ointment to the Vehicle in Adult Patients with Atopic Dermatitis

This is a multinational (China and Korea), multicenter, randomized, double-blind, vehicle-controlled, parallel-group, comparison trial to demonstrate the superiority of 1% OPA-15406 ointment to the vehicle in adult AD subjects.

Start Date06 Feb 2023

Sponsor / Collaborator

Otsuka Beijing Research Institute

NCT05608343

/ CompletedPhase 3

A Phase 3, Randomized, Double-Blind, Vehicle-Controlled, Multicenter Study to Assess the Efficacy and Safety of Difamilast Ointment 1% in Children, Adolescents, and Adults With Mild to Moderate Atopic Dermatitis

This is a Phase 3 Double Blind multi-center study conducted at 40 investigational sites in United States to assess the efficacy and safety of Difamilast Ointment 1% in subjects ≥2 years of age with mild to moderate atopic dermatitis.

Start Date01 Oct 2022

Sponsor / Collaborator

Acrotech Biopharma LLC

100 Clinical Results associated with Difamilast

100 Translational Medicine associated with Difamilast

100 Patents (Medical) associated with Difamilast

Literatures (Medical) associated with Difamilast

01 Jul 2025·CLINICAL AND EXPERIMENTAL ALLERGY

DIFENSE Study Protocol: Early Intervention With Difamilast Ointment in Infantile Early‐Onset Atopic Dermatitis for Prevention of Transcutaneous Sensitisation

Article

Author: Narita, Masami ; Okamoto, Kazuyoshi ; Yamamoto‐Hanada, Kiwako ; Natsume, Osamu ; Kobayashi, Tohru ; Tsuchiya, Kunihiko ; Ohya, Yukihiro ; Takemura, Yutaka ; Kishimoto, Nobuharu

01 Jun 2025·PEDIATRIC ALLERGY AND IMMUNOLOGY

New topical molecular targeted therapies for atopic dermatitis in children: A systematic review and meta‐analysis

Review

Author: Okada, Yuki ; Ohya, Yukihiro ; Murai, Hiroki ; Saeki, Hidehisa ; Kawamoto, Norio ; Futamura, Masaki ; Arima, Tomoyuki ; Miyamoto, Manabu ; Takeuchi, Haruko ; Yamamoto‐Hanada, Kiwako

Abstract:

Topical molecular targeted therapies have recently emerged for the treatment of atopic dermatitis (AD), but their efficacy and safety, particularly in children, remain underexplored. This systematic review and meta‐analysis aim to evaluate the efficacy and safety of topical targeted therapies in children with AD. We conducted a comprehensive search of the CENTRAL, MEDLINE, Embase, and ICHUSHI databases for articles published up to January 7, 2023, based on a protocol registered in PROSPERO (CRD42022366449). Randomized controlled trials (RCTs) investigating new topical targeted therapies in children (≤18 years) with AD were included. The primary outcomes were the Eczema Area and Severity Index (EASI) scores and treatment‐related adverse events. Secondary outcomes included additional efficacy and safety analyses. A meta‐analysis was performed using Revman 5.4, with bias risk assessed via the RoB 2 tool. Nine studies (reported in eight articles) involving 2182 patients were included, with 1469 children treated with Janus kinase inhibitors (ruxolitinib and delgocitinib) and phosphodiesterase‐4 inhibitors (crisaborole, lotamilast, and difamilast). These interventions significantly improved EASI scores, with the least square mean change (mean difference: −56.67%; 95% confidence interval [−59.16% to −54.18%]). Additionally, topical targeted therapies did not increase the incidence of treatment‐emergent adverse events (risk difference: 0.00; 95% confidence interval [−0.02 to 0.02]). The risk of bias was low across all outcomes. New topical targeted therapies administered over 4 weeks are effective and safe for children with atopic dermatitis aged ≤18 years. Further studies are needed to establish their long‐term safety and efficacy.

01 Jun 2025·JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Difamilast topically ameliorates pruritus, dermatitis, and barrier dysfunction in atopic dermatitis model mice by inhibiting phosphodiesterase 4, especially the 4B subtype

Article

Author: Shibamori, Masafumi ; Hiyama, Hidetaka ; Hoshino, Yuya ; Wadatsu, Takashi ; Kakumoto, Yusuke ; Kirima, Kazuyoshi ; Arichika, Naoya

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder, characterized by itchy eczema. The complex interplay among pruritus, skin inflammation, and barrier dysfunction contributes to the development, progression, and chronicity of AD. Phosphodiesterase 4 (PDE4), an enzyme that specifically degrades cAMP, is expressed in a variety of cell types, including immune cells, fibroblasts, and keratinocytes. PDE4 is involved in the persistence and exacerbation of chronic inflammatory diseases such as chronic obstructive pulmonary disease, asthma, psoriasis, and AD. One of the topical PDE4 inhibitors, difamilast, has been shown to be effective in the clinical treatment of AD. However, its pharmacological effects and mechanisms of action are not completely understood. Therefore, we evaluated the effects of difamilast on pruritus, dermatitis, and skin barrier dysfunction in MC903-induced AD model mice. The results revealed that a single application of difamilast dramatically reduced the number of scratching events, an indicator of pruritus, and repeated application of difamilast reduced the increase in ear thickness, an indicator of dermatitis, and transepidermal water loss, an indicator of barrier dysfunction. In addition, these symptoms were milder in PDE4B-deficient mice than in wild-type mice, and difamilast treatment had little or no further therapeutic effects on attenuating AD symptoms. In summary, our study demonstrated that difamilast effectively alleviates the primary symptoms of AD through the inhibition of PDE4B, as one of its mechanisms. SIGNIFICANCE STATEMENT: This study characterized the therapeutic effects of difamilast on the major symptoms of atopic dermatitis, including pruritus, dermatitis, and skin barrier dysfunction. The study also revealed a detailed mechanism of action of difamilast, in which its therapeutic effect is mediated mainly by PDE4B inhibition. This study may provide new insights into the use of difamilast for the treatment of atopic dermatitis.

News (Medical) associated with Difamilast

06 Oct 2022

·www.biospace.com

Devonian Health Group Announces Peer-Reviewed Publication of Thykamine™ Positive Phase 2 Clinical Trial Results in Journal of Drugs in Dermatology

Clinical Study demonstrated dual benefit mode of action of Thykamine™ in mild-to-moderate Atopic Dermatitis: Statistically significant effect on Atopic Dermatitis evaluated by measure of IGA, BSA and POEM Statistically beneficial effect on Pruritis (‘‘itch’’) QUEBEC CITY--(BUSINESS WIRE)-- Devonian Health Group Inc. (“Devonian” or the “Corporation”) (TSXv: GSD ; OTCQB: DVHGF), a clinical stage botanical pharmaceutical corporation, focused on developing a unique portfolio of botanical pharmaceutical and cosmeceutical products, today announced the publication of Thykamine™ positive phase 2 trial in adult patients with mild-to-moderate Atopic Dermatitis (AD) in the peer-reviewed Journal of Drugs in Dermatology (JDD). This article, titled ‘‘Phase 2 Trial of Topical Thykamine in Adults with Mild to Moderate Atopic Dermatitis’’ has been published in a JDD special issue focus on Atopic Dermatitis (J Drugs Dermatol 21(10): 1091-1097, October 2022). The paper by Lynde et al. discloses the results of the Phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted in 162 adult patients with mild-to-moderate AD. In this 4-week multicentre study, a significantly greater proportion of adult patients treated with Thykamine™ cream 0.10% achieved an IGA of clear/almost clear and at least a 2-grade improvement from baseline in IGA (30.8%) compared to placebo (6.7%; P =.014). The benefit of Thykamine™ cream 0.10% was supported by a statistically significant effect on secondary endpoints of Body Surface Area (BSA), pruritis, and Patient-Oriented Eczema Measure score (POEM). A significant reduction in %BSA affected from baseline was demonstrated at all study visits. These changes differentiated significantly from placebo from Day 14 until Day 29 (p ≤ 0.001). Pruritus (‘‘itch’’) was rapidly improved from baseline by Day 7 with a statistically difference vs placebo at Day 21 and Day 29 (p ≤ 0.01). POEM outcome was statistically significant from placebo at day 21 and 29 (p ≤ 0.01). Thykamine™, at all doses, was well tolerated with an adverse event pro placebo. ‘‘We are proud to have our innovative Thykamine™ study results published in a reputable, peer-reviewed scientific journal,” said Dr André P. Boulet, PhD, Chief Scientific Officer of Devonian. ‘‘The efficacy of Thykamine™ obtained in this clinical trial compared favourably to published results of other therapeutic products such as the phosphodiesterase inhibitors (PDE4)1,2 and calcineurin inhibitors.3 To our knowledge, it is the first time that clinical data revealed that a Botanical Drug candidate can be as potent as a product derived from chemical synthesis. Furthermore, the use of Thykamine™ was associated with a rapid improvement in itch in patients with mild to moderate AD. The fast onset of action and magnitude of itch relief associated with Thykamine™ cream treatment suggests that it may provide meaningful improvement in quality of life and addresses an unmet need for patients with AD,’’ added Dr Boulet. About Atopic Dermatitis (AD) AD, also known as eczema, is a type of inflammation of the skin. It results in itchy, red, swollen, and cracked skin that may lead to secondary infection. The condition typically starts in childhood with changing severity over the years. Although the cause of AD is unknown, it is believed to involve genetics, a compromised immune system and can be triggered by environmental factors. AD is the most common skin disease4 and its prevalence continues to increase worldwide. In the United States, the incidence has been reported to be 15-30% of children5. The severity of AD can be categorized into three stages, mild, moderate, and severe. The mild and moderate forms constitute approximately 67% and 26% respectively of the AD childhood patient population. A similar distribution has been reported in the adult patient population (71% and 26% respectively) 6,7. There is currently an enormous unmet need for new, effective, and well-tolerated treatment options in AD8. The global atopic dermatitis market is expected to exceed US $21,8 billion in sales by 20279. About Thykamine Thykamine™, the first pharmaceutical product issued from Devonian’s SUPREX™ platform, is a highly innovative product for the prevention and treatment of health conditions related to inflammation and oxidative stress including ulcerative colitis, atopic dermatitis, psoriasis, rheumatoid arthritis, and other autoimmune disorders. The anti-inflammatory, anti-oxidative and immunomodulatory properties of Thykamine™ have been demonstrated by a considerable number of in vitro and in vivo studies as well as in a Phase IIa clinical study in patients with mild-to-moderate distal ulcerative colitis and in a phase II clinical study in patients with mild-to-moderate atopic dermatitis. Both Thykamine™ and SUPREX™ platform are protected by several patents in North America, Europe and Asia. About Devonian Devonian Health Group Inc. (Devonian)is a late-stage botanical pharmaceutical corporation with novel therapeutic approaches to targeting unmet medical needs. Devonian's core strategy is to develop prescription botanical drugs from plant materials and algae for the treatment of inflammatory-autoimmune diseases including but not limited to ulcerative colitis and atopic dermatitis. Based on a foundation of over 15 years of research, Devonian’s focus is further supported by a US-FDA set of regulatory guidelines favouring a more efficient drug development pathway for prescription botanical drug products over those of traditional prescription medicines. Devonian’s flagship product, Thykamine™, the first pharmaceutical product issued from Devonian’s SUPREX™ platform, is a highly innovative product for the prevention and treatment of health conditions related to inflammation and oxidative stress. The anti-inflammatory, anti-oxidative and immunomodulatory properties of Thykamine™ have been demonstrated by a considerable number of in vitro and in vivo studies as well as in a Phase IIa clinical study in patients with Mild-to-Moderate distal Ulcerative Colitis and in a large phase 2 clinical trial in adult patients with Mild-to-Moderate Atopic Dermatitis. Devonian is also involved in the development of high-value cosmeceutical products leveraging the same proprietary approach employed with their pharmaceutical offerings. Devonian Health Group Inc. was incorporated in 2015 and is headquartered in Québec, Canada where it owns a state-of-the art extraction facility with full traceability ‘from the seed to the pill’. Acquired in 2018, Altius Healthcare Inc., its commercialization subsidiary, brings opportunities for further diversification and growth potential. Devonian is listed on the TSX Venture Exchange (TSXV:GSD) as well as the OTCQB Venture Exchange (OTCQB:DVHGF) For more information, visit References Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesteras 4 (PDE4) inhibitors for the topical treatment of atopic dermatitis (AD) in children and adults. J. Am. Acad. Dermatol., Vol 75 (3), 494-503, 2016. Hanifin JM., Ellis CN, Frieden IJ, et al. OPA-15406, a novel topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (A): A phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol, Vol 75 (2), 297-305, 2016. Product Monograph, Elidel Cream 1%, Valeant Canada, 2014 Peng W., Novak N. Pathogenesis of atopic dermatitis. Clinical et Experimental Allergy 2015, 45 : 566-574. Amy Huang, MD, Christine Cho, MD, Donald Y.M. Leung, MD, PhD, and Kanwaljit Brar, MD. Atopic Dermatitis: Early Treatment in Children. Curr Treat Options Allergy. 2017 Sep; 4(3): 355–369. Silverberg JI, Simpson EL. Associations of childhood eczema severity: A US population-based study. Dermatitis 2014; 25(3):107-114. Chaplin S. Guide to treatments used for atopic dermatitis in adults. Prescriber 2016: 27(10): 30-39. Leung DYM. Guttman-Yassky E. Assessing the current treatment of atopic dermatitis: Unmet needs. J. of Allergy and Clinical Immunology. 2017; 139(4) Suppl.: S47-48. Market Data Forecast, Global Atopic Dermatitis Treatment Market Size, Share, Trends, COVID-19 Impact & Growth Analysis Report - Segmented By Treatment Type, Route Of Administration, Distribution Channel & Region - Industry Growth, Trends & Forecast (2021 to 2026), April 2021. Forward-Looking Statements This press release contains forward-looking statements about Devonian’s objectives, strategies and businesses that involve risks and uncertainties. These statements are “forward-looking” because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to, the intended use of proceeds of the Offering, the final approval of the TSX Venture Exchange in connection with the Offering, the above “About Devonian” paragraph, Devonian’s ability to develop, manufacture, and successfully commercialize value-added pharmaceutical and cosmeceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of Devonian to take advantage of business opportunities in the pharmaceutical and cosmeceutical industries, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations in Devonian’s prospectus dated April 21st, 2017 under the heading “Risk Factors” related to Devonian’s business. As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update any forward-looking statement even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

26 May 2022

·www.biospace.com

Devonian Health Group Announces the Journal of Drugs in Dermatology Acceptance for Publication of Thykamine™ Positive Phase 2 Clinical Trial Results in Atopic Dermatitis

May 26, 2022 12:45 UTC QUEBEC CITY--(BUSINESS WIRE)-- Devonian Health Group Inc. (“Devonian” or the “Corporation”) (TSXv: GSD ; OTCQB: DVHGF), a clinical stage botanical pharmaceutical corporation, focused on developing a unique portfolio of botanical pharmaceutical and cosmeceutical products, today announced the acceptance for publication of results from its positive phase 2 trial of Thykamine™ in patients with mild-to-moderate Atopic Dermatitis (AD) in the peer-reviewed Journal of Drugs in Dermatology (JDD). This JDD article, titled ‘‘Phase 2 Trial of Topical Thykamine™️ in Adults with Mild to Moderate Atopic Dermatitis’’ will be published in a special issue on Atopic Dermatitis planned for October 2022. The Phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in 162 patients with mild-to-moderate AD. In this 4-week, multicentre study, adult patients were randomized to receive Thykamine™ cream 0.05%, 0.10%, 0.25% or vehicle cream (placebo) twice daily. The primary efficacy endpoint was the Investigator Global Assessment (IGA) success rate defined as percentage of patients with an IGA score of 0 or 1 with greater than or equal to 2-grade reduction at week 4. Secondary endpoints included body surface area (BSA), pruritus and the Patient-Oriented Eczema Measure (POEM), among others. The benefit of Thykamine™ cream 0.10% was supported by a statistically significant effect on the primary and secondary endpoints of Body Surface Area (BSA), pruritis, and Patient-Oriented Eczema Measure score (POEM). “We are excited that Journal of Drugs in Dermatology has elected to publish, in a special issue on Atopic Dermatitis, the results of our Phase 2 study on Thykamine™️ which shows significant positive results posted by our product for the treatment of mild-to-moderate atopic dermatitis. These positive results should validate the potential of Thykamine™️ in the armamentarium to treat this condition affecting millions of children and adults around the world,” said Dr André P. Boulet, PhD, President and Chief Executive Officer of Devonian. “The efficacy of Thykamine™ obtained in this Phase 2 clinical trial compared favourably to published results posted by other therapeutic products such as phosphodiesterase inhibitors ((PDE4)1,2 and calcineurin inhibitors.3 To our knowledge, it is the first time that clinical trial data has demonstrated that a botanical drug candidate can be as potent as a product derived from chemical synthesis,” added Dr. Boulet. About Atopic Dermatitis (AD) Atopic Dermatitis or eczema,is a chronic inflammatory disease of the skin that is recurrent. It is characterized by itchy, red, swollen and cracked skin that may lead to secondary infections. The condition typically starts in childhood with changing severity over the years. Although the cause of AD is unknown, it is believed to involve genetics, a compromised immune system and can be triggered by environmental factors. AD is the most common skin disease4 and its prevalence continues to increase worldwide. In the United States, the incidence has been reported to be 10-20% of children with new diagnoses at almost 11% per year5. The severity of AD can be categorized into three stages, mild, moderate, and severe. The mild and moderate forms constitute approximately 67% and 26% respectively of the AD childhood patient population. A similar distribution has been reported in the adult patient population (71% and 26% respectively) 6,7. There is currently an enormous unmet need for new, effective, and well-tolerated treatment options in AD8. The global atopic dermatitis market is expected to exceed US $21,8 billion in sales by 20279. About Thykamine™ Thykamine™, the first pharmaceutical product issued from Devonian’s SUPREX™ platform, is a highly innovative product for the prevention and treatment of health conditions related to inflammation and oxidative stress including ulcerative colitis, atopic dermatitis, psoriasis, rheumatoid arthritis, and other autoimmune disorders. The anti-inflammatory, anti-oxidative and immunomodulatory properties of Thykamine™ have been demonstrated by a considerable number of in vitro and in vivo studies as well as in a Phase IIa clinical study in patients with mild-to-moderate distal ulcerative colitis and in a phase II clinical study in patients with mild-to-moderate atopic dermatitis. Both Thykamine™ and SUPREX™ platform are protected by several patents in North America, Europe and Asia. About Devonian Devonian Health Group Inc. (Devonian) is a late-stage botanical pharmaceutical corporation with novel therapeutic approaches to targeting unmet medical needs. Devonian's core strategy is to develop prescription botanical drugs from plant materials and algae for the treatment of inflammatory-autoimmune diseases including but not limited to ulcerative colitis and atopic dermatitis. Based on a foundation of over 15 years of research, Devonian’s focus is further supported by a US-FDA set of regulatory guidelines favouring a more efficient drug development pathway for prescription botanical drug products over those of traditional prescription medicines. Devonian is also involved in the development of high-value cosmeceutical products leveraging the same proprietary approach employed with their pharmaceutical offerings. Devonian is listed on the TSX Venture Exchange (TSXV:GSD) as well as the OTCQB Venture Exchange (OTCQB:DVHGF) For more information, visit References Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesteras 4 (PDE4) inhibitors for the topical treatment of atopic dermatitis (AD) in children and adults. J. Am. Acad. Dermatol., Vol 75 (3), 494-503, 2016. Hanifin JM., Ellis CN, Frieden IJ, et al. OPA-15406, a novel topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (A): A phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol, Vol 75 (2), 297-305, 2016. Product Monograph, Elidel Cream 1%, Valeant Canada, 2014 Peng W., Novak N. Pathogenesis of atopic dermatitis. Clinical et Experimental Allergy 2015, 45 : 566-574. Eichenfield F, Ellis CN, Mancini AJ, Paller AS, Simpsom EL. Atopic Dermatitis: Epidemiology and Pathogeneses Update. Semin Cutan Med Surg 2012, Sep; 31 (3 Suppl): S3-5. Silverberg JI, Simpson EL. Associations of childhood eczema severity: A US population-based study. Dermatitis 2014; 25(3):107-114. Chaplin S. Guide to treatments used for atopic dermatitis in adults. Prescriber 2016: 27(10): 30-39. Leung DYM. Guttman-Yassky E. Assessing the current treatment of atopic dermatitis: Unmet needs. J. of Allergy and Clinical Immunology. 2017; 139(4) Suppl.: S47-48. Market Data Forecast, Global Atopic Dermatitis Treatment Market Size, Share, Trends, COVID-19 Impact & Growth Analysis Report - Segmented By Treatment Type, Route Of Administration, Distribution Channel & Region - Industry Growth, Trends & Forecast (2021 to 2026), April 2021. Forward-Looking Statements This press release contains forward-looking statements about Devonian’s objectives, strategies and businesses that involve risks and uncertainties. These statements are “forward-looking” because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to, the intended use of proceeds of the Offering, the final approval of the TSX Venture Exchange in connection with the Offering, the above “About Devonian” paragraph, Devonian’s ability to develop, manufacture, and successfully commercialize value-added pharmaceutical and cosmeceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of Devonian to take advantage of business opportunities in the pharmaceutical and cosmeceutical industries, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations in Devonian’s prospectus dated April 21st, 2017 under the heading “Risk Factors” related to Devonian’s business. As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update any forward-looking statement even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

25 Mar 2021

·www.biospace.com

Devonian Health Group Provides More Details on Previously Announced Positive Topline Results From Phase 2 Clinical Trial of Thykamine™ in Adult Population with Mild-to-Moderate Atopic Dermatitis and the Grant of Stock Options.

QUEBEC CITY--(BUSINESS WIRE)-- Devonian Health Group Inc. (“Devonian” or the “Corporation”) (TSXv: GSD), a clinical stage botanical pharmaceutical corporation, focused on developing a unique portfolio of botanical pharmaceutical and cosmeceutical products, provides further details on previously announced results of Thykamine™ Phase 2 clinical trial for the treatment of mild-to-moderate atopic dermatitis (AD). In this 4-week, phase 2, randomized, double-blind, multicentre, placebo-controlled study, adult patients with mild-to-moderate AD were randomized to receive Thykamine™ cream 0.05%, 0.10%, 0.25% or vehicle cream (placebo) twice daily. The primary efficacy endpoint was the Investigator Global Assessment (IGA) success rate defined as percentage of patients with an IGA score of 0 or 1 with greater than or equal to 2-grade reduction at week 4. Secondary endpoints included Body Surface Area (BSA) and Eczema Area and Severity Index (EASI). A total of 162 patients, spread over several sites in Canada, were recruited for this study. IGA success rates at week 4 were 6.7% for placebo (vehicle cream), 19.0% for Thykamine™ cream 0.05% (p=0.053 vs placebo), 30.8% Thykamine™ cream 0.10% (p=0.014 vs placebo) and 12.1% for Thykamine™ cream 0.25% (p=0.461 vs placebo). Success rate over placebo of Thykamine™ cream 0.1% was not only reached at week 4 but also at week 3 (p = 0.04), resulting in a fast onset of the therapeutic effect. As such, Thykamine™ cream 0.10% has been retained for Phase 3 trials. In addition, Thykamine™ achieved statistically significant differences, compared to placebo, in its key secondary efficacy endpoint, i.e. BSA. Lastly, Thykamine™ was well-tolerated, as very few adverse events were reported. "The efficacy of Thykamine™ obtained in this clinical trial was as expected and compared favourably to published results of other therapeutic products such as the phosphodiesterase inhibitors (PDE4)1,2 and calcineurin inhibitors,3 demonstrating that a Botanical Drug candidate can be as potent as a product derived from chemical synthesis." said Dr André P. Boulet, President and CEO of Devonian. "With the successful completion of this dose ranging study, we can now move into phase 3 clinical development in the adult patients. We are also planning a clinical trial within the pediatric patient population" added Dr Boulet. Grant of Stock Options In addition, the Company announces that the Board of Directors has approved the grant of 60,000 stock options (the "Options") to a member of the Board of Directors. These options are exercisable on the grant date, at a price of $ 0.20, for a period of 10 years. About Atopic Dermatitis (AD) AD, also known as eczema, is a type of inflammation of the skin. It results in itchy, red, swollen, and cracked skin that may lead to secondary infection. The condition typically starts in childhood with changing severity over the years. Although the cause of AD is unknown, it is believed to involve genetics, a compromised immune system and can be triggered by environmental factors. AD is the most common skin disease4 and its prevalence continues to increase worldwide. In the United States, the incidence has been reported to be 10-20% of children with new diagnoses at almost 11% per year5. The severity of AD can be categorized into three stages, mild, moderate, and severe. The mild and moderate forms constitute approximately 67% and 26% respectively of the AD childhood patient population. A similar distribution has been reported in the adult patient population (71% and 26% respectively) 6,7. There is currently an enormous unmet need for new, effective, and well-tolerated treatment options in AD8. About Thykamine™ Thykamine™, the first pharmaceutical product issued from Devonian’s SUPREX™ platform, is a highly innovative product for the prevention and treatment of health conditions related to inflammation and oxidative stress including ulcerative colitis, atopic dermatitis, psoriasis, rheumatoid arthritis, and other autoimmune disorders. The anti-inflammatory, anti-oxidative and immunomodulatory properties of Thykamine™ have been demonstrated by a considerable number of in vitro and in vivo studies as well as in a Phase IIa clinical study in patients with mild-to-moderate distal ulcerative colitis. Thykamine™ is currently under development as treatment for ulcerative colitis and atopic dermatitis. Both Thykamine™ and SUPREX™ platform are protected by several patents in North America, Europe and Asia. About Devonian Devonian Health Group Inc. is a late-stage botanical pharmaceutical corporation with novel therapeutic approaches to targeting unmet medical needs. Devonian's core strategy is to develop prescription botanical drugs from plant materials and algae for the treatment of inflammatory-autoimmune diseases including but not limited to ulcerative colitis and atopic dermatitis. Based on a foundation of over 15 years of research, Devonian’s focus is further supported by a US-FDA set of regulatory guidelines favouring a more efficient drug development pathway for prescription botanical drug products over those of traditional prescription medicines. Devonian is also involved in the development of high-value cosmeceutical products leveraging the same proprietary approach employed with their pharmaceutical offerings. Devonian Health Group Inc. was incorporated in 2015 and is headquartered in Québec, Canada where it owns a state-of-the art extraction facility with full traceability ‘from the seed to the pill’. Acquired in 2018, Altius Healthcare Inc., its commercialization partner, brings opportunities for further diversification and growth potential. Devonian is traded publicly on the TSXV Exchange (TSXv:GSD). For more information, visit References Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesteras 4 (PDE4) inhibitors for the topical treatment of atopic dermatitis (AD) in children and adults. J. Am. Acad. Dermatol., Vol 75 (3), 494-503, 2016. Hanifin JM., Ellis CN, Frieden IJ, et al. OPA-15406, a novel topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (A): A phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol, Vol 75 (2), 297-305, 2016. Product Monograph, Elidel Cream 1%, Valeant Canada, 2014 Peng W., Novak N. Pathogenesis of atopic dermatitis. Clinical et Experimental Allergy 2015, 45 : 566-574. Eichenfield F, Ellis CN, Mancini AJ, Paller AS, Simpsom EL. Atopic Dermatitis: Epidemiology and Pathogeneses Update. Semin Cutan Med Surg 2012, Sep; 31 (3 Suppl): S3-5. Silverberg JI, Simpson EL. Associations of childhood eczema severity: A US population-based study. Dermatitis 2014; 25(3):107-114. Chaplin S. Guide to treatments used for atopic dermatitis in adults. Prescriber 2016: 27(10): 30-39. Leung DYM. Guttman-Yassky E. Assessing the current treatment of atopic dermatitis: Unmet needs. J. of Allergy and Clinical Immunology. 2017; 139(4) Suppl.: S47-48. Forward Looking Statements This press release contains forward-looking statements about Devonian’s objectives, strategies and businesses that involve risks and uncertainties. These statements are “forward-looking” because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to, Devonian’s ability to develop, manufacture, and successfully commercialize value-added pharmaceutical and cosmeceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of Devonian to take advantage of business opportunities in the pharmaceutical and cosmeceutical industries, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations in Devonian’s prospectus dated April 21st, 2017 under the heading “Risk Factors” related to Devonian’s business. As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update any forward-looking statement even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

100 Deals associated with Difamilast

External Link

KEGG	Wiki	ATC	Drug Bank
D11314	-	-	DB14987

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Dermatitis, Atopic	Japan	Otsuka Pharmaceutical Co., Ltd.	27 Sep 2021

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Mild Atopic Dermatitis	Phase 2	United States	Otsuka Pharmaceutical Development & Commercialization, Inc.	20 Jun 2014
Mild Atopic Dermatitis	Phase 2	Australia	Otsuka Pharmaceutical Development & Commercialization, Inc.	20 Jun 2014
Mild Atopic Dermatitis	Phase 2	Poland	Otsuka Pharmaceutical Development & Commercialization, Inc.	20 Jun 2014
Moderate Atopic Dermatitis	Phase 2	United States	Otsuka Pharmaceutical Development & Commercialization, Inc.	20 Jun 2014
Moderate Atopic Dermatitis	Phase 2	Australia	Otsuka Pharmaceutical Development & Commercialization, Inc.	20 Jun 2014
Moderate Atopic Dermatitis	Phase 2	Poland	Otsuka Pharmaceutical Development & Commercialization, Inc.	20 Jun 2014

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05372653 (CTgov)	Phase 3	Dermatitis, Atopic	41	OPA-15406 (0.3% OPA-15406)	wspmvrhxsm = jcjqzjrsee pnjesihbbr (rdyhqzpovt, qdmosvmdsh - tfwetepciz) View more	-	30 Mar 2025
				OPA (1% OPA-15406)	tckbhlgngn(kchroycdrq) = lzshifgfak dfproyuupg (avtsjaltdr, hkuvyeecxy - xgfeozuvav) View more
NCT05372653 (Pubmed)	Phase 3	Dermatitis, Atopic	41	Difamilast 0.3% ointment	ihsohhnsjx(obrqkcklnm) = Adverse events (AEs) were reported in 22 (53.7%) infants in the primary evaluation period: of those the most frequent AE was nasopharyngitis (19.5%) followed by dermatitis contact (7.3%). As of the interim report, 36 (87.8%) infants experienced AEs: of those, nasopharyngitis (70.7%) and gastroenteritis (22.0%) were most frequently observed. The total AEs were mostly mild or moderate in severity. No investigational medicinal product-related AEs and no AEs leading to discontinuation were reported. quaqrzegfb (hrlpsjkong )	Positive	29 Jul 2024
NCT03961529 (Pubmed) Manual	Phase 3	Dermatitis, Atopic	366	difamilast (Adult patients)	dfwuaztvbw(tliqlbypib) = rcunaiymec ryoyyaclif (hvuhbaskua ) View more	Positive	18 Jun 2022
				difamilast (pediatric patients)	dfwuaztvbw(tliqlbypib) = ymvojlftnt ryoyyaclif (hvuhbaskua ) View more
NCT02068352 (CTgov)	Phase 2	Moderate Atopic Dermatitis \| Mild Atopic Dermatitis	121	OPA-15406 (0.3% OPA-15406)	hbhyjkymxr = xzqkaujzud kmvojcxunp (hnbajykviy, yihorivjlz - rsgomrzvrt) View more	-	23 Nov 2021
				OPA-15406 (1% OPA-15406)	hbhyjkymxr = qcyceilzld kmvojcxunp (hnbajykviy, wvmasonqla - ndskzfqgdj) View more
NCT03961529 (CTgov)	Phase 3	Dermatitis, Atopic	366	OPA-15406 (Adult: 1% OPA-15406 Ointment)	vghjwehpqg = dwqtxhgztg fmppehajsp (awambvkoif, lzskppeimm - ajtzabbimq) View more	-	19 Nov 2021
				OPA-15406 (Pediatric: 0.3% OPA-15406 Ointment)	vghjwehpqg = zbtzizoyhb fmppehajsp (awambvkoif, aprqcnugtk - xawemwzkeq) View more
NCT03911401 (CTgov)	Phase 3	Dermatitis, Atopic	251	0.3% OPA-15406 (0.3% OPA-15406)	kifwmagtbt = cpkgfguboj sduksousuf (wtfalwgdra, eaqubxfajp - qebhvmawso) View more	-	25 Jan 2021
				1% OPA-15406 (1% OPA-15406)	kifwmagtbt = siwcxcygil sduksousuf (wtfalwgdra, zbaorhtmgp - qmardeqwzr) View more
NCT03908970 (CTgov)	Phase 3	Dermatitis, Atopic	364	1% OPA-15406 (1% OPA-15406)	japobclsju = ifhhnlpdmj cghotjggdn (ancuuuzmxr, dwskqiorfj - dyhvmpjgty) View more	-	25 Jan 2021
				Placebos (Placebo)	japobclsju = atgaejwfku cghotjggdn (ancuuuzmxr, trizsxowmd - hlfopvupnl) View more
NCT03018691 (CTgov)	Phase 2	Dermatitis, Atopic	73	OPA-15406 (0.3% OPA-15406 Ointments)	fgaacevbff = sovqnatglv npoqissobi (mybhixbmcx, iidtqmuiur - qoyhwaheqo) View more	-	23 Jul 2020
				OPA-15406 (1% OPA-15406 Ointments)	fgaacevbff = tusoxcokbh npoqissobi (mybhixbmcx, tntdefmygd - bawuqhukae) View more
NCT02914548 (CTgov)	Phase 2	Dermatitis, Atopic	200	OPA-15406 (0.3% OPA-15406)	ekaytazjxx = ctvnbnkvcr migtjpwwdb (hwznjlgdge, ptxnmqdejo - oksxnzpcgk) View more	-	29 Jun 2020
				OPA-15406 (1% OPA-15406)	ekaytazjxx = ggmcpyotgh migtjpwwdb (hwznjlgdge, wwbxbegoyx - mnhwlvofdy) View more
NCT02945657 (MEDI-MM36-206, CTgov)	Phase 2	Dermatitis, Atopic	32	MM36	koywpphijh(zxzwmsnzke) = xgdwzvmljo jmjmmqnvmr (mhacmwwjho, 23.4) View more	-	19 Nov 2018

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis