Morten Praestegaard - Academia.edu (original) (raw)

Papers by Morten Praestegaard

Research paper thumbnail of Sensory properties analysis of a calcipotriol and betamethasone dipropionate cream vehicle formulated with an innovative PAD Technology for the treatment of plaque psoriasis on the skin and scalp

Research paper thumbnail of Phase 3 Trial Demonstrating High Efficacy, Favourable Safety, and Convenience of a Novel Calcipotriene and Betamethasone Dipropionate Cream

SKIN The Journal of Cutaneous Medicine

• Also at week 4, the proportion of patients achieving PGA treatment success was higher in the CA... more • Also at week 4, the proportion of patients achieving PGA treatment success was higher in the CAL/BDP PAD-cream group (25.2%) compared to the vehicle group (0.6%) and numerically higher than the CAL/BDP TS/gel group (18.7%; p=0.0510) (Figure 2). • The patient reported PTCS score for CAL/BDP PAD-cream was rated superior to CAL/BDP TS/gel at week 8 (p<0.0001) and was also significantly higher at week 4 (p<0.0001), demonstrating that CAL/BDP PAD-cream has superior treatment convenience compared to CAL/BDP TS/gel. • The mean change in Dermatology Life Quality Index (DLQI) score from baseline to week 8 improved statistically significantly more in the CAL/BDP PAD-cream group compared to both vehicle (p<0.0001) and CAL/BDP TS/gel (p=0.0110) (Figure 3). A statistically significant difference was also observed at week 4 for CAL/BDP PAD-cream compared to vehicle (p<0.0001) and CAL/BDP TS/gel (p=0.0159) (Figure 3). • Safety assessments during the trial demonstrated that CAL/BDP PAD-cream was well-tolerated with all adverse reactions reported at a frequency below 1%. • Overall, 490 patients were randomised, 213 patients were in the CAL/BDP PADcream group, 209 patients were in the CAL/BDP TS/gel group, and 68 patients were in the cream vehicle group. Overall, all demographic characteristics were comparable between the three treatment groups (Table 1). • The percentage mean change from baseline to week 8 in mPASI for CAL/BDP PAD-cream (67.5%) was superior compared to vehicle (11.7%; p<0.0001) and non-inferior to CAL/BDP TS/gel (63.5%) (Figure 1).

Research paper thumbnail of A novel, fixed‐dose calcipotriol and betamethasone dipropionate cream for the topical treatment of plaque psoriasis: Direct and indirect evidence from phase 3 trials discussed at the 30 <sup>th</sup> <scp>EADV</scp> Congress 2021

Journal of The European Academy of Dermatology and Venereology, Dec 22, 2022

Research paper thumbnail of Enhanced Skin Deposition of Betamethasone Dipropionate into the Skin of Human Volunteers from Calcipotriene/Betamethasone Dipropionate Cream Compared to Topical Suspension

SKIN The Journal of Cutaneous Medicine

Research paper thumbnail of Pooled Analysis Demonstrating Superior Patient- Reported Psoriasis Treatment Outcomes for Calcipotriene/ Betamethasone Dipropionate Cream Versus Suspension/Gel

Journal of Drugs in Dermatology, Mar 1, 2022

BACKGROUND Calcipotriene and betamethasone dipropionate (CAL/BDP) cream is a novel treatment of p... more BACKGROUND Calcipotriene and betamethasone dipropionate (CAL/BDP) cream is a novel treatment of plaque psoriasis based on PAD™ Technology (PAD-cream) designed to improve patient reported treatment satisfaction and quality of life (QoL). METHOD A pooled analysis of patient reported outcomes from two phase 3, multicenter, randomized, investigator-blind, active, and vehicle-controlled trials evaluating a total of 1271 patients with mild to moderate plaque psoriasis according to the Physician Global Assessment (PGA) scale. Products were applied once daily for 8 weeks. RESULTS The proportion of patients evaluating their treatment to have improved by 2 grades to clear or very mild disease on the 5-grade Subject Global Assessment (SGA) scale, defined as SGA Success, was significantly higher in the CAL/BDP PAD-cream group compared to active comparator (CAL/BDP suspension/gel) (week 8, 44.2% vs 27.9%, P<0.0001). A Dermatology Life Quality Index (DLQI) score of 0 or 1, indicating no impact of disease on the patient's life, was obtained by 43.8% of patients at week 8 in the CAL/BDP cream group versus 34.2% in the CAL/BDP suspension/gel group (P=0.0005). CAL/BDP PAD-cream demonstrated significantly greater psoriasis treatment convenience compared to CAL/BDP suspension/gel at all studied time points, including questions addressing greasiness of the formulation and overall satisfaction of treatment. CONCLUSION CAL/BDP PAD-cream is a novel topical treatment for psoriasis, which through PAD™ Technology offers substantial improvement in QoL and treatment satisfaction for patients. Given these data, CAL/BDP PAD-cream may lead to better adherence to treatment, which ultimately could result in better treatment outcomes in clinical practice. CLINICALTRIALS gov: NCT03308799 and NCT03802344. J Drugs Dermatol. 2022;21(3):242-248. doi:10.36849/JDD.6611.

Research paper thumbnail of SAT0164 MC2-03 (Ciclosporin Eyedrops) Improves Tear Production in Sjögren’s Patients with Moderate-To-Severe Keratitis: Results from a Phase 2B Randomized, Controlled Trial

Annals of the Rheumatic Diseases, 2020

Background: Sjogren Syndrome (SS) is a multifaceted disease with variable symptoms, but the SS as... more Background: Sjogren Syndrome (SS) is a multifaceted disease with variable symptoms, but the SS associated keratoconjunctivitis is one of the most frequent disease manifestations of the syndrome and the manifestation that has the greatest impact on the quality of life for these patients. Objectives: To report the clinical efficacy of MC2-03 eyedrops in Sjogren’s patients with moderate-to-severe keratitis from a 6-month trial looking at the Schirmer score which assess the tear production by the lacrimal gland. A Schirmer score of ≤5mm/5 min is one of the criteria used in the 2016 final classification of ACR/EULAR to diagnose Sjogren`s syndrome. Methods: The NORTHERN LIGHTS trial is a randomized, double masked, controlled multicentre European trial that assessed MC2-03 eyedrops (ciclosporin 0.03% and 0.06%) for the treatment of moderate-to-severe dry eye disease in 255 patients having corneal fluorescein staining score 3 or 4 at baseline. The Schirmer score (per 5 min) was assessed dur...

Research paper thumbnail of MC2-01 Cream Has Improved Overall Psoriasis Treatment Efficacy Compared to Calcipotriene Plus Betamethasone Dipropionate Topical Suspension

Introduction: MC2-01 cream is a novel topical treatment of psoriasis containing the active ingred... more Introduction: MC2-01 cream is a novel topical treatment of psoriasis containing the active ingredients calcipotriene and betamethasone dipropionate (0.005%/0.064% [wt/wt], CAL/ BDP). MC2-01 cream is based on PAD Technology and designed for high penetration of the actives combined with excellent cosmetic elegance. Data from a phase 3 trial are presented comparing overall efficacy of MC2-01 cream to CAL/BDP topical suspension (\u27CAL/BDP TS\u27) in adults with mild-to-moderate psoriasis. Methods: The phase 3, randomized, multicenter, investigatorblind, parallel-group trial evaluated the efficacy and safety of MC2-01 cream compared to MC2-01 vehicle and CAL/BDP TS (sourced as Taclonex Topical Suspension) in adult patients with psoriasis vulgaris on the body. The trial enrolled 796 patients at 55 clinical sites across the United States: MC2-01 cream (n=343), CAL/BDP TS (n=338), and MC2-01 vehicle (n=115). Patients applied trial medication once daily for 8 weeks. The primary objective was to show therapeutic noninferiority of MC2-01 cream to CAL/BDP TS, as well as to characterize the safety profile of MC2-01 cream in patients with psoriasis vulgaris. The primary efficacy end point was the proportion of patients with treatment success at week 8, defined as minimum 2-point decrease from baseline in Physician Global Assessment (PGA) score. Results: The phase 3 trial met its primary objective to demonstrate noninferiority of MC2-01 cream to CAL/BDP TS on PGA treatment success at week 8 (MC2-01 cream 40.1% vs CAL/BDP TS 24.0% vs MC2-01 vehicle 4.5%). The primary objective was also met for the secondary end point percentage reduction in mPASI from baseline to week 8. Additional analysis of PGA treatment success showed that MC2-01 cream is superior to CAL/BDP TS at week 4 (P \u3c .0001) and week 8 (P \u3c .0001). Further analyses of percentage reduction in mPASI from baseline confirmed that MC2-01 cream has superiority to CAL/BDP TS throughout treatment from week 1 (26.2% vs 18.9%, P \u3c .001) to week 8 (64.8% vs 52.3%, P \u3c .0001). MC2-01 cream also provided reduction in itch compared to vehicle measured by the proportion of patients having minimum 4-points improvement on an 11-point numeric rating scale of itch severity (60.2% vs 21.4% at week 4, P \u3c .01). The safety profile of MC2-01 cream was similar to that known for CAL/BDP products. Conclusions: The phase 3 trial showed that MC2-01 cream is a substantial improvement in overall efficacy and onset of action for topical treatment of psoriasis compared to CAL/BDP TS. Enhanced patient satisfaction enabled by the MC2-01 cream PAD Technology may increase treatment compliance among patients, and positively impact real-life treatment outcomes even further. As such, PAD Technology holds the promise of redefining topicals

Research paper thumbnail of Phase 3 Trial Demonstrates that MC2-01 Cream has Improved Treatment Efficacy Compared to Calcipotriene Plus Betamethasone Dipropionate Topical Suspension in Patients with Mild to Moderate Psoriasis Vulgaris

SKIN The Journal of Cutaneous Medicine, 2020

Phase 3 trial demonstrates that MC2-01 cream has improved treatment efficacy compared to calcipot... more Phase 3 trial demonstrates that MC2-01 cream has improved treatment efficacy compared to calcipotriene plus betamethasone dipropionate topical suspension in patients with mild to moderate psoriasis vulgaris Betamethasone diproponate (BDP) Requires pH>8 for stability Vitamin D analogue Requires pH 4-6 for stability Potent corticosteroid Calcipotriene (CAL)  Dual additive efficacy of CAL and BDP  Improved safety profile compared to the individual actives alone-BDP counteracts potential skin irritation of CAL-CAL mitigates potential skin atrophogenic effect of BDP  PAD™ Technology uniquely enables stable aqueous cream combining CAL and BDP 8 week treatment period 1x daily Follow-up

Research paper thumbnail of Calcipotriene and betamethasone dipropionate cream demonstrates superior efficacy in moderate plaque psoriasis compared to topical suspension: a subgroup analysis of a phase 3 trial

SKIN The Journal of Cutaneous Medicine, 2022

Research paper thumbnail of Polyaphron Dispersion Technology, A Novel Topical Formulation and Delivery System Combining Drug Penetration, Local Tolerability and Convenience of Application

Dermatology and Therapy

Topical formulation and delivery technologies for pharmaceutical application should simultaneousl... more Topical formulation and delivery technologies for pharmaceutical application should simultaneously address efficacy, safety and convenience of therapy. This has historically proven

Research paper thumbnail of Pharmacokinetic characterization of a novel ocular formulation of ciclosporin

Investigative Ophthalmology & Visual Science, 2016

Research paper thumbnail of Ocular tolerability of a ciclosporin eye drop based on PAD™ technology

Investigative Ophthalmology & Visual Science, 2017

Research paper thumbnail of A Phase 3, Randomized Trial Demonstrating the Improved Efficacy and Patient Acceptability of Fixed Dose Calcipotriene and Betamethasone Dipropionate Cream

Journal of Drugs in Dermatology, 2021

BACKGROUND The fixed dose combination of calcipotriene and betamethasone dipropionate (CAL/BDP) i... more BACKGROUND The fixed dose combination of calcipotriene and betamethasone dipropionate (CAL/BDP) is a well-established, efficacious, and safe topical treatment of psoriasis. METHOD A Phase 3, multicenter, randomized, investigator-blind, active, and vehicle-controlled trial enrolling 796 patients with moderate to severe psoriasis according to the Physician Global Assessment (PGA) scale. Products were applied once daily for 8 weeks. RESULTS The proportion of patients achieving PGA treatment success after 8 weeks was statistically significantly greater for CAL/BDP cream (37.4%) compared to CAL/BDP TS (22.8%, P<0.0001), and vehicle (3.7%, P<0.0001). A similar statistically significant difference in favor of CAL/BDP cream at week 8 was demonstrated for the percentage change in mPASI from baseline and the proportion of patients obtaining mPASI75. Patient reported treatment convenience for CAL/BDP cream was rated superior to CAL/BDP TS. Safety assessments during the trial demonstrated that CAL/BDP cream was well-tolerated with no adverse reactions with a frequency greater than 1%. CONCLUSION CAL/BDP cream is a novel topical treatment of psoriasis, which in a single product, offers a unique combination of high efficacy combined with favorable safety and excellent treatment convenience. For these reasons, CAL/BDP cream offers a distinctive advantage for the topical treatment of plaque psoriasis. ClinicalTrials.gov: NCT03308799J Drugs Dermatol. 20(4):420-425. doi:10.36849/JDD.5653.

Research paper thumbnail of Clinical efficacy of MC2‐03 (ciclosporin eye drop) in treatment of dry eye disease patients with severe keratitis randomized in the NORTHERN LIGHTS phase 2b trial

Acta Ophthalmologica, 2019

Research paper thumbnail of An anchored matching-adjusted indirect comparison of fixed-dose combination calcipotriol and betamethasone dipropionate (Cal/BDP) cream versus Cal/BDP foam for the treatment of psoriasis

Journal of Dermatological Treatment

Research paper thumbnail of Complementation dependante de la translocation pour le criblage de medicaments

La presente invention concerne diverses utilisations de proteines de complementation, de fragment... more La presente invention concerne diverses utilisations de proteines de complementation, de fragments de proteines de maniere a decouvrir des composes chimiques ou des medicaments interferant avec la translocation/ la redistribution de proteines et/ou des interactions entre proteines. La methode de cette invention tire profit du fait que plusieurs proteines a interaction se trouvent a des emplacements distincts et separes, avant l'activation des voies de signalisation, dans lesquelles elles remplissent leur role, ainsi que du fait que des domaines d'interaction (FRBP, FKBP12) peuvent etre induits pour interagir. Ladite invention a notamment trait a la complementation (EGFP, EYFP mute en F64L).

Research paper thumbnail of Translocation Dependent Complementation for Drug Screening

Research paper thumbnail of Novel Small-Molecule AKT1 Inhibitors Discovered by Redistribution™-Based High- Throughput Screening

Research paper thumbnail of Identification of Akt Pathway Inhibitors Using Redistribution Screening on the FLIPR and the IN Cell 3000 Analyzer

SLAS Discovery, 2005

The PI3-kinase/Akt pathway is an important cell survival pathway that is deregulated in the major... more The PI3-kinase/Akt pathway is an important cell survival pathway that is deregulated in the majority of human cancers. Despite the apparent druggability of several kinases in the pathway, no specific catalytic inhibitors have been reported in the literature. The authors describe the development of a fluorometric imaging plate reader (FLIPR)-based Akt1 translocation assay to discover inhibitors of Akt1 activation. Screening of a diverse chemical library of 45,000 compounds resulted in identification of several classes of Akt1 translocation inhibitors. Using a combination of classical in vitro assays and translocation assays directed at different steps of the Akt pathway, the mechanisms of action of 2 selected chemical classes were further defined. Protein translocation assays emerge as powerful tools for hit identification and characterization. ( Journal of Biomolecular Screening 2005:20-29)

Research paper thumbnail of Nuclear Export Inhibitors and Kinase Inhibitors Identified Using a MAPK-Activated Protein Kinase 2 Redistribution®Screen

ASSAY and Drug Development Technologies, 2004

Redistribution ® (BioImage ® A/S, Søborg, Denmark) is a novel high-throughput screening technolog... more Redistribution ® (BioImage ® A/S, Søborg, Denmark) is a novel high-throughput screening technology that monitors translocation of specific protein components of intracellular signaling pathways within intact mammalian cells, using green fluorescent protein as a tag. A single Redistribution assay can be used to identify multiple classes of compounds that act at, or upstream of, the level of the protein target used in the primary screening assay. Such compounds may include both conventional and allosteric enzyme inhibitors, as well as protein-protein interaction modulators. We have developed a series of Redistribution assays to discover and characterize compounds that inhibit tumor necrosis factor-a biosynthesis via modulation of the p38 mitogen-activated protein kinase (MAPK) pathway. A primary assay was designed to identify low-molecular-weight compounds that inhibit the activation-dependent nuclear export of the p38 kinase substrate MAPKactivated protein kinase 2 (MK2). Hits from the primary screen were categorized, using secondary assays, either as direct inhibitors of MK2 nuclear export, or as inhibitors of the upstream p38 MAPK pathway. Activity profiles are presented for a nuclear export inhibitor, and a compound that structurally and functionally resembles a known p38 kinase inhibitor. These results demonstrate the utility of Redistribution technology as a pathway screening method for the identification of diverse and novel compounds that are active within therapeutically important signaling pathways.

Research paper thumbnail of Sensory properties analysis of a calcipotriol and betamethasone dipropionate cream vehicle formulated with an innovative PAD Technology for the treatment of plaque psoriasis on the skin and scalp

Research paper thumbnail of Phase 3 Trial Demonstrating High Efficacy, Favourable Safety, and Convenience of a Novel Calcipotriene and Betamethasone Dipropionate Cream

SKIN The Journal of Cutaneous Medicine

• Also at week 4, the proportion of patients achieving PGA treatment success was higher in the CA... more • Also at week 4, the proportion of patients achieving PGA treatment success was higher in the CAL/BDP PAD-cream group (25.2%) compared to the vehicle group (0.6%) and numerically higher than the CAL/BDP TS/gel group (18.7%; p=0.0510) (Figure 2). • The patient reported PTCS score for CAL/BDP PAD-cream was rated superior to CAL/BDP TS/gel at week 8 (p<0.0001) and was also significantly higher at week 4 (p<0.0001), demonstrating that CAL/BDP PAD-cream has superior treatment convenience compared to CAL/BDP TS/gel. • The mean change in Dermatology Life Quality Index (DLQI) score from baseline to week 8 improved statistically significantly more in the CAL/BDP PAD-cream group compared to both vehicle (p<0.0001) and CAL/BDP TS/gel (p=0.0110) (Figure 3). A statistically significant difference was also observed at week 4 for CAL/BDP PAD-cream compared to vehicle (p<0.0001) and CAL/BDP TS/gel (p=0.0159) (Figure 3). • Safety assessments during the trial demonstrated that CAL/BDP PAD-cream was well-tolerated with all adverse reactions reported at a frequency below 1%. • Overall, 490 patients were randomised, 213 patients were in the CAL/BDP PADcream group, 209 patients were in the CAL/BDP TS/gel group, and 68 patients were in the cream vehicle group. Overall, all demographic characteristics were comparable between the three treatment groups (Table 1). • The percentage mean change from baseline to week 8 in mPASI for CAL/BDP PAD-cream (67.5%) was superior compared to vehicle (11.7%; p<0.0001) and non-inferior to CAL/BDP TS/gel (63.5%) (Figure 1).

Research paper thumbnail of A novel, fixed‐dose calcipotriol and betamethasone dipropionate cream for the topical treatment of plaque psoriasis: Direct and indirect evidence from phase 3 trials discussed at the 30 <sup>th</sup> <scp>EADV</scp> Congress 2021

Journal of The European Academy of Dermatology and Venereology, Dec 22, 2022

Research paper thumbnail of Enhanced Skin Deposition of Betamethasone Dipropionate into the Skin of Human Volunteers from Calcipotriene/Betamethasone Dipropionate Cream Compared to Topical Suspension

SKIN The Journal of Cutaneous Medicine

Research paper thumbnail of Pooled Analysis Demonstrating Superior Patient- Reported Psoriasis Treatment Outcomes for Calcipotriene/ Betamethasone Dipropionate Cream Versus Suspension/Gel

Journal of Drugs in Dermatology, Mar 1, 2022

BACKGROUND Calcipotriene and betamethasone dipropionate (CAL/BDP) cream is a novel treatment of p... more BACKGROUND Calcipotriene and betamethasone dipropionate (CAL/BDP) cream is a novel treatment of plaque psoriasis based on PAD™ Technology (PAD-cream) designed to improve patient reported treatment satisfaction and quality of life (QoL). METHOD A pooled analysis of patient reported outcomes from two phase 3, multicenter, randomized, investigator-blind, active, and vehicle-controlled trials evaluating a total of 1271 patients with mild to moderate plaque psoriasis according to the Physician Global Assessment (PGA) scale. Products were applied once daily for 8 weeks. RESULTS The proportion of patients evaluating their treatment to have improved by 2 grades to clear or very mild disease on the 5-grade Subject Global Assessment (SGA) scale, defined as SGA Success, was significantly higher in the CAL/BDP PAD-cream group compared to active comparator (CAL/BDP suspension/gel) (week 8, 44.2% vs 27.9%, P<0.0001). A Dermatology Life Quality Index (DLQI) score of 0 or 1, indicating no impact of disease on the patient's life, was obtained by 43.8% of patients at week 8 in the CAL/BDP cream group versus 34.2% in the CAL/BDP suspension/gel group (P=0.0005). CAL/BDP PAD-cream demonstrated significantly greater psoriasis treatment convenience compared to CAL/BDP suspension/gel at all studied time points, including questions addressing greasiness of the formulation and overall satisfaction of treatment. CONCLUSION CAL/BDP PAD-cream is a novel topical treatment for psoriasis, which through PAD™ Technology offers substantial improvement in QoL and treatment satisfaction for patients. Given these data, CAL/BDP PAD-cream may lead to better adherence to treatment, which ultimately could result in better treatment outcomes in clinical practice. CLINICALTRIALS gov: NCT03308799 and NCT03802344. J Drugs Dermatol. 2022;21(3):242-248. doi:10.36849/JDD.6611.

Research paper thumbnail of SAT0164 MC2-03 (Ciclosporin Eyedrops) Improves Tear Production in Sjögren’s Patients with Moderate-To-Severe Keratitis: Results from a Phase 2B Randomized, Controlled Trial

Annals of the Rheumatic Diseases, 2020

Background: Sjogren Syndrome (SS) is a multifaceted disease with variable symptoms, but the SS as... more Background: Sjogren Syndrome (SS) is a multifaceted disease with variable symptoms, but the SS associated keratoconjunctivitis is one of the most frequent disease manifestations of the syndrome and the manifestation that has the greatest impact on the quality of life for these patients. Objectives: To report the clinical efficacy of MC2-03 eyedrops in Sjogren’s patients with moderate-to-severe keratitis from a 6-month trial looking at the Schirmer score which assess the tear production by the lacrimal gland. A Schirmer score of ≤5mm/5 min is one of the criteria used in the 2016 final classification of ACR/EULAR to diagnose Sjogren`s syndrome. Methods: The NORTHERN LIGHTS trial is a randomized, double masked, controlled multicentre European trial that assessed MC2-03 eyedrops (ciclosporin 0.03% and 0.06%) for the treatment of moderate-to-severe dry eye disease in 255 patients having corneal fluorescein staining score 3 or 4 at baseline. The Schirmer score (per 5 min) was assessed dur...

Research paper thumbnail of MC2-01 Cream Has Improved Overall Psoriasis Treatment Efficacy Compared to Calcipotriene Plus Betamethasone Dipropionate Topical Suspension

Introduction: MC2-01 cream is a novel topical treatment of psoriasis containing the active ingred... more Introduction: MC2-01 cream is a novel topical treatment of psoriasis containing the active ingredients calcipotriene and betamethasone dipropionate (0.005%/0.064% [wt/wt], CAL/ BDP). MC2-01 cream is based on PAD Technology and designed for high penetration of the actives combined with excellent cosmetic elegance. Data from a phase 3 trial are presented comparing overall efficacy of MC2-01 cream to CAL/BDP topical suspension (\u27CAL/BDP TS\u27) in adults with mild-to-moderate psoriasis. Methods: The phase 3, randomized, multicenter, investigatorblind, parallel-group trial evaluated the efficacy and safety of MC2-01 cream compared to MC2-01 vehicle and CAL/BDP TS (sourced as Taclonex Topical Suspension) in adult patients with psoriasis vulgaris on the body. The trial enrolled 796 patients at 55 clinical sites across the United States: MC2-01 cream (n=343), CAL/BDP TS (n=338), and MC2-01 vehicle (n=115). Patients applied trial medication once daily for 8 weeks. The primary objective was to show therapeutic noninferiority of MC2-01 cream to CAL/BDP TS, as well as to characterize the safety profile of MC2-01 cream in patients with psoriasis vulgaris. The primary efficacy end point was the proportion of patients with treatment success at week 8, defined as minimum 2-point decrease from baseline in Physician Global Assessment (PGA) score. Results: The phase 3 trial met its primary objective to demonstrate noninferiority of MC2-01 cream to CAL/BDP TS on PGA treatment success at week 8 (MC2-01 cream 40.1% vs CAL/BDP TS 24.0% vs MC2-01 vehicle 4.5%). The primary objective was also met for the secondary end point percentage reduction in mPASI from baseline to week 8. Additional analysis of PGA treatment success showed that MC2-01 cream is superior to CAL/BDP TS at week 4 (P \u3c .0001) and week 8 (P \u3c .0001). Further analyses of percentage reduction in mPASI from baseline confirmed that MC2-01 cream has superiority to CAL/BDP TS throughout treatment from week 1 (26.2% vs 18.9%, P \u3c .001) to week 8 (64.8% vs 52.3%, P \u3c .0001). MC2-01 cream also provided reduction in itch compared to vehicle measured by the proportion of patients having minimum 4-points improvement on an 11-point numeric rating scale of itch severity (60.2% vs 21.4% at week 4, P \u3c .01). The safety profile of MC2-01 cream was similar to that known for CAL/BDP products. Conclusions: The phase 3 trial showed that MC2-01 cream is a substantial improvement in overall efficacy and onset of action for topical treatment of psoriasis compared to CAL/BDP TS. Enhanced patient satisfaction enabled by the MC2-01 cream PAD Technology may increase treatment compliance among patients, and positively impact real-life treatment outcomes even further. As such, PAD Technology holds the promise of redefining topicals

Research paper thumbnail of Phase 3 Trial Demonstrates that MC2-01 Cream has Improved Treatment Efficacy Compared to Calcipotriene Plus Betamethasone Dipropionate Topical Suspension in Patients with Mild to Moderate Psoriasis Vulgaris

SKIN The Journal of Cutaneous Medicine, 2020

Phase 3 trial demonstrates that MC2-01 cream has improved treatment efficacy compared to calcipot... more Phase 3 trial demonstrates that MC2-01 cream has improved treatment efficacy compared to calcipotriene plus betamethasone dipropionate topical suspension in patients with mild to moderate psoriasis vulgaris Betamethasone diproponate (BDP) Requires pH>8 for stability Vitamin D analogue Requires pH 4-6 for stability Potent corticosteroid Calcipotriene (CAL)  Dual additive efficacy of CAL and BDP  Improved safety profile compared to the individual actives alone-BDP counteracts potential skin irritation of CAL-CAL mitigates potential skin atrophogenic effect of BDP  PAD™ Technology uniquely enables stable aqueous cream combining CAL and BDP 8 week treatment period 1x daily Follow-up

Research paper thumbnail of Calcipotriene and betamethasone dipropionate cream demonstrates superior efficacy in moderate plaque psoriasis compared to topical suspension: a subgroup analysis of a phase 3 trial

SKIN The Journal of Cutaneous Medicine, 2022

Research paper thumbnail of Polyaphron Dispersion Technology, A Novel Topical Formulation and Delivery System Combining Drug Penetration, Local Tolerability and Convenience of Application

Dermatology and Therapy

Topical formulation and delivery technologies for pharmaceutical application should simultaneousl... more Topical formulation and delivery technologies for pharmaceutical application should simultaneously address efficacy, safety and convenience of therapy. This has historically proven

Research paper thumbnail of Pharmacokinetic characterization of a novel ocular formulation of ciclosporin

Investigative Ophthalmology & Visual Science, 2016

Research paper thumbnail of Ocular tolerability of a ciclosporin eye drop based on PAD™ technology

Investigative Ophthalmology & Visual Science, 2017

Research paper thumbnail of A Phase 3, Randomized Trial Demonstrating the Improved Efficacy and Patient Acceptability of Fixed Dose Calcipotriene and Betamethasone Dipropionate Cream

Journal of Drugs in Dermatology, 2021

BACKGROUND The fixed dose combination of calcipotriene and betamethasone dipropionate (CAL/BDP) i... more BACKGROUND The fixed dose combination of calcipotriene and betamethasone dipropionate (CAL/BDP) is a well-established, efficacious, and safe topical treatment of psoriasis. METHOD A Phase 3, multicenter, randomized, investigator-blind, active, and vehicle-controlled trial enrolling 796 patients with moderate to severe psoriasis according to the Physician Global Assessment (PGA) scale. Products were applied once daily for 8 weeks. RESULTS The proportion of patients achieving PGA treatment success after 8 weeks was statistically significantly greater for CAL/BDP cream (37.4%) compared to CAL/BDP TS (22.8%, P<0.0001), and vehicle (3.7%, P<0.0001). A similar statistically significant difference in favor of CAL/BDP cream at week 8 was demonstrated for the percentage change in mPASI from baseline and the proportion of patients obtaining mPASI75. Patient reported treatment convenience for CAL/BDP cream was rated superior to CAL/BDP TS. Safety assessments during the trial demonstrated that CAL/BDP cream was well-tolerated with no adverse reactions with a frequency greater than 1%. CONCLUSION CAL/BDP cream is a novel topical treatment of psoriasis, which in a single product, offers a unique combination of high efficacy combined with favorable safety and excellent treatment convenience. For these reasons, CAL/BDP cream offers a distinctive advantage for the topical treatment of plaque psoriasis. ClinicalTrials.gov: NCT03308799J Drugs Dermatol. 20(4):420-425. doi:10.36849/JDD.5653.

Research paper thumbnail of Clinical efficacy of MC2‐03 (ciclosporin eye drop) in treatment of dry eye disease patients with severe keratitis randomized in the NORTHERN LIGHTS phase 2b trial

Acta Ophthalmologica, 2019

Research paper thumbnail of An anchored matching-adjusted indirect comparison of fixed-dose combination calcipotriol and betamethasone dipropionate (Cal/BDP) cream versus Cal/BDP foam for the treatment of psoriasis

Journal of Dermatological Treatment

Research paper thumbnail of Complementation dependante de la translocation pour le criblage de medicaments

La presente invention concerne diverses utilisations de proteines de complementation, de fragment... more La presente invention concerne diverses utilisations de proteines de complementation, de fragments de proteines de maniere a decouvrir des composes chimiques ou des medicaments interferant avec la translocation/ la redistribution de proteines et/ou des interactions entre proteines. La methode de cette invention tire profit du fait que plusieurs proteines a interaction se trouvent a des emplacements distincts et separes, avant l'activation des voies de signalisation, dans lesquelles elles remplissent leur role, ainsi que du fait que des domaines d'interaction (FRBP, FKBP12) peuvent etre induits pour interagir. Ladite invention a notamment trait a la complementation (EGFP, EYFP mute en F64L).

Research paper thumbnail of Translocation Dependent Complementation for Drug Screening

Research paper thumbnail of Novel Small-Molecule AKT1 Inhibitors Discovered by Redistribution™-Based High- Throughput Screening

Research paper thumbnail of Identification of Akt Pathway Inhibitors Using Redistribution Screening on the FLIPR and the IN Cell 3000 Analyzer

SLAS Discovery, 2005

The PI3-kinase/Akt pathway is an important cell survival pathway that is deregulated in the major... more The PI3-kinase/Akt pathway is an important cell survival pathway that is deregulated in the majority of human cancers. Despite the apparent druggability of several kinases in the pathway, no specific catalytic inhibitors have been reported in the literature. The authors describe the development of a fluorometric imaging plate reader (FLIPR)-based Akt1 translocation assay to discover inhibitors of Akt1 activation. Screening of a diverse chemical library of 45,000 compounds resulted in identification of several classes of Akt1 translocation inhibitors. Using a combination of classical in vitro assays and translocation assays directed at different steps of the Akt pathway, the mechanisms of action of 2 selected chemical classes were further defined. Protein translocation assays emerge as powerful tools for hit identification and characterization. ( Journal of Biomolecular Screening 2005:20-29)

Research paper thumbnail of Nuclear Export Inhibitors and Kinase Inhibitors Identified Using a MAPK-Activated Protein Kinase 2 Redistribution®Screen

ASSAY and Drug Development Technologies, 2004

Redistribution ® (BioImage ® A/S, Søborg, Denmark) is a novel high-throughput screening technolog... more Redistribution ® (BioImage ® A/S, Søborg, Denmark) is a novel high-throughput screening technology that monitors translocation of specific protein components of intracellular signaling pathways within intact mammalian cells, using green fluorescent protein as a tag. A single Redistribution assay can be used to identify multiple classes of compounds that act at, or upstream of, the level of the protein target used in the primary screening assay. Such compounds may include both conventional and allosteric enzyme inhibitors, as well as protein-protein interaction modulators. We have developed a series of Redistribution assays to discover and characterize compounds that inhibit tumor necrosis factor-a biosynthesis via modulation of the p38 mitogen-activated protein kinase (MAPK) pathway. A primary assay was designed to identify low-molecular-weight compounds that inhibit the activation-dependent nuclear export of the p38 kinase substrate MAPKactivated protein kinase 2 (MK2). Hits from the primary screen were categorized, using secondary assays, either as direct inhibitors of MK2 nuclear export, or as inhibitors of the upstream p38 MAPK pathway. Activity profiles are presented for a nuclear export inhibitor, and a compound that structurally and functionally resembles a known p38 kinase inhibitor. These results demonstrate the utility of Redistribution technology as a pathway screening method for the identification of diverse and novel compounds that are active within therapeutically important signaling pathways.