POS1079 Pharmacodynamic Response of JNJ-77242113 in Serum and Skin of Patients with Moderate-to-Severe Psoriasis: 1-Year Results from FRONTIER 1 & 2

Le résumé fourni par la source

Background: JNJ-77242113 (JNJ-2113), a targeted oral peptide that binds the interleukin (IL)-23-receptor to inhibit IL-23 signaling, showed superior clinical efficacy vs placebo at Week(W) 16 of FRONTIER-1 in patients with moderate-to-severe plaque psoriasis, which correlated with strong serum and skin pharmacodynamic (PD) responses [1]. Objectives: To evaluate JNJ-2113 systemic PD responses through W52 and further characterize the JNJ-2113 skin PD effect, including relationships with clinical response, utilizing tape-strip skin sampling. Methods: FRONTIER-1 randomized (1:1:1:1:1:1) 41-43 participants per arm to 25mg once daily (QD), 25mg twice daily (BID), 50mg QD, 100mg QD, 100mg BID, or placebo through W16. Patients who continued in FRONTIER-2 received the same JNJ-2113 regimen, while those who were in the placebo group switched to the 100 mg QD dose, continuing for a total of 52-weeks of treatment. Both targeted (β-Defensin-2 [BD-2]/IL-22/IL-17A/IL-17F/IL-23) and broad (5400+ protein Olink® Explore HT) proteomics were conducted using serum samples collected through W52. The BD-2 and Olink® Explore-HT assays were performed on protein lysates extracted from tape-strip samples of lesional and non-lesional skin collected through W16, and the correlation between BD-2 levels and Psoriasis Area and Severity Index (PASI) scores was evaluated. Results: JNJ-2113 drove significant, rapid, dose-related reductions in serum psoriasis disease biomarker (BD-2/IL-22/IL-17A/IL-17F) levels that continued through W52; largest reductions were generally seen with JNJ-2113 100mg BID (W52 fold-change [FC] from baseline: -3.69/-1.19/-1.05/-1.46, respectively). Notably, through W52, JNJ-2113 had minimal impact on serum IL-23 (W52 FC from baseline: -0.13) or cytokines involved in broad immune response through W52 as assessed via Olink® Explore-HT. Consistent with serum results, JNJ-2113 100mg BID significantly reduced BD-2 levels in W16 lesional skin to levels seen in non-lesional skin; this reduction correlated with PASI. Broad proteomics of tape-strip samples showed baseline lesional samples were significantly enriched for psoriasis-relevant proteins (BD-2/IL-22/IL-17A/IL-19 and others) and clustered away from non-lesional samples. Importantly, JNJ-2113 100mg BID reduced psoriasis-related proteins in W16 tape-strip lesional samples, with a protein signature like non-lesional samples but distinct from baseline lesional and W16 placebo samples, suggesting JNJ-2113 attenuated skin inflammation. Conclusion: JNJ-2113 selectively blocked IL-23-driven inflammation and induced a dose-related PD response, with rapid and sustained reduction of biomarkers of the IL-23 pathway and psoriasis disease severity through 1-year of treatment. JNJ-2113 also attenuated skin inflammation with robust reduction in psoriasis-relevant disease biomarkers. Our novel approach to tape-strip derived proteomics demonstrates this minimally invasive alternative to skin biopsies can be used to evaluate disease biology and characterize local treatment response in psoriatic patients. REFERENCES: [1] Bissonnette R, Pinter A, Ferris LK et al. An oral interleukin-23-receptor antagonist peptide for plaque psoriasis. N Engl J Med 2024; 390:510-21. Acknowledgements: NIL . Disclosure of Interests: Kilian Eyerich Speaker's fees from, and/or advisory board member: AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Hexal, Janssen, Leo, Novartis, Pfizer, Sanofi, Sitryx, and UCB, Co-founder and shares of Dermagnostix and Dermagnostix R&D, Laura K. Ferris Speaker: AbbVie, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Regeneron, Consultant: AbbVie, Amgen, Apogee, Arcutis, Boehringer-Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, DermTech, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Takeda, Investigator: AbbVie, Acelyrin, Amgen, Apogee, Arcutis, Aristea, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, DermTech, Eli Lilly, Galderma, GRAIL, Incyte, Janssen, Leo Pharma, Moberg, Mobius, Novartis, Regeneron, SkinAnalytics, Takeda, UCB, James G. Krueger Consultant/honoraria: AbbVie, Aclaris, Allergan, Almirall, Amgen, Arena, Aristea, Asana, Aurigene, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Escalier, Galapagos, Janssen, MoonLake, Nimbus, Novartis, Pfizer, Sanofi, Sienna, Sun, Target-Derm, UCB, Valeant, and Ventyx, Amy Paller Consultant: AbbVie, Abeona, Apogee, Arcutis, Aslan, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Incyte, Johnson and Johnson, Krystal Biotech, LEO, Mitsubishi Tanabe, Nektar, Primus, Procter and Gamble, Regeneron, Sanofi, Seanergy, TWI Biotech, and UCB, Investigator: AbbVie, Applied Pharma Research, Biomendics, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, Regeneron, Timber, and UCB; Data Safety Monitoring Board member: AbbVie, Abeona, and Galderma, Andreas Pinter Advisor, received speaker's honoraria, received grants, and/or participated in clinical trials: AbbVie, Almirall Hermal, Amgen, Biogen Idec, BioNTech, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Galderma, GSK, Hexal, Janssen-Cilag GmbH, Klinge Pharma, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pascoe, Pfizer, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi Genzyme, Schering-Plough, Tigercat Pharma, UCB Pharma, Zuellig Pharma, Arun Kannan May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, David Strawn May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Sunita Bhagat May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Dylan Richards May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Dan Horowitz May own stock/stock options in Johnson & Johnson, Employees of Janssen Research & Development, LLC, Kate Paget May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Ching-Heng Chou May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Joseph F. Merola Consultant of: AbbVie, Amgen, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Janssen, Leo, Novartis, Pfizer, Sanofi-Regeneron, Sun, and UCB, Grant/research support from: AbbVie, Amgen, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Janssen, Leo, Novartis, Pfizer, Sanofi-Regeneron, Sun, and UCB, Elizabeth Chen May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Cynthia DeKlotz May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Paul Newbold May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Dawn Waterworth May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Monica Leung May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Bradford McRae May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Megan Miller May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Takayuki Ota May own stock/stock options in Johnson & Johnson, Employee of Janssen Research & Development, LLC, Darren Ruane May own stock/stock options in Johnson & Johnson, Employees of Janssen Research & Development, LLC, Ya-Wen Yang May own stock/stock options in Johnson & Johnson, Employee of Janssen Pharmaceutical Companies of Johnson & Johnson, Robert Bissonnette Shareholder of Innovaderm Research, Employee of Innovaderm Research, Advisory Board Member, consultant, speaker and/or investigator for and received honoraria and/or grants: AbbVie, Alumis, Arcutis, Amgen, Bausch Health, Boston, BMS/Celgene,

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.