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

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, Dermavant, Eli Lilly, Janssen, LEO Pharma, Nimbus, Novartis, Pfizer, Regeneron, UCB, VentyxBio, and Xencor. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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