izokibep (ABY-035) / Affibody - LARVOL DELTA

Positive 52-week Phase 2b/3 Data of Izokibep in Psoriatic Arthritis to be Presented at ACR Convergence 2025 (Affibody Press Release) - "Continued improvement after week 16 was seen for patients randomized to either of the izokibep groups (160 mg once every two weeks (Q2W) or 160 mg QW), and rapid improvement was observed in patients following crossover from placebo to izokibep treatment. By week 52, approximately half of all patients achieved ACR50 (izokibep Q2W: 50%, izokibep QW: 57%, placebo-izokibep QW: 51%)...Substantial percentages of patients in all groups also achieved the high-hurdle endpoints of ACR70 (izokibep Q2W: 36%, izokibep QW: 42%, placebo-izokibep QW: 42%), PASI90 (izokibep Q2W: 63%, izokibep QW: 69%, placebo-izokibep QW: 65%), PASI100 (izokibep Q2W: 55%, izokibep QW: 64%, placebo-izokibep QW: 58%), and MDA (izokibep Q2W: 47%, izokibep QW: 52%, placebo-izokibep QW: 47%) at week 52."

P2/3 data • Psoriatic Arthritis

Efficacy and Safety of Izokibep, a Novel IL-17A Inhibitor, in Patients with Active Psoriatic Arthritis: Week 52 Results from a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2b/3 Study (ACR Convergence 2025) - P2/3 | "IZO demonstrated durable efficacy across several measures of PsA disease activity over 52 wks. Substantial percentages of pts originally randomized to IZO or switching from PBO to IZO achieved ACR50/70, PASI 90/100, and MDA by the end of the study. IZO treatment was well tolerated, with a safety profile generally consistent with that of legacy IL-17A inhibitors."

Clinical • Late-breaking abstract • P2/3 data • P2b data • Candidiasis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Arthritis • Inflammatory Bowel Disease • Musculoskeletal Diseases • Pruritus • Psoriatic Arthritis • Psychiatry • Rheumatology • Seronegative Spondyloarthropathies • Suicidal Ideation • Ulcerative Colitis • IL17A

Efficacy and safety of izokibep, a novel interleukin-17A inhibitor, in moderate to severe hidradenitis suppurativa: Week 16 results from a randomised, double-blind, placebo-controlled, multicentre, phase 3 study (EADV 2025) - P3 | "Conclusion Early improvements previously reported with izokibep over placebo were sustained across key HS disease measures at week 16, with over one-third of patients achieving HiSCR75. No new safety signals were observed with izokibep."

Clinical • Late-breaking abstract • P3 data • Candidiasis • Dermatology • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hidradenitis Suppurativa • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Psychiatry • Respiratory Diseases • Suicidal Ideation • IL17A

Positive 16-week Phase 3 Data of Izokibep in Hidradenitis Suppurativa Presented at EADV 2025 (Affibody Press Release) - "Data from week 16 demonstrate deepening of responses over time with statistically significant improvement across multiple efficacy endpoints. 37% of patients treated with 160 mg izokibep weekly (QW) achieved HiSCR75 compared to 20% of patients receiving placebo (p<0.01)...In higher order endpoints, 24% of patients treated with izokibep achieved HiSCR90, compared to 12% with placebo (p<0.05), and 21% of patients treated with izokibep achieved HiSCR100, compared to 9% with placebo (p<0.01)....Izokibep was generally well-tolerated with a favorable safety profile consistent with previous studies. There were no reports of Candida infection, inflammatory bowel disease, or suicidal ideation with izokibep."

Late-breaking abstract • P3 data • Hidradenitis Suppurativa

Efficacy and safety of izokibep in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. (PubMed, Ann Rheum Dis) - "Izokibep resulted in significant and clinically meaningful improvements over placebo across multiple disease domains, and the originally randomised 80-mg dose showed continued improvements to week 46. There were no unexpected safety risks identified. Izokibep's small size and high potency have the potential for further improved disease control, justifying additional investigation of higher doses."

Journal • P2 data • Dermatology • Immunology • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • IL17A

Hidradenitis Suppurativa Study of Izokibep (clinicaltrials.gov) - P3 | N=258 | Terminated | Sponsor: ACELYRIN Inc. | Completed ➔ Terminated; Per our 13Aug24 press release, we announced discontinuation of internal development in this indication. This decision was not due to safety reasons.

Trial termination • Dermatology • Hidradenitis Suppurativa • Immunology

Hidradenitis Suppurativa Study of Izokibep (clinicaltrials.gov) - P3 | N=258 | Completed | Sponsor: ACELYRIN Inc. | Active, not recruiting ➔ Completed

Trial completion • Dermatology • Hidradenitis Suppurativa • Immunology

Next-Generation Anti-IL-17 Agents for Psoriatic Disease: A Pipeline Review. (PubMed, Am J Clin Dermatol) - "Key agents under investigation include netakimab, vunakizumab, xeligekimab, gumokimab, HB0017, CJM 112, JS005, 608, LZM012, ZL-1102, izokibep, sonelokimab, DC-806, DC-853, and LEO 153339. Both preclinical and clinical trial data for each agent are summarized, with an emphasis on their efficacy, adverse effects, immunogenicity, and future outlooks."

Journal • Dermatology • Immunology • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies

Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis (clinicaltrials.gov) - P2 | N=96 | Terminated | Sponsor: ACELYRIN Inc. | Active, not recruiting ➔ Terminated; Study primary and secondary endpoints did not achieve statistical significance.

Trial termination • Ocular Inflammation • Ophthalmology • Uveitis

Affibody regains worldwide rights to izokibep (Affibody Press Release) - "Affibody today announced that the company will regain all rights to izokibep...In 2021, Affibody and ACELYRIN, INC. entered into a license and collaboration agreement granting ACELYRIN worldwide development and commercialization rights to izokibep, except in selected Asian countries. Following ACELYRIN’s previous announcement to halt internal development of izokibep the agreement will now be terminated. The termination will be effective after a three-month notice period after which all rights will revert, and the asset will be transferred to Affibody."

Commercial • Hidradenitis Suppurativa • Psoriatic Arthritis

Interleukin-17: A pleiotropic cytokine implicated in inflammatory, infectious, and malignant disorders. (PubMed, Cytokine Growth Factor Rev) - "Four FDA-approved drugs-secukinumab (for ankylosing spondylitis, enthesitis-related arthritis, hidradenitis suppurativa, non-radiographic axial spondyloarthritis, plaque psoriasis, and psoriatic arthritis), ixekizumab (for ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis, and psoriatic arthritis), brodalumab (for plaque psoriasis), and bimekizumab (for plaque psoriasis)-suppress the IL-17 pathway, with more in development, including netakimab, sonelokimab, izokibep, and CJM112. These agents and others are being studied across a spectrum of disorders. Understanding the complicated interplay between IL-17 and other immune mediators may yield new treatments for inflammatory/autoimmune conditions and malignancies."

Journal • Ankylosing Spondylitis • Dermatology • Genetic Disorders • Hidradenitis Suppurativa • Idiopathic Arthritis • Immunology • Infectious Disease • Inflammatory Arthritis • Oncology • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Skin Cancer • Solid Tumor • Spondylarthritis • IL17A • IL17C • IL17RA • IL23A

Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis (clinicaltrials.gov) - P2 | N=96 | Active, not recruiting | Sponsor: ACELYRIN Inc. | Trial completion date: Aug 2025 ➔ Feb 2025 | Trial primary completion date: Aug 2025 ➔ Feb 2025

Trial completion date • Trial primary completion date • Ocular Inflammation • Ophthalmology • Uveitis

ACELYRIN, INC. Announces Topline Results From Phase 2b/3 Study of Izokibep for the Treatment of Uveitis (GlobeNewswire) - P2b/3 | N=96 | NCT05384249 | Sponsor: ACELYRIN Inc. | "ACELYRIN, INC...today announced that its Phase 2b/3 trial of izokibep in non-infectious, non-anterior uveitis did not meet the primary endpoint of a statistically significant improvement in time to treatment failure versus placebo as measured by treatment failure rates at 24 weeks. Based on these data, and previously announced guidance regarding other indications, ACELYRIN will not make any additional internal investment in developing izokibep....In the trial, the treatment failure rate at 24 weeks was 45.0% (p-value: 0.4914) for izokibep and 50.7% for placebo. Statistical significance was not reached for any secondary endpoint and no clinical benefit was observed. Izokibep was well-tolerated in the trial, with a safety profile consistent with previous data and the IL-17A class."

Discontinued • P2/3 data • Immunology • Uveitis

Interleukin-17 Inhibitors in the Treatment of Hidradenitis Suppurativa. (PubMed, BioDrugs) - "Recently, secukinumab received approval from both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), while bimekizumab received approval from the EMA, for the treatment of moderate-to-severe HS in adults, with ongoing clinical trials aiming to further clarify the efficacy and safety of other drugs within this class...On the other hand, innovative drugs such as sonelokimab and izokibep show promising results and are currently in phase III clinical trials. This review provides a comprehensive overview of current knowledge and scientific advances in HS, focusing on the IL-17 pathway's role and its inhibition as a treatment strategy, alongside examining the most recent and significant clinical studies on various IL-17 inhibitors in the treatment of HS."

Journal • Review • Dermatology • Hidradenitis Suppurativa • Immunology • IL17A

Psoriatic Arthritis Study of Izokibep (clinicaltrials.gov) - P2/3 | N=351 | Terminated | Sponsor: ACELYRIN Inc. | Active, not recruiting ➔ Terminated; Per our 13Aug24 press release, we announced discontinuation of internal development in this indication. This decision was not due to safety reasons.

Trial termination • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies

Efficacy and safety of izokibep, a novel IL-17A inhibitor, in moderate-to-severe hidradenitis suppurativa: Week 12 results from a randomized, double-blind, placebo-controlled, multicenter, phase 3 study (EADV 2024) - P3 | "In this phase 3 study, IZO 160 mg QW met the primary endpoint, with one-third of patients with moderate-to- severe HS achieving HiSCR75 at wk 12. Additionally, IZO-treated patients demonstrated early improvements at wk 12 across other key disease measurements, including HiSCR90, HiSCR100, pain, and quality of life. IZO treatment was well tolerated, with no new safety signals and a safety profile generally consistent with that of other IL-17A– selective inhibitors."

Clinical • Late-breaking abstract • P3 data • Candidiasis • Dermatology • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hidradenitis Suppurativa • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Pain • Psychiatry • Suicidal Ideation • IL17A

ACELYRIN, INC. Announces Positive Results from Global Phase 3 Clinical Trial of Izokibep in Hidradenitis Suppurativa to be Highlighted in Late-Breaking Oral Presentation at EADV 2024 (GlobeNewswire) - "ACELYRIN, INC...today announced that positive results from the company’s global Phase 3 clinical trial of izokibep in moderate-to-severe hidradenitis suppurativa (HS) patients will be shared as a late-breaking oral presentation at the 2024 European Academy of Dermatology and Venereology taking place September 25-28, 2024 in Amsterdam, Netherlands."

P3 data • Hidradenitis Suppurativa • Immunology

Izokibep Enthesitis Benefit Lacking in Phase 2b/3 PsA Trial (Medscape) - P2/3 | N=351 | NCT05623345 | Sponsor: ACELYRIN Inc. | "This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint. Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.... A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity."

P2/3 data • Immunology • Psoriasis • Psoriatic Arthritis

EFFICACY AND SAFETY OF IZOKIBEP, A NOVEL IL-17A INHIBITOR, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: WEEK 16 RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER PHASE 2b/3 STUDY (EULAR 2024) - P2/3 | "IL-17A selective inhibition by IZO in pts with active PsA resulted in rapid improvement in disease activity across multiple disease domains. In addition to meeting the primary endpoint of ACR50, a substantial portion of IZO-treated pts achieved responses for the high-hurdle endpoints of ACR70, PASI90, PASI100, and MDA. These findings are consistent with the hypothesis that the IZO molecular construct allows optimal efficacy by IL-17A inhibition, without requiring blockade of IL-17F."

Clinical • Late-breaking abstract • P2/3 data • P2b data • Candidiasis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Musculoskeletal Diseases • Ocular Inflammation • Ophthalmology • Psoriasis • Psoriatic Arthritis • Psychiatry • Rheumatology • Seronegative Spondyloarthropathies • Suicidal Ideation • Ulcerative Colitis • Uveitis • IL17A

ACELYRIN, INC. Announces Positive 16-week Data From its Global Phase 2b/3 Trial of Izokibep in Psoriatic Arthritis to be Shared During Late-Breaking Oral Presentation at EULAR 2024 (GlobeNewswire) - "ACELYRIN, INC...announced that positive results from the company’s global Phase 2b/3 clinical trial of izokibep in psoriatic arthritis (PsA) will be shared as a late breaking oral presentation at the 2024 European Alliance of Associations for Rheumatology Congress taking place June 12-15 in Vienna, Austria."

P2/3 data • Immunology • Psoriasis • Psoriatic Arthritis

Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis (clinicaltrials.gov) - P2 | N=96 | Active, not recruiting | Sponsor: ACELYRIN Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2024 ➔ Aug 2025 | Trial primary completion date: Oct 2024 ➔ Aug 2025

Enrollment closed • Trial completion date • Trial primary completion date • Ocular Inflammation • Ophthalmology • Uveitis

ACELYRIN, INC. Provides Business Update And Highlights Key Upcoming Milestones (ACELYRIN) - "Izokibep in Hidradenitis Suppurativa (HS): The ongoing Phase 3 trial, expected to be the first of two registrational trials, enrolled more rapidly than forecasted and enrollment is now completed with 258 patients. Top line data are now expected in the third quarter of 2024."

Enrollment closed • P3 data: top line • Dermatology • Hidradenitis Suppurativa • Immunology

Hidradenitis Suppurativa Study of Izokibep (clinicaltrials.gov) - P3 | N=258 | Active, not recruiting | Sponsor: ACELYRIN Inc. | N=189 ➔ 258 | Trial completion date: Dec 2025 ➔ May 2025 | Trial primary completion date: Jun 2025 ➔ Jul 2024

Enrollment change • Trial completion date • Trial primary completion date • Dermatology • Hidradenitis Suppurativa • Immunology

Efficacy and safety of pharmacological treatment of psoriatic arthritis: a systematic literature research informing the 2023 update of the EULAR recommendations for the management of psoriatic arthritis. (PubMed, Ann Rheum Dis) - "The results of this SLR informed the task force responsible for the 2023 update of the European Alliance of Associations for Rheumatology recommendations for pharmacological management of PsA."

Journal • Cardiovascular • Hepatology • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Influenza • Oncology • Psoriatic Arthritis • Psychiatry • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Tuberculosis • Varicella Zoster • Venous Thromboembolism • IL12A • IL17A • IL23A

An Update on Current Clinical Management and Emerging Treatments in Hidradenitis Suppurativa. (PubMed, Skin Therapy Lett) - "However, HS is often refractory to traditional treatments, prompting the need for newer and more effective therapies. Herein, we review current and emerging HS therapies."

Journal • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • Pain