NLGase

Data from FRONTIER 1, a Phase 2b clinical trial, show JNJ-2113, the first and only targeted oral peptide that selectively blocks the IL-23 receptor, achieved the primary and all secondary endpoints including PASIa 100 and IGAb 0 responses of 40.5 percent and 45.2 percent, respectively SPRING HOUSE, Penn., Feb. 7, 2024 /PRNewswire/ -- Johnson & Johnson today announced publication in the New England Journal of Medicine (NEJM) of the Phase 2b FRONTIER 1 trial results for JNJ-2113.1 JNJ-2113 is the first and only investigational targeted oral peptide inhibitor designed to block the IL-23 receptor.2 IL-23 plays a critical role in pathogenic T-cell activation in moderate-to-severe plaque psoriasis (PsO) and underpins the inflammatory response in PsO and other dermatological and gastroenterological IL-23-mediated diseases.3,4 The FRONTIER 1 clinical trial achieved the primary and all secondary efficacy endpoints evaluating JNJ-2113 in adults with moderate-to-severe plaque PsO.1 The primary endpoint of the study was a reduction from baseline of at least 75 percent in the Psoriasis Area and Severity Index score (PASI 75 response) at Week 16. Study results demonstrated a significant dose-response on PASI 75 at Week 16 for adult patients who received JNJ-2113 compared to patients treated with placebo, with 79 percent of patients achieving a PASI 75 response in the highest dose group tested of 100 mg twice-daily. The data were consistent with the secondary endpoints, with patients who received the highest dose of JNJ-2113 achieving PASI 100 of 40.5 percent and IGA 0 (clear skin) of 45.2 percent.1 "The science behind advanced treatments for immune-mediated inflammatory diseases like PsO has advanced over the last few decades and patients desire treatment options that combine standard of care efficacy, an acceptable safety profile and flexible routes of administration," said Robert Bissonnette, M.D., Chief Executive Officer and Medical Director at Innovaderm Research, Montreal, Canada.d "The Phase 2b FRONTIER 1 data, as reported in NEJM, are very encouraging for the ongoing clinical development program and offer a reason to look forward to the continued research of investigational JNJ-2113 as an oral therapy that may offer an attractive and convenient treatment option for patients." Improvements were also consistent across Patient Reported Outcomes through Week 16.1 Patients who were treated with JNJ-2113 demonstrated greater improvements from baseline in the severity of their disease-related symptoms by Week 16, as assessed by the Psoriasis Symptoms and Signs Diary (PSSD)c.1 Among patients with baseline Dermatology Life Quality Index (DLQI)e scores greater than 1, significantly higher proportions of JNJ-2113-treated patients compared with placebo-treated patients achieved DLQI scores of 0/1 (no impact on quality of life) at Week 16.1 In this phase 2 study, rates of adverse events (AEs) were generally similar between the JNJ-2113 and placebo groups.1 The most common (≥5 percent of any treatment group) AEs were COVID-19 infection, nasopharyngitis, upper respiratory tract infection, diarrhea, headache, and cough.1 No relationship between the JNJ-2113 dose group and the occurrence of AEs or serious AEs was observed.1 Treatment with JNJ-2113 was also associated with lower serum levels of human beta-defensin 2 (hBD-2), relative to placebo, as early as Week 4.1 The lowest hBD-2 level was observed with the 100 mg twice-daily dose, beginning by Week 8.1 Lower levels of hBD-2 were observed with clinical response and indicate inhibition of the IL-17/IL-23 axis.5,6,7 "The impacts of living with moderate-to-severe plaque PsO are felt across all aspects of life and many patients do not seek advanced treatments because they have concerns with injectables and prefer an oral therapeutic option," said Lloyd Miller, M.D., Ph.D., Vice President, Immunodermatology Disease Area Leader, Johnson & Johnson. "We are encouraged by the study findings published in NEJM, including consistency across clinician and patient-reported outcomes and objective biomarkers. If approved, JNJ-2113 has the potential to improve both clinical and quality of life outcomes." The pivotal Phase 3 ICONIC clinical development program of JNJ-2113 in adult and adolescent patients with moderate-to-severe plaque PsO was initiated with two studies in Q4 2023 – ICONIC-LEAD and ICONIC-TOTAL – pursuant to the license and collaboration agreement between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc.8 ICONIC-LEAD is a randomized controlled trial (RCT) to evaluate the safety and efficacy of JNJ-2113 compared with placebo in participants with moderate-to-severe plaque PsO, with the higher efficacy bar of PASI 90 and IGA score of 0 or 1 with at least a 2-grade improvement as co-primary endpoints.9 ICONIC-TOTAL is a RCT to evaluate the efficacy and safety of JNJ-2113 compared with placebo for the treatment of PsO in participants with at least moderate severity affecting special areas (e.g., scalp, genital, and/or palms of the hands and the soles of the feet) with overall IGA score of 0 or 1 with at least a 2-grade improvement as the primary endpoint.10 Other Phase 3 studies in the development program are expected to begin in Q1 2024, including ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, which will evaluate the safety and efficacy of JNJ-2113 compared with both placebo and deucravacitinib.11 The findings from the FRONTIER 1 clinical trial suggest the potential of JNJ-2113 across the spectrum of additional IL-23-mediated diseases.2,12 The Company has initiated the Phase 2b ANTHEM-UC study to evaluate the safety and effectiveness of JNJ-2113 compared with placebo in participants with moderately to severely active ulcerative colitis.12 Editor's Notes: a. The PASI score grades the amount of surface area on each body region that is covered by PsO plaques and the severity of plaque redness, thickness, and scaliness.13 b. The IGA is a five-point scale with a severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe disease.1 c. The PSSD is a patient-reported instrument that assesses severity of six symptoms (itch, skin tightness, burning, stinging, and pain) and five signs (dryness, cracking, scaling, shedding/flaking, redness, and bleeding) of PsO. An improvement (reduction) of 40 points or more is considered clinically meaningful.1 d. Dr. Robert Bissonnette is a paid consultant for Johnson & Johnson. He has not been compensated for any media work. e. The DLQI measures impact of any skin disease on daily life, and assesses symptoms, feelings, daily activities, leisure, work/school, relationships/sex, and treatment effects.14 About FRONTIER 1 (NCT05223868) The FRONTIER 1 Phase 2b trial (NCT05223868) is a randomized, multicenter, double-blind, placebo-controlled clinical trial that evaluated three once-daily dosages and two twice-daily dosages of JNJ-2113 taken orally.1,15 It was designed to assess the efficacy and safety of JNJ-2113 in patients with moderate-to-severe plaque PsO.1 A total of 255 participants were randomized into six treatment groups (placebo [n=43], 25 mg daily [n=43], 25 mg twice-daily [n=41], 50 mg daily [n=43], 100 mg daily [n=43], and 100 mg twice-daily [n=42]).1 The total duration of the trial was up to 24 weeks, which included a four-week screening period, a 16-week treatment period and a four-week safety follow-up period.1 The primary endpoint of the clinical trial was the proportion of patients achieving PASI 75 at 16 weeks.1 Secondary endpoints at Week 16 included change from baseline in PASI total score, proportion of participants achieving PASI 90 and PASI 100 score, proportion of participants achieving an Investigator's Global Assessment (IGA) score of cleared (0) or minimal (1), change from baseline in Body Surface Area (BSA), change from baseline in Psoriasis Symptoms and Signs Diary (PSSD) symptoms scores, percentage of participants achieving PSSD symptoms score=0 among participants with a baseline symptom score ≥1, proportion of participants achieving a Dermatology Life Quality Index (DLQI) of 0 or 1 among participants with baseline DLQI Score >1, change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS-29) domain score, proportion of participants who achieve ≥ 5-point improvement from baseline in PROMIS-29 domain score, and number of participants with adverse events and serious adverse events up to 24 weeks.15 About Plaque Psoriasis (PsO) Plaque PsO is an immune-mediated disease resulting in overproduction of skin cells, which causes inflamed, scaly plaques that may be itchy or painful.16 It is estimated that eight million Americans and more than 125 million people worldwide live with the disease.17 Nearly one-quarter of all people with PsO have cases that are considered moderate-to-severe.17 Living with PsO can be a challenge and impact life beyond a person's physical health, including emotional health, relationships, and handling the stressors of life.18 About JNJ-77242113 (JNJ-2113) JNJ-2113 was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist Therapeutics and Johnson & Johnson. Johnson & Johnson retains exclusive worldwide rights to develop JNJ-2113 in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications.19, 20, 21 Investigational JNJ-2113 is the first targeted oral peptide designed to block the IL-23 receptor,2 which underpins the inflammatory response in moderate-to-severe plaque PsO and other IL-23-mediated diseases.3,4 JNJ-2113 binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cells.22 The license and collaboration agreement established between Protagonist and Janssen Biotech, Inc., in 2017 enabled the companies to work together to discover and develop next-generation compounds that ultimately led to JNJ-2113.23 About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JNJInnovMed. Janssen Research & Development, LLC is a Johnson & Johnson Company. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding JNJ-2113. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. Neither Janssen Research & Development, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. © Johnson & Johnson, Inc. 2024. All rights reserved. Bissonnette R, et al. An oral interleukin-23–receptor antagonist peptide for plaque psoriasis. N Engl J Med. 2024;390:510-21. DOI: 10.1056/NEJMoa2308713. Bissonnette R, et al. Data presentation. A phase 2, randomized, placebo-controlled, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis: FRONTIER 1. Presented at WCD 2023, July 3-8. Razawy W, et al. The role of IL‐23 receptor signaling in inflammation‐mediated erosive autoimmune arthritis and bone remodeling. Eur J Immunol. 2018 Feb; 48(2): 220–229. Tang C, et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2012 Feb; 135(2): 112–124. Kolbinger F, et al. β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis. J Allergy Clin Immunol 2017;139:923-32. Morita A, et al. Assessment of serum biomarkers in patients with plaque psoriasis on secukinumab. J Dermatol 2020;47:452-7. Jansen PA, et al. β-Defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin. PLoS One. 2009 Mar; 4(3): e4725. doi: 10.1371/journal.pone.0004725. PMID: 19266104; PMCID: PMC2649503. Protagonist Therapeutics. Press release. Protagonist announces advancement of JNJ-2113 across multiple indications. Available at: . Accessed February 2024. Clinicaltrials.gov. A study of JNJ-2113 in adolescent and adult participants with moderate-to-severe plaque psoriasis (ICONIC-LEAD). Identifier NCT06095115. . Accessed January 2024. Clinicaltrials.gov. A study of JNJ-2113 for the treatment of participants with plaque psoriasis involving special areas (scalp, genital, and/or palms of the hands and the soles of the feet) (ICONIC-TOTAL). Identifier NCT06095102. . Accessed January 2024. Protagonist Therapeutics. Press release. Protagonist announces two new phase 3 ICONIC studies in psoriasis evaluating JNJ-2113 in head-to-head comparisons with deucravacitinib. Available at: . Accessed February 2024. Clinicaltrials.gov. A study of JNJ-2113 in participants with moderately-to-severely active ulcerative colitis (ANTHEM-UC). Identifier NCT06049017. . Accessed January 2024. Thompson Jr, D. How the Psoriasis Area and Severity Index works. Everyday Health. Available at: . Accessed January 2024. Finlay AY, et al. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994 May;19(3):210-6. doi: 10.1111/j.1365-2230.1994.tb01167.x. PMID: 8033378. Clinicaltrials.gov. A study of JNJ-2113 in participants with moderate-to-severe plaque psoriasis (FRONTIER 1). Identifier NCT05223868. . Accessed January 2024.EU Clinical Trials Register. A study of JNJ-2113 in participants with moderate-to-severe plaque psoriasis (FRONTIER 1). EudraCT 2021-003700-41. . Accessed January 2024. National Psoriasis Foundation. About psoriasis. Available at: . Accessed January 2024. National Psoriasis Foundation. Psoriasis statistics. Available at: . Accessed January 2024. National Psoriasis Foundation. Life with psoriasis. Available at: . Accessed January 2024. Protagonist Therapeutics. Press release. Protagonist Therapeutics announces amendment of agreement with Janssen Biotech for the continued development and commercialization of IL-23 antagonists. Available at: . Accessed January 2024. Protagonist Therapeutics. Press release. Protagonist Reports positive results from Phase 1 and pre-clinical studies of oral Interleukin-23 receptor antagonist JNJ-2113. Available at: . Accessed January 2024. Protagonist Therapeutics. Press release. Protagonist Therapeutics announces positive topline results for Phase 2b FRONTIER 1 clinical trial of oral IL-23 receptor antagonist JNJ-2113 (PN-235) in psoriasis. Available at: . Accessed January 2024. Pinter A, et al. Data Presentation. JNJ-77242113 Treatment Induces a Strong Systemic Pharmacodynamic Response Versus Placebo in Serum Samples of Patients with Plaque Psoriasis: Results from the Phase 2, FRONTIER 1 Study. Presented at EADV 2023, October 11-14. Johnson & Johnson. Press release. Janssen enters into worldwide exclusive license and collaboration agreement with Protagonist Therapeutics, Inc. for the oral Interlukin-23 receptor antagonist drug candidate for the treatment of Inflammatory Bowel Disease. Available at: . Accessed January 2024. SOURCE Johnson & Johnson

After the spring reductions in the workforce that left thousands of biotech employees searching for jobs, larger companies are, for the most part, moving forward, while some of the smaller ones are struggling to optimize operations and cut costs. Further reductions in the workforce can be expected, along with more mergers and acquisitions as some financial analysts say the U.S. is in – or will soon be in – a recession (defined as two consecutive quarters of declining economic growth), as the Federal Reserve Board increased the primary credit interest rate 1.75% – a 0.75 percentage point increase - effective June 16. In contrast, NASDAQ, citing consumer spending, predicts a recession “probably won’t occur for at least the next year.” Here’s a look at what some of the biotech companies are doing now, after their layoffs and what prompted their employee furloughs. Athersys Considering Options Following Phase III Failure Athersys laid off 70% of its staff in June – including its COO, CSO and CFO – after its stroke therapy failed in Phase II/III trials. The company's stock closed at $0.27 on June 17, down from its 52-week high of $1.81. The company postponed its annual shareholder’s meeting from June 15 to July 28 to allow time for a proposal authorizing the board of directors to amend the company’s certificate of incorporation to create a reverse stock split in an attempt to return share prices to the $1 minimum required for NASDAQ listing. After Aduhelm, Biogen Prioritizes Biosimilars, Emerging Markets In March, Biogen began laying off employees after lower-than-anticipated sales of its Alzheimer's drug, Aduhelm. It also backed out of its agreement to purchase Karyopharm Therapeutics and its amyotrophic lateral sclerosis (ALS) asset. Biogen's stock opened at $192.11 per share on June 17, down from a 52-week high of $391. The company has stated plans “to continue to return cash to shareholders through share repurchases.” In June the company announced positive Phase III data for its biosimilar version of tocilizumab for rheumatoid arthritis, a license and collaboration agreement for a GBA2 inhibitor to treat Parkinson’s disease and launched the biosimilar Byooviz (ranibizumab-nuna) in the U.S. for three ophthalmology indications. Biogen expects two more regulatory filings this year and plans call for expanding its biosimilars business, as well as increasing its focus on R&D, reducing costs and enhancing productivity. The company said it will be focusing on “key emerging markets, such as China and certain markets in both Latin America and the Middle East.” It is also providing support for humanitarian efforts in Ukraine. bluebird bio Bounces on Positive Gene Therapy Recommendation In April, bluebird bio announced a comprehensive restructuring that has resulted in a 30% reduction in the workforce as part of its effort to save approximately $160 million over the next two years. The company is transitioning to new headquarters in an effort to save $120 million over the next six years. An FDA Advisory Committee unanimously recommended that the FDA approve betibeglogene autotemcel (beti-cel) and elivaldogene autotemcel (eli-cel) recently. Beti-cel is scheduled to come before the U.S. Food and Drug Administration on August 19, while eli-cel is scheduled for review on September 16. After falling from a 52-week high of $21.74, bluebird bio’s stock rallied on positive news, jumping more than 34% to $3.84 in midday trading on June 1 before closing at $3.56. The surge was attributed to a positive message from CEO Andrew Obenshain at the European Hematology Association Hybrid 2022 Congress regarding its cell therapies for sickle cell disease and beta thalassemia. Gilead Realigns Following Immunomedics Acquisition Gilead laid off 114 employees in March after acquiring Immunomedics in 2020. First-quarter revenue this year was up 3% in year-over-year earnings. It made a $725 million collaboration opt-in payment to Arcus Biosciences, repaid $500 million in debt, paid $945 million in dividends and repurchased $352 million of common stock. Its stocks opened at $57.37 on June 19, down from a 52-week high of $74.12. The Q1 report said the company's effective tax rate for the quarter was 107.9%, compared to 23.9% for Q1 2021 because of a $2.7 billion in process research and development (IPR&D) impairment related to the Immunomedics deal in 2020. Merck Invests in U.S. and Global R&D Infrastructure After acquiring Acceleron in 2021, Merck laid off 143 employees in March. That doesn’t make a dent in its 71,000-employee headcount but is part of the larger biotech trend this spring as companies realign their workforces. Going forward, Merck says it is “making significant investments in [its] research and discovery facilities and infrastructure in the U.S. and around the world.” That includes the recent expansions of the Exploratory Science Center in Cambridge, MA and its West Point, PA site, as well as the development of the 220,000-square-foot London Discovery Center. Merck’s website lists hundreds of job openings throughout the company. Novartis Axes 8,000 Jobs in Accelerated Restructuring Novartis accelerated its restructuring in April to accelerate its overall growth and strengthen its pipeline. On Tuesday, the company revealed it would be cutting 8,000 jobs in hopes of saving at least $1 billion by 2024. Sales, operating income, net income and earnings per share all increased in Q1, although free cash flow, core net income and core earnings per share each decreased. Q2 results are not yet available. A Strategy and Growth function is being created, along with a new operations unit to generate economies of scale and enhance productivity. Since its Q1 report was issued, Novartis has resumed its business in Ukraine and is supplying medical and humanitarian aid. It has signed a manufacturing deal with Samsung Biologics while Greece has filed a bribery lawsuit for €214 million, alleging a payout to doctors. Overall Layoffs didn’t cease with the March culling and may continue as the economy slows. For example, in June, Genocea ceased operations, Atreca announced layoffs are part of corporate restructuring and Praxis reduced its workforce after the failure of a Phase II/III clinical trial. Amarin and Vincerx Pharma also announced layoffs. Biotech employees, therefore, should prepare for tumultuous times ahead.

Biogen announced a deal with Canadian biotech Alectos Therapeutics on Monday to develop a drug aimed at restoring lysosome function, adding another candidate to the pharma’s Parkinson’s pipeline. The potential drug, which is still in preclinical studies, would inhibit GBA2 — an enzyme that breaks down a large glycolipid into its sugar and fat components. According to Biogen and Alectos, inhibiting GBA2 can also increase the lysosome’s proton pump activity and possibly restore lysosome function, which may be implicated in a broad range of neurodegenerative diseases. For the GBA2 inhibitor and “additional unnamed backup molecules,” Biogen will pay $15 million upfront. Biogen could also pay Alectos $77.5 million in development milestones and up to $630 million further down the line if the drug makes it to market. “Through this collaboration with Alectos, we hope to improve the lives of people living with Parkinson’s disease by advancing the research and development of a potential-first-in-class oral treatment that may slow disease progression,” Biogen interim R&D head Priya Singhal said in a press release . Last year, Biogen quietly put away another Parkinson’s drug after a Phase II fail . The pharma has been reeling as it struggled to commercialize its controversial Alzheimer’s drug Aduhelm, and last month announced its CEO Michel Vounatsos was on his way out . Alongside that news, Biogen said it would be looking for new deals as it tried to revamp its R&D focus. Mutations to the GBA2 gene and its partner GBA1 have been associated with Gaucher disease, which can lead to the buildup of glycolipids in the body and results in liver, lung and brain damage. Mutations to GBA1 are also a risk factor for GBA-PD, a form of Parkinson’s that impacts a small subset of patients. OrbiMed-backed Vanqua Bio is creating an activator to target the GBA1 pathway in hopes of treating GBA-PD. However, Biogen and Alectos’ new drug would be a potential first-in-class inhibitor of GBA2. “I think the subset of GBA Parkinson’s patients that carry mutations in GBA, that’s really just additional evidence that points to dysfunction of lysosomal pathway in this disease among others. I think that’s really supporting evidence that GBA2 inhibition as a general mechanism to activate lysosomal function may be effective in this disease,” Alectos CEO Ernest McEachern told Endpoints News . Alectos is also partnered with Merck to develop a different inhibitor targeted at OGA, also meant to resolve lysosome dysfunction in Parkinson’s and other neurodegenerative diseases. As their candidate is still in preclinical studies, McEachern said they didn’t have a strict timeline for development yet. This article has been updated to include comment from Ernest McEachern.