Risankizumab-RZAA

In the field of immunotherapy, the market for oral peptide therapies is gradually emerging. Recently, AbbVie announced that it has reached a final acquisition agreement with Nimble Therapeutics. This transaction will enable AbbVie to obtain Nimble's core assets, including its oral peptide IL-23 inhibitor project, which is in the preclinical research stage and aims to treat psoriasis, as well as an innovative pipeline of oral peptide candidates targeting various autoimmune diseases. Additionally, AbbVie will gain access to Nimble's peptide synthesis, screening, and optimization platform, which employs proprietary technology to accelerate the discovery and optimization of peptide candidates targeting multiple pathways. AbbVie has long been active in the field of immunotherapy, and as its flagship product Humira faces patent expiration, the company is actively seeking new growth opportunities. This acquisition of Nimble Therapeutics not only enriches AbbVie's product pipeline but also strengthens its research and development capabilities in the field of oral peptide therapies. In the realm of oral medications for psoriasis, Johnson & Johnson's JNJ-2113 shows best-in-class potential, leading over other competitors. Just last month, Johnson & Johnson announced that the ICONIC-LEAD clinical trial achieved top-line results, marking the imminent market entry of the world's first targeted oral peptide Icotrokinra that selectively blocks IL-23 receptors. In light of Johnson & Johnson's progress, AbbVie is making every effort to ensure it maintains a leading position in this competition. Globally, there are over 125 million psoriasis patients, and this chronic disease requires long-term treatment, giving rise to a substantial treatment market. The global psoriasis market has reached $26.5 billion, and it is expected to maintain a 8.6% compound annual growth rate (CAGR) from 2022 to 2030. For the treatment of plaque psoriasis, 22 targeted therapies have been approved worldwide. Among these therapies, AbbVie and Johnson & Johnson are undoubtedly market leaders. Oral medications are increasingly favored by long-term treatment patients due to their convenience. Current oral medications include PDE4 inhibitor apremilast, TYK2 allosteric inhibitor deucravacitinib, and JAK inhibitor upadacitinib. Moreover, numerous multinational companies are actively entering the oral medication market for psoriasis. Johnson & Johnson's JNJ-2113 (Icotrokinra), as the world's first oral IL-23 receptor antagonist, relies on Protagonist Therapeutics' unique peptide technology platform, successfully overcoming challenges related to the low bioavailability, permeability, and stability of oral peptides, as well as gastrointestinal degradation. In the Phase III ICONIC-LEAD study, it demonstrated superior data compared to other oral competitors. With strong efficacy data, Johnson & Johnson is highly confident in JNJ-2113, predicting that the drug could achieve a market potential of $5 billion. Observing Johnson & Johnson's breakthrough progress in the oral medication space for psoriasis, AbbVie is also stepping up its efforts to expand its product line and maintain its leadership in the treatment of autoimmune diseases. AbbVie has turned its attention to Nimble Therapeutics, a biotechnology company focused on developing oral peptide therapies. Nimble's research achievements, particularly the IL-23R inhibitor, are noteworthy; this is a preclinical oral therapy designed to provide new treatment options for patients with psoriasis and inflammatory bowel disease (IBD). Importantly, this target shares the same profile as AbbVie's existing blockbuster injectable Risankizumab, indicating that Nimble's research results could synergize with AbbVie's current product line. Nimble claims that its designed drugs not only inherit the strong activity of injectable IL-23 medications but also have an extended half-life. Furthermore, Nimble has disclosed two additional candidates targeting systemic severe myasthenia gravis and IBD, both of which are also in preclinical testing. Through this acquisition, AbbVie will not only incorporate Nimble's product line but also gain advanced technology from this Madison, Wisconsin-based company for synthesizing, screening, and optimizing peptide candidates. This will provide powerful technical support for AbbVie in the field of oral peptide therapies, accelerating its R&D progress in this emerging area. In fact, AbbVie’s acquisition of Nimble marks its third significant acquisition in the immunotherapy developer space this year. This series of consecutive acquisitions not only highlights AbbVie's proactive positioning in the field of immunotherapy but also reveals the company's urgency in maintaining its market leadership, especially against the backdrop of competitors like Johnson & Johnson making strides in oral medications for psoriasis. The peptide industry is currently experiencing an unprecedented golden development period. Compared to small molecular chemical drugs, peptide drugs exhibit higher bioactivity and specificity; compared to biological drugs, they stand out due to low immunogenicity, high purity, and lower production costs. Overall, peptide drugs are favored for their high activity, low dosage, and low toxicity. Frost & Sullivan predicts that the global peptide drug market will grow from $60.7 billion in 2018 to $89.5 billion in 2023, and is expected to reach $189 billion by 2028. When efficacy reaches a certain level, oral medications often become the treatment choice for patients due to their adherence advantages. However, due to the unique chemical and biological characteristics of peptide drugs, their oral delivery remains one of the significant challenges in the pharmaceutical field. Since the discovery of insulin, research on oral peptides has never ceased. Due to the poor permeability of peptide drugs and their susceptibility to degradation by proteases in the gastrointestinal tract, most available peptide drugs are in injectable form. However, the long-term repeated injection not only affects patients' quality of life but also increases the complexity of manufacturing and storage, ultimately leading to higher medical costs. Thus, although the development of oral peptide drugs has been a research hotspot in the pharmaceutical field, few successful products have emerged due to the numerous challenges in absorption. With in-depth studies on the absorption mechanisms of peptides, innovative technologies developed by scientists are gradually breaking the barriers to peptide absorption in the gastrointestinal tract, and some oral peptide drugs have successfully hit the market. For example, the recently spotlighted Semaglutide is a GLP-1 peptide drug that traditionally has been administered via subcutaneous injection. With the help of the innovative SNAC absorption enhancer, the Semaglutide tablet (Rybelsus) has successfully overcome technical barriers, achieving a historic breakthrough in the oral administration of GLP-1 drugs, thus becoming the first truly oral peptide drug. The active pharmaceutical ingredient (API) of Rybelsus is identical to that of its injectable counterpart and is modified with a fatty acid chain, additionally incorporating 300 mg of SNAC molecules. The inclusion of SNAC instantaneously raises the gastric pH, promoting transcellular absorption through the gastric mucosa at specific concentrations. In human NCI-N87 gastric epithelial cell models, adding SNAC increased the absorption capacity of gastric epithelial cells by 100 times. After entering the market, Rybelsus also performed impressively, with demand so great that it led to supply shortages. In the first half of 2024, Rybelsus achieved sales of $1.587 billion, representing a 32% year-over-year growth. Equally noteworthy is the Israeli pharmaceutical company Chiasma Inc., which successfully developed the oral capsule Mycapssa through innovative formulation and received approval in the U.S. in 2020 via the 505(b)(2) regulatory pathway. Mycapssa is the first and only approved oral somatostatin analog capsule for treating acromegaly, offering patients a new treatment option. The transient permeability enhancer (TPE™) technology employed by Chiasma provides critical technical support for developing oral peptide drugs. Merck has also recognized the potential of oral peptides. In January 2024, Merck signed a $220 million collaboration agreement with Unnatural Products. Through this collaboration, Merck intends to leverage Unnatural Products' technology to develop cyclic peptide candidates, primarily targeting the challenging oncology field. Merck has previously likened cyclic peptides to "Goldilocks," as their molecular size falls between small molecules and biologics, offering numerous unique advantages. Previously, Merck launched the Phase III clinical project for MK-0616, a cyclic peptide that binds to PCSK9. Currently, PCSK9-targeted therapies can only be administered via injection, and the cost-effectiveness issues related to using biologics to lower cholesterol have yet to be effectively addressed. Developing an oral PCSK9 inhibitor is a goal in this field, and the R&D of MK-0616 cyclic peptide is expected to make significant breakthroughs in this area. According to a report by MARKET MONITOR GLOBAL, INC (MMG), the global oral peptide therapeutic drug market was approximately $1886.4 million in 2023, with an expected annual compound growth rate (CAGR) of 15.8% over the next six years, reaching $7843.2 million by 2030. Industry perspectives generally indicate that the treatment market for autoimmune diseases is experiencing rapid growth. As the technology for oral peptide therapies continues to advance and the market expands quickly, AbbVie is solidifying its R&D position in the oral peptide field through the acquisition of Nimble Therapeutics. Whether AbbVie can reclaim the title of "King of Immunology" and continue leading innovation in the treatment of autoimmune diseases will be closely monitored by Pharmaceutical Economic News.

Pharmacokinetic and safety data from healthy volunteers anticipated in the second half of 2025 On track to initiate a proof-of-concept study in psoriasis in the second half of 2025, with initial efficacy data expected in the second half of 2026 Preclinical data with ORKA-001 demonstrate the potential for once- or twice-yearly dosing, a significant improvement over standard of care MENLO PARK, CA, USA I December 19, 2024 I Oruka Therapeutics, Inc. (“Oruka”) (Nasdaq: ORKA), a biotechnology company developing novel biologics designed to set a new standard for the treatment of chronic skin diseases including plaque psoriasis, today announced that it has initiated dosing of healthy volunteers in its first clinical trial of ORKA-001, the Company’s novel, subcutaneously administered, half-life extended monoclonal antibody targeting IL-23p19. “The initiation of this Phase 1 study of ORKA-001 marks an important milestone for Oruka, which our team has delivered ahead of schedule,” said Lawrence Klein, PhD, Chief Executive Officer of Oruka. “We look forward to sharing initial data for ORKA-001 in the second half of 2025, which could validate ORKA-001’s half-life and safety profile, supporting extended dosing intervals and best-in-class potential.” The ORKA-001 Phase 1 trial is a double-blind, placebo-controlled, single ascending dose study evaluating the safety, tolerability, and pharmacokinetics (PK) of ORKA-001 in healthy volunteers. The study is expected to enroll approximately 24 healthy volunteers across three subcutaneous dose cohorts. Oruka expects to share interim data from this study in the second half of 2025. Pending data from the Phase 1 trial, Oruka plans to initiate a proof-of-concept study of ORKA-001 in moderate-to-severe psoriasis in the second half of 2025. This study is anticipated to evaluate the safety and efficacy of a single dose level of ORKA-001 versus placebo in approximately 80 subjects, followed by randomization to one of two maintenance dosing arms. In one maintenance arm, subjects will receive ORKA-001 every six months. In the other, subjects will receive only induction dosing to assess the length of time patients maintain clear skin, which could support once-yearly dosing or even longer-term durability in some patients. Subjects then can continue to an open-label extension study. The company expects to share initial data from the proof-of concept study in the second half of 2026. “We believe that ORKA-001 has the potential to set a new standard in the treatment of plaque psoriasis in terms of both depth and duration of response,” said Joana Goncalves, MBChB, Chief Medical Officer of Oruka. “We hear consistently that people with psoriasis want to achieve freedom from their disease, and that is what we hope to offer with this program. The initiation of this Phase 1 study brings us one step closer to that goal.” Additionally, the Company announced that it has entered into a license agreement with Paragon Therapeutics granting it worldwide exclusive rights to ORKA-001 in all indications other than inflammatory bowel disease. About ORKA-001 ORKA-001 is a novel, subcutaneously administered, half-life extended monoclonal antibody targeting IL-23p19. Inhibitors of IL-23p19 have become the preferred first-line therapy for patients with moderate-to-severe PsO given their strong efficacy and safety profile. Currently approved therapies are dosed four to six times per year and deliver PASI 100, or fully clear skin, for less than half of patients after four months. ORKA-001 has the potential to be dosed just once or twice a year and is designed to achieve higher exposures than currently marketed IL-23p19 antibodies, which could lead to higher rates of disease clearance. Data from studies in non-human primates and other preclinical assays show that ORKA-001 binds to a similar epitope with similar affinity as risankizumab and has a significantly extended half-life over three times longer than risankizumab. About Oruka Therapeutics Oruka Therapeutics is developing novel biologics designed to set a new standard for the treatment of chronic skin diseases. Oruka’s mission is to offer patients suffering from chronic skin diseases like plaque psoriasis the greatest possible freedom from their condition by achieving high rates of complete disease clearance with dosing as infrequently as once or twice a year. Oruka is advancing a proprietary portfolio of potentially best-in-class antibodies that were engineered by Paragon Therapeutics and target the core mechanisms underlying plaque psoriasis and other dermatologic and inflammatory diseases. For more information, visit www.orukatx.com and follow Oruka on LinkedIn. SOURCE: Oruka Therapeutics