IgE

SAN DIEGO, March 12, 2024 /PRNewswire/ -- Longbio Pharma (Suzhou) Co., Ltd. (referred to as "Longbio Pharma"), a leading biotech company dedicated to developing innovative protein treatments for allergy, respiratory, dermatology, hematology, ophthalmology, and other autoimmune and rare diseases, proudly announced the Phase I data of LP-003 (new generation of anti-IgE antibody) at the 2024 American Academy of Dermatology Association annual meeting (2024AAD). The presentation of the poster titled "A Phase 1 study in healthy subjects of LP-003, a novel long-acting, high affinity anti-IgE antibody" by Longbio Pharma marked a significant moment during the conference. Title: A Phase 1 study in healthy subjects of LP-003, a novel long-acting, high affinity anti-IgE antibody Abstract Submission ID: 50484 Presentation Time: Mar 8-12, 2024 Location: Poster Exhibits Center Results: In a randomized, double-blind, single-ascending-dose Phase I clinical study (CTR20221413), 32 healthy subjects were randomly divided into 5 groups to receive a single intravenous dose of 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 6 mg/kg and 10 mg/kg respectively. Safety, pharmacokinetics, and pharmacodynamics (free IgE levels) profile was evaluated. LP-003 exhibited a non-linear PK characteristic with T1/2 ranging from 44.6 days to 76.5 days, which is approximately 2～3 fold of Omalizumab. Moreover, the free-IgE was suppressed to below detection range for more than 168 days at 1 mg/kg group (except one with high baseline IgE level) to 10 mg/kg group. LP-003 appears to show good safety profile. No Grade 3 and above TEAE was reported, establishing a solid foundation for further investigation and advancement. Chronic spontaneous urticaria (CSU) stands as a prevalent skin disorder affecting approximately 1–2% of the global population. Despite SoC treatment, the efficacy and duration of relief remain significant challenges for patients and healthcare providers alike. Anti-IgE therapy was approved as a second-line treatment, however, only approximately 40% of patients achieving complete response following 300 mg Omalizumab dosing. Thus, a novel anti-IgE treatments offering higher efficacy and prolonged relief is needed. The successful Phase II study of Ligelizumab points a way that anti-IgE antibody with higher IgE affinity and more potent efficacy (FcεRI inhibition) retains the potential to be superior against Omalizumab. In this study, Longbio Pharma developed a new generation of anti-IgE antibody, LP-003, of higher IgE binding affinity, stronger FcεRI inhibition bioactivity, compared to Omalizumab and even Ligelizumab. Meanwhile, LP-003 has a much longer half-life (approximately 45∽76 days) compared to Omalizumab (approximately 17∽20 days). Moreover, a Phase II clinical trial (NCT06228560) of total 200 adult refractory CSU patients, despite up-dosing anti-histamine (H1) treatment, are being enrolled into 5 distinct groups (n=40/group), including three LP-003 treatment groups, one omalizumab treatment group, to provide a head-to-head comparison, and one placebo group. The topline results are expected to be released in early 2025. About LP-003 LP-003, a novel monoclonal anti-IgE antibody was generated, humanized, and engineered by Dr. Sun, Nai-chau, who is the inventor of Omalizumab, and co-founder of Tanox. Based on the 30+ years R&D experience on IgE target, Dr Sun developed a new generation of anti-IgE antibody (LP-003). Its extensive characterization including: affinity, bioactivity (FcεRI and FcεRII/CD23 inhibition), off-target binding and animal study (Tox and efficacy) was conducted. LP-003 just accomplished its Phase II study of allergic rhinitis. The current data shows LP-003 has the potential to become a best-in-class treatment. About Longbio Pharma LongBio Pharma is a biotech company located in Shanghai/Changshu, China. The company, which was founded in 2018, focuses on autoimmune and complement diseases, serving patients and society. For more information, please visit: or please contact: [email protected]. SOURCE Longbio Pharma

Upstream announces the first global Phase 2 asthma study of a biologic inhibiting TSLP signaling including a 24-week dosing regimen and the potential to achieve best-in-class efficacy based on highly differentiated potency in asthma patients. WALTHAM, Mass.--(BUSINESS WIRE)-- Upstream Bio, a clinical-stage biotech company advancing new therapies to treat inflammation, today announced the dosing of the first patients in its Phase 2 VALIANT clinical trial of verekitug (UPB-101) in patients with severe asthma. Verekitug is a recombinant fully human immunoglobulin G1 monoclonal antibody designed to block the thymic stromal lymphopoietin receptor (TLSPR) and thus inhibit TSLP-driven inflammation. Verekitug is currently under investigation in a Phase 2 study for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). “We are thrilled to initiate the Phase 2 study in severe asthma after the findings from our multiple ascending dose (MAD) study in asthma patients demonstrated that verekitug produces a compelling reduction in disease-related biomarkers,” said Aaron Deykin, Head of R&D and Chief Medical Officer. “The 100 mg dose in the MAD study showed a 54% reduction from baseline in FeNo and EOS at week 12 that was sustained through week 32, which was 24 weeks after the last dose. These observations not only demonstrate the higher potency of verekitug compared to published data from tezepelumab, but also enable Upstream to study extended dosing regimens in Phase 2 including every 24 weeks.” The VALIANT study is a randomized, double-blind, placebo-controlled study evaluating verekitug in doses of 100 mg every 24 weeks (Q24W), 400 mg Q24W, 100 mg every 12 weeks (Q12W), or placebo administered subcutaneously in a single injection. The study will evaluate verekitug’s efficacy in the treatment of severe asthma as reflected by the registrational primary endpoint of the annual asthma exacerbation rate (AAER). “Verekitug has the potential to be a best-in-class inhibitor of TSLP signaling based on its swift, substantial and sustained effect on clinically relevant biomarkers that are known to correlate with impact on AAER,” said Sam Truex, Chief Executive Officer. “Our team is thrilled to carry our momentum from Phase 1b into our global Phase 2 studies where we intend to demonstrate how verekitug’s high potency translates to clinical outcomes that will benefit patients with many types of asthma.” About Verekitug (UPB-101) Verekitug is a novel recombinant fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to the human thymic stromal lymphopoietin (TSLP) receptor (TSLPR) to inhibit signaling. In preclinical studies, verekitug demonstrated inhibition of cytokine production from both CD4+ T cells and ILC2, suggesting that it may be effective against multiple types of inflammation. Data in three Phase 1 studies conducted to date demonstrate that verekitug is safe and well-tolerated. In a Phase 1b study, verekitug became the first TSLP signaling inhibitor to demonstrate sustained target engagement and maintain maximal inhibition of disease-related biomarkers in patients with asthma 24- weeks after the last study dose. Results of the Phase 1b study demonstrated that verekitug is a potent inhibitor of TSLP-driven biology. It is the most advanced TSLP signaling inhibitor in global development and is the only agent with clinical data out to 32 weeks from a completed study in asthmatic patients. The company’s lead indication is asthma, a chronic disease of the lungs that affects approximately 350 million people worldwide and is often underdiagnosed and under-treated.1 Of the more than 25 million people in the U.S. living with asthma2, about 5-10% suffer from severe asthma. CRSwNP is a chronic disease of the upper airway that obstructs the sinuses and nasal passages. CRSwNP is highly comorbid with asthma, in fact up to 65% of patients with CRSwNP suffer from asthma.3 About TSLP and TSLPR Blockade Thymic Stromal Lymphopoietin (TSLP) is a cytokine that is a key driver of the inflammatory response in major allergic and inflammatory diseases, such as asthma, where disruption of TSLP signaling has been clinically validated as an effective therapeutic strategy. TSLP signaling is one of the first events in the inflammatory cascade stimulated by allergens, viruses, and other triggers. TSLP signaling activates downstream targets such as IL-4, IL-5, IL-13, IL-17 and IgE. Because TSLP is a target upstream in the inflammatory cascade, there is an opportunity to address disease at its root, prior to the influence of other disease-related cytokines. Inhibiting TSLP signaling by blocking the TSLP receptor presents an opportunity for a single treatment to impact the drivers of multiple pathological inflammatory processes across a broad set of diseases. About Upstream Bio At Upstream Bio we strive to reach the source of inflammation and conquer it. Our lead program, verekitug (UPB101), is a clinical-stage monoclonal antibody that inhibits the TSLP receptor. TSLP is a validated target positioned upstream of multiple signaling cascades that affect a variety of immune cells pivotal to common and rare diseases. We have completed Phase 1b in asthma and have initiated Phase 2 studies in both CRSwNP (Chronic rhinosinusitis with nasal polyps) and asthma in Q1 2024. We are leveraging our diverse roots and the team’s substantial industry experience to develop verekitug to ease the burden of inflammatory and allergic diseases on patients and their loved ones. _________________________________________________________________ 1 EEACI Global Atlas of Asthma, April 2021 2 American Lung Association, website, 2023 3 Bachert C, Bhattacharyya N, Desrosiers M, Khan AH. Burden of Disease in Chronic Rhinosinusitis with Nasal Polyps. J Asthma Allergy. 2021 Feb 11;14:127-134. doi: 10.2147/JAA.S290424. PMID: 33603409; PMCID: PMC7886239

ROCKVILLE, Md. and SUZHOU, China, Feb. 29, 2024 /PRNewswire/ -- Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, announces that the first participant has been dosed in Australia in a first-in-human (FIH) phase 1 clinical trial of IBI3002, a global first-in-class bispecific antibody targeting Interleukin 4 receptor α (IL-4Rα) and thymic stromal lymphopoietin (TSLP). This FIH study (NCT06213844) is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) (only in participants with asthma) of IBI3002 in healthy participants and participants with mild to moderate asthma, and to support further global clinical development of IBI3002. IBI3002 is a humanized bispecific antibody targeting cell surface IL-4Rα and the alarmin cytokine TSLP, discovered and developed by Innovent for the treatment of inflammatory diseases, including asthma. IL-4 receptors mediate the IL-4 signaling (both type 1 and type 2) and the IL-13 signaling (type 2). Both cytokine signaling pathways play key roles in the pathophysiology of type 2 (T2) inflammatory disorders1. TSLP is an epithelial cell-derived alarmin cytokine and triggers both T2 and non-T2 inflammation in asthma2. IBI3002 has high-efficient dual-blocking function on both IL-4Rα and TSLP. In-vitro assays have shown superiority over the marketed monoclonal antibodies to respective target. By targeting both IL-4Rα and TSLP, IBI3002 is hypothesized to have potential effect in suppressing T2 and non-T2 inflammation. The potential synergistic effect in suppressing T2 inflammation is believed to be the basis of its superior efficacy in the treatment of T2 inflammatory disorders. Dr. Lei Qian, Vice President of Clinical Development at Innovent, stated, "In the last few decades, knowledge about both pathophysiological mechanisms, clinical phenotypes and therapeutic options for asthma have significantly increased. In particular, the introduction of biologics for severe asthma paved the way to a true revolution in the field of asthma management, by potentially allowing a precision medicine approach. Targeting specific steps of the immune-inflammatory cascade through highly selective drugs represents a true revolution in the field of severe asthma management, and brings with it the potential of achieving optimal disease control in different severe asthma inflammatory phenotypes. We are looking forward to the development of this molecule in asthma and other inflammatory diseases." About Asthma Asthma is a heterogeneous disease driven by multiple immune cells, cytokines and inflammatory mediators, affecting all age groups. Characterized by variable symptoms of wheeze, shortness of breath, cough, and chest tightness, asthma is associated with chronic airway inflammation, reversible airflow limitation, and airway hyperresponsiveness3. According to the 2015 Global Burden of Disease (GBD) study, about 358 million people are suffering from asthma4. Asthma can be broadly classified as eosinophilic or non-eosinophilic on the basis of airway or peripheral blood cellular profiles. Eosinophilic inflammation is driven predominantly by T2 inflammation, including T-helper cells type 2 and group 2 innate lymphoid cells5. Compared with eosinophilic asthma, non-eosinophilic asthma is poorly understood6. Up to 10% of adults and 2.5% of children with asthma have severe asthma7. Patients with severe asthma have persistent symptoms or frequent exacerbations that require repetitive systemic glucocorticoid bursts or maintenance, despite adequate treatment with high-dose inhaled treatments8. In these patients, add-on treatment, which may include biologic therapies, is needed to reduce the disease burden2,3. About IBI3002 IBI3002 is a global first-in-class bispecific antibody targeting cell surface IL-4Rα and the alarmin cytokine TSLP. It has high-efficient dual-blocking function on both IL-4Rα and TSLP. In-vitro assays have shown superiority over the marketed monoclonal antibodies to respective targets. By simultaneously targeting IL-4Rα and TSLP, IBI3002 has the potential of treating several inflammatory disorders, including asthma. IL-4 is a central mediator of type 2 lymphocyte cell differentiation; it induces the production of type 2 associated cytokines such as IL-5, IL-9, IL-13, and/or type 2 related chemokines as thymus and activation-regulated chemokine (TARC/CCL17) and eotaxins-3. IL-4 involved in B cells regulated isotype class switching to produce serum IgE, and the eosinophils recruitment through IL-5 releasement. Although IL-13 displays some redundancies in these pro-inflammatory processes, it has additional roles in mediating goblet cell hyperplasia, mucus production, smooth muscle contractility, and airway hyperresponsiveness. Together, IL-4 and IL-13 play critical roles in T2 inflammation1. TSLP is an epithelial cell-derived alarmin cytokine that occupies an upstream position in the T2 inflammation induction and Th2 cells differentiation and maturation via IL-4, IL-5 and IL-13 production. TSLP is also believed to be a trigger of non-T2 inflammation in asthma 2. About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable illnesses. Its pioneering therapies to treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 3 new drug applications under the NMPA review, 4 assets in Phase III or pivotal clinical trials and 20 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit , or follow Innovent on Facebook and LinkedIn. Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s). Forward-looking statement This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions. The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect. References: 1. Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production[J]. Cytokine, 2015, 75(1): 14-24. 2. Brusselle G G, Koppelman G H. Biologic therapies for severe asthma[J]. New England Journal of Medicine, 2022, 386(2): 157-171. 3. Global Initiative for Asthma. 2023 GINA Report, Global Strategy for Asthma Management and Prevention. 2023. 4. GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 [published correction appears in Lancet Respir Med. 2017 Oct;5(10 ):e30]. Lancet Respir Med. 2017;5(9):691-706. 5. Gans MD, Gavrilova T. Understanding the immunology of asthma: Pathophysiology, biomarkers, and treatments for asthma endotypes. Paediatr Respir Rev. 2020;36:118-127. 6. Israel E, Reddel H K. Severe and difficult-to-treat asthma in adults[J]. New England Journal of Medicine, 2017, 377(10): 965-976. 7. Settipane RA, Kreindler JL, Chung Y, Tkacz J. Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States. Ann Allergy Asthma Immunol 2019; 123(6): 564-572.e3. 8. Caminati M, Vaia R, Furci F, Guarnieri G, Senna G. Uncontrolled Asthma: Unmet Needs in the Management of Patients. J Asthma Allergy. 2021;14:457-466. SOURCE Innovent Biologics