IL-5

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

↵ CHAPEL HILL, N.C.--(BUSINESS WIRE)-- Areteia Therapeutics, Inc. (“Areteia”) today announced the appointment of Daniel Becker to the Areteia Board of Directors, effective immediately. Dr. Becker will serve as a member of the audit committee of the board. This press release features multimedia. View the full release here: (Photo: Business Wire) “I am excited that Dan has been appointed to our board,” said Jorge Bartolome, President and Chief Executive Officer of Areteia. “He is an incredibly accomplished executive whose depth of biotech experience, proven leadership and scientific expertise will be invaluable to me and the Board of Directors as we focus on delivering on the Company’s strategy and further advancing the Phase III program for dexpramipexole, the first potential oral drug for eosinophilic asthma.” Commenting on his appointment, Dr. Becker said, “I am thrilled to serve as a director and look forward to continuing to work with Jorge and the team. This is a compelling opportunity to address a high unmet need for severe asthmatics by bringing a new oral medicine to market and offer patients and health systems an alternative to injectable biologics.” Dr. Becker is a managing director at Access Biotechnology. Prior to joining Access in 2019, he was a Principal at New Leaf Venture Partners, where he played a key role in multiple private and public biopharma investments, and a Principal in the Health Care practice at the Boston Consulting Group, where he led projects across the health care sector with an emphasis on biopharma R&D. Dr. Becker trained clinically in internal medicine and nephrology at Brigham and Women’s Hospital and Massachusetts General Hospital and was a Research Fellow at Harvard Medical School. He obtained both his M.D. and Ph.D. (Cellular and Molecular Biology) degrees from the University of Michigan and received his B.S. in Physiology from the University of Illinois at Urbana-Champaign. About Access Biotechnology Access Biotechnology is the life science investment arm of Access Industries, a privately held US-based holding company with global long-term holdings. Access Biotechnology invests in transformative therapies for conditions with high unmet needs and that have the potential to meaningfully impact human health. It has a broad scope, flexible mandate, and long-term orientation. For more information, please visit: About Areteia Therapeutics Areteia Therapeutics, Inc. (areteiatx.com) is a clinical stage biotechnology company whose purpose is to develop and deliver novel Inflammation and Immunology therapies that put respiratory patients in better control of their disease and back in control of their lives. Our initial focus is developing the first potential oral drug for severe eosinophilic asthma. Areteia’s lead drug candidate is dexpramipexole, and if approved, will be a first-in-class oral eosinophil maturation inhibitor that targets eosinophilic inflammation by lowering blood and tissue eosinophils. Areteia was created by Population Health Partners and Knopp Biosciences. A syndicate of leading life sciences and strategic investors led by Bain Capital Life Sciences with participation from Access Biotechnology, GV, ARCH Venture Partners, Saturn Partners, Sanofi, Maverick Capital, and Population Health Partners, committed to invest up to $350 million in Series A financing to establish Areteia and advance dexpramipexole through Phase III clinical trials, secure commercial supply, and pursue potential next-generation medicines. $75MM in expanded financing has now been committed by Viking Global Investors, Marshall Wace and the original syndicate. As a result, the Series A total financing now commits up to $425MM. Areteia has initiated late-stage development of dexpramipexole in eosinophilic asthma, including three Phase III clinical trials in partnership with Population Health Partners’ development unit, Validae Health. About Dexpramipexole Dexpramipexole is an oral small molecule eosinophil lowering drug currently in Phase III development for eosinophilic asthma. Dexpramipexole inhibits the maturation of eosinophils in the bone marrow, based on evidence from cell cultures and human biopsies, thereby lowering peripheral blood eosinophil levels. Most recently in a Phase II study in patients with moderate-to-severe eosinophilic asthma, treatment with dexpramipexole resulted in a significant, dose-dependent reduction in blood absolute eosinophil count at all doses tested compared to placebo. Dexpramipexole was well tolerated in the trial, with adverse events balanced across treatment and placebo groups, no serious adverse events, and no adverse events leading to discontinuation. About Eosinophilic Asthma Asthma disrupts the lives of more than a quarter of a billion people worldwide. More than half of asthma patients have eosinophilic asthma, which is driven by an oversupply of eosinophils, a type of white blood cell, in blood and tissue. By inhibiting the maturation of eosinophils, oral dexpramipexole acts to lower eosinophils. Similarly, currently approved injectable anti-IL-5/5R biologic therapies provide clinical benefit through eosinophil lowering. The asthma biologic market is valued today at around $8 billion, with IL-5 biologic therapies approaching $4 billion of that figure. If approved as a first-to-market oral, dexpramipexole could provide a compelling alternative to injectable biologics, and could potentially expand the use of targeted therapy to address Type 2 eosinophilic inflammation in asthma. View source version on businesswire.com: Contacts Mark Kreston Mark.Kreston@areteiatx.com Tamsin Berry Tamsin.Berry@areteiatx.com Source: Areteia Therapeutics, Inc. Smart Multimedia Gallery Photo (Photo: Business Wire) Logo View this news release and multimedia online at: