Geographic atrophy (GA) is a progressive form of age-related macular degeneration (AMD) that leads to severe visual impairment and central vision loss. Traditional treatment options for GA are limited, highlighting the need for new therapeutic approaches. In recent years, targeting the complement system has emerged as a promising strategy for the treatment of GA.

AREAS COVERED:

This expert opinion article reviews the investigational drugs inhibiting the complement cascade for the treatment of GA. Specifically, it focuses on the recent FDA approved pegcetacoplan, a C3 complement inhibitor, and avacincaptad pegol, a C5 complement inhibitor, highlighting their potential efficacy and safety profiles based on clinical trial data.

EXPERT OPINION:

FDA approval of intravitreal pegcetacoplan and avacincaptad pegol marks significant progress in the landscape of GA treatment. However, variable results from trials underscore the complex nature of GA and the importance of patient selection. Complement inhibition holds promise, but ongoing research is vital to refine treatment strategies and offer improved outcomes for GA patients.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Coronavirus Disease 2019-Associated Thrombotic Microangiopathy: A Single-Center Experience

Article

作者: Aleš-Rigler, Andreja ; Večerić-Haler, Željka ; Borštnar, Špela ; Malgaj Vrečko, Marija

Coronavirus disease 2019 (COVID-19) can lead to various multisystem disorders, including thrombotic microangiopathy (TMA). We present here eight patients with COVID-19-associated TMA who were treated at our center. Our aim was to summarize the demographic and clinical characteristics of the patients and discuss the possible role of COVID-19. One patient presented with thrombotic thrombocytopenic purpura (TTP) and seven with atypical hemolytic–uremic syndrome (aHUS.) Most patients had no obvious symptoms of COVID-19, and TMA occurred after viremia. Two patients had concomitant non-COVID-19-related triggers for TMA: exposure to tacrolimus and everolimus; first presentation of antiphospholipid syndrome. The patient with TTP was treated with therapeutic plasma exchange (TPE), steroids and caplacizumab, resulting in complete hematologic recovery. Six patients with aHUS were treated with TPE with or without steroids, four of whom received a C5 complement inhibitor and one an intravenous immunoglobulin. One patient with aHUS was treated with a C5 complement inhibitor and a steroid. We observed one partial and one complete recovery of renal function, while five patients experienced renal failure. There were no deaths. We believe that COVID-19 may act as a trigger for TMA in patients who have either pre-existing endothelial injury or an underlying predisposition to complement activation, and may also trigger autoimmune diseases. As a consequence of the different underlying pathophysiologies, the treatment of COVID-19-associated TMA requires a specific approach based on the subtype of the syndrome and possible concomitant triggers.

TRANSPLANT INTERNATIONAL

Normothermic Machine Perfusion Reconstitutes Porcine Kidney Tissue Metabolism But Induces an Inflammatory Response, Which Is Reduced by Complement C5 Inhibition

Article

作者: Thorgersen, Ebbe Billmann ; van Goor, Harry ; Christiansen, Dorte ; Jager, Neeltina M ; Pettersen, Kristin ; Schjalm, Camilla ; Maassen, Hanno ; Weiss, Marc G ; Jespersen, Bente ; Pischke, Søren E ; Sokolova, Marina ; Mollnes, Tom E ; Ludviksen, Judith Krey ; de Boer, Eline ; Leuvenink, Henri G D ; Liavåg, Olav M

Normothermic machine perfusion (NMP) is a clinical strategy to reduce renal ischemia-reperfusion injury (IRI). Optimal NMP should restore metabolism and minimize IRI induced inflammatory responses. Microdialysis was used to evaluate renal metabolism. This study aimed to assess the effect of complement inhibition on NMP induced inflammatory responses. Twenty-two pig kidneys underwent 18 h of static cold storage (SCS) followed by 4 h of NMP using a closed-circuit system. Kidneys were randomized to receive a C5-inhibitor or placebo during SCS and NMP. Perfusion resulted in rapidly stabilized renal flow, low renal resistance, and urine production. During SCS, tissue microdialysate levels of glucose and pyruvate decreased significantly, whereas glycerol increased (p < 0.001). In the first hour of NMP, glucose and pyruvate increased while glycerol decreased (p < 0.001). After 4 h, all metabolites had returned to baseline. Inflammatory markers C3a, soluble C5b-9, TNF, IL-6, IL-1β, IL-8, and IL-10 increased significantly during NMP in perfusate and kidney tissue. C5-inhibition significantly decreased perfusate and urine soluble C5b-9 (p < 0.001; p = 0.002, respectively), and tissue IL-1β (p = 0.049), but did not alter other inflammatory markers. Microdialysis can accurately monitor the effect of NMP on renal metabolism. Closed-circuit NMP induces inflammation, which appeared partly complement-mediated. Targeting additional immune inhibitors should be the next step.

项与 C5 Inhibitor (Nimble Therapeutics) 相关的新闻（医药）

2024-12-02

·Business Wire

Rallybio to Initiate RLYB116 Confirmatory Clinical PK/PD Study in Second Quarter 2025

NEW HAVEN, Conn.--( BUSINESS WIRE )--Rallybio Corporation (Nasdaq: RLYB), a clinical-stage biotechnology company translating scientific advances into transformative therapies for patients with devastating rare diseases, today announced results of new biomarker characterization analyses and data from the recently completed manufacturing process enhancements for RLYB116, the Company’s innovative, once-weekly, small volume, subcutaneously injected C5 inhibitor in development for the treatment of patients with complement-mediated diseases. Based on this recently completed work, Rallybio believes that RLYB116 has the potential to be a best-in-class C5 inhibitor and intends to initiate a confirmatory clinical pharmacokinetic/pharmacodynamic (PK/PD) study in the second quarter of 2025. “Recently completed efforts to better understand the disconnect between the compelling preclinical potency data of RLYB116 and the results of the Phase 1 study indicate that RLYB116 achieved greater complement inhibition in the Phase 1 study than initially reported,” said Stephen Uden, M.D., Chief Executive Officer of Rallybio. “This, together with successful manufacturing process enhancements to further improve the tolerability profile, uniquely positions RLYB116 as a potentially best-in-class C5 inhibitor that can meet patient demand for a once-weekly, small volume, subcutaneous, self-administered therapeutic. We look forward to bringing RLYB116 into a confirmatory clinical PK/PD study in the second quarter of 2025 and expect RLYB116 to demonstrate complete and sustained complement inhibition and an improved tolerability profile.” Following the completion of the RLYB116 Phase 1 single- and multiple-ascending dose (SAD/MAD) study in the fourth quarter of 2023, Rallybio conducted a series of biomarker characterization analyses. These analyses indicate the RLYB116 assay used to measure free C5 overestimated the levels of free C5 by approximately ten-fold, indicating that RLYB116 produced greater complement inhibition than initially reported. Additionally, Rallybio completed manufacturing process enhancements in the third quarter of 2024 that are expected to further improve the tolerability of RLYB116. Based on the results of enhanced analytical techniques, including mass spectrometry, process enhancements have successfully further purified the RLYB116 drug substance. As a result, RLYB116 is expected to have a favorable tolerability profile at doses at and above those evaluated in the Phase 1 MAD study. Rallybio plans to initiate a RLYB116 confirmatory clinical PK/PD study in the second quarter of 2025 to demonstrate improved tolerability as well as complete and sustained complement inhibition. This single-blind multiple ascending dose study will evaluate a 4-week treatment duration that will include two cohorts of 8 participants each. It is planned that Cohort 1 will evaluate weekly dosing of 150 mg and Cohort 2 will evaluate weekly dosing of 225 mg. Follow-up will continue for 10 weeks after the conclusion of treatment. Webcast Information The live webcast will be accessible through the Events and Presentations section of Rallybio’s investor relations website at https://investors.rallybio.com . A replay and accompanying slides of the webcast will be available on the Rallybio website for 30 days following the event. About RLYB116 Phase 1 Study RLYB116 is an innovative, once-weekly, small volume, subcutaneously injected C5 inhibitor in development for the treatment of patients with complement-mediated diseases. A Phase 1 single- and multiple-ascending dose (SAD/MAD) study was conducted in healthy participants. The MAD portion of the study had an adaptive single-blind design with a 4-week treatment duration and 10-week follow-up period. The study was designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RLYB116 and included 4 cohorts: Cohort 1 (weekly dosing of 100 mg), Cohort 2 (3 doses of 100 mg the first week followed by weekly dosing), Cohort 3 (150 mg weekly dosing reduced to 125 mg weekly dosing), and Cohort 4 (75 mg twice the first week followed by 100 mg twice per week). The study was completed in the fourth quarter of 2023. About Rallybio Rallybio (NASDAQ: RLYB) is a clinical-stage biotechnology company with a mission to develop and commercialize life-transforming therapies for patients with severe and rare diseases. Rallybio has built a broad pipeline of promising product candidates aimed at addressing diseases with unmet medical need in areas of maternal fetal health, complement dysregulation, hematology, and metabolic disorders. The Company has two clinical stage programs: RLYB212, an anti-HPA-1a antibody for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT) and RLYB116, a C5 inhibitor with the potential to treat several diseases of complement dysregulation, as well as additional programs in preclinical development. Rallybio is headquartered in New Haven, Connecticut. For more information, please visit www.rallybio.com and follow us on LinkedIn and Twitter . Forward-Looking Statements This press release contains forward-looking statements that are based on our management’s beliefs and assumptions and on currently available information. All statements, other than statements of historical facts contained in this press release are forward-looking statements. In some cases, forward-looking statements can be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements concerning the timing of initiation of the planned RLYB116 confirmatory clinical PK/PD study, the expected dosing for RLYB116 in future clinical trials and whether RLYB116 will produce complete and sustained inhibition of C5, the frequency of administration of RLYB116, whether RLYB116 will be a best-in-class C5 inhibitor, whether the RLYB116 manufacturing process enhancements will improve tolerability or be successful at the desired doses, and our characterization of the actual level of complement inhibition delivered by RLYB116. The forward-looking statements in this press release are only predictions and are based largely on management’s current expectations and projections about future events and financial trends that management believes may affect Rallybio’s business, financial condition and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions, including, but not limited to, our ability to successfully initiate and conduct our planned clinical trials, including the RLYB116 confirmatory clinical PK/PD study, the FNAIT natural history study, and the Phase 2 clinical trial for RLYB212, and complete such clinical trials and obtain results on our expected timelines, or at all, whether our cash resources will be sufficient to fund our operating expenses and capital expenditure requirements and whether we will be successful raising additional capital, our ability to enter into strategic partnerships or other arrangements, competition from other biotechnology and pharmaceutical companies, and those risks and uncertainties described in Rallybio’s filings with the U.S. Securities and Exchange Commission (SEC), including Rallybio’s Quarterly Report on Form 10-Q for the period ended September 30, 2024, and subsequent filings with the SEC. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Except as required by applicable law, we are not obligated to publicly update or revise any forward-looking statements contained in this press release, whether as a result of any new information, future events, changed circumstances or otherwise.

临床1期临床结果临床2期

2020-04-01

·SYNAPSE

UCB completes the acquisition of Ra Pharmaceuticals – to deliver differentiated therapies to patients

· The transaction, which was announced October 10, 2019, will enhance UCB’s potential to be a leader in myasthenia gravis by adding zilucoplan, a peptide inhibitor of complement component 5 (C5) currently in phase 3, to the UCB pipeline alongside rozanolixizumab, UCB’s FcRn targeting antibody which is also in phase 3 · Zilucoplan will enhance UCB’s pipeline and Ra Pharma’s ExtremeDiversity[™ ]technology platform will accelerate UCB’s long-term innovation capabilities · The acquisition is expected to enable accelerated top and bottom line company growth from 2024 onwards · Innovative research and development unit in Cambridge, MA adds to UCB’s network and presence in Massachusetts and the greater Boston area of the U.S. · Total transaction cash value of approximately US$ 2.3 billion / € 2.1 billion based on US$ 48 in cash per Ra Pharma share and taking Ra Pharma cash and settlement of acquisition related expenses into consideration · The closing of this acquisition leads to an update of UCB’s 2020 financial guidance and the mid-term target Brussels (Belgium) 2 April 2020 – 15:00 (CEST) – UCB today announced that the acquisition of Ra Pharmaceuticals, Inc. has been successfully completed and Ra Pharma is now a wholly-owned subsidiary of UCB. The former Ra Pharma shareholders received US$ 48 in cash for each Ra Pharma share held at closing. Jean-Christophe Tellier, CEO UCB said: “In the last 15 months, we made several significant steps on UCB’s strategic growth path, namely the “Accelerate and Expand” phase. This acquisition is a key part of this progress and an excellent strategic fit with UCB’s strategy. Ra Pharma builds upon our collective strengths and talents and adds to our strong internal growth opportunities. Zilucoplan gives us the opportunity to become a leader in treating people living with myasthenia gravis, an auto-antibody mediated neurological orphan disease with high unmet medical need. The acquisition also strengthens our neurology and immunology franchises with late and early-stage pipeline projects and adds a highly productive technology platform to our innovation engine. Financial guidance updated - The closing of this acquisition leads to an update of UCB’s 2020 financial guidance – as announced with the FY 2019 results press release on 20 February 2020. For 2020, UCB is aiming for revenues in the range of € 5.05 – 5.15 billion thanks to the current core product growth and new patient populations being served. UCB will continue to advance its strong development pipeline to offer potential new solutions for patients and to explore complementary external opportunities. Hence, the underlying profitability, rEBITDA, in the range of 26-27% of revenue, will reflect the high R&D investment level, including the investment for the Ra Pharma pipeline. Core earnings per share are therefore now expected in the range of € 4.40 – 4.80 based on an average of 187 million shares outstanding. The inclusion of Ra Pharma will be dilutive to UCB’s mid-term earnings level due to R&D investments. As a result, the mid-term target of UCB reaching a rEBITDA ratio (to revenue) of 31% moves to 2022 from 2021 as previously guided. The acquisition is expected to be Core EPS accretive from 2024 onwards and to enable accelerated top and bottom line growth for UCB from 2024 onwards. The updated financial guidance above does not reflect any potential impacts from the evolving COVID-19 pandemic. The company is following these developments diligently to assess the financial significance of this pandemic to UCB. Funding The acquisition of Ra Pharma was financed by a combination of a US$ 2.07 billion bank term loan and existing cash resources. The bank term loan had initially been arranged and underwritten by BNP Paribas Fortis and Bank of America Merrill Lynch and was successfully syndicated in November 2019. About Ra Pharmaceuticals, Inc. Ra Pharma, now a wholly-owned subsidiary of UCB, is a clinical-stage biopharmaceutical company leveraging a proprietary peptide chemistry platform to develop novel therapeutics for the treatment of serious diseases caused by excessive or uncontrolled activation of the complement system, a critical component of the innate immune system. The company’s ExtremeDiversity™ platform enables the production of synthetic macrocyclic peptides combining the diversity and specificity of antibodies with the pharmacological properties of small molecules. About Zilucoplan The phase 3 product candidate, zilucoplan, is a once-daily self-administered, subcutaneous peptide inhibitor of C5 and is currently being tested in phase 3 for the treatment of gMG with top-line results expected in early 2021. Further indications that are potentially addressable by zilucoplan include immune-mediated necrotizing myopathy (IMNM), amyotrophic lateral sclerosis (ALS) and other tissue-based complement-mediated disorders with high unmet medical need. In early December 2019, Ra Pharma started the Phase 2 clinical trial of zilucoplan for the treatment of immune-mediated necrotizing myopathy (IMNM). Zilucoplan was selected as one of the first drugs to be tested in a multi-center amyotrophic lateral sclerosis (ALS) platform study sponsored by the Sean M. Healey & AMG Center for ALS at Mass General. An extended release formulation of zilucoplan, as well as a potential first-in-class oral small molecule C5 inhibitor, are in early development. Zilucoplan is in clinical development and is not approved in any region of the world. About Generalized Myasthenia Gravis (gMG) Generalized myasthenia gravis is an unpredictable, chronic auto-immune condition in which auto-antibodies attack specific proteins in the neuro-muscular junction. This disrupts the way that nerves can communicate with muscles, resulting in muscle weakness and fatigue. Both men and women are impacted equally, and it can occur at any age and in any race. Myasthenia Gravis is a rare disease impacting almost 200,000 patients in the US, EU and Japan (Gilhus N, N Engl J Med 2016;375:2570-812015). Those living with gMG can experience a variety of symptoms, including drooping eyelids and double vision as well as severe muscular weakness that can result in life threatening weakness of muscles of respiration. About UCB UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 7 500 people in approximately 40 countries, UCB generated revenue of € 4.9 billion in 2019. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news For further information – Investor Relations Antje Witte Investor Relations, UCB T +32.2.559.94.14 antje.witte@ucb.com Isabelle Ghellynck, Investor Relations, UCB T+32.2.559.9588, isabelle.ghellynck@ucb.com Corporate Communications Laurent Schots Media Relations, UCB T+32.2.559.92.64 Laurent.schots@ucb.com Forward looking statements UCB This press release contains forward-looking statements based on current plans, estimates and beliefs of management. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, political, regulatory or clinical results and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions which could delay, divert or change any of them this year and the next several years, that are difficult to predict, may be beyond UCB’s control and could cause UCB’s actual future financial results, goals, plans and objectives to differ materially from those that may be expressed in, or implied by, such forward-looking statements contained in this press release. Important factors that could result in such differences include: the global spread and impact of COVID-19, changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, product liability claims, challenges to patent protection for products or product candidates, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws and hiring and retention of its employees. Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction. UCB is providing this information as of the date of this document and expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report a change in its expectations. There is no guarantee that new product candidates in the pipeline will progress to product approval or that new indications for existing products will be developed and approved. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences between the partners. Also, UCB or others could discover safety, side effects or manufacturing problems with its products after they are marketed. Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement. The updated financial guidance above does not reflect any potential impacts from the evolving COVID-19 pandemic. The company is following the development diligently to assess the financial significance of this pandemic to UCB.

临床2期并购临床3期

100 项与 C5 Inhibitor (Nimble Therapeutics) 相关的药物交易

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