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- | Fabhalta (iptacopan) / Novartis
Journal: Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy. (Pubmed Central) - Oct 25, 2024
P3
Among patients with IgA nephropathy, treatment with iptacopan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo. (Funded by Novartis; APPLAUSE-IgAN ClinicalTrials.gov number, NCT04578834.).
- Soliris (eculizumab) / AstraZeneca
Postkidney Transplant Thrombotic Microangiopathy Effectively Treated with Eculizumab in a Tertiary Care Center () - Oct 12, 2024 - Abstract #KIDNEYWEEK2024KIDNEY_WEEK_5439;
Prompt eculizumab therapy may benefit PT-TMA irrespective of etiology, especially those developing early post-transplant, suggesting the role of complement activation. A prospective study on the effectiveness of eculizumab in treating PT-TMA from different etiologies is important to inform further practice..
- | Journal: Complement Biosensors Identify a Classical Pathway Stimulus in Complement-Mediated Thrombotic Microangiopathy. (Pubmed Central) - Oct 2, 2024
Using specific complement pathway inhibitors, this model identifies IgM-driven classical pathway stimulus during both acute disease and in many patients during clinical remission. This provides a potential explanation for ~50% of CM-TMA patients who lack an alternative pathway "driving" variant and suggests at least a subset of CM-TMA is characterized by a breakdown of IgM immunologic tolerance.
- Soliris (eculizumab) / AstraZeneca
Use of Eculizumab in the Management of Drug-Induced Thrombotic Microangiopathy: A Case Report (Exhibit Hall, Convention Center) - Sep 23, 2024 - Abstract #KIDNEYWEEK2024KIDNEY_WEEK_4314;
Skin biopsy revealed +ve staining for C5b-9 in 8-10 dermal capillaries.Patient was started on Eculizumab 900mg on day 1.There was immediate improvement in hematological markers; however,sCr continued to rise upto 14 over next few days.She underwent a kidney biopsy(10 days after presentation),which revealed severe acute tubular injury with intraluminal material suggestive of hemoglobin casts,diffuse C5b-9 positivity, and focal subacute endothelial injury involving glomeruli with thickening of capillary walls.Patient continued to receive Eculizumab weekly then biweekly with sCr trending down to 1.0 over the course of a month. This case highlights the immediate reversal of microangiopathic hemolytic anemia with the use of Eculizumab.Early use of eculizumab likely reduced the severity of kidney injury and aided in the complete recovery of kidney function.
- Empaveli (pegcetacoplan SC) / Apellis, SOBI
Long-Term Safety and Efficacy of Pegcetacoplan in Patients with C3 Glomerulopathy or Primary Immune-Complex Membranoproliferative Glomerulonephritis: The Long-Term VALE Extension Study (Exhibit Hall, Convention Center) - Sep 23, 2024 - Abstract #KIDNEYWEEK2024KIDNEY_WEEK_4287;
P3
This case highlights the immediate reversal of microangiopathic hemolytic anemia with the use of Eculizumab.Early use of eculizumab likely reduced the severity of kidney injury and aided in the complete recovery of kidney function. The VALE extension will assess long-term efficacy and safety of PEG in C3G and primary IC-MPGN.
- | Journal: Urine complement proteins are associated with kidney disease progression of type 2 diabetes in Korean and American cohorts. (Pubmed Central) - Sep 1, 2024
Urinary proteomic profiling confirms the association between the complement pathway and rapid DKD progression in two independent cohorts. These results suggest a need to further investigate complement pathway inhibition as a novel treatment for DKD.
- | CSL040 / CSL Behring
Journal: Mechanistic insights into complement pathway inhibition by CR1 domain duplication. (Pubmed Central) - Jul 26, 2024
We have previously used our knowledge of this domain structure to identify CSL040, a soluble extracellular fragment of CR1 containing the long homologous repeat (LHR) domains A, B, and C. CSL040 retains the ability to bind both C3b and C4b but is also a more potent complement inhibitor than other recombinant CR1-based therapeutics...Interestingly, multiplication of the C4b-binding LHR-A domain resulted in only minor increases in classical/lectin pathway inhibitory activity. The CR1 duplication variants characterized in these in vitro potency assays, as well as in affinity in solution C3b and C4b binding assays, not only provides an opportunity to identify new therapeutic molecules, but also additional mechanistic insights to the multiple interactions between CR1 and C3b/C4b.
- | Journal: Complement Biosensors Identify a Classical Pathway Stimulus in Complement-Mediated Hemolytic Uremic Syndrome. (Pubmed Central) - Jun 10, 2024
This provides a potential explanation for ~50% of CM-HUS patients who lack an alternative pathway "driving" variant and suggests at least a subset of CM-HUS is characterized by a breakdown of IgM immunologic tolerance. CM-HUS has a CP stimulus driven by polyreactive IgM, addressing the mystery of why 40% of CM-HUS lack complement specific variantsComplement biosensors and the bioluminescent mHam can be used to aid in diagnosis of CM-HUS and monitor complement inhibitor therapy.
- | Undisclosed factor H therapeutic / Eleva
Journal: Moss-produced human complement factor H with modified glycans has an extended half-life and improved biological activity. (Pubmed Central) - May 27, 2024
Furthermore, CPV-104 showed comparable functionality to serum-derived FH in vitro, as well as similar performance in ex vivo assays involving samples from patients with atypical hemolytic uremic syndrome, C3 glomerulopathy and paroxysomal nocturnal hematuria. CPV-104 - the human FH analog expressed in moss - will therefore allow the treatment of complement-associated human diseases by rebalancing instead of inhibiting the complement cascade.
- Delivery to the Suprachoroidal Space of an AAV Vector Encoding a Complement Pathway Inhibitor as a Possible Treatment for Dry Age-Related Macular Degeneration (Exhibit Hall) - Apr 2, 2024 - Abstract #ASGCT2024ASGCT_2237;
- AAV Vectorized Antibody Fragment-Mediated Dual Complement Pathway Inhibition for the Treatment of AMD (Room 318-323) - Apr 2, 2024 - Abstract #ASGCT2024ASGCT_1780;
- Thrombotic microangiopathy (TMA) response during index atypical haemolytic uremic syndrome (aHUS) hospitalisation (Focussed Oral Room 2) - Mar 23, 2024 - Abstract #ERAEDTA2024ERA_EDTA_1804;
Small sample size limited assessment of clinical characteristics associated with complete TMA response; however, achievement of each TMA response criterion was associated with unique clinical and patient characteristics. Future efforts should focus on characterising patients with aHUS at high risk at discharge and on developing novel precision therapies to improve outcomes.
- || Soliris (eculizumab) / AstraZeneca
P4 data, Journal: Eculizumab treatment in paediatric patients diagnosed with aHUS after haematopoietic stem cell transplantation: a HSCT-TMA case series from Japanese aHUS post-marketing surveillance. (Pubmed Central) - Mar 11, 2024
In this analysis, eculizumab showed benefit in over half of this paediatric patient population. Ongoing clinical studies are expected to optimize the treatment regimen of terminal complement pathway inhibitor, and it may become a therapeutic option for paediatric HSCT-TMA in the future.
- Fabhalta (iptacopan) / Novartis
PHARMACOKINETICS OF SINGLE DOSES OF IPTACOPAN (MON-083; Exhibition Hall and Main Foyer) - Mar 8, 2024 - Abstract #ISNWCN2024ISN_WCN_816;
A 200 mg twice daily (BID) dose would be expected to result in an iptacopan concentration of ?1000 ng/mL over the dosing interval, and thus near maximal alternative complement pathway inhibition over this time. These results support the iptacopan clinical dose of 200 mg BID and provide the promise of durable, orally-dosed alternative complement pathway inhibition in patients on iptacopan therapy.This abstract was also submitted for the NKF'23 congress.
- | Preclinical, Journal: GenX analogs exposure induced greater hepatotoxicity than GenX mainly via activation of PPAR? pathway while caused hepatomegaly in the absence of PPAR? in female mice. (Pubmed Central) - Jan 14, 2024
receptor or not. These chemicals, especially PFDMO2HpA and PFDMO2OA, may not be appropriate PFOA alternatives.
- || Fabhalta (iptacopan) / Novartis
Biomarker, Clinical, P2 data, Journal: Results of a randomized double-blind placebo-controlled Phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy. (Pubmed Central) - Jan 8, 2024
P2, P3
Iptacopan was well-tolerated, with no reports of deaths, treatment-related serious adverse events or bacterial infections, and led to strong inhibition of alternative complement pathway activity and persistent proteinuria reduction in patients with IgAN. Thus, our findings support further evaluation of iptacopan in the ongoing Phase 3 trial (APPLAUSE-IgAN; NCT04578834).
- || Syfovre (pegcetacoplan intravitreal) / Apellis
Review, Journal: Treatment of dry age-related macular degeneration: A review. (Pubmed Central) - Nov 14, 2023
Two intravitreal anti-complement factors (pegcetacoplan and avacincaptad pegol) have recently shown phase 3 clinical trial evidence of a reduction in the growth of geographic atrophy. In this review, we provide an update on treatment options currently undergoing clinical research trials for the management of dAMD and preventing the progression of Geographic Atrophy (GA).
- || Review, Journal: A narrative review of potential drug treatments for nephritis in children with IgA vasculitis (HSP). (Pubmed Central) - Nov 13, 2023
In this review, we provide an update on treatment options currently undergoing clinical research trials for the management of dAMD and preventing the progression of Geographic Atrophy (GA). Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab.
- Fabhalta (iptacopan) / Novartis
Setting Cost-Effective Price Thresholds before FDA Approval: Cost-Effectiveness of Iptacopan Monotherapy Versus Standard-of-Care Anti-C5 Therapy in Transfusion-Dependent, Treatment-Experienced Adult Patients with Paroxysmal Nocturnal Hemoglobinuria in the United States (Halls G-H (San Diego Convention Center)) - Nov 3, 2023 - Abstract #ASH2023ASH_6510;
If the monthly price is no more than 149% of SOC, iptacopan monotherapy can be a cost-effective therapeutic option for transfusion-dependent, treatment-experienced patients with PNH. This is achieved by increasing the proportion of transfusion-independence in this patient population and, in turn, decreasing the burden of both the risks and costs associated with health resource utilization for patients with PNH.
- KP104 / Kira Pharma
KP104, a Bifunctional C5 Antibody/Factor H Fusion Protein, Effectively Controls Both Intravascular and Extravascular Hemolysis: Interim Results from a Phase 2 Study in Complement Inhibitor-N... (SDCC - Room 7) - Nov 3, 2023 - Abstract #ASH2023ASH_3247;
P2
The findings provide compelling clinical evidence that a bifunctional inhibitor targeting the AP and TP can properly address the current treatment gaps associated with single complement pathway inhibitors, potentially eliminating the need for cumbersome and costly combination therapies (Notaro et al. N Engl J Med 2022;387:160-6).
- || CSL040 / CSL Behring
Review, Journal: The Molecular Mechanisms of Complement Receptor 1-It Is Complicated. (Pubmed Central) - Oct 28, 2023
Evidence for the interaction of CR1 with additional ligands such as C1q will also be reviewed. Finally, we will bring the mechanistic understanding of CR1 activity together to provide an explanation for the differential complement pathway inhibition recently observed with CSL040, a soluble CR1-based therapeutic candidate in pre-clinical development.
- | Journal: Shiga toxin targets the podocyte causing hemolytic uremic syndrome through endothelial complement activation. (Pubmed Central) - Oct 21, 2023
Finally, we will bring the mechanistic understanding of CR1 activity together to provide an explanation for the differential complement pathway inhibition recently observed with CSL040, a soluble CR1-based therapeutic candidate in pre-clinical development. This study potentially explains why systemic Stx exposure targets the glomerulus and supports the early use of terminal complement pathway inhibition in this devastating disease.
- Enjaymo (sutimlimab) / Sanofi
Sutimlimab Provides Sustained Improvements in Patient-Reported Outcomes and Quality of Life in Patients with Cold Agglutinin Disease: Open-label Extension of the Randomized, Phase 3 CADENZA Study (Y1) - Sep 30, 2023 - Abstract #DGHO2023DGHO_1474;
P3
This study potentially explains why systemic Stx exposure targets the glomerulus and supports the early use of terminal complement pathway inhibition in this devastating disease. Continued inhibition of the classical CP with SUT therapy results in meaningful long-term improvement in fatigue and PROs beyond one year.
- Enjaymo (sutimlimab) / Sanofi
Sustained Complement C1s Inhibition with Sutimlimab in Patients With Cold Agglutinin Disease Results in Continued Efficacy During Part B of the Randomized Placebo-Controlled Phase 3 CADENZA Study (NCT03347422) (X2) - Sep 30, 2023 - Abstract #DGHO2023DGHO_1212;
P3
Continued inhibition of the classical CP with SUT therapy results in meaningful long-term improvement in fatigue and PROs beyond one year. Long-term SUT maintained mean Hb levels >11 g/dL, normalized bilirubin, and improved FACIT-Fatigue scores with a favorable safety profile.
- || Review, Journal: Complement in immune thrombocytopenia (ITP): The role of complement in refractory ITP. (Pubmed Central) - Sep 26, 2023
A recent early-phase clinical trial of a classical complement pathway inhibitor has demonstrated efficacy in a subset of ITP patients refractory to conventional immune modulation. In this review, we will analyse the role of complement in refractory ITP.
- Current Data in the Therapeutic Management of CAD: Targeted therapies: complement pathway inhibition (Marriott Marquis San Diego Marina, San Diego Ballroom AB; Virtual) - Sep 23, 2023 - Abstract #ASH2023ASH_471;
Supported by Sanofi. Provided by Clinical Care Options, LLC.
- | Journal: The Functional Roles and the Potential as Drug Targets of Glycoproteins Regulating Complement and Coagulation Pathways (Pubmed Central) - Sep 7, 2023
Crry dysfunction promotes the activation of C on the surface of endothelial cells. The prevention of C3 cleavage on endothelial cells might be a useful therapy targeting acute lung injury.
- | Preclinical, Journal: Ldlr-/-.Leiden mice develop neurodegeneration, age-dependent astrogliosis and obesity-induced changes in microglia immunophenotype which are partly reversed by complement component 5 neutralizing antibody. (Pubmed Central) - Jul 17, 2023
The anti-C5 treatment restored the HFD-induced effect on molecular pathways to a large extent. This study shows that the Ldlr-/-.Leiden mouse model is suitable to study brain histopathology and associated biological processes in a context of obesity and provides evidence of the potential therapeutic value of anti-complement therapy against obesity-induced neuroinflammation.
- ||| lampalizumab (RG7417) / Roche
P3 data, Journal: Alternative Complement Pathway Inhibition by Lampalizumab: Analysis of Data From Chroma and Spectri Phase III Clinical Trials. (Pubmed Central) - May 25, 2023
Lampalizumab inhibited the alternative complement pathway in the eyes of patients with GA; however, this did not translate into a measurable reduction in either classical or total complement activity, based on absence of changes in C4 and C3 processing, respectively. Proprietary or commercial disclosure may be found after the references.
- | Soliris (eculizumab) / AstraZeneca
Journal: Atypical Hemolytic Uremic Syndrome in a Pregnant Patient with a Thrombomodulin Gene Variant Treated with Plasma Exchange and Eculizumab. (Pubmed Central) - May 4, 2023
CONCLUSIONS This case shows the potential of severe renal manifestation of aHUS, and the need for a kidney biopsy in cases of severe uncontrolled hypertension presenting with kidney injury. If evidence of aHUS is found, prompt treatment with plasma exchange and eculizumab should be initiated.
- || SAR445088 / Sanofi
P1 data, Journal: First-in-Human Study with SAR445088-A Novel Selective Classical Complement Pathway Inhibitor. (Pubmed Central) - Apr 12, 2023
In summary, SAR445088 was well tolerated and had favorable PD and PK profiles after single (IV or SC) and multiple (SC) doses in humans. These findings warrant further clinical investigations in patients with classical complement-mediated disorders.
- Development of AAV-Expressed C5 Inhibitor to Locally Suppress Complement Pathway Activation in the Eye as a Potential Treatment for Dry Age-Related Macular Degeneration (Board No. 364) - Apr 6, 2023 - Abstract #ASGCT2023ASGCT_553;
All TPs tested showed high levels of expression and bioactivity. Collectively, our data support the potential of vectorized C5 inhibitors as a treatment for dry AMD.
- Enjaymo (sutimlimab) / Sanofi
Inhibition of complement C1s with sutimlimab in patients with cold agglutinin disease (CAD): 2-Year follow-up from the CARDINAL Study (Walker Hall) - Mar 31, 2023 - Abstract #ICKSH2023ICKSH_165;
P3
This abstract was previously presented at EHA 2022. Keyword : Cold aglutinin disease, Sutimlimab, CARDINAL study, Hemolytic markers, FACIT-Fatigue score
- iptacopan (LNP023) / Novartis
ALTERNATIVE COMPLEMENT PATHWAY PHARMACODYNAMICS OF IPTACOPAN () - Mar 28, 2023 - Abstract #ISNWCN2023ISN_WCN_1214;
Finally, even one day after stopping iptacopan 200 mg BID treatment, >70% inhibition was still present. These results support the iptacopan clinical dose of 200 mg BID and provide the promise of durable alternative pathway inhibition in patients on iptacopan therapy.
- | Enjaymo (sutimlimab) / Sanofi
Journal: Safety and Efficacy of Classical Complement Pathway Inhibition with Sutimlimab in Chronic Immune Thrombocytopenia. (Pubmed Central) - Mar 21, 2023
P1
These results demonstrate that in some ITP patients autoantibodies activate the classical complement pathway, accelerating platelet destruction or impairing platelet production, contributing to treatment failure. C1s inhibition may be a safe and beneficial therapeutic approach for patients with chronic/refractory ITP.
- iptacopan (LNP023) / Novartis
Dose–Exposure–Response Relationships of Biomarkers and Efficacy Measures with Iptacopan, a Complement Factor B Inhibitor, in Patients (pts) with Paroxysmal Nocturnal Hemoglobinuria (PNH) with or without Concomitant Anti-C5 Therapy (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_3993;
P2, P3
The dose–exposure–response relationship was similar between pts regardless of whether they had a partial response to C5 inhibition (X2201) or were anti-C5-naïve (X2204), supporting the use of iptacopan 200 mg bid in both populations. Based on clinical efficacy and safety data from these two studies (Risitano et al.
- || iptacopan (LNP023) / Novartis
Clinical, Journal: Alternative Complement Pathway Inhibition With Iptacopan for the Treatment of C3 Glomerulopathy-Study Design of the APPEAR-C3G Trial. (Pubmed Central) - Oct 12, 2022
P3
Key secondary endpoints will assess kidney function measured by eGFR, histological disease total activity score, and fatigue. This study aims to demonstrate the clinical benefits of AP inhibition with iptacopan in C3G.
- | Journal: Classical Complement Pathway Inhibition in a "Human-On-A-Chip" Model of Autoimmune Demyelinating Neuropathies. (Pubmed Central) - Oct 11, 2022
TNT005 rescued the serum-induced complement deposition and functional deficits while treatment with an isotype control antibody had no rescue effect. These data indicate that complement activation by CIDP and MMN patient serum is sufficient to mimic neurophysiological features of each disease and that complement inhibition with TNT005 was sufficient to rescue these pathological effects and provide efficacy data included in an investigational new drug application, demonstrating the model's translational potential.
- | APL-9 / Apellis
Journal: Pre-existing humoral immunity and complement pathway contribute to immunogenicity of adeno-associated virus (AAV) vector in human blood. (Pubmed Central) - Oct 4, 2022
By using a compstatin-based C3 and C3b inhibitor, APL-9, we demonstrated that complement pathway inhibition lowered CD86 levels on APCs, AAV uptake, and cytokine/chemokine secretion in response to AAV. Together these results suggest that the pre-existing humoral immunity to AAV may contribute to trigger adverse immune responses observed in AAV-based gene therapy, and that blockade of complement pathway may warrant further investigation as a potential strategy for decreasing immunogenicity of AAV-based therapeutics.
- | Comirnaty (tozinameran) / Pfizer, Fosun Pharma, BioNTech, Soliris (eculizumab) / AstraZeneca
Journal: Severe refractory warm autoimmune haemolytic anaemia after the SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA) managed with emergency splenectomy and complement inhibition with eculizumab. (Pubmed Central) - Sep 20, 2022
AIHA is rare but described after the SARS-CoV-2 Pfizer-BioNTech vaccine. This case highlights the rare complication of AIHA, the use of emergency splenectomy for disease control, and the use of eculizumab.
- | Journal: The role of the alternative pathway in paroxysmal nocturnal hemoglobinuria and emerging treatments. (Pubmed Central) - Sep 10, 2022
Alternative complement pathway inhibitors may offer further benefit as long as terminal complement is completely inhibited to reduce IVH and disease activity. This may lead to improvements in adherence and health-related quality of life for patients with PNH.
- | Journal: Development and Optimization of Bifunctional Fusion Proteins to Locally Modulate Complement Activation in Diseased Tissue. (Pubmed Central) - Jul 6, 2022
Preclinical in vivo studies further demonstrate that anti-C3d fusion proteins effectively distribute to injured tissue and reduce C3 fragment deposition for periods beyond 14 days. The in vitro and in vivo profiles support the further evaluation of C3d mAb-CR1 as a novel approach to restore proper complement activation in diseased tissue in the absence of continuous systemic complement blockade.
- | Empaveli (pegcetacoplan SC) / Apellis, SOBI
Journal: Paroxysmal nocturnal hemoglobinuria: advances in the understanding of pathophysiology, diagnosis, and treatment. (Pubmed Central) - Jul 2, 2022
Among the new therapeutic agents, crovalimab and C5 inhibitors at a less advanced stage of research are discussed: tesidolumab, pozelimab, zilucoplan, nomacopan, and cemdisiran. The first approved proximal complement pathway inhibitors that primarily prevent extravascular hemolysis, pegcetacoplan, danikopan, and iptacopan, are presented and their potential benefits are highlighted.
- || PK/PD data, Preclinical, Journal: Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. (Pubmed Central) - May 18, 2022
Further studies showed that this effect was dose dependent and observed with both CSL040 and the full-length extracellular domain of HuCR1. Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared to full-length soluble HuCR1.
- Enjaymo (sutimlimab) / Sanofi
INHIBITION OF COMPLEMENT C1S WITH SUTIMLIMAB IN PATIENTS WITH COLD AGGLUTININ DISEASE (CAD): 2-YEAR FOLLOW-UP FROM THE CARDINAL STUDY (Hall Lehar 1-2) - May 13, 2022 - Abstract #EHA2022EHA_2691;
P3
Sutimlimab continued to improve FACIT-Fatigue scores, with no newly identified safety concerns at 2 years of treatment. This study has demonstrated that sutimlimab is an effective and well-tolerated long-term therapy for the management of chronic CAD through continued upstream inhibition of the classical CP.
- Enjaymo (sutimlimab) / Sanofi
INHIBITION OF COMPLEMENT C1S WITH SUTIMLIMAB IN PATIENTS WITH COLD AGGLUTININ DISEASE (CAD): RESULTS FOLLOWING 9-WEEK WASHOUT PERIOD IN PHASE 3 CARDINAL STUDY (NCT03347396) () - May 13, 2022 - Abstract #EHA2022EHA_1346;
P3
Conclusion In the 9-week washout period following the final dose of sutimlimab, classical complement pathway inhibition was reversed, and hemolytic markers and fatigue scores approached pre-sutimlimab values. Most of the TEAEs were due to exacerbation of underlying CAD.
- Effects of Complement Component 1 (C1) Inhibition on AAV-based Gene Transfer Efficacy and Immunogenicity in Mice (Ballroom C) - Apr 20, 2022 - Abstract #ASGCT2022ASGCT_1165;
Transduction efficiency dropped to 50% in the mice injected with the high AAV dose, and immunized mice in the low AAV dose groups showed no transgene expression and did not develop IgG or IgM following vector infusion, most likely due to immediate AAV clearance by the NAbs. These results indicate the potential impact of C1 inhibition which warrants further investigation to better understand and optimize the potential for lower vector immunogenicity and dose-sparing effect in AAV-based gene transfer.
- Characterization of the Innate Immune Response to AAV in Human Blood and the Central Role of Complement (Room 102 A/B) - Apr 20, 2022 - Abstract #ASGCT2022ASGCT_1003;
These findings warrant further investigation of the complement inhibitors in AAV-based gene transfer. Disclaimer: This communication reflects the views of the authors and neither the IMI nor the European Union, EFPIA or any other partners are liable for any use that may be made of the information contained herein.
- | Journal: Troxerutin-Mediated Complement Pathway Inhibition is a Disease-Modifying Treatment for Inflammatory Arthritis. (Pubmed Central) - Apr 19, 2022
Our dosimetry study suggests that a TXR dose of 200 mg/kg body weight for 15 days is sufficient to bring the arthritis score to basal levels in AIA rats. We have shown the importance of TXR as an antiarthritic agent in the AIA model and after additional investigation, its arthritic ameliorating properties could be exploited for clinical usability.
- RLS-0071 / ReAlta
RLS-0071 Reduces Inflammatory Biomarkers in T2 Low (neutrophilic) Asthma Animal Model (Room 303-304 (South Building, Level 3), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_3992;
Compared to animals not receiving RLS-0071, BALF of animals treated with RLS-0071 showed a reduction in neutrophil count, MPO and free DNA demonstrating that RLS-0071 can reduce neutrophil sequestration and activation in the lung modulating neutrophil-mediated asthma in this rat model. The ability of RLS-0071 to mitigate neutrophilic asthma in this rodent model has potential for utility as a therapeutic in acute neutrophil-mediated pulmonary exacerbations including steroid refractory, T2 low asthma.