A Phase 2b, Multidose, Multicenter, Double-blind, Placebocontrolled, 24 Week Study to Evaluate the Efficacy and Safety of Intravenous Infusion with Recombinant Human Soluble Fc-gamma IIB Receptor SM101 in Subjects with Systemic Lupus Erythematosus (SLE)

Start Date01 Jul 2017

Sponsor / Collaborator

Baxalta Innovations GmbH

NCT02605525

/ WithdrawnPhase 2

A Phase 2 Study to Assess the Efficacy and Safety of Intravenous Infusion With Human Soluble Recombinant Fc-gamma Receptor IIB (SM101/BAX 1810) in Subjects With Immunoglobulin A Nephropathy (IgAN)

The purpose of this study is to assess the efficacy and safety of SM101 in the treatment of Immunoglobulin A nephropathy (IgAN)

Start Date31 Dec 2015

Sponsor / Collaborator

Baxalta, Inc.

EUCTR2009-014842-28-BE

/ Not yet recruitingPhase 1/2

A Randomised, Multi-centre, Double-Blind, Placebo-Controlled, Single/Multiple Dose Escalation Phase Ib/IIa Clinical Trial to Investigate the Safety and Efficacy of Recombinant Human Soluble Fc-gamma Receptor IIb (SM101) for Intravenous Application in the Treatment of Patients with Chronic Adult Idiopathic Thrombocytopenic Purpura (ITP).

Start Date06 Jan 2010

Sponsor / Collaborator

SuppreMol GmbH

100 Clinical Results associated with Valziflocept

100 Translational Medicine associated with Valziflocept

100 Patents (Medical) associated with Valziflocept

Literatures (Medical) associated with Valziflocept

15 Apr 2020·Avian DiseasesQ4 · AGRICULTURAL & FORESTRY SCIENCE

Comparison of the Pathogenicity of Five Clostridium perfringens Isolates Using an Eimeria maxima Coinfection Necrotic Enteritis Disease Model in Commercial Broiler Chickens

Q4 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Sun, Zhifeng ; Wang, Yunfei ; Gu, Changqin ; Zhao, Hongyan ; Yan, Xianghe ; Lillehoj, Hyun ; Melville, Stephen ; Liu, Liheng ; Li, Charles ; Lu, Mingmin ; Xianyu, Zhezi ; Lee, Youngsub

Clostridium perfringens (CP) is the etiologic agent of necrotic enteritis (NE) in broiler chickens that is responsible for massive economic losses in the poultry industry in response to voluntary reduction and withdrawal of antibiotic growth promoters. Large variations exist in the CP isolates in inducing intestinal NE lesions. However, limited information is available on CP isolate genetics in inducing NE with other predisposing factors. This study investigated the ability of five CP isolates from different sources to influence NE pathogenesis by using an Eimeria maxima (EM) coinfection NE model: Str.13 (from soil), LLY_N11 (healthy chicken intestine), SM101 (food poisoning), Del1 (netB+tpeL-) and LLY_Tpel17 (netB+tpeL+) for NE-afflicted chickens. The 2-wk-old broiler chickens were preinfected with EM (5 × 103 oocysts) followed by CP infection (around 1 × 109 colony-forming units per chicken). The group of the LLY_Tpel17 isolate with EM coinfection had 25% mortality. No mortality was observed in the groups infected with EM alone, all CP alone, or dual infections of EM/other CP isolates. In this model of EM/CP coinfections, the relative percentages of body weight gain showed statistically significant decreases in all EM/CP groups except the EM/SM101 group when compared with the sham control group. Evident gut lesions were only observed in the three groups of EM/LLY_N11, EM/Del1, and EM/LLY_Tpel17, all of which possessed an essential NE pathogenesis locus in their genomes. Our studies indicate that LLY_Tpel17 is highly pathogenic to induce severe gut lesions and would be a good CP challenge strain for studies investigating pathogenesis and evaluating the protection efficacy for antibiotic alternative approaches.

01 May 2016·Journal of Clinical ImmunologyQ2 · MEDICINE

The FcγR/IgG Interaction as Target for the Treatment of Autoimmune Diseases

Q2 · MEDICINE

Review

Author: Sondermann, Peter

FcγRs are a crucial component of the antibody response as they mediate the cellular effector functions in response to IgG-containing immune complexes (ICs). Therefore, they also play a central role in the pathogenesis of autoimmune diseases which offers an attractive option to specifically target this class of molecules and their interaction with IgG for treatment of immune disorders. In detail, two strategies are discussed in this article. SM101, a soluble FcγR that is already in clinical development competes with the interaction of IgG with membrane FcγRs. Oppositely, SM201 recruits the inhibitory FcγRIIB for a broad down-modulation of the immune system. The presented approaches for the treatment of autoimmune diseases have the potential be more efficacious with fewer side effects than the currently used therapeutic options.

01 Mar 2015·Journal of Investigative DermatologyQ1 · MEDICINE

Recombinant Soluble CD32 Suppresses Disease Progression in Experimental Epidermolysis Bullosa Acquisita

Q1 · MEDICINE

Letter

Author: van Beek, Nina ; Iwata, Hiroaki ; Vorobyev, Artem ; Sondermann, Peter ; Ludwig, Ralf J ; Möckel, Nicole ; Zillikens, Detlef ; Pipi, Elena

TO THE EDITOR: Epidermolysis bullosa acquisita (EBA) is a prototypic organ-specific autoimmune disease, which is characterized by chronic mucocutaneous subepidermal blistering (Gupta et al., 2012; Schmidt and Zillikens, 2013).The autoimmune response is directed against a 290-kDa protein located at the dermal-epidermal junction (DEJ), which has been identified as the type VII collagen (Woodley et al., 1988).Despite major achievements in the understanding of EBA pathogenesis (Gupta et al., 2012), therapy of EBA patients remains difficult, and, because of the low incidence of the disease, data from clin. trials are still missing.Most commonly corticosteroids in combination with other (immunosuppressive) drugs are used (Engineer and Ahmed, 2001), which is associated with severe and potentially life-threatening adverse reactions.Therefore, there is a great and so far unmet medical need for effective and safe treatment options in EBA.We have recently established a mouse model of EBA induced by immunization with an immunodominant domain located within the non-collagenous 1 domain of murine type VII collagen (Iwata et al., 2013).Induction of skin blistering in exptl. EBA depends on the expression of activating Fc gamma receptor (FcγR; Kasperkiewicz et al., 2012).The detrimental contribution of FcγR binding to tissue-deposited immune complexes (ICs) has been well documented in models of autoantibody-mediated diseases, such as rheumatoid arthritis (Kleinau et al., 2000), immune-mediated thrombocytopenia (McKenzie et al., 1999), and autoimmune bullous dermatoses (Ludwig et al., 2013).On the basis of these findings, FcγR seems to be a promising therapeutic target for the treatment of autoantibody-mediated inflammatory diseases.Currently, several novel compounds targeting the interaction of ICs with FcγR are pursued either in preclin. model systems or in clin. trials.Notably, pharmacol. modifications of IgG glycosylation at the Fc fragment, which alters IgG's affinity to FcγR, have prophylactic and therapeutic effects in several models of autoimmunity (Collin and Ehlers, 2013).Other potentially promising FcγR targeting strategies, such as competitive binding of ICs by recombinant soluble FcγR2B (soluble CD32, sCD32, and SM101) in idiopathic thrombocytopenia or systemic lupus erythematosus, are already evaluated in phase I/II clin. trials (http://www.controlled-trials.com/isrctn/search.htmlsrch=SM101).Here, we evaluated whether treatment with sCD32 has therapeutic effects in exptl. EBA. sCD32 binds to IC and thereby blocks the binding of FcγR expressed on the surface of immune cells.Eventually, effector cells cannot be activated via FcγR (Ierino et al., 1993).First, we investigated the effect of sCD32 on activating FcγR-dependent reactive oxygen species (ROS) release from IC-activated neutrophils (Supplementary Materials and Methods online). sCD32 inhibited IC-induced neutrophil ROS production in a dose-dependent manner (Figure 1a).In detail, compared with pos. control, 0.01, 0.1, and 0.5 mg ml^-1 sCD32 significantly reduced ROS production by 30, 65, and 75%, resp.Next, we tested whether sCD32 could hinder dermal-epidermal separation in an ex vivo model of autoimmune bullous dermatoses.Accordingly, in the presence of leukocytes, sCD32 successfully impaired FcγR-dependent dermal-epidermal separation on cryosections of human skin incubated with sera containing pathogenic antibodies against DEJ structures (Figure 1b and c; Supplementary Materials and Methods online).To validate this ex vivo inhibitory activity of sCD32 on antibody-induced tissue injury in vivo, we next induced exptl. EBA in mice by immunization with vWFA2 (Supplementary Materials and Methods online).After immunization, mice were allocated to sCD32 or phosphate-buffered saline (PBS) treatment if individual mice had 2% or more of their body-surface area affected by skin lesions (Supplementary Materials and Methods online).Compared with PBS-injected mice, sCD32 treatment led to a significantly lower clin. disease severity (Figure 2a, left, *P<0.05, t-test).At inclusion to treatment (week 0), average disease scores were not different between the groups (3.4±0.21% and 3.4±0.20%) of affected body-surface area in PBS and sCD32 treatment, resp.Cumulative disease severity expressed as area under the curve during the entire observation period was also significantly lower in sCD32-treated mice as compared with PBS control mice (Figure 2a, right, P=0.031, t-test).At the end of the 4-wk treatment period, PBS-treated mice showed diffuse erythema and crusts on the ear and tail, and hair loss around the eyes (Figure 2b, left).In contrast, less erythema on the ear and no disease on tail or around the eyes in mice treated with sCD32 were observed (Figure 2b, right).Histol., mice treated with sCD32 showed a significant decrease in the dermal leukocyte infiltration, compared with PBS-treated mice (P<0.05, Figure 2c). sCD32 treatment also led to an ∼20% reduction in circulating antigen-specific autoantibodies compared with PBS-treated mice (Figures 2d, P=0.048; t-test), whereas total IgG levels were not significantly different (data not shown).At the same time point, all mice showed similar IgG deposits at DEJ as determined by direct immunofluorescence (Figure 2e, upper).Representative pictures of direct immunofluorescence show IgG deposits at DEJ (Figure 2e, down).This discrepancy between circulating and tissue bound autoantibodies may be because of their different half-lives. sCD32 treatment has also demonstrated beneficial effects in models of other autoantibody-mediated diseases, such as nephritis in lupus-prone NZB/NZW F(1) hybrid mice (Werwitzke et al., 2008) and joint inflammation in collagen-induced arthritis (Magnusson et al., 2008).On the basis of our observations ex vivo and in vivo, the therapeutic effect of sCD32 can be attributed to both direct and indirect mechanisms, which mean the inhibition of neutrophil function and autoantibody production, resp.On the basis of our observation of therapeutic efficacy in exptl. EBA, it is tempting to speculate that sCD32 binds to the in situ deposited ICs.This assumption, however, needs further exptl. exploration.Regarding the effect on autoantibody production, controversial results have been reported.In the lupus-prone NZM/NZW mouse model neither prophylactic nor therapeutic treatment with sCD32 affected anti-double stranded DNA serum titers (Werwitzke et al., 2008).In contrast, sCD32 suppressed secondary and primary in vitro antibody responses (Varin et al., 1989) and caused a temporary decrease in collagen-specific autoantibodies in CIA (Magnusson et al., 2008).In support of these later observations, we here report a sustained reduction of antigen-specific but not of total circulating IgG in immunization-induced EBA.This effect may be mediated through a blockade of the IgG2a-mediated enhancement of antibody and T-cell responses via increased antigen presentation to CD4+ T cells by FcγR-expressing antigen-presenting cells (Getahun et al., 2004).Taken together, our findings provide evidence for a beneficial role of sCD32 in exptl. EBA.As this model mostly reflects the inflammatory variant of EBA, our findings may pave the way for its clin. application in patients with autoimmune bullous dermatoses, where disease manifestation depends on an interaction of ICs with effector myeloid cells.

News (Medical) associated with Valziflocept

19 Jan 2022

·www.biospace.com

BioInvent: The FDA Grants Orphan Drug Designation to BI-1206 for the Treatment of Follicular Lymphoma

BioInvent International AB ("BioInvent") (Nasdaq Stockholm:BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, today announces that its anti-FcyRllB antibody BI-1206 has been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for the treatment of follicular lymphoma (FL), the most common form of slow-growing Non-Hodgkin lymphoma. The FDA's Office of Orphan Drug Products grants orphan status to support the development of medicines for rare disorders that affect fewer than 200,000 people in the U.S. ODD provides benefits, including market exclusivity upon regulatory approval, exemption of FDA biologic license application fee and tax credits for qualified clinical trials. BI-1206 previously received ODD from the FDA for the treatment of mantle cell lymphoma (MCL) in January 2019. BI-1206 is BioInvent's lead drug candidate and is currently being investigated in two Phase 1/2 trials. One is evaluating the BI-1206 combination with rituximab for the treatment of Non-Hodgkin lymphoma, which includes patients with FL, MCL and marginal zone lymphoma (MZL) who have relapsed or are refractory to rituximab. A second Phase 1/2 trial is investigating BI-1206 in combination with anti-PD1 therapy Keytruda® (pembrolizumab) in solid tumors. "The granting of orphan drug status for BI-1206 for follicular lymphoma is another important step forward in the development of our lead drug candidate. The clinical update we presented recently clearly suggests BI-1206 may restore the response to rituximab in patients who have few treatment alternatives, with the results in follicular lymphoma being particularly impressive. We are looking forward to continuing to progress this anti-FcγRIIB antibody through clinical development to meet the needs of this underserved patient population," said Martin Welschof, CEO of BioInvent. About BioInvent BioInvent International AB (Nasdaq Stockholm: BINV) is a clinical-stage biotech company that discovers and develops novel and first-in-class immuno-modulatory antibodies for cancer therapy, with currently three drug candidates in four ongoing clinical programs in Phase 1/2 trials for the treatment of hematological cancer and solid tumors, respectively and a fifth program just initiating clinical development. The Company's validated, proprietary F.I.R.S.T™ technology platform simultaneously identifies both targets and the antibodies that bind to them, generating many promising new drug candidates to fuel the Company's own clinical development pipeline or for additional licensing and partnering. The Company generates revenues from research collaborations and license agreements with multiple top-tier pharmaceutical companies, as well as from producing antibodies for third parties in the Company's fully integrated manufacturing unit.

CollaborateAntibodyOrphan DrugFirst in ClassImmunotherapy

100 Deals associated with Valziflocept

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Indication	Highest Phase	Country/Location	Organization	Date
Glomerulonephritis, IGA	Phase 2	-	Baxalta, Inc.	31 Dec 2015
Purpura, Thrombocytopenic, Idiopathic	Phase 2	Poland	Shire Plc	-
Purpura, Thrombocytopenic, Idiopathic	Phase 2	Russia	Shire Plc	-
Purpura, Thrombocytopenic, Idiopathic	Phase 2	Germany	Shire Plc	-
Purpura, Thrombocytopenic, Idiopathic	Phase 2	Belgium	Shire Plc	-
Purpura, Thrombocytopenic, Idiopathic	Phase 2	Ukraine	Shire Plc	-

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