Delving into the Latest Updates on Protherics Plc with Synapse

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Background Sarilumab is the first fully human monoclonal antibody (mAb) directed against the interleukin-6 receptor alpha (IL-6Rα). Sarilumab was developed using VelocImmune ® mice immunized with the human IL-6 (hIL-6) receptor. VelocImmune mice are genetically-engineered to express human antibody variable domain genes in the same robust fashion that the replaced mouse genes are typically expressed. Sarilumab is currently being explored as a new therapeutic modality for the treatment of rheumatoid arthritis. Objectives To evaluate the kinetic binding parameters and in vitro functional activity of two monoclonal antibodies directed against IL-6Rα: the fully human mAb sarilumab and the humanized mAb tocilizumab. Methods Kinetic binding parameters were measured using Surface Plasmon Resonance (SPR) technology. The ability to block hIL-6 induced activation of the human IL-6Rα was investigated using several bioassays; a human hepatocellular carcinoma cell line HepG2, transfected with a STAT3-luciferase reporter plasmid, as well as a proliferation assay using the human B-lymphoma cell line, DS-1. Results Sarilumab bound with high affinity to recombinant monomeric human and monkey IL-6 receptor with a K D value of 61.9 pM and 71.9 pM, respectively. The binding affinity of sarilumab to the dimeric human IL-6 receptor Fc-fusion was 12.8 pM. Cross-reactivity to mouse IL-6 receptor was not observed using SPR, indicating that sarilumab is specific to human and monkey IL-6 receptor. In contrast, tocilizumab bound to monomeric and dimeric forms of the human IL-6 receptor with a 15-22 fold weaker affinity than that of sarilumab as determined by SPR. In the HepG2 cell luciferase reporter assay, sarilumab effectively blocked luciferase activity induced by 50 pM hIL-6 with an IC 50 of 146 pM and was ∼4 fold more potent than tocilizumab. Similarly, in the DS-1 cell proliferation assay, sarilumab effectively blocked growth induced by 1.0 pM hIL-6 with an IC 50 of 226 pM and was several fold more potent than tocilizumab. Conclusions Based on these in vitro assay data, sarilumab has both a higher relative binding affinity for IL-6Rα, blocks IL-6Rα activation, and inhibits IL-6-induced cellular responses such as cell proliferation at lower concentrations than tocilizumab. Acknowledgements VelocImmune ® is a registered trademark of Regeneron Pharmaceuticals, Inc. Disclosure of Interest A. Rafique Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., J. Martin Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., M. Blome Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., T. Huang Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., A. Ouyang Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., N. Papadopoulos Employee of: Regeneron Pharmaceuticals, Inc.

15 Jul 2004·Journal of Clinical Oncology

A dose-escalation, Phase I study of a depot formulation of paclitaxel administered intralesionally in end-stage cancer patients with solid malignant tumors

Author: Nemunaitis, J. J. ; Vukelja, S. J. ; Anthony, S. P. ; Arseneau, J. C. ; Fowers, K. D. ; Samlowski, W. E. ; Berman, B. S. ; Callahan, K. S. ; Cunningham, C. C.

2131 Background: To determine the systemic plasma levels, safety and maximum tolerated dose (MTD) of a depot formulation of paclitaxel, OncoGel (paclitaxel/ReGel). This is a cremophor-free formulation which is liquid at administration temperature and rapidly forms a gel depot upon injection. The depot slowly degrades over several weeks allowing controlled release of paclitaxel within the tumor. Methods: A Phase I, dose-escalation study was conducted in 16 end-stage cancer patients with 18 superficially accessible solid malignant lesions at 6 investigative sites. Four paclitaxel dosages based on tumor volume were administered with 3 patients receiving 0.06 mg/cm3, 3 patients at 0.24 mg/cm3, 6 patients with 8 tumors at 0.48 mg/cm3, and 4 patients at 1.92 mg/cm3. There were 7 females and 9 males, ages 41 to 89, with treated tumors ranging from 0.7 cm3 to 19.0 cm3. The primary diagnoses included lymphoma, melanoma, lung, head and neck, laryngeal, thyroid, and breast cancer. Results: Blood samples were collect...

01 Oct 2000·Biochemical Society Transactions

High Affinity, Slow Binding FXa Inhibitors Are Poor Inhibitors Of Clot Formation in vitro

Author: Dyas, S ; Martin, H ; Liebeschuetz, J ; Mahler, J ; Auton, T

3

News (Medical) associated with Protherics Plc

03 Dec 2008

·www.biospace.com

Protherics PLC Release: Court confirmation of Reduction of Capital

Further to the announcement dated 1 December 2008, Protherics (LSE: PTI) and BTG plc ("BTG") (LSE: BCG) are pleased to announce that the High Court of Justice in England and Wales has today made an order confirming the reduction of Protherics' share capital in connection with the Scheme of Arrangement by which BTG's Acquisition of Protherics is being implemented. This follows the Court's sanction of the Scheme at a hearing held on 1 December 2008.

Acquisition

31 Mar 2008

·www.biospace.com

Encorium Group, Inc. Announces $1.6 Million Contract for a Phase 2 Trial of an Innovative Immunotherapeutic Vaccine for the Treatment of Hypertension

WAYNE, Pa.--(BUSINESS WIRE)--Encorium Group, Inc. (Nasdaq: ENCO - News), a full-service multinational contract research organization (CRO) that provides design, development, and management capabilities for clinical trials and patient registries for many of the world's leading pharmaceutical and biotechnology companies today announced the signing of a $1.6 million contract with Protherics, a leading UK biopharmaceutical company, for a Phase 2 trial of its novel immunotherapeutic vaccine, Angiotensin Therapeutic Vaccine (ATV), for the treatment of hypertension.

Vaccine

22 May 2007

·www.biospace.com

Protherics PLC Release: VoraxazeTM Update

London, UK; Brentwood, TN, US; 22 May 2007 - Protherics PLC ("Protherics" or the "Company"), the international biopharmaceutical company focused on critical care and cancer, today provided an update on its VoraxazeTM marketing applications in the US and EU. VoraxazeTM is an adjunctive therapy for patients with impaired renal function who are experiencing, or at risk of, toxicity from methotrexate ("MTX"), a widely used anti-cancer agent.

100 Deals associated with Protherics Plc

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100 Translational Medicine associated with Protherics Plc

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Pipeline

Pipeline Snapshot as of 01 Feb 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Antivenom PolongaTAb (Protherics)	Snake Bites More	Clinical
Anti-gonadotrophin releasing hormone vaccine(Protherics Plc) ( GnRHR )	Prostatic Cancer More	Discontinued
Polyclonal antibody TriTAb(Protherics Plc)	Poisoning More	Discontinued
AZD-9773(BTG Ltd.) ( TNF-α )	Coronary Disease More	Discontinued
NISV	Rheumatoid Arthritis More	Discontinued