Hansa Biopharma is a research-based company leveraging its proprietary enzyme technology platform to enable immunomodulatory treatments for transplants, rare immunoglobulin G (IgG)-mediated autoimmune conditions, gene therapy and cancer. The European Commission has conditionally approved Idefirix (imlifidase) for the desensitization treatment of highly sensitized adult kidney transplant patients with a positive crossmatch against an available deceased donor. Hansa Biopharma is also pursuing a path for regulatory approval with the U.S. FDA. Imlifidase has orphan designation in EU and the U.S. for several rare immunologic indications with a high unmet medical need.
Hansa’s research and development program is also advancing the Company’s technology to develop the next generation of IgG cleaving enzymes with lower immunogenicity, to potentially enable repeat dosing in relapsing autoimmune diseases, chronic transplant rejection, oncology and gene therapy. Imlifidase is protected by a strong patent portfolio.
Broad Pipeline in Transplantation and Autoimmune Diseases
Imlifidase Mode of Action
Pre-clinical & Clinical Trial Overview
In 2008 Hansa Medical, today named Hansa Biopharma, began to study the therapeutic effect of imlifidase in various disease models; e.g. collagen antibody induced arthritis, idiopathic thrombocytopenic purpura and anti-GBM antibody disease. Imlifidase was observed to neutralize IgG in all models studied. Experiments on serum from highly sensitized kidney patients showed that imlifidase rapidly reduced the level of anti-HLA antibodies.
Our initial clinical studies focused on desensitization of HLA-immunized patients before kidney transplantation. We started the first in-human Phase 1 study in 2013 to assess safety, efficacy in IgG cleavage, pharmacokinetics and immunogenicity of imlifidase. Based on these data we decided to move into patients where it is possible to measure not only imlifidase effect on plasma IgG but also the effect on specific pathogenic IgG.
During 2015-18 we completed four Phase 2 studies in sensitized and highly sensitized patients, awaiting kidney transplantation.
In 2019 we started a Phase 2 study to evaluate safety and efficacy of imlifidase in eliminating Donor Specific Antibodies (DSA´s) in acute AMR in kidney transplant patients, the main cause of graft dysfunction after transplantation. We are initiating a Phase 2 study of imlifidase in combination with standard immunoglobulin care in GBS and participating in an investigator-led Phase 2 study with imlifidase in the rare anti-GBM antibody disease.
We are advancing our enzyme technology to develop the next generation of IgG-cleaving enzymes with lower immunogenicity, suitable for repeat dosing.
Novel Immunoglobulin G Cleaving Enzymes for Repeat dosing
Hansa Biopharma is developing novel IgG-degrading enzymes to enabling repeat dosing in autoimmune conditions, oncology and transplantation. The Company has patented several IgG-cleaving enzymes.
In March 2019 a lead candidate for clinical development was selected. Development of a manufacturing process under GMP (Good Manufacturing Process), and preparations for toxicology studies and a clinical Phase 1 study have been initiated.
Enzyme-based antibody Enhancement
EnzE (Enzyme-based antibody Enhancement) is a pre-clinical research and development program under which the combined use of approved antibody-based cancer treatments with IgG-modulating enzymes is explored.
High levels of plasma IgG have been associated with limiting the efficacy of therapeutic antibodies, as plasma IgG can saturate the Fc-receptors of the patient’s immune cells and thereby prevent them from effectively killing the cancer cells.
Heparin Binding Protein Assay
The Heparin Binding Protein Assay for measurement of heparin binding protein (HBP) in plasma is a diagnostic method originally developed and patented by researchers at Lund University in collaboration with Hansa to assist in predicting severe sepsis in patients with infectious disease symptoms at the emergency units of hospitals.
Severe sepsis affects 300 of 100,000 people annually. Many of these infections can be effectively treated with antibiotics in order to prevent progression to severe sepsis.
The HBP assay has been out-licensed by Hansa to UK-based Axis-Shield Diagnostics, a subsidiary of Abbott. Hansa Biopharma holds the right to royalty payments from Axis-Shield.
Patents & Intellectual Property
Imlifidase is protected by seven patent families, including granted patents and pending patent applications. They cover use of our antibody cleaving enzyme
- to create antibody fragments
- in IgG-mediated conditions including prevention and treatment of transplant rejection and autoimmune disease
- in combination with other treatments such as transplantation, oncology,
- new IgG -modulating molecules
These patents cover the United States, Europe, Japan and other jurisdictions. Significant patents are protecting our technology beyond 2035, with the possibility of five years of supplemental protection.
Hansa Biopharma continuously evaluates the opportunities for market exclusivity for drug candidates through orphan drug designations and data exclusivity.
Orphan Drug Designation
In Europe orphan designation is granted to drugs intended for the treatment of life-threatening or chronically debilitating rare diseases where no therapeutic options are either authorized or where the drugs will be of significant benefit to those affected. The designation provides ten years of market exclusivity in the EU after marketing authorization against similar medicinal products with a similar therapeutic indication, protocol assistance on the development of the drug, including clinical studies and certain exemptions or reductions in regulatory fees. In the US, orphan-designated products are granted market exclusivity against the same drug for the same indication for seven years.
In September 2015 imlifidase was granted orphan drug designation for treatment of antibody-mediated organ rejection in solid organ transplant patients by the FDA. In January 2017 the EMA approved our application for orphan drug designation of imlifidase for the prevention of graft rejection following solid organ transplantation.
In February 2018 the FDA granted orphan drug designation to imlifidase for the treatment of Guillain-Barré syndrome. In July 2018 the FDA granted Orphan Drug Designation for imlifidase for treatment of the rare and acute kidney disease anti-GBM antibody disease, also known as Goodpasture’s disease. In October 2018, the Committee for Orphan Medicinal Products of the European Medicines Agency (EMA) issued a positive opinion on Orphan Drug Designation for imlifidase for the treatment of anti-glomerular basement membrane (anti-GBM) antibody disease. Subsequently, the European Commission officially designated imlifidase as an orphan drug in this indication. Data exclusivity can be granted by regulatory agencies, such as the FDA and EMA, for protection of clinical data submitted in an application for market authorization.
Manufacturing is done in close collaboration with two highly experienced and European based third party CMOs. During 2016-2017 the drug substance production process was transferred to Biotechpharma in Vilnius, Lithuania, while the drug product process and upscaling of imlidase was transferred to Baxter in Halle in Westfalen, Germany.
Full process characterization and validation for commercial supply was completed during 2018 and the manufacturing process has gone through optimization for improved product yield.