SuppreMol GMBH
This article was originally published in Start Up
Executive Summary
SuppreMol GMBH is developing a recombinant version of human Fcy receptor FcyRIIb, now in Phase IIa for SLE. This candidate competes with membrane-bound Fcy receptors on immune cells, preventing binding of immune complexes containing autoantigens and inhibiting re-stimulation of immune cells. This down-regulates the B cells specifically involved in the autoimmune response, but does not affect B cells that are part of the normal immune response.
Unlocking the therapeutic potential of Fc γ receptors in autoimmune diseases
Am Klopferspitz 19
82152 Martinsried
Munich, Germany
Phone: +49 89 30 90 50 680
Web Site: www.suppremol.com
Contact: Peter Buckel, PhD, CEO
Industry Segment: Biotechnology
Business: Drugs for lupus and other autoimmune disorders
Founded: June 2002
Founders: Robert Huber, PhD; Uwe Jacob, PhD; Peter Sondermann, PhD, CSO
Employees: 15
Financing: €35.3 million
Investors: ZETACUBE SRL; KfW Mittelstandsbank; Bayern Kapital GMBH; MIG AG; BioMedPartners AG; Santo Holding GMBH; FCP Biotech Holding GMBH
Board of Directors: Thomas Hecht, Chairman; Ernst-Günter Afting; Michael Motschmann (MIG AG); Markus Hosang (BioMedPartners AG); Ulrich Mahr (Max Planck Innovation)
Scientific Advisory Board: Robert Huber, Chairman (Max Planck Institute of Biochemistry); Uwe Jacob (Westend Innovation); Christoph Huber, PhD (Johannes-Gutenberg University); Helmut Lenz; Fritz Melchers, PhD (University of Basel); Zoltan Nagy, PhD; Falk Nimmerjahn, PhD (University of Erlangen-Nürnberg); Jeffrey V. Ravetch, MD, PhD (Rockefeller University, New York)
According to the US Centers for Disease Control and Prevention, autoimmune disease affects around 5 to 8% of the US population. In autoimmune disease, the immune system attacks the body's own tissues; this is largely incurable, with most current therapeutics targeting symptom alleviation and control. German start-up SuppreMol GMBH has based its research around the Fcγ receptor, which modulates the cellular response to immune complexes. SuppreMol believes that therapeutics blocking this interaction have the potential to target and block the cause of autoimmune diseases at an early stage, potentially leading to a cure.
SuppreMol grew out of a small research group at the Max Planck Society's Max Planck Institute of Biochemistry in Martinsried, in Germany. Robert Huber of the Max Planck Institute of Biochemistry (Nobel Laureate 1989), Uwe Jacob and Peter Sondermann (now SuppreMol's Chief Science Officer) founded the company.
Professor Huber's group was the first to solve the structure of the Fcγ receptor and express recombinant soluble receptors using Escherichia coli. The group has also developed an anti-Fcγ monoclonal antibody that binds very specifically to the receptor. The realization that the soluble Fcγ receptors and monoclonal antibodies could be used as therapeutics with potential in autoimmune disease was the trigger for the foundation of the company. The Max Planck Institute license and transfer office granted an exclusive license for the discoveries to the founders and provided support to the new start-up, in return for license fees and downstream success-based milestone payments and royalties.
"The company really took off in 2005, when we moved to the incubator at Martinsried," says CEO Peter Buckel.
SuppreMol's lead molecule, SM101, is a recombinant, soluble, non-glycosylated version of the human Fcγ receptor FcγRIIb. This competes with membrane-bound Fcγ receptors on immune cells, preventing the binding of immune complexes containing autoantigens and inhibiting the re-stimulation of the immune cells. This down-regulates the B cells specifically involved in the autoimmune response, but does not affect B cells that are part of the normal immune response, and was effective in animal models. SM101 has completed a Phase 0/Ia clinical trial in 48 healthy volunteers. The Phase Ib stage of a European Phase Ib/IIa dose-escalation study in patients with primary immune thrombocytopenia (ITP), an immune-mediated condition resulting in a low platelet count, started in April 2010 in 36 patients. The company expects to start the Phase IIa part of the study in this indication in 2011, in 15 patients.
"This is a proof-of-concept trial in ITP patients, and we are planning two Phase IIb/IIIa trials in the US and Europe, though we may seek a partner to help us with this," says Sascha Tillmanns, medical director. "SM101 received Orphan Drug status in Europe in 2007, and in the US in April 2010 in ITP, and the Orphan Drug status could help us to get SM101 to the market more quickly."
Based on data from preclinical trials, SuppreMol is planning a Phase IIa trial in patients with the autoimmune disease systemic lupus erythematosus (SLE). This study should begin in the first half of 2011, and will look at low and high doses of SM101.
"If we can get positive results in SLE, this could open up a huge potential market for us in other autoimmune diseases, including multiple sclerosis, type 1 diabetes and rheumatoid arthritis," says Buckel. "There hasn't been a new treatment in SLE for more than 20 years," adds Tillmanns. The company is likely to look to partners with experience in specific disease areas for these indications, as they will require studies in larger groups of patients. Buckel has seen much interest from potential partners so far, but the company plans to wait for clinical trial outcomes before it makes any decisions.
Further back in the pipeline, SuppreMol has a number of products in the discovery phase, including two antibodies that will move into preclinical trials in 2011. These will target autoimmune disease and allergy, including asthma.
There are many companies working in therapeutics for the treatment of autoimmune disease, but the majority focus on the treatment of the symptoms of autoimmune disease, including inflammation.
"Some companies aim to treat autoimmune disease by inhibiting the overall B cell activation of the immune system, and this general down-regulation opens up the potential risk of infections or cancer," says Tillmanns. "Our approach is more specific, and has been very well tolerated in studies so far, with no SM101-related side effects seen in the Phase Ia trial in healthy volunteers. Because our approach focuses on the origins and mechanisms of the disease rather than the symptoms, with a potential to cure the disease, we believe that we have no direct competitors," says Buckel.
SuppreMol currently has a staff of 15 full-time equivalents. "It has been quite a challenge to achieve everything within a company of this size, and we have relied on a network of clinical research organizations. We expect to recruit another two people in 2011, but this obviously depends on clinical data and the progress of our projects," says Buckel.
In May 2006, SuppreMol completed a Series A round of funding worth €4 million, from a group of investors including ZETACUBE SRL, the venture capital subsidiary of Zambon Company SPA and the German banks KfW Mittelstandsbank and Bayern Kapital GMBH. This money was set aside for two years worth of preclinical work, and was followed by a Series B round of funding in July 2008, worth €15.7 million. The Series B funding paid for the preparation of GMP material to begin a Phase Ib clinical trial of SM101 in ITP, and the company has created an optimized process to create material for other trials. This funding involved the original investors, along with MIG AG, BioMedPartners AG and Santo Holding GMBH. [See Deal]
The next stage of fundraising, a Series C round, closed in December 2010, and raised €15.5 million. The funding involved existing investors as well as FCP Biotech Holding GMBH, and will support up-scaling and GMP production of SM101, and will allow the company to fund its SLE trials, as well as an extension study for ITP. The funds will also be used for the preclinical development of an anti-FcγRIIb monoclonal antibody. [See Deal]
In December 2010, SuppreMol received an additional €2.6 million grant from the German Federal Ministry of Education and Research (BMBF) to assess SM101 in SLE as part of the biotechnology initiative "m4 – Personalized Medicine and Targeted Therapies – New Dimension in Drug Development in the Munich Region." This will provide SuppreMol with access to the m4 cluster's clinical study centers. SuppreMol also received a €1 million grant from BMBF in September 2009 to assess SM101 and develop diagnostic tools to stratify patients with multiple sclerosis.
"In addition to the patents from the Max Planck Institute, we have created our own patents on new forms of the protein including soluble receptors, on monoclonal antibodies, and on applications of the technology including as a diagnostic. We think we have covered the field well," says Buckel.
Tillmanns spent 15 years working in four pharmaceutical companies, and joined SuppreMol in January 2009. Buckel has worked in the pharmaceutical industry for 23 years, including as head of global pharma research at Boehringer Mannheim, and has been part of SuppreMol since 2005, after having worked with Huber on x-ray structures out of Boehringer Mannheim and Roche.
"During 2010, we achieved everything that we promised when we raised our Series B funding, and on time, too. We started the Phase Ib proof-of-concept trial of SM101 in ITP, developed an up-scaled GMP production process for the protein, and put the plans in place for the SM101 SLE study for mid-2011," says Buckel. "We have a first-in-class drug with great potential. Our long-term plan is to be a major player in autoimmune and allergic diseases, and asthma, with a number of molecules on the market and more in the pipeline, or to go for a trade sale to a large pharma company, but this depends on the clinical data, as well as financial and R&D partnerships." – Suzanne Elvidge