A global leader in optimizing the sugar chains (glycosylation) of biopharmaceuticals, announced full details of its first-in-man Phase I trial for PankoMab-GEX™ at this year’s European Cancer Congress (ECCO 17). PankoMab-GEX™ is a potent humanized and glycoengineered antibody with respect to its specificity and anti-tumor activity recognizing the novel tumor-specific epitope TA-MUC1 expressed in the majority of solid cancer indications and patients and virtually absent on normal cells.
In conclusion, PankoMab-GEX™ clearly demonstrated clinical activity as single agent in heavily pre-treated progressive patients with far advanced cancers and could be safely administered at all tested doses and schedules with a very favorable safety, side-effect and pharmacokinetic profile.
In the open label Phase I dose escalation study (3+3 design), 74 patients with TA-MUC1-positive advanced solid tumors, all progressing after standard treatments, were treated with various doses of PankoMab-GEX™ from 1 to 2200 mg with three dosing schedules (once every three weeks, once every two weeks and weekly). The primary objective of the study was to evaluate the safety and tolerability profile of this novel compound and to define the recommended Phase II dosing regimen. Secondary endpoints included pharmacokinetics, immunogenicity and object-tumor response.
Activity was seen over all dose levels, with a clinical benefit rate of 50% at dose levels of ≥600 mg (19/34). One complete response in ovarian cancer for 485 days and one partial response for 295 days in non-small cell lung cancer (NSCLC) were observed (RECIST 1.1). The other patients showed continuing sustained clinical benefit in various cancers with an average duration of >240 days and the longest duration of 25 months (patient with pseudomyxoma peritonei with >20% tumor reduction). In the subgroup of ovarian cancer patients the clinical benefit rate at dose levels of ≥600 mg was 60% (9/15) including one complete responder. Progressive ovarian cancer patients previously sensitive or resistant to their last platinum therapy, regardless of additional refractory treatments, showed clinical benefit in all platinum sensitive (5/5) and in most resistant (3/5) patients. One patient refractory to platinum (1/5) showed an extended clinical benefit. NSCLC patients, albeit only treated with lower doses of PankoMab-GEXTM, showed in 4 of 7 patients a clinical benefit including one partial responder.
PankoMab-GEX™ showed a very favorable side-effect profile with mild to moderate adverse events, mainly infusion related reactions during the first infusion. No maximum tolerated dose was reached. As expected due to its high specificity, pharmacokinetics were linear over all doses with a long half-life allowing administration schedules once every three weeks or shorter.
Steffen Goletz, CEO, CSO and Founder of Glycotope, commented: “We are very pleased with these data. PankoMab-GEX™ has shown an excellent safety profile at all dose levels and promising efficacy results in heavily pre-treated cancer patients already as a single agent. Due to its high specificity and long duration of action, PankoMab-GEX™ is a highly attractive option for the future treatment of various solid tumors and will be further developed in Phase II trials.”
PankoMab-GEX™ is a potent humanized and glycooptimized therapeutic antibody (IgG1) recognizing Glycotope’s novel carbohydrate-induced conformational TA-MUC1 epitope expressed on the majority of tumor cells in a wide variety of cancers. The epitope comprises a tumor-specific carbohydrate antigen together with the immunodominant peptide region of MUC1, combining high tumor-specificity, high number of binding sites and affinity. It is abundantly present on primary tumors, metastasis and cancer stem cells and virtually absent on normal cells. Main target indications include ovarian, lung, breast and gastrointestinal tumors, mostly with over 90% of the patients and tumor cells. PankoMab-GEX™ expresses a series of potent anti-tumor modes of action, including antibody-dependent cellular cytotoxicity (ADCC), tumor cell phagocytosis and apoptosis induction, strongly enhanced by glycooptimization through Glycotope’s GlycoExpress™ platform. This allows a significantly improved treatment outcome compared to non-glycooptimized biotherapeutics. PankoMab-GEX™ is the lead molecule of Glycotopes’s GlycoBody technology which represents the Company’s treasure box of more than 200 monoclonal antibodies.
Glycotope, founded in 2001 in Berlin, focuses on the development of innovative antibodies for the treatment of various cancer types. These GlycoBodies™ target glycostructures on cell surfaces. In addition, Glycotope develops so-called BioSuperiors, antibody and non-antibody recombinant biopharmaceuticals with optimized and fully human sugar structures for clinical superiority. Key to the glycooptimization technology is a toolbox of glycoengineered proprietary human cell lines that allow the glycooptimization of proteins in respect to a whole series of different determining sugars and is based on fully human glycosylation. GlycoExpress™ allows the selection of the most appropriate and best suitable human glycoform of a product and a high yield production superior in reproducibility, quality and yield. Glycooptimization via GlycoExpress™ provides improved efficacy, bioavailability, immunogenicity and broadens the potential patient populations and indications, as well as providing a much improved cost-effectiveness. Glycotope has currently four products in clinical development from late stage Phase I to late stage Phase II. The Company’s additional pipeline includes preclinical non-antibody and antibody biopharmaceuticals for various indications.
Together with its subsidiary Glycotope Biotechnology in Heidelberg, Glycotope has evolved into a leading fully integrated glycobiology company, covering the entire workflow from discovery, molecule optimization, clone and process development, preclinical and clinical drug development to GMP production. With more than 160 employees and a strong and broad IP-platform, Glycotope today is one of the largest biotechnology companies in Germany.