Symphogen Reports New Data on Anti-EGFR Monoclonal Antibody Mixture

Symphogen has announced at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO) the results of two proof-of-concept studies of SYM004, an anti-EGFR monoclonal antibody (mAb) mixture.

Symphogen entered the antibody mixture into the clinic in 2010, and subsequently partnered with Merck KGaA, Darmstadt, Germany, in September 2012.

In sessions this morning, Abstract #3551 provided data on SYM004’s clinical evaluation in patients with anti-EGFR mAb-resistant/refractory KRAS wild-type (wt) metastatic colorectal cancer (mCRC) and Abstract #6002 in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) refractory to anti-EGFR mAb.

Both studies provided data supportive of the anticipated mechanism of action of the antibody mixture.

Professor Jean-Pascal Machiels, Head of Department of Medical Oncology, Université Catholique de Louvain, Clinique Universitaires St-Luc, Brussels, Belgium, lead investigator in the Sym004-02 study who made the oral presentation, commented, "These datasets suggest an anti-tumor effect. The achievement of stable disease and tumor shrinkage in heavily pretreated patient populations is of interest for any potential treatment. The studies are in line with Symphogen’s published data on the mechanism of action. The fact that these patients had progressed on other EGFR mAbs suggest a potentially additive effect against the EGF receptor."

Squamous Cell Carcinoma of the Head and Neck (SCCHN) Phase 2 Open Label Study Results
Weekly doses of 12 mg/kg Sym004 showed clinical response of stable disease in half of the heavily pretreated SCCHN patients resistant/refractory to previous anti-EGFR mAb treatment.
• Tumor shrinkage was observed in 8/26 patients by central and blinded review of CT scans. SD was observed in 13/26 patients.
• Median PFS was 2.7 months (95% CI 1.4-4.7 months).
• The observed safety profile was similar to other anti-EGFR mAbs except for skin related toxicity
• EGFR down-modulation was observed in paired skin and tumor biopsies, supporting the proposed mechanism-of-action.

Metastatic Colorectal Cancer Phase 1 / 2 Results
Weekly doses of Sym004 showed clinical responses in mCRC patients failing previous anti-EGFR mAb treatment. Partial responses were seen at both the 12 mg/kg and 9 mg/kg doses:
• A central and blinded review of CT scans was performed in 27/29 patients treated with 12 mg/kg Sym004 and showed tumor shrinkage >10% in 7/27 (26%) pts. A partial response (PR) PR was observed in 3/27 (11%) and stable disease (SD) in 16/27 (59%).
• A central and blinded review of CT scans was performed in 12/13 patients treated with 9 mg/kg Sym004 and showed tumor shrinkage >10% in 4/12 (33%) pts. A PR was observed in 1/12 (8%) and SD in 8/12 (67%).
• PFS for 9 mg/kg and 12 mg/kg was 14 weeks (95% CI 5.3 - 22.1%) and 14.3 weeks (95% CI 6.0 - 18.6), respectively.
• The observed safety profile was similar to other anti-EGFR mAbs, except for skin related toxicity.
• EGFR down-modulation was observed in paired skin and tumor biopsies supporting the proposed mechanism-of-action.

Symphogen has an exclusive worldwide license agreement with Merck KGaA, of Darmstadt, Germany, for Sym004. Under the agreement, Merck gained exclusive worldwide rights to develop and commercialize Sym004.

Symphogen received from Merck in 2012 an upfront payment of € 20 million.

Symphogen is eligible to receive up to € 225 million for meeting clinical development and regulatory milestones, and € 250 million in potential sales performance milestones and royalties on net worldwide sales.