Symphogen Reports New Data on Anti-EGFR Monoclonal Antibody Mixture

ASCO Presentation and Poster on Sym004 in mCRC and SCCCHN

Copenhagen, Denmark – Symphogen, ­­­­­­a private biopharmaceutical company developing recombinant antibody mixtures, announced today 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.

About Sym004

Sym004 is comprised of two antibodies that are not only designed to block ligand binding, receptor activation and downstream signaling but are also thought to elicit removal of the EGFR receptors from the cancer cell surface by inducing EGFR internalization and degradation.

As of 21-May-2013, 105 patients have been treated with Sym004 in clinical trials. The most frequently reported adverse events from the preliminary clinical data include, skin rash, dermatitis acneiform, erythema, nausea, fatigue hypocalcemia and hypomagnesemia. Exposure data from the patients, after weekly repeated infusions, do not indicate an anti-drug antibody response.

About Symphogen A/S

Symphogen is developing next-generation antibody therapeutics for the treatment of cancer and is dedicated to bringing truly innovative oncology products to the market. The company has advanced the frontier of antibody discovery by creating well characterized antibody mixtures that address multiple oncology targets in a single drug product. The company has matured its oncology pipeline and has currently brought two product candidates into the clinic. The company’s productive technology suite - capable of identifying, selecting and manufacturing optimal antibody mixtures – fuels Symphogen’s innovative pipeline. The lead oncology product, Sym004, was out-licensed to Merck KGaA in 2012 following phase 2 clinical data in late stage cancer patients. In total, the company has raised € 249 million in equity capital from premier international investors, and employs 90 people, most of whom are based at Symphogen’s facilities in Copenhagen.