Symphogen A/S’s Antibody Mixtures Highlighted In Three Peer-Reviewed Journals

COPENHAGEN, Denmark--(BUSINESS WIRE)--Symphogen, a private biopharmaceutical company developing recombinant antibody mixtures, announced today the publication in May 2015 of two papers with new clinical data for its lead anti-EGFR antibody mixture, Sym004, in the journals Cancer Discovery and in Cancer Chemotherapy and Pharmacology. In addition, a paper in Clinical Cancer Research described preclinical findings relating to the company’s pan-HER product candidate, Sym013, a mixture of six antibodies targeting each of EGFR, HER2 and HER3 with a pair of synergistic antibodies. This body of evidence represents strong mechanistic validation for Symphogen’s novel and pioneering antibody mixture approach to innovative oncology therapeutics. The clinical efficacy data published provided the basis for advancing Sym004 into a randomized Phase 2b study, currently ongoing in the USA and Europe.

In the June issue of Cancer Discovery (Cancer Discovery; 5(6)), Dienstmann et al. report for the first time positive efficacy clinical findings for Sym004’s study in patients with metastatic colorectal cancer (mCRC) and with acquired resistance to anti-EGFR antibody therapies.

According to Josep Tabernero, MD, Principal Investigator for the study, who is affiliated with the Vall D’Hebron Institute of Oncology in Barcelona, Spain, “Sym004 is a unique antibody mixture that double targets EGFR, and as a result, appears to cause superior EGFR internalization and degradation than we’ve seen with cetuximab or panitumumab. Given this advantage, we believe the novel mixture will ultimately provide better outcomes for patients than drugs that block EGFR at only one region of it extracellular domain.”

The Phase 1 study enrolled a total of 62 patients; of which 20 patients had advanced solid epithelial tumors and were enrolled to the dose-escalation phase of the study. They received different doses of Sym004, ranging from 0.4 mg/kg to 12 mg/kg, administered weekly. The remaining 42 enrolled patients had metastatic colorectal cancer and had previously been treated with anti-EGFR antibodies with brief responses, and were enrolled to the dose-expansion phase of the trial. Patients in the dose-expansion cohort received weekly doses of 9 mg/kg or 12 mg/kg of Sym004.

Of the patients in the dose-expansion cohort, five (13 percent) had a partial response, and overall, 17 (44 percent) had some degree of tumor shrinkage during treatment with Sym004. The overall disease-control rate, which includes partial responses and stable disease, was 67 percent.

Dr. Tabernero commented, “We’ve not previously seen results such as those we are reporting in a patient population of anti-EGFR antibody-resistant colorectal cancer. Importantly, the study is the culmination of diligent research in preclinical models that has now translated to clinical activity. Importantly, the significant antitumor activity of Sym004 in patients whose tumors have become resistant to anti-EGFR therapies suggests that some colorectal cancers that progress after treatment with cetuximab or panitumumab, both anti-EGFR therapies, remain dependent on EGFR signaling.”

In the paper, Tabernero said that Sym004 was found to be well tolerated with no unexpected toxicities. Specifically, he pointed to a toxicity profile that is consistent with other approved anti-EGFR antibodies (grade 3 skin toxicity and low magnesium levels, among others), and observed that these effects were controlled with supportive care (topical and systemic antibiotics, and steroids), dose delays, and dose reductions.

Ivan Horak, Chief Scientific and Medical Officer of Symphogen, added, “Sym004 has demonstrated the ability to not only block ligand binding, receptor activation and downstream signaling but also to elicit removal of the EGFR receptors from the cancer cell surface by inducing EGFR internalization and degradation. Clearly, these data suggest these mechanisms are working and hold great promise for the future. By removing receptor tyrosine kinase receptors from cancer cells, we believe we have identified an effective therapeutic strategy for patients resistant to anti-EGFR antibodies, and which may also provide a better outcome for patients naïve to therapy than that provided by currently approved EGFR antibodies.”

In Cancer Chemotherapy and Pharmacology (Machiels et al.), Symphogen also reported data from a proof-of-concept Phase 2 trial of Sym004 in patients with late-stage squamous cell carcinoma of the head and neck (SCCHN). After studying the efficacy and tolerability of the novel antibody mixture, the company said it observed a best overall response of stable disease in 13 of 26 patients, and down-regulation of EGFR in target skin and tumor tissues, supporting the proposed hypothesis of the Sym004’s mechanism of action. In the extensively pretreated advanced SSCHN patients studied, the trial revealed modest anti-tumor activity. The safety of the mixture was found to be consistent with prior studies’ findings of adverse events related to EGFR, and no anti-drug antibodies were detected.

Separately, Symphogen reported also in April, in Clinical Cancer Research, preclinical findings from the company’s Pan-HER program showing that Pan-HER overcomes primary and acquired resistance due to HER family expression heterogeneity and plasticity. According to Symphogen, this data supports advancing the program into clinic in patients with HER family-dependent tumors.

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. Sym004 was the subject of data presentations at the 2013 and 2014 ASCO Annual Meetings in Chicago, IL. At these meetings, reported Phase 2 proof-of-concept data in squamous cell carcinoma of the head & neck (SCCHN) and in metastatic colorectal cancer signaled clinical activity and were supportive of the proposed mechanism of action. The company has two ongoing trials studying Sym004: a Phase 2b study in patients with metastatic colorectal cancer (mCRC) and a Phase 1b study in patients with Non-Small Cell Lung Cancer (NSCLC). In addition, a Phase 1 study expansion study in patients with esophageal squamous cell carcinoma is currently on-going in Japan.

About Sym013

Sym013 or Pan-HER is an advanced product in Symphogen’s pre-clinical oncology pipeline. Pan-HER is a mixture of six humanized full length monoclonal antibodies targeting EGFR, HER2 and HER3, all validated targets for cancer treatment, that effectively induces simultaneous down-modulation of all three targets and prevents compensatory receptor up-regulation. In Symphogen’s research, simultaneous targeting of three receptors has been shown to provide broader efficacy than targeting of a single receptor or any combination of two receptors in the HER family.

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 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.