Intrexon, Oragenics to pursue development of biotherapeutics for oral cavity

OM results in the painful inflammation and ulceration of the membranes lining the oral cavity, throat, and esophagus and is among the most frequently reported adverse events associated with cancer therapy affecting up to 500,000 patients annually.

At present there is no drug approved to prevent the condition broadly and therapies are primarily palliative, alleviating symptoms without addressing the underlying pathology, resulting in a significant unmet medical need.

"We are eager to advance therapeutic programs through the established clinical foundations of the ActoBiotics platform, and moving forward in the clinic with AG013 is a natural fit for our focus on the treatment of oral cavity diseases with innovative biopharmaceuticals," said Frederick Telling, Ph.D., Chairman of the Board of Oragenics.

"Work continues under our current collaboration with Intrexon centered on the development of a novel class of antibiotics known as lantibiotics, and we are excited to build on this relationship in the field of oral health to realize the promise of microbial approaches in the generation of efficacious new medicines."

"I am pleased that this new collaboration provides an opportunity for continued development of AG013 as an intervention for oral mucositis," said Stephen T. Sonis, DMD, DMSc, Senior Surgeon, Divisions of Oral Medicine, Brigham and Women’s Hospital and the Dana-Farber Cancer Institute.

"AG013’s successful attenuation of chemotherapy-induced oral mucositis in the Phase 1B trial suggests that this innovative delivery platform may offer a new approach to the treatment of this important unmet clinical need."

Through the molecular engineering of food-grade microbes (Lactococcus lactis), biologically-contained ActoBiotics allow for in situ expression and secretion of novel biotherapeutic proteins and peptides. AG013 is formulated as a convenient oral rinsing solution and designed to deliver the therapeutic molecule Trefoil Factor 1 (TFF1) to the mucosal tissues in the oral cavity.

TFFs are a class of peptides that are involved in protection of the gastrointestinal tissues against mucosal damage and have an important role in subsequent repair.

A phase 1B clinical trial with AG013 in 25 cancer patients with OM across 5 cancer referral centers showed that AG013 was safe and well tolerated. Data published in the journal Cancer showed a 35% reduction of the duration of ulcerative OM in the AG013-treated patients versus the placebo-treated patients.

Furthermore, close to 30% of the patients treated with AG013 were full responders while all placebo-treated patients developed ulcerative OM. Additionally, a phase 1 pharmacokinetic (PK) study in 10 healthy volunteers showed that live AG013 bacteria adhere to the buccal mucosa and actively secrete protein locally, resulting in homogeneous exposure to the entire mucosal surface up to 24 hours after administration of a rinse.

AG013 has already been granted Orphan Drug status in the European Union and has potential eligibility for Biologic License Application exclusivity as well as Fast Track designation with the United States Food and Drug Administration.

Under the terms of the agreement, Oragenics will have access to Intrexon’s technologies and expertise to develop products for the treatment of oral mucositis or products containing genetically modified Lactococcus lactis expressing trefoil factors in the oral cavity, throat, and esophagus for a technology access fee and will reimburse Intrexon for the research and development costs.

The agreement also provides for commercial and regulatory milestone payments to Intrexon, as well as a low double-digit percentage royalty based on the net sales from collaboration products.

"AG013 represents a promising product from a truly innovative platform for the prevention of oral mucositis in cancer patients," commented Gregory Frost, Ph.D., Senior Vice President and Head of Intrexon’s Health Sector.

"We are very pleased with the expanded collaboration with Oragenics, especially given their unique experience in the field of oral health using novel approaches. This ECC will further the clinical development of AG013 in the hope of providing cancer patients with a much needed adjunctive therapy for oral mucositis, a challenging side effect that can become a treatment-limiting toxicity for effective cancer therapy."