Early-stage immunotherapy

PARIS & BRUSSELS—Of the 300 million women infected with HPV, 500,000 new cases of cervical cancer are identified annually, and 275,000 women succumb to the disease. Seventy percent of cervical cancer cases are caused by two HPV types, and Genticel—a French biotechnology company and developer of innovative immunotherapies to prevent cancers caused by the human papillomavirus (HPV)—aims to eliminate them at an early stage.

Genticel recently announced positive preclinical in-vivo proof-of-concept results of GTL002, its multivalent HPV therapeutic vaccine candidate based on the company’s Vaxiclase platform. No treatment options are available for women infected with oncogenic HPV types but who have not yet developed high-grade lesions or cervical cancer: GTL002 seeks to eradicate the six most oncogenic HPV types affecting 158 million women worldwide.

GTL001, Genticel’s first-in-class therapeutic vaccine candidate currently in Phase 2 in Europe, already targets the two most oncogenic HPV types. With GTL001 and GTL002, Genticel is the first company that has established a staged pipeline of HPV therapeutic vaccines for the large female population burdened by this unmet medical need, according to the company. The proof-of-concept data of GTL002 demonstrated that an in-vivo immune response was induced against each of the six HPV-derived proteins present in the therapeutic vaccine. In addition, in-vivo therapeutic efficacy was shown by tumor eradication in the most widely used and broadly accepted reference model.

In 2002, Genticel licensed from Institut Pasteur a modified adenylate cyclase from Bordetella pertussis to be used as an antigen delivery vector able to induce a specific immune response against a pathogen carrying the delivered antigen. The company chose to target HPV-induced diseases to develop its first therapeutic vaccine candidate, GTL001, because the most aggressive forms of HPV induce cancers and thus represent a major health issue, according to Martin Koch, CEO of Genticel.

He added, “Other reasons we chose it are that the virus is present at the onset of the disease and thus represents an ideal biomarker and allows for a possible therapeutic approach with an immunotherapy at an early stage of the disease; the virus is a foreign agent and it is easier to trigger an immune response against a non-self antigen; and HPV testing is widely available and increasingly used in first-line cervical cancer screening, making it possible to identify patients at risk of developing cancer.”

When HPV molecular testing began to emerge as the first-line recommended screening for cervical cancer, Genticel decided to develop a therapeutic option for the population of infected women who had not yet developed high-grade lesions. Previously, screening was based only on regular Pap smear tests. HPV molecular testing unveils a wide population of women who are infected with HPV but who have yet to develop cervical dysplasia or cancer. This population represents over 90 million women worldwide for the two HPV types responsible for 70 percent of cervical cancer cases, HPV 16 and HPV 18. For these women, Genticel began to develop GTL001.

Vaxiclase has the same mode of action as the CyaA technology, licensed from Institut Pasteur, according to Marie-Christine Bissery, chief scientific officer of Genticel. While CyaA is a valuable antigen delivery vector, it can only accommodate small antigens. Thus, Genticel reengineered the original adenylate cyclase from B. pertussis, enabling it to host several or large antigens as well as antigens with acidic domains. This new proprietary vector, Vaxiclase, is the basis for Genticel’s follow-on candidate, GTL002, a multivalent HPV therapeutic vaccine targeting the six most relevant HPV types responsible for 85 percent of cervical cancer worldwide. The versatility of Vaxiclase, which could be used with multiple antigens for multiple indications, generated a first licensing agreement with Serum Institute of India Ltd. for the development of new multivalent prophylactic vaccines against a variety of diseases.

GTL001 is in Phase 2 in Europe and will be tested in the United States in a Phase 1 study this year. The first efficacy data from the Phase 2 study are expected in the first half of 2016, and the final results in the first half of 2017. If successful, Phase 3 trials could then start leading to a potential market entry in 2021 or 2022. GTL002 could enter a Phase 1 trial in 2017. The goal of this follow-on candidate is to provide a potential partner with a long-lasting HPV therapeutic franchise.

Genticel estimates a market potential of more than $1 billion per year for GTL001 and $2 billion for GTL002. The company currently has no direct competition in the segment of infected women with no or mild dysplasia.

“Achieving in-vivo preclinical proof of concept of GTL002 efficacy is an important milestone in strengthening Genticel’s HPV therapeutic vaccine pipeline,” concluded Koch. “These positive data show our ability to deliver a follow-on HPV product candidate and support our confidence in Vaxiclase’s substantial value in other therapeutic indications.”