Curie-Cancer, the body responsible for developing Institut Curie’s industry partnership activities, and DNA Therapeutics, a biopharmaceutical company developing a new class of cancer drugs, are renewing their partnership. The ongoing collaboration aims to provide a new class of therapeutic cancer products to patients, including those resistant to conventional therapies.

Based on Dbait technology, DT01 is currently is being assessed in combination with radiation therapy in a phase I clinical trial for approximately 20 patients with cutaneous metastatic chemotherapy-resistant melanoma. DT01 is the result of the partnership between Curie-Cancer and DNA Therapeutics. Dr. Christophe Le Tourneau, head of early-phase clinical trials at the Institut Curie and Principal Investigator for the trial, already has treated the first patients with this unique class of drugs.

Cancer cells easily can repair damage incurred in their DNA from conventional therapies such as chemotherapy and radiation therapy. A proposal has been made to limit this ability to repair by inhibiting an enzyme involved in the process. “There are multiple DNA repair pathways but there is no single enzyme that is common to all repair pathways,” said Marie Dutreix, CNRS research director at the Institut Curie. “In addition to being effective, the therapeutic approach should also be non-toxic to healthy cells. With Dbait we have a very unique approach.”

“Instead of targeting a specific enzyme of a repair pathway, Dbait works upstream of all repair pathways with regards to detecting damage caused by radiation therapy and/or chemotherapy. By disrupting the localization of the site of this damage, Dbait prevents any repair and kills cancer cells when they divide. What’s noteworthy is that the specific characteristics of cancer cells make them more vulnerable to the effects of Dbait than healthy cells, ensuring that the latter do not die,” said Dutreix. 

Initial results indicate cancers resistant to conventional therapies, including advanced-stage melanoma, can be treated with Dbait technology; DT01 is effective and very well-tolerated in combination with radiation therapy; and DT01 has a high potential for development, pending validation by other early-phase clinical trials, particularly in combination with chemotherapy for advanced-stage cancer.

The full results from phase I are expected within the next year.

The companies will focus their work on five key areas:

• Further understanding of the Dbait mechanisms of action, to better explain the lack of toxicity of these inhibitors on normal tissue
• Characterize the most responsive tumors as well as the most efficacious combinations with standard therapies to prepare for future clinical trials
• Identify potential resistance mechanisms to Dbait
• Identify predictive biomarkers for responding to Dbait
• Develop second-generation Dbait molecules with improved pharmacokinetic properties.

Professor Jian-Sheng Sun, CEO and founder of DNA Therapeutics, said, “While we are in the clinical assessment stage, Curie-Cancer is ready to launch, in partnership with Marie Dutreix and ourselves, a translational research program to support our efforts. The results of this program will be crucial in shortening time-to-market of our product in the best possible conditions.”

“Seeing a drug developed in our laboratory then become available to our patients is immensely rewarding. We look forward to the results of the current assessments and hope that this new class of drug can soon be offered to more patients,” says Damien Salauze, director of Curie-Cancer. “Supporting a French SME in its development and seeing these efforts rewarded are another source of satisfaction. This is another example of the values enshrined in the Institut Carnot label we received from the French government in 2011 for our commitment to providing practical solutions for our industry partners and ultimately, for patients."