Curie-Cancer, DNA Therapeutics renew partnership to identify new class of cancer drugs

Their clinical and translational research program has developed Dbait molecules now in Phase I clinical trial in patients with advanced melanoma

Curie-Cancer, the body responsible for developing Institut Curie’s industry partnership activities, and DNA Therapeutics, a biopharmaceutical company that is developing a new class of cancer drugs, are renewing their partnership.

The ongoing collaboration will aim to provide a new class of therapeutic cancer products to patients, including those who are resistant to conventional therapies.

Initial clinical results are encouraging

The first molecule based on Dbait technology, DT01, is currently 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 this trial, has already treated the first patients with this unique class of drugs.

Initial results indicate that:

• Cancers that are 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 
• 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.

Dbait, a new class of cancer drugs

Cancer cells can easily 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,” says 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,” says Marie Dutreix.

Curie-Cancer alongside DNA Therapeutics throughout the entire research process

To support this highly promising clinical research program, DNA Therapeutics and Curie-Cancer 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

“We find all the expertise and support that we need from Curie-Cancer,” says Prof. Jian-Sheng Sun, CEO and founder of DNA Therapeutics. “The reputation of the Institut Curie, in terms of the quality of its fundamental and clinical research, speaks for itself. However, the continued support, even during difficult times, from Curie-Cancer and its ability to apply complementary expertise throughout the development process of a drug have definitely contributed the most to our success. 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.”

“The Institut Curie is pleased with this long-term partnership, which started at the fundamental research stage and continues today to the clinical research stage. 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."