DNA Therapeutics to present DT01 phase 1/2a trial results at ASCO 2015

DNA Therapeutics, a private biopharmaceutical company developing DT01, a first-in-class clinical pan DNA repair inhibitor to treat tumors resistant to conventional treatments, will today present the results of the first-in-man phase 1/2a trial of DT01 in combination with radiation therapy in patients with cutaneous metastatic melanoma. The results will be presented in a poster session at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, USA.

The trial consisted of 23 patients with melanoma skin metastasis, recruited across seven centers in France. All patients followed a two-week treatment plan and were evaluable for safety and pharmacokinetics. 21 patients were evaluable for efficacy on 76 irradiated lesions of which 41 were injected with DT01. No dose-limiting toxicity was observed. The most frequent adverse events were reversible grade 1 and 2 injection site reactions. Pharmacokinetics analyses demonstrated a systemic passage of DT01. Objective responses were observed in 51 lesions (67%), including 23 complete responses (30%). The overall response rate was correlated with DT01 systemic exposure in the subgroup of lesions that were not directly injected with DT01, suggesting a systemic effect.

Cancer cells can easily repair themselves after damage incurred in their DNA from conventional therapies such as chemotherapy and radiation. To limit this, researchers have tried to inhibit enzymes involved in the repair process. ‘There are multiple DNA repair pathways but there is no single enzyme that is common to all of them,’ said Dr. Marie Dutreix, CNRS research director at the Institut Curie. ‘As well as being effective, a therapeutic approach should also be non-toxic to healthy cells. With DT01, we have a unique approach.’

Instead of targeting a specific enzyme of a repair pathway, DT01 works upstream of all repair pathways by preventing the detection of damage caused by chemotherapy and/or radiation therapy. By disrupting the signaling of the damage sites, DT01 prevents repair and triggers the death of cancer cells as they divide. Worldwide, DNA Therapeutics is the only company working on disrupting the damage signal. The specific characteristics of cancer cells make them more vulnerable to the effects of DT01 than healthy cells, ensuring that the latter are not damaged by this novel therapy.

‘DT01 in combination with radiation therapy is safe and provides antitumor activity in patients with melanoma skin metastases,’ said Dr. Christophe Le Tourneau, head of early-phase clinical trials at the Institut Curie and principal investigator for this trial. ‘The DT01 systemic passage and the correlation between DT01 blood exposure and efficacy suggest a systemic effect. This trial opens the path for DT01 systemic administration in combination with chemo/radiotherapy.’

‘The efficacy of the combination was much better than the usually observed response rate obtained with radiation therapy alone, i.e. 9% of complete responses,’ said Dr. Youlia Kirova, the radiation oncologist in charge of the treatment.

The results of the DRIIM trial have been submitted to a peer-review publication.

‘We are very grateful to all the patients and the investigators who made these encouraging data available. We are excited about DT01 potential systemic activity. We will strive to demonstrate DT01 efficacy in combination with standard of care therapies in advanced solid tumors through our Phase 1/2 trial,’ said Prof. Jian-Sheng Sun, chairman of the board and chief executive officer of DNA Therapeutics. ‘Proving DT01 systemic activity will help address highly unmet medical needs in aggressive late stage cancers, such as triple negative breast cancer. We are liaising with potential pharma partners and investors to streamline the development and shorten time-to-market for the benefit of patients and all stakeholders. We are thankful to our investors, the Institut Curie, Genopole, Medicen and other institutions and agencies (Bpifrance, ANR, INCa,).’

Following the positive results of the DRIIM trial, DNA Therapeutics' next step is to demonstrate DT01 systemic anticancer activity in combination with chemotherapy in advanced stage cancers non responsive to standard therapy through a comprehensive Phase 1/2 clinical development program. Positive results generated in such a program would establish DT01 as a breakthrough therapy for the treatment of advanced cancers.