Defence Therapeutics to begin phase 1 trial for new anti-cancer treatment
Defence Therapeutics Inc., a Canadian biopharmaceutical company specialising in the development of immune-oncology vaccines and drug delivery technologies, is pleased to announce the successful completion of all GLP studies related to its anti-cancer treatment, AccuTOX.
The Company is planning to meet with the FDA in the coming weeks to obtain approval for launching its Phase I trial against solid tumours.
AccuTOXTM: an aggressive anti-cancer treatment
In the past 16 months, Defence engineered a large library of AccumTMvariants exhibiting differential effects on both immune and cancer cells. One of these lead molecules is AccuTOX, a small compound capable of effectively killing a large set of murine and human tumours by inducing the production of reactive oxygen species, causing immunogenic cell death and triggering direct DNA damage akin to chemotherapeutic agents. Interestingly, AccuTOX administration synergises with different immune checkpoints (anti-PD-1, anti-CTLA4 and anti-CD47) making it a highly mouldable molecule adaptable to a myriad of solid cancer indications. For instance, AccuTOX dosed at 16 mg/kg halts the growth of solid T-cell lymphoma, melanoma, and breast cancer in mice with a survival rate of more than 90%. These results combined with the molecular characterization of AccuTOX’s mechanism of action highlight the anti-neoplastic potential of this molecule as a next-generation anti-cancer treatment for various cancer types.
GLP studies in rodents revealed no adverse effects for AccuTOX
Building upon the impressive results obtained in different pre-clinical murine cancer models, a set of GLP studies was then conducted in male and female Sprague-Dawley rats to determine the toxicity potential and toxicokinetic profile of AccuTOX when administered through the subcutaneous route for 14 days (delivered every 48h for a total of seven repetitive injections). Besides slight erythema/edema at the injection site, no clinical signs of morbidity or mortality were observed in both sexes using a dose as high as 30 mg/kg, which is twice as high as the therapeutic dose used in pre-clinical studies. Animals’ body weight, food consumption, coagulation and urine parameters were unaffected at all tested doses in both male and female rates. Haematological changes were considered minimal with no noticeable side effects to report. Furthermore, the time to reach peak plasma concentration (Tmax) was ~1h in both genders. In conclusion, AccuTOXTM exhibits no adverse effects in rats and is well tolerated even at repetitive dosing of 30 mg/kg.
AccuTOX is safe and well-tolerated in canines
Upon completing the GLP study in rats, Defence followed up with a second set of GLP studies in Beagle dogs. In this case, higher AccuTOX doses were used (up to 100 mg/kg, which is 6.2-fold higher than the therapeutic dose used in mice). Although no clinical signs were observed up to 50 mg/kg, very slight erythema was observed at the injection site following single dosing. Repetitive dosing, on the other hand, revealed very limited erythema and hardness at injection sites, which made minimal impact. No mortalities were observed in male or female dogs up to 100 mg/kg and body weights of all treated animals were consistent despite a small decrease in food consumption. No apparent changes were noticed in the conducted electrocardiograms in both genders, nor in their haematological, coagulation and urinalysis parameters. Chronic inflammation was apparent at the injection sites associated with mild leukocyte infiltration. The Tmax for AccuTOX in dogs varied between 0.25 and 1h in both genders, with a detected T1/2 of ~0.553h. In summary, AccuTOX is safe and well tolerated by Beagles with limited local effects observed at injection sites.
A Phase I trial in the pipeline
“The AccuTOX programme has greatly matured since its inception in mid-2021. The molecule is highly effective as an anti-cancer molecule and exhibits no toxic effects in different animal models (mice, rats, and dogs). The fact that dogs can tolerate AccuTOX up to 100 mg/kg demonstrates a larger than the expected therapeutic window for this anti-cancer treatment”, says Mr Plouffe, the CEO of Defence Therapeutics.
Defence is currently preparing to meet with the FDA in the coming weeks to present its pre-clinical and GLP studies to get approval for initiating a Phase I trial on a basket of solid tumours. The primary objective will be to demonstrate the safety and tolerability of the drug in cancer patients while assessing some form of potency as a secondary objective. Data Bridge Market Research shows that the solid tumours market was valued at USD 209.61 billion in 2021 and is expected to reach USD 901.27 billion by 2029, registering a CAGR of 20.0% during the forecast period of 2022 to 2029.