SHERBROUK, Quebec—Exploring a new frontier in search of next-generation macrocyclic molecules and hit-to-clinical candidates are emerging pharmaceutical Cyclenium Pharma Inc. and Granada, Spain-based non-profit Fundación MEDINA (Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía). The two have signed a drug discovery agreement aimed at finding new anti-infective drug candidates to fight multidrug-resistant (MDR) infections. The terms of the deal have not been disclosed.
A major lynchpin of this international collaboration is Quebec-based Cyclenium’s proprietary QUEST Library of next-generation macrocyclic molecules in concert with Fundación MEDINA’s expertise in infective disease research.
“We are extremely excited about entering into this unique drug discovery collaboration with the Fundación MEDINA in one of our therapeutic focus areas,” Helmut Thomas, president and CEO of Cyclenium, stated in a Feb. 23 news release. “The combination of their superb team and world-class expertise in anti-infective research with our CMRT [customized macrocycles for recognition of topologies] technology and proven development success in the macrocycle arena offers an excellent opportunity for discovering desperately needed novel pharmaceutical agents against high-priority, treatment-resistant bacterial and fungal organisms.”
Thomas says the agreement with Fundación MEDINA is just one aspect of Cyclenium’s business strategy from the beginning.
Cyclenium Pharma was formed in December 2013 “to exploit a next-generation macrocyclic drug discovery technology designed to address the limitations of the early efforts in this area,” Thomas tells DDNews. “As a chemistry-focused company, we rely on select collaborators to provide biological and pharmacological expertise on targets in our three focus therapeutic areas: oncology, anti-infectives and inflammation/pain. The agreement with Fundación MEDINA allows us to capitalize on the synergy between our novel technology and successful track record in macrocycle drug discovery with (MEDINA’s) extensive experience in anti-infective discovery and preclinical development.”
The QUEST Library “is certainly the key asset that Cyclenium is contributing to in the first stage of the collaboration,” Thomas says. “However, that component only provides the starting point for our joint efforts with MEDINA. Once hits are identified, Cyclenium’s proprietary CMRT Technology, which is also used in the construction of the QUEST Library, will enable rapid hit-to-lead candidate optimization.”
For its part, Fundación MEDINA “brings a long and impressive track record in anti-infective and natural product drug discovery, which originated within the Merck Research Laboratories,” according to Thomas. “MEDINA initially will contribute its exceptional high-throughput screening platform for the identification and validation of new active compounds from the QUEST Library, then will apply their expertise in other appropriate assays for the selection and preclinical characterization of leads.”
The emergence of resistant organisms and the de-emphasis of antibiotic discovery by major pharmaceutical firms have resulted in a significant need in this therapeutic area, Thomas notes, adding, “Of paramount interest for the collaboration will be the discovery of novel macrocycles against the ESKAPE multidrug-resistant Gram negative pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Enterobacter species), which are responsible for an ever-increasing percentage of infections encountered in the clinic.
“For antifungals, the exploration of new agents to control systemic Candidiasis and respiratory Aspergillosis infections with lower toxicity will be an emphasis,” he said.
“At this early stage, it would be quite premature to speculate on the form of eventual pharmaceuticals or the specific indications, although it should be noted that the macrocyclic compounds we are focused on are suitable for oral formulations,” Thomas explains.
Olga Genilloud, scientific director of Fundación MEDINA, stated in a news release, “This relationship represents a strategic collaboration to identify novel drugs in the area of infectious diseases from the exploitation of Cyclenium’s unique library complementing the chemical diversity of our natural product libraries.”
“MEDINA, as a non-profit research organization focused on drug discovery from microbial natural products and as part of our strategy, we are seeking to establish collaborations that can leverage our extended drug discovery expertise and translate these capacities into the identification of new potential leads,” Genilloud tells DDNews. “The agreement with Cyclenium is a joint effort perfectly aligned with our strategic objectives in the field of anti-infectives and derives from the existing synergy between both organizations aiming at the discovery of new anti-infectives to treat MDR pathogens.”
MEDINA is directly descended from one of the longest operating and most successful natural products drug discovery programs in the pharmaceutical industry, and traces its roots back through more than 50 years of experience at Merck Research Laboratories, Genilloud says. “MEDINA has a long track record in the discovery of new anti-infectives, and will contribute … its platform of assays for the identification and validation of potential new bioactive compounds and their early preclinical characterization, enabling the joint development of the most promising new anti-infective leads.”
This partnership “will complement our current internal discovery efforts and will be totally aligned with MEDINA’s participation in international consortia aimed at the discovery of novel antibiotics, such as is the case of the IMI-ND4BB ENABLE program,” she adds.