MedImmune and 3M Drug Delivery Systems said today they will partner to develop new toll-like receptor (TLR) agonist cancer therapies. The value of their research collaboration was not disclosed.
The global biologics R&D arm of AstraZeneca has in-licensed from 3M MEDI9197 (formerly 3M-052), a TLR 7/8 dual agonist for which the FDA has accepted an IND for a Phase I safety and tolerability study as a potential treatment for patients with solid tumors. The study was not yet open for participant recruitment as of September 21, according to Clinicaltrials.gov.
MEDI9197 will be the first dual TLR7 and 8 agonist administered directly into a tumor in a clinical setting.
The collaboration further supports AstraZeneca’s strategy of developing combination treatments designed to fight cancer by targeting multiple mechanisms in the immune system.
MedImmune has agreed to oversee clinical development and strategy for MEDI9197. 3M will continue to develop additional TLR agonists in oncology and other therapy areas, with MedImmune holding exclusive rights to conduct research on new molecules resulting from the collaboration and to determine which to progress to clinical development.
MedImmune has agreed to pay 3M an upfront payment and payments tied to development milestones for MEDI9197 in addition to research funding. 3M retains the rights to the compound in certain topical applications and use in vaccine admixtures.
MEDI9197 is designed to activate a broad range of innate immune cells by targeting both TLR7 and 8, thus producing a more robust adaptive immune response. As a TLR7 and 8 dual agonist, the drug candidate is also designed to convert immune suppressive cells in the tumor to those with anti-tumor properties, allowing a more effective anti-tumor response.
In preclinical studies, the companies said, intratumoral dosing of MEDI9197 resulted in inhibited tumor growth of both the injected and distant lesions in multiple types of cancer, including melanoma.
“By targeting tumor antigen presentation, MEDI9197 adds a unique mechanism of immune activation to our growing portfolio and supports our strategy of maximizing anti-tumor immunity through scientifically rational combinations,” Yong-Jun Liu, M.D., Ph.D., MedImmune svp, R&D and head of research, said in a statement.
According to 3M, the drug candidate is similar to its Aldara (imiquimod 5% cream), the first TLR7 agonist product. Aldara was approved in 1997 for the topical treatment of external genital warts, actinic keratosis, and basal cell carcinoma. Since then, 3M said, it has synthesized more than 10,000 distinct molecules that act either as selective TLR7, selective TLR8, or as TLR7/8 agonists.
On its website, 3M says the compound is envisioned as a treatment for head and neck cancer. The company said current treatments for head and neck cancer were effective only for 40% to 50% of recipients due to major side-effects that include pain from feeding tubes, difficulty swallowing, rash, cardiac arrest.
“Initially indicated for patients who can’t receive surgery, we believe 3M-052 will eventually replace surgery as the standard of care,” 3M stated. “It’s not just a treatment. This next-generation immunotherapy could lead to a cure with far fewer side effects than standard surgical and radiation treatments.”