Obsidian Therapeutics has raked in $115 million to realize the long-unfulfilled therapeutic promise of tumor-infiltrating lymphocytes (TILs). The series B gives Obsidian a shot at showing whether freeing TILs from IL-2 can finally unleash power that research has hinted at for almost 30 years.
Researchers at the NIH began revealing the therapeutic potential of TILs in patients with metastatic melanoma in the 1990s. Given with high-dose IL2, the TILs triggered responses in around 70% of the participants. However, TILs struggled in indications beyond melanoma over the following years and toxicities linked to IL-2, notably fluid leakage from small blood vessels, held the modality back.
Obsidian wants to finally realize the potential of TILs by freeing the cells from the toxicities linked to IL-2. Typically, IL-2 is used to support the growth and activity of TILs. Obsidian is betting it can tackle tumors without IL-2 by adding membrane-bound IL-15 to its cells.
IL-15 drives expansion and persistence of T and natural killer cells. However, continuously exposing the body to IL-15 could cause its own toxicity problems. Obsidian’s solution is to fuse a new element to IL-15 that makes it possible to regulate its expression using acetazolamide, an FDA-approved drug used in the treatment of diseases including glaucoma.
Obsidian has preclinical evidence that IL-15 is found at normal levels on its engineered cells in the absence of acetazolamide. Administering acetazolamide increases IL-15 expression. So far, it looks like giving more or less acetazolamide moves IL-15 expression up and down, empowering physicians to tweak the effects of the cell therapies as they already adjust dosing of traditional drug modalities.
The series B round sets Obsidian up to test that idea in the clinic. Obsidian plans to use the series B funding to file an IND for its cytoTIL15 therapy around the middle of next year and go on to generate clinical data in metastatic melanoma, the indication in which TILs first showed promise back in the 1990s. Other solid tumor types are also on Obsidian’s hit list.
The Column Group Crossover Fund led the series B with assists from fellow new investors including RA Capital Management. Existing investors such as Atlas Venture, Amgen Ventures, and Bristol Myers Squibb chipped in, too. The money positions Obsidian as a player in a nascent TIL space that features other biotechs such as Iovance Biotherapeutics and Turnstone Biologics.