After just two years, Five Prime Therapeutics has ducked out of an immuno-oncology collaboration with InhibRx that on signing had a value of more than $460 million.
In a short notice to the SEC, Five Prime said it had delivered a notice of termination to InhibRx for the agreement, which included a wide-ranging license to antibodies targeting the glucocorticoid-induced tumor necrosis factor receptor (GITR) as well as an option on other targets.
Five Prime paid $10 million upfront in July 2015 for the rights to the GITRs, proteins expressed by the body's T cells that it hoped would help stimulate an immune system attack on cancerous cells. Another $450 million plus—in cash or Five Prime stock—was dependent on progress with the program.
GITR has been proposed as a particularly promising target in immuno-oncology, with research suggesting that drugs targeting it can inhibit regulatory T cells that dampen down the immune response, whilst activating effector T cells which can attack tumors.
The collaboration between Five Prime and InhibRx had already yielded lead candidate INBRX-110 (FPA-154), which according to the partners differs from other GITR drugs as it can work independent of Fc binding, avoiding the possibility of serum antibodies competing with and reducing the activity of the drug.
A number of anti-GITR drugs have been pushed into early-stage clinical development by biopharma companies, according to a review article published last year in the European Journal of Cancer, including small biotech GITR Inc as well as bigger players such as Merck & Co, Bristol-Myers Squibb, Amgen and AstraZeneca's Medimmune unit.
In its second-quarter update earlier this month the company indicated the program was still active and heading for an Investigational New Drug (IND) application early next year. Now, it tells FierceBiotech: "At Five Prime, we want to strike an appropriate balance between moving fast, prioritizing programs, maximizing optionality and wisely managing our expenses. Terminating this program is such an example and there were many factors to consider. As a company, we have multiple pre-clinical and clinical opportunities to pursue and are judicious about our allocation of resources. As such, we made the decision to terminate the FPA154 program."
Aside from FPA-154, Five Prime is working on two other immuno-oncology programs that have come out of its own labs, namely FPA150, and anti-B7-H4 drug in development for breast, ovarian and endometrial cancers and FPT155, which combines CTLA4 and PD-L1 inhibition with CD28 stimulation. Both are still in preclinical testing.
The loss of Five Prime as a partner still leaves InhibRx with a $500 million alliance with cancer specialist Celgene covering INBRX-103/CC-90002, an anti-CD47 antibody that started clinical testing in 2015.
CC-9002 is designed to remove a brake on the immune system that prevents cancer cells being attacked and eliminated by tumor-associated macrophages and, according to Celgene's latest pipeline report, is in phase 1 trials for acute myeloid leukemia and solid tumors.