Five Prime Therapeutics bets $452.5 million on novel immune checkpoint antibodies

Five Prime Therapeutics (NASDAQ: FPRX) announced a license agreement with Inhibrx for novel GITR antibodies on Thursday. Under the terms of the agreement, Five Prime will pay Inhibrx a $10 million license fee and up to $442.5 million milestone payments.

Inhibrx was co-founded by Dr. Quinn Deveraux who leads the R&D for the company. Prior to founding Inhibrx, Deveraux spent 10 years at the Genomics Institute of the Novartis Research Foundation. In 1997, Deveraux revealed the mechanism of IAP (inhibitor of apoptosis protein)[1], the first known cellular inhibitor of caspases.

Inhibrx’s lead candidate, INBRX-103, was licensed by Celgene for 500 million in June 2012. The mAb targets CD47 on cancer cells. CD47 interacts with SIRPα on macrophages and sends a “don’t eat me” signal. INBRX-103 has entered clinical studies in early 2015.

Back to the topic, GITR (also known as TNFRSF18) is a member of the TNF receptor superfamily. The protein is mainly expressed on regulatory T cells (Tregs, CD4+CD25+) that suppress immune responses. GITR agonists suppress Tregs and thereby enhance immune responses.

Thirteen years ago, Japanese immunologists first found that activation of GITR abrogated Tregs-mediated immune suppression[2]. GITR Inc. (Tolerx Inc.) is developing a first-in-class GITR agonist called TRX518 in melanoma. The Phase I trial of TRX518 was initiated in 2010, but it is still recruiting patients at present.

Inhibrx believes its INBRX-110 is the best-in-class GITR antibody. Based on Inhibrx’s multivalent antibody technology, INBRX-110 activates GITR independent of Fc binding. This is in contrast to conventional GITR antibodies.

Genentech, Bristol-Myers Squibb, and AstraZeneca are developing co-stimulatory antibodies that target other members of the TNF receptor superfamily such as CD40 (TNFRSF5), OX40 (TNFRSF4), 4-1BB (TNFRSF9). It is commonly believed that adding co-stimulatory antibodies to anti-PD1 therapy can enhance the antitumor immunity.

[1] Nature. 1997, 388(6639), 300-304.
[2] Nat Immunol. 2002, 3(2), 135-142.

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