21 December 2017 - - US-based biopharmaceutical company FLX Bio, Inc has closed a USD 60m Series C private financing, the company said.

The financing included new investments from GV (formerly Google Ventures) and other undisclosed investors as well as existing investors including The Column Group, Kleiner Perkins, Topspin Partners and Celgene Corp.

In addition to announcing its financing, FLX Bio recently dosed its first subject in a Phase 1 clinical trial for FLX475, a best-in-class, oral small molecule antagonist of CCR4.

The company's strategy is to accelerate early clinical development in cancer patients by first rapidly obtaining pharmacokinetic, pharmacodynamic, and preliminary safety data in healthy volunteers.

Findings from the healthy volunteer study will enable a more focused and efficient Phase 1 study in cancer patients, potentially resulting in faster achievement of clinical proof of concept.

FLX475 is a best-in-class oral, small molecule antagonist of CCR4. In preclinical studies, FLX475 inhibited tumor growth and increased tumor regression as a single agent.

In addition, FLX475 enhanced the antitumor effects of various checkpoint inhibitors including anti-PD-L1 and anti-CTLA4 antibodies as well as immune agonists such as anti-4-1BB.

FLX475 also has the potential to enhance cell-based immunotherapies such as CAR-T and cancer vaccines.

Unlike antibodies to CCR4, FLX475 selectively blocks the recruitment of regulatory T cells to the tumor site, and does not deplete cells beneficial to an anti-tumor response or regulatory T cells in healthy tissue such as blood, spleen and skin cells.

In addition to the study ongoing in healthy volunteers, FLX Bio intends to initiate a clinical trial of FLX475 alone and in combination with a checkpoint inhibitor in oncology patients in 2018.

Ubiquitin specific protease 7 plays a key role in two important cancer pathways: it promotes the formation and function of regulatory T cells by deubiquitinating and stabilizing FOXP3; and it maintains low levels of p53, a prevalent tumor suppressor protein, thereby allowing the tumor to grow unchecked.

USP 7 is an enzyme that removes a tag called ubiquitin from proteins and stabilizes the expression of those proteins in the cell. USP7 stabilises a regulatory protein called FOXP3 found within regulatory T cells, and promotes the number and activity of regulatory T cells.

In addition, USP7 stabilizes MDM2, causing p53 levels go down, thus allowing cancer cells to proliferate. A USP7 inhibitor elicits two beneficial effects increased immune system response to the tumor and enhanced tumor suppression by p53. FLX Bio expects to select a clinical candidate in late 2018.

GCN2 is a myeloid-derived suppressor cell target that works downstream of IDO and arginase. GCN2 inhibition has the potential for superior efficacy as it can reverse immune-suppression caused by depletion of both tryptophan and arginine. 

FLX Bio is an immuno-oncology company focused on the discovery and development of orally-available, small molecule drugs to activate the immune system and eradicate cancer.

Using its integrated immuno-oncology drug discovery platform, FLX Bio's small molecule compounds specifically target proteins and pathways important for regulatory T cells or myeloid cells within the tumor microenvironment.

Its lead candidate, a best-in-class CCR4 inhibitor, entered Phase 1 studies in December 2017 and has the potential to be used alone or in combination with checkpoint inhibitors to treat a variety of cancers. 

The company employs a precision medicine strategy for prospective patient selection in clinical studies, applying its robust computational and translational biology capabilities to identify key biomarkers that should maximize clinical response and increase the probability of clinical success.

Located in South San Francisco, California, and funded by leading investors, including The Column Group, Kleiner Perkins, Topspin Partners, GV and Celgene Corp., FLX Bio has assembled a leadership team and advisory group with a proven track record of success and team of scientists with substantial knowledge and expertise in drug discovery and translational areas essential to execute on this approach.