$37.5M in hand, Termeer-backed X4 maps a fast pace on cancer immunotherapy R&D

X4 CEO Paula Ragan

Over the last 18 months Genzyme founder Henri Termeer has been helping organize and finance a new biotech called X4, which has taken up residence in Cambridge, MA, and is now going public with a $37.5 million A round and a plan to make its mark in the hot field of immuno-oncology.

Unlike most of the new biotechs that have been popping up in the fertile grounds of Cambridge, X4 has steered a course around the venture headliners that have been growing a big crop of upstart drug developers. Cormorant Asset Management came in as the lead investor, with Termeer joining a list of private investors who are sticking to the background.

They're putting their money behind a drug asset outlicensed by Sanofi ($SNY), which has cut back sharply on a plan to go big in cancer after its in-house group floundered badly in oncology R&D, forcing a significant reduction in its ranks of cancer investigators.

The biotech's lead drug is X4P-001, a CXCR4 inhibitor that is slated to begin a Phase Ib/IIa dose escalating/proof-of-concept trial in Q1 2016, part of a program that will encompass refractory clear cell renal cell carcinoma (ccRCC) along with a second solid tumor indication. And there's a second drug being lined up specifically designed for brain cancer--the key here is penetrating the blood-brain barrier that keeps drugs out of the brain--that should start in the clinic in 2017 as the company pieces together its pipeline.

X4 is playing at a popular intersection of oncology R&D. CXCR4, or C-X-C receptor type 4, is the receptor for the chemokine CXCL12. New research has highlighted how that receptor-ligand pair scrambles an immune response, stunting a T cell attack while mustering immunosuppressive stromal cells that can protect cancer. That makes it a candidate for combinations with other drugs, particularly the checkpoint inhibitors that have been making waves in the cancer field.

CXCR4, by the way, is also used by HIV to get into cells, and Sanofi had been studying this particular drug in HIV before abandoning it and later outlicensing the drug to X4. That earlier work provided some key insights on safety and activity.

X4 isn't the only company that has focused on the field. Sanofi markets a CXCR4 injectable named Mozobil (plerixafor). The small Israeli biotech BioLineRx ($BLRX) has a peptide drug dubbed BL-8040 in Phase II. And GlycoMimetics is active as well. But X4 sees a next-gen role for itself.

"We're the only company with an oral, small molecule CXCR4 agonist," says Paula Ragan, a Genzyme vet who's taken the helm at the startup. And Ragan--the former BD exec at Lysosomal Therapeutics, another Termeer company--says their rather unusual group of backers in the company will set the stage for a much faster development campaign than traditional VCs would be comfortable with. All the A round is in the bank, she adds, and once the proof-of-concept study is completed the company plans to move into a pivotal trial as the team explores new partnerships with biopharma players.

X4 is the latest in a series of biotech investments for Termeer, who's been playing an active startup role in Cambridge since selling Genzyme to Sanofi for $20 billion. A few months ago he joined a syndicate that put up $10 million to fund the startup Artax, which is focused on autoimmune diseases. He helped seed Auro Biosciences' work on a nano-sized drug delivery vehicle for cancer. Termeer co-founded Lysosomal Therapeutics with Bob Carpenter, another Genzyme vet and chairman of Hydra Biosciences. He backed the Dutch biotech ProQR. And he sits on the boards at Moderna, which has been raising vast sums, Allergan ($AGN), Verastem and Aveo, which is trying now to mount a comeback.

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