X4, nearing late-phase trials of ex-Sanofi drug, raises $27M

X4 has seized on a rare disease opportunity that offers it a faster route to market.

X4 Pharmaceuticals has raised $27 million to advance a CXCR4 inhibitor it picked up from Sanofi. The series B equips X4 to move deeper into the clinic on two fronts, with phase 2 and 3 trials in cancers and rare diseases on the horizon.

Cambridge, Massachusetts-based X4 first broke cover when it unveiled its $37.5 million series A in 2015. Back then, X4, with money and support from Genzyme founder Henri Termeer, was taking forward an oncology asset that had fallen out of favor at Sanofi. X4 has delivered on that front with clinical data in renal cell carcinoma and melanoma. But it has also seized on a separate, rare disease opportunity that offers it a faster route to market.

X4 was yet to advance the idea of testing a low dose of lead candidate X4P-001 in WHIM syndrome beyond exploratory discussions at the time of the series A. And as recently as this time last year the program was absent from X4’s public pipeline.

Things have moved quickly since then. With regulators on both sides of the Atlantic supporting the running of a single, potentially-pivotal phase 2/3, X4 is now working toward data that could bring X4P-001-RD to market. 

“We felt we were in a position to jump start the program,” X4 CEO Paula Ragan, Ph.D. said. “It's a phenomenal leap forward in this development path for us as a company.”

The fast advance is underpinned by safety and pharmacodynamic data generated for the oncology indications, plus recognition of the need for treatments for the rare primary immunodeficiency disease WHIM syndrome. X4 thinks X4P-001-RD can normalize the overactive CXCR4 signaling that drives WHIM syndrome, thereby fixing the immune system dysfunctions that render patients very susceptible to bacterial infections. 

X4 expects to finalize the dose for the phase 3 portion of the trial in the first half of 2018 and go on to start that stage of the study around the end of next year. The series B funds from Cormorant Asset Management, the lead investor in the series A, and other existing and new financiers will see X4 through to the start of the phase 3. 

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The move between the phase 2 and 3 portions of the WHIM syndrome trial is part of the broader evolution of X4 into a mid to late-phase biotech. Next year will also see X4 complete enrollment in the phase 2 portion of its kidney cancer trial. Upon completing enrollment in the first half of next year, Ragan thinks it will be another six to 12 months before X4 has data. 

Ragan is optimistic PFS and durability data will support the move into a pivotal trial. in the phase 1b portion of the trial, the combination of X4P-001-IO—a higher dosage form of X4P-001-RD—and Inlyta achieved a disease control rate of 92%, higher than is seen when the Pfizer drug is given as a monotherapy. One of the 14 participants experienced a complete response, something that didn’t happen in far larger trials of Inlyta. 

The phase 2 data will go some way to showing whether that is a statistical quirk or evidence the CXCR4 inhibitor has a big future in kidney cancer. 

X4 is also working to assess whether X4P-001-IO has a future in melanoma. The candidate is one of a sea of assets being developed to make checkpoint inhibitors more broadly effective by turning cold tumors hot. X4’s first task is to show the complementary mechanism works as hoped, a step Ragan thinks some other companies are skipping.

“Often times people are just rushing into combination trials without truly understanding the underlying mechanism of how the drug is working,” Ragan said.

X4 now has data from longitudinal biopsies linking X4P-001-IO to infiltration of CD8+ T cells into the tumor microenvironment, suggesting the combination is worth exploring further.

To advance on these multiple fronts, while also pushing forward a blood-brain barrier penetrating preclinical program, X4 plans to grow its headcount from 20 up to around 30.