With Pivotal WHIM Readout Ahead, 2022 Could be Decisive Year for X4

X4_Paula Reagan

X4 Pharma CEO and President Paula Ragan, Ph.D./Courtesy X4

Boston-based X4 Pharmaceuticals reported its first-quarter financial report Thursday. Of note was the company cash, cash equivalents & restricted cash, which was $ 67.7 million as of March 31. X4 said that this will fund company operations into the fourth quarter of this year.

This places plenty of pressure on X4’s upcoming data readings, which include topline data from a pivotal 4WHIM Phase III trial in the fourth quarter. WHIM syndrome is a rare congenital immune deficiency. It is marked by warts, hypogammaglobulinemia, infections and myelokathexis. There are no approved therapies for WHIM syndrome.

The 4WHIM study is evaluating mavorixafor, an oral, once-daily treatment for WHIM syndrome. In the Phase II trial, researchers achieved clinical proof of concept and demonstrated a decrease in severe neutropenia and significant lymphopenia. The drug was generally well-tolerated. Patients also had decreased infection rates and substantial and visible reductions in wart lesions.

“As we quickly approach top-line results from our 4WHIM pivotal Phase III trial for WHIM syndrome by the end of this year, the X4 team continues to identify and expand the breadth of individuals diagnosed with this rare disease,” said Paula Ragan, Ph.D. .D., President and CEO of X4. “Initiatives aimed at supporting diagnosis and driving disease awareness, such as our Path4Ward program offering free genetic sequencing to patients, and publishing peer-reviewed research to help define novel pathogenic genetic variants, are adding to the population of those known to be affected by WHIM and chronic neutropenia. ”

To that end, Ragan said X4 is “expanding the availability of genetic testing through Path4Ward and evaluating patients with congenital, idiopathic and cyclic chronic neutropenia in our ongoing Phase Ib study. We look forward to providing both clinical data and regulatory updates over the coming months on this important initiative. ”

X4 has finished enrollment in the ongoing Phase Ib trial of mavorixafor in combination with ibrutinib (Janssen and Pharmacyclics‘Imbruvica) in Waldenstrom’s Macroglobulinemia (WM), a rare B-cell lymphoma whose tumors express mutations in MYD88 and CXCR4. Results are expected in the second half of this year.

Despite this, on the conference call, Ragan indicated X4 did not expect to submit mavorixafor to the US Food and Drug Administration for WHIM syndrome until the second half of 2023.

“With three readouts this year, we’re extremely excited for what’s to come,” she said.

The company is developing mavorixafor in WHIM, Waldenstrom’s and chronic neutropenia. It also has two preclinical programs, X4P-002 for oncology indications, and X4P-003 for primary immuno-deficiencies. Ragan describes the company as focused on “rare disorders of the immune system.”

On Feb. 9, the company amended its deals with several banks and financial institutions. On Dec. 21, 2020, X4 had a term loan advance of $ 7.5 million, added to the $ 25 million term loan it had prior. The company can make additional term loan advances in an aggregate amount of up to $ 17.5 million through Dec. 31, 2022.

The company filings noted that the Initial test date for the loans was Apr. 1, 2022, or the date when the Phase III trial of mavorixafor was discontinued or interrupted for safety concerns or futility. Since it was not, the next initial test date is Sept. 1, 2022.

Ragan suggested on the conference call that she believed the company was capable and preparing to handle WHIM indications in the US, but that “the world is a big place,” and X4 would be open to partnerships to expand the company reach outside the US Meanwhile , X4 is “revving up for a successful launch after our successful Phase III readout later this year.”