Partner Therapeutics, Inc. (PTx) announced a collaboration with the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services to fund a phase 2 study in patients with sepsis to assess the safety and enable dose selection of LEUKINE (sargramostim, rhu GM-CSF). The partners also will evaluate monocyte human leukocyte antigen-DR (mHLA-DR) and other biomarkers of immune status that could enable more precise identification of patients with sepsis who could benefit from LEUKINE treatment in addition to standard of care.

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, characterized by altered immune homeostasis.¹ It represents a critical unmet public health need urgently requiring safe and effective therapeutics guided by biomarkers to enable precise treatment approaches to reduce morbidity and mortality.^2,3 In 2017, 1.7 million sepsis cases were reported in the US and 48.9 million cases were reported globally resulting in 11 million deaths.²¹ Since much of the morbidity and mortality from chemical, biological, radiological and nuclear (CBRN) threats is due to sepsis, the availability of a host-directed therapy to treat sepsis utilizing validated biomarkers to inform treatment would greatly enhance health security. Leukine is currently held for use by ASPR-Strategic National Stockpile (SNS) for the treatment of hematopoietic acute radiation syndrome (H-ARS) as a host-directed therapy.

The PTx-BARDA partnership seeks to enhance patient care through restoration of immune homeostasis in patients with sepsis exhibiting a persistent immune suppressed state. Research shows that patients with sepsis with persistent immune suppression are unable to mount a sufficient immune response and experience significant mortality.^2,4,5 The clinical study will further evaluate the safety of LEUKINE in these critically ill patients and seeks to confirm the utility of mHLA-DR as a marker to identify sepsis-associated immune dysregulation.^2,6-10 Additional promising biomarkers of immune status in patients with sepsis also will be evaluated. Under a prior collaboration, BARDA and PTx supported the establishment of a Laboratory Developed Test (LDT) for mHLA-DR, which will be utilized in this collaboration.

"We are grateful to BARDA for their support of this program, which has the potential to advance medical care for patients with sepsis by evaluating potential tools for measuring immune status to inform targeted immunomodulatory therapy," stated John L. McManus, President, Health Security and Critical Care of Partner Therapeutics, Inc.

In small randomized clinical trials in critically ill patients with severe sepsis or septic shock, LEUKINE has been shown to promote immune homeostasis, as measured by a rapid and sustained improvement in mHLA-DR expression, as well as other markers of innate and adaptive immune function.^7,11-16 The observed changes in immune status were accompanied by improved clinical outcomes including 28-day survival and resolution of infection.

GM-CSF helps maintain immune homeostasis via innate and adaptive responses, and promotes tissue repair mechanisms.^2,7,17 While classically known for promoting differentiation of bone marrow (BM) precursor cells, and stimulating proliferation, differentiation, and maturation of myeloid cells, GM-CSF also induces mHLA-DR and plays important roles in antigen presentation, T-cell activation, and myeloid cell survival and function.^7,17-19 HLA-DR is part of the heterodimeric major histocompatibility complex class II (MHC II) on monocytes and is a measure of the cells' capacity for antigen-presentation. MHC II regulates monocytes' crosstalk with T helper cells, enabling the activation of the adaptive immune system.^4,20