BARDA and Partner Therapeutics foster a new partnership around their FDA-approved drug, Leukine® to improve patient care for sepsis patients

1 October 2021

LEXINGTON, Mass., Sep. 20, 2021 — Partner Therapeutics, Inc. (PTx) announced a collaboration with the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services, and Labcorp Drug Development to advance a new diagnostic approach to select immunoparalyzed sepsis patients that could benefit most from Leukine (sargramostim). Through advancement of a Laboratory Developed Test (LDT) for monocyte HLA-DR, Partner Therapeutics will be able to identify sepsis patients exhibiting an immune suppressed, or immunoparalyzed (IP) state and clinically evaluate Leukine as a study therapy in these individuals. The ability to identify patients with IP sepsis enables a precision medicine approach to maximize clinical benefit from immune boosting study therapy with Leukine.

This partnership will leverage Partner Therapeutics’ prior experience developing Leukine for Acute Radiation Syndrome, an FDA approved indication, as well as current clinical research for use of Leukine in patients with diverse immunosuppressed conditions. Use of Leukine in sepsis patients would expand disease indications of this therapeutic beyond those reliant on growth factor activity alone. GM-CSF is now known to influence differentiation, maturation, and metabolic capacity of mononuclear phagocytes, including circulating monocytes, tissue resident macrophages, and dendritic cells that may be either circulating or tissue bound. This pleiotropic cytokine may be beneficial in diverse disease states that are driven in part or in whole by GM-CSF deficiency.

“We are grateful to BARDA for their support of this program, which has potential to advance medical care for sepsis patients by selecting patients with immunoparalysis who would be most likely to benefit from immune enhancement by Leukine,” stated Debasish Roychowdhury, MD, Chief Technology Officer of Partner Therapeutics, Inc. “We look forward to working with Labcorp Drug Development to develop and validate the HLA-DR LDT and utilizing the LDT in two upcoming placebo-controlled studies of Leukine to enroll more than 1,000 patients with IP sepsis.”

Sepsis is a life-threatening complication of infection or other disease that occurs when the body has an extreme host response that can lead to organ failure and death. While some sepsis patients show evidence of severe, systemic inflammation, a subset of patients may present or transition to an immune suppressed IP stage. This diversity of states presents significant challenges for an effective treatment approach. IP state can be measured by the level of HLA-DR (class II MHC) on the surface of circulating monocytes. Monocyte HLA-DR expression level reflects the capability of these antigen presenting cells to present MHC-restricted antigens to T lymphocytes, a crucial link between innate and adaptive immunity. IP sepsis patients with low HLA-DR have elevated risk of early death. Leukine raises the level of HLA-DR expression, facilitating T cell activation and consequent specific immunity. Upcoming trials will support randomized study therapy with Leukine to evaluate its ability to increase survival in patients with IP sepsis.

Although immunomodulating therapeutics may be an effective approach to restore immune balance in IP sepsis patients, there are currently no approved FDA therapeutics nor companion diagnostic approaches that can effectively stratify patients who will benefit from such treatment.

Partner Therapeutics offers a novel assay that, if successful, will have the potential to endotype sepsis patients that may benefit from targeted clinical management with Leukine. This award will support development by Labcorp Drug Development of a quantitative flow cytometric laboratory developed test (LDT), able to detect HLA-DR protein on circulating monocytes, identifying patients in an IP state. The HLA-DR LDT can then be utilized in subsequent validation studies in adult and pediatric sepsis clinical trials. Partner Therapeutics will also collaborate with a commercial partner to initiate transition of the HLA-DR LDT to a commercial diagnostic for use with Leukine for sepsis and to support IND enabling activities for the IP sepsis indication of Leukine with the companion diagnostic.

If successful, development of the HLA-DR companion diagnostic would address the clinical need to match therapeutics to appropriate patient populations that maximize clinical outcomes. This precision medicine approach has tremendous potential to impact clinical management and improve patient outcomes. Further development of monocyte HLA-DR based endotyping technology may enable more effective treatment options for hospitalized sepsis patients.

This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under Contract No. 75A50121C00080.

ABOUT LEUKINE

LEUKINE® (sargramostim) is a yeast-derived recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF) Leukine is approved by the FDA and is also held by the U.S. Government for national preparedness.

Safety and efficacy of inhaled sargramostim for the treatment of COVID-19 has not been established and sargramostim is not approved for the treatment of COVID-19. Sargramostim has a different mechanism of action from recombinant G-CSFs products and data should not be extrapolated.

Leukine is indicated:

To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML).
For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients.
For the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation in adult and pediatric patients 2 years of age and older.
For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older.
For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older.
To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]).

Important Safety Information for Leukine (sargramostim)

Contraindications

LEUKINE is contraindicated in patients with known hypersensitivity to human granulocyte-macrophage colony stimulating factor such as sargramostim (GM-CSF), yeast-derived products, or any component of LEUKINE.

Warnings and Precautions

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If any serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy and institute medical management. Permanently discontinue LEUKINE in patients with serious allergic reactions.
LEUKINE can cause infusion-related reactions, including respiratory distress, hypoxia, flushing, hypotension, syncope and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease, as dose adjustment or discontinuation may be required.
Do not administer LEUKINE simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.
Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported in patients after LEUKINE administration. LEUKINE should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure.
Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a previous history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease.
If ANC > 20,000 cells/mm3 or if WBC counts > 50,000/mm3, LEUKINE administration should be interrupted or the dose reduced by half. Twice weekly monitoring of CBC with differential should be performed.
LEUKINE therapy should be discontinued if disease progression is detected during treatment.
Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration required.
Liquid solutions containing benzyl alcohol (including LEUKINE Injection) or LEUKINE for Injection reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates and low birth weight infants.
Concomitant use of drugs that can potentiate the myeloproliferative effects of LEUKINE should be avoided.

Adverse Reactions
Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported in a higher frequency than placebo are:

In Autologous bone marrow transplantation (BMT) patients–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
In Allogeneic BMT patients–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin
In AML patients–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema

ABOUT PARTNER THERAPEUTICS

PTx, an integrated biotechnology company, focuses on development and commercialization of late-stage therapeutics to improve health outcomes in treatment of cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit www.partnertx.com

MEDIA CONTACT

Bill McClements