Research we fund

Emory University

Our recent studies have identified specific bacteria that can potentially promote the growth of human myeloma tumor cells. We are now testing if eradicating these bacteria in MGUS patients will be effective for prevention of myeloma.

Program Name(s)

Academic Clinical Trials Program (ACT)

Albert Einstein College of Medicine

Survival rates for those afflicted with MDS have not improved despite extensive effort to identify the key genetic events in its pathogenesis. This project elucidates the contributions of aberrant NPM1 to hematological disorders, with a focus on mitochondrial fitness and inflammasome activation. The resulting insights into the metabolic, genetic and proteomic requirements of homeostasis that are critical to preventing aging will have a major impact on the treatment of hematological malignancies.

Program Name(s)

Discovery

University of Colorado Denver, Anschutz Medical Campus

The goal of this SCOR project is to identify and eradicate the root cause of acute myeloid leukemia, the so-called leukemia stem cell (LSC). In the previous cycle of this SCOR grant, we developed two unique strategies, each of which efficiently eradicates LSCs in the laboratory. Going forward, we will expand our scientific efforts to further improve these approaches and also conduct clinical trials to determine whether our approaches to killing LSCs will benefit AML patients.

Program Name(s)

Specialized Center of Research Program

TAP Partner

In June 2022, LLS made an equity investment in ImCheck Therapeutics to "Support Clinical Development of the ICT01 Program for Blood Cancer Indications."ImCheck Therapeutics is designing and developing a new generation of immunotherapeutic antibodies targeting butyrophilins, a novel super-family of immunomodulators.ICT01 is a humanized, anti-BTN3A (also known as CD277) monoclonal antibody that selectively activates γ9δ2 T cells, which are part of the innate immune system that is responsible for immunosurveillance of malignancy and infections. The EVICTION study is currently enrolling a Phase 2 cohort expansion of ICT01 in combination with azacitidine and venetoclax in patients with newly diagnosed acute myeloid leukemia (NCT04243499).

Program Name(s)

Therapy Acceleration Program

TAP Partner

In January 2023, LLS made an equity investment in BioInvent to "Support Clinical Development of BI-1206 for NHL Indications and BI-1808 for T-Cell Lymphoma Indications Including CTCL."BioInvent International AB is a clinical-stage biotech company that discovers and develops novel and first-in-class immuno-modulatory antibodies for cancer therapy, with currently four drug candidates in five ongoing clinical programs in Phase 1/2 trials for the treatment of hematological cancer and solid tumors, respectively. The Company's validated, proprietary F.I.R.S.T™ technology platform identifies both targets and the antibodies that bind to them, generating many promising new drug candidates to fuel the Company's own clinical development pipeline and providing licensing and partnering opportunities.BI-1808 is an anti-TNFR2 antibody being evaluated in a Phase 2 trial, as a single agent and in combination with the anti-PD-1 therapy Keytruda® (pembrolizumab) in patients with ovarian cancer, non-small cell lung cancer and cutaneous T-cell lymphoma (NCT04752826).

Program Name(s)

Therapy Acceleration Program

Albert Einstein College of Medicine

Overactivation of the inflammasome is seen in CMML and leads to worsening of this condition. We will explore the potential of a new inflammasome inhibitor drug, HT-6184, in CMML patient samples and in animal models. Our preliminary results show that this drug can decrease inflammation and improve red cell development in CMML models. The new drug is approved for clinical trial use and our work will potentially lead to its use in clinical investigations in CMML.

Program Name(s)

CMML Initiative

The therapeutic landscape of acute myeloid leukemia (AML) has witnessed considerable expansion following recent U.S. FDA endorsements of novel therapies; however, the 5-year survival rate for most adult patients remains below 10%. The absence of immunotherapeutic options for AML can be attributed, in part, to the dearth of identified antigens that selectively discriminate between AML cells and normal hematopoietic precursor cells. Through extensive investigative efforts, our laboratory has made a significant discovery of a membrane antigen, U5 snRNP200, which exhibits promising potential for Fc-engineered anti-U5 snRNP200 therapy. The overarching objective of this endeavor is to engender a novel cellular immunotherapeutic modality with the potential for broad therapeutic impact across a diverse spectrum of myeloid and lymphoid hematologic malignancies.

Board of Trustees of the Leland Stanford Junior University

Chronic myelomonocytic leukemia (CMML) is a rare but poorly understood blood cancer often presenting with crippling inflammatory symptoms that frequently evolves into acute leukemia. In an ongoing clinical trial, we have compelling molecular and clinical data that this disease responds effectively to blockade of GM-CSF with lenzulimab, a well-tolerated and safe antibody, in combination with azacitidine. Here, we propose an integrated research program to investigate targeting of the GM-CSF pathway in high risk CMML using our carefully matched patient samples, proprietary GM-CSF tools, and humanized in vivo CMML models.

Program Name(s)

CMML Initiative

Garvan Institute of Medical Research

Multiple myeloma causes devastating bone disease characterised by focal bone lesions and generalise bone loss, which leads to an increase in bone fractures. Current therapies only stop bones from getting worse so patients continue to suffer fractures. We discovered that inhibiting a molecule called sclerostin in mice increases bone and is much better than current treatments. In this program we will investigate whether inhibiting sclerostin is able to restore lost bone and reduce fractures in patients with myeloma.

Program Name(s)

Translational Research Program

University of California, San Francisco

This project will significantly advance the treatment and prevention of CNS lymphomas in two key areas. One, we will further develop and validate candidate genomic biomarkers that identify high risk disease and that are useful in risk stratification in future clinical investigations in primary CNS lymphoma. Two, we will evaluate novel pharmacologic interventions that we hypothesize will: a) potentiate both the anti-lymphoma immune response, including agonists of the toll like receptor 7 and 8 pathway, as well as the combination of the anti-CD19 monoclonal antibody tafasitamab plus lenalidomide; and b) antagonize the NFkB pathway, via the orally-administered BTK degrader, Nx-5948, that we have demonstrated to be active in preclinical models using patient-derived CNS lymphomas.

Program Name(s)

Translational Research Program

TAP Partner

In March 2020, LLS made an equity investment in Kymera Therapeutics to "Support Studies with Protein Degraders for Development in Hematological Patients."Kymera Therapeutics is a clinical-stage biopharmaceutical company founded with the mission to discover, develop, and commercialize transformative therapies while leading the evolution of targeted protein degradation, a transformative new approach to address previously intractable disease targets. Whereas most targeted therapies inhibit or inactivate the proteins or genes that drive the cancer, targeted protein degradation harnesses the body’s natural system of ridding itself of unwanted, “old” or “broken” components of cells.KT-253 is a MDM2 protein degrader and is enrolling AML patients in a Phase 1 clinical trial (NCT05775406).

Program Name(s)

Therapy Acceleration Program

Memorial Sloan Kettering Cancer Center

A major limitation of immunotherapy approaches for AML has been the lack of known targetable cell surface antigens specific to AML cells. This project characterizes the pathologic and biologic effects of a novel cell surface antigen complex uniquely present on AML cells but not normal hematopoietic precursors, known as the U5 snRNP complex. Furthermore, we will interrogates U5 snRNP complex components as novel AML-associated antigens and CAR T cells targets for AML treatment.

Program Name(s)

Career Development Program