Research we fund

Emory University

Winship Cancer Institute is the only NCI-Designated Comprehensive Cancer Center in Georgia, the largest state by land area east of the Mississippi River, and 8th largest state by population. The Winship IMPACT program will leverage existing relationships throughout the state to bring hematology trials to patients in their communities. The goals are to strengthen our relationship with community sites and to increase opportunities for patients to access cutting edge trials throughout our state.

Program Name(s)

IMPACT

Dana-Farber Cancer Institute

Blood cancers called myeloproliferative neoplasms occur when one of the blood stem cells picks up a mutation. Some patients stay in the chronic phase of the disease for years whereas others rapidly progress with poor outcome. We recently measured when the cancer mutation first occurs and the rate of expansion of the cancer cells in individual patients. We will develop a method that uses the history of disease in each patient to identify those that are at risk of progression.

Program Name(s)

Discovery

Columbia University Medical Center

We recently identified a pervasive, pathogenically relevant mutational mechanism that targets super-enhancers (SE) in DLBCL, leading to target gene deregulation. Here we will dissect the mechanistic role of 3 highly recurrent hotspots in the BCL6, BTG2 and CXCR4 SEs in driving lymphomagenesis and tumor dependency in vitro and in vivo using novel mouse models. These studies will significantly transform our understanding of DLBCL and identify novel therapeutic targets.

Program Name(s)

Discovery

University of Cincinnati

Based on our preliminary data, we hypothesize that IRAK4 inhibition leads to LSPC reprogramming in MDS and AML. Aim 1 will evaluate the mechanism by which IRAK4 inhibition leads to LSPC reprogramming in cell lines, mice, and PDX samples. Aim 2 will concentrate on understanding of how IRAK4 inhibition creates synthetic lethal dependencies with the CELMoD CC-885 and how neosubstrates of CC-885 mediate the synergy upon IRAK4 inhibition in leukemic cells.

Program Name(s)

Career Development Program

Dana-Farber Cancer Institute

Our research focuses on the preclinical evaluation of new targeted therapies for high-risk subtypes of childhood AML. We are deploying screening approaches to delete each gene, one-by-one, to identify genes whose deletion leads to death of the leukemia cells. We will evaluate drugs developed against these targets in state-of-the-art models of pediatric AML. Our goal is to translate the most promising findings to clinical trials for children with these very poor outcome subsets of AML.

Program Name(s)

Dare to Dream

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.