Research we fund

Common genetic variation explains a large share of childhood leukemia in children of European ancestry and may explain the differing incidence in children of other ancestries. The Childhood Cancer and Leukemia International Consortium seeks to better understand the genomic architecture of childhood leukemia risk using its collective genomic datasets comprising >20,000 diverse children with leukemia. The results will inform risk prediction for and possibly prevention of childhood leukemia.

Project Term: March 1, 2022 - February 29, 2024

In June 2022, LLS made an equity investment in Faron Pharmaceuticals to "Support Clinical Development of the Bexmarilimab Program for Leukemia Indications." Faron is a clinical stage biopharmaceutical company developing novel treatments for medical conditions with significant unmet needs caused by dysfunction of our immune system. The Company currently has a pipeline based on the receptors involved in regulation of immune response in oncology, organ damage and bone marrow regeneration.  Bexmarilimab, a novel anti-Clever-1 humanized antibody, is its investigative precision immunotherapy with the potential to provide permanent immune stimulation for difficult-to-treat cancers through targeting myeloid function. A Phase 1 study (BEXMAB) of bexmarilimab in combination with azacitidine or azacitidine/venetoclax is currently enrolling AML, MDS or CMML patients in the US and Finland (NCT05428969).

Project Term: June 30, 2022 - TBD

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. A clinical trial (EVICTION) is currently enrolling a cohort expansion of ICT01 in combination with azacitidine and venetoclax in patients with acute myeloid leukemia (NCT04243499).

Project Term: June 13, 2022 - TBD

Our research consortium of diagnostic, translational and clinical researchers will undertake an integrated and novel exploration of the immune and genomic landscape in hairy cell leukemia (HCL) and correlate those data with response to both conventional and newly emerging therapies. We will apply our innovative platforms of digital spatial profiling, whole genome sequencing and circulating tumor DNA to provide highly novel data from our already collected sample bank from over 60 patients with HCL.  

Project Term: October 1, 2021 - September 30, 2023

Coming soon.

Project Term: April 1, 2022 - November 30, 2022

Dr. Olszewski’s trial will examine mosunetuzumab as a first-line treatment for follicular and marginal zone lymphomas—slow-growing types of B-cell lymphoma which remain incurable using current therapies. Mosunetuzumab is a “bispecific antibody” that can trigger an immune attack of patients’ own cancer-killing T-cells against the lymphoma. Dr. Olszewski team will look for characteristics that predict complete responses when this novel immunotherapy is applied as first-line treatment.

Project Term: April 1, 2022 - March 31, 2027

The goal of our work is to use a “bench to bedside and back” approach to develop new treatments for patients with relapsed/refractory AML. Through genetic analysis of patients who relapse or do not respond to standard and investigational treatments, we discover potential resistance mechanisms. In the lab, we test novel drugs and identify new drug targets that may address these resistance mechanisms when used in combination with other therapies. The overall goal of our research program is to improve treatment options and survival of patients with refractory AML.

Project Term: October 1, 2021 - September 30, 2026

Young Black patients diagnosed with acute myeloid leukemia (AML) have significantly shorter survival compared to White patients. To comprehensively assess genetic, genomic and biologic contributors to the race-associated survival disparity, we propose a complementary approach that addresses major knowledge gaps in our current understanding of AML biology in Black patients, including the overdue characterization of the Black AML genome and subsequent delineation of biologic response to treatment.

Project Term: October 1, 2021 - September 30, 2024

RNA splicing is a central metabolic pathway that is frequently perturbed in hematopoietic malignancies (HMs) that harbor mutations in spliceosome components (most commonly affecting SRSF2, SF3B1, U2AF1, or ZRSR2). These mutations are particularly prevalent in myeloid malignancies (e.g., MDS, MDS/MPN, sAML), but recent pan-cancer studies have implicated aberrant splicing in >30 tumor types. The Project Leaders have probed the molecular consequences of aberrant splicing and identified critical pathways that are amenable to targeted inhibition, including the DNA damage response (Graubert/Walter), the nonsense-mediated RNA decay (NMD) pathway (You/Walter), the spliceosome itself (Abdel-Wahab/Walter/Graubert), and others. To date, effective therapies for HMs have not capitalized on these unique vulnerabilities. The goal of this SCOR is to generate testable clinical hypotheses based on careful mechanistic studies in pre-clinical models and to rapidly move these ideas into the clinic in the near term.

Project Term: October 1, 2021 - September 30, 2026

To optimize treatment of HCL, we dissect the tumors` surface proteome to understand a) surface mediated signals and b) the dependence on BRAFV600E activity, to c) eradicate remaining cell populations after BRAF inhibitor treatment. We use chemoproteomics, which enable mass-spectrometric-based surfaceome discovery to quantitatively investigate HCL. We expect to identify HCL specific and BRAF-dependent surfaceomes and identify new and critical targets for treatment.

Project Term: October 1, 2021 - September 30, 2023

Despite the success of Chimeric antigen receptor T cell (CAR-T) immunotherapies, disease relapse occurs in a majority of patients. We have developed a novel ligand based BAFF-CAR, that utilizes B cell activating factor (BAFF) as a ligand, which can bind to all three receptors of BAFF, which are expressed by malignant B cells including Hairy Cell Leukemia (HCL). We hypothesize BAFF CAR-T will be an effective therapeutic strategy for HCL.

Project Term: October 1, 2021 - September 30, 2023

In March 2020, LLS made an equity investment in Kymera Therapeutics to "Support Key Studies with STAT3 Protein Degraders for Future 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-333 is a STAT3 protein degrader. KT-333 is in a Phase 1 clinical trial currently enrolling NHL patients including T-cell lymphoma (PTCL, CTCL) and LGLL (NCT05225584).

Project Term: March 11, 2020 - TBD