Research we fund

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).

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).

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.

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.

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.

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.

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.

p>SIRT5 is a master regulator of central energy metabolism. The survival and growth of Acute Myeloid Leukemia (AML) cells depend on SIRT5. I will employ genetic SIRT5 disruption and small molecule inhibitors to target SIRT5 in Acute Lymphoblastic Leukemia (ALL) cells and primary samples. This study aims to 1) determine the effects of SIRT5 inhibition on ALL in vitro and in vivo, and 2) identify SIRT5-regulated pathways and mechanisms underlying SIRT5 dependency in T-ALL.

AML risk stratification established by previous studies do not reflect survival outcomes observed in Black patients. Exome sequencing of 100 Black AML patients revealed the novel variants previously not affiliated with AML, including PHIP. Using multiomic patient sample captures and GEMMs, we will functionalize variants in PHIP and assess if they drive leukemogenesis and/or therapy resistance. The overall goal of this work is to implement inclusive genetic assessment tools for AML diagnosis.

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 2 study (BEXMAB) of bexmarilimab in combination with azacitidine is currently enrolling high-risk MDS patients in the US and Finland (NCT05428969).