Research we fund

In November 2010, LLS made an equity investment in BioTheryX originally to support the development of a promising LLS-funded project with Toronto-based University Health Network and is currently supporting "An Open Label, Escalating Multiple Dose Study to Evaluate the Safety, Toxicity, Pharmacokinetics, and Preliminary Activity of BTX-1188 in Subjects With Advanced Malignancies." BioTheryX has a technology platform in the field of targeted protein degradation. This technology utilizes the body's own protein disposal system to selectively degrade and remove disease-causing proteins. It has potential applicability to a very broad range of disease targets, including a wide range of targets that have to date been considered "undruggable."  BTX-1188 is a dual target protein degrader specifically engineered to degrade GSPT1 and IKZF1/3. A clinical study of BTX-1188 in patients with advanced hematologic (AML or NHL) and solid tumor malignancies is currently enrolling (NCT05144334).

Project Term: November 16, 2010 - TBD

Chromosomal rearrangements involving a gene called TP63 have been found in 5-10% of several subtypes of lymphomas and patients with TP63-rearrangements have dismal outcomes, with nearly 0% of patients surviving 5 years after diagnosis. We investigate the oncogenic mechanisms of TP63-rearrangements to find the unique cancer cell vulnerabilities to this rearrangement using different models. Our study will develop an effective therapeutic strategy for patients with TP63-rearranged lymphomas.

Project Term: July 1, 2019 - June 30, 2022

We focus on blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive blood cancer with limited treatment options and poor outcomes. We want to understand what causes the disease, develop laboratory tools, and identify new treatments and ways to overcome therapy resistance. We have translated our discoveries to clinical trials. Our goal is to continue this bench to beside approach to develop the next generation of BPDCN therapies that improve survival and minimize treatment toxicity.

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

In previous studies of recurrently amplified 1q21 genes in myeloma, we identified ILF2 as a modulator of the DNA repair pathway, which promotes adaptive responses to genotoxic stress. Thus, ILF2 may have clinical utility as a biomarker of aggressive myeloma and blocking the ILF2-mediated repair signaling may enhance the effectiveness of current DNA-damaging agent-based therapies. We are seeking to determine the feasibility of therapeutically targeting ILF2 with antisense nucleotides and identify DNA repair effectors whose loss of function induces synthetic lethality in ILF2-depleted myeloma.

Project Term: July 1, 2018 - June 30, 2023

In February 2021, LLS made an equity investment in Caribou Biosciences to "Support allogeneic CD371 (CLL-1) CAR development for acute myeloid leukemia." Caribou is a clinical-stage biotechnology company, co-founded by CRISPR pioneer and Nobel Prize winner Jennifer Doudna, Ph.D., using next-generation CRISPR genome-editing technology to develop “off-the-shelf” (allogeneic) CAR therapies for hard-to-treat blood cancers. CB-012, Caribou’s third allogeneic CAR-T cell therapy, an allogeneic anti-CD371 CAR-T cell therapy for the treatment of relapsed or refractory acute myeloid leukemia (AML) is in preclinical development for the treatment of acute myeloid leukemia with a projected IND filing in the second half of 2023. CD371 is expressed on the surface of AML tumor cells and leukemic stem cells, but it is not expressed on normal hematopoietic stem cells, which makes it a compelling target for the treatment of AML. Caribou is applying their genome editing expertise to armor the CB-012 CAR-T product in order to drive persistence and seek maximum patient benefit.  

Project Term: February 28, 2021 - TBD

In February 2021, LLS made an equity investment in Caribou Biosciences to support "A Phase 1, Multicenter, Open-Label Study of CB-011, a CRISPR-Edited Allogeneic Anti-BCMA CAR-T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma." Caribou is a leading clinical-stage biotechnology company, co-founded by CRISPR pioneer and Nobel Prize winner Jennifer Doudna, Ph.D., using next-generation CRISPR genome-editing technology to develop “off-the-shelf” (allogeneic) CAR therapies for hard-to-treat blood cancers.CB-011, Caribou’s second allogeneic CAR-T cell therapy, targets BCMA for the treatment of relapsed/refractory multiple myeloma and is immunologically cloaked for enhanced persistence. The CaMMouflage Phase 1 clinical trial, a multicenter, open-label study to evaluate the safety and efficacy of a single dose of CB-011 in adult patients with relapsed or refractory multiple myeloma (r/r MM), is currently enrolling (NCT05722418).

Project Term: February 28, 2021 - TBD

This project investigates immunogenetic determinants of relapse following allogeneic stem cell transplant for myeloid neoplasia. Herein we will determine molecular modes of inactivation of HLA immunodominant peptide-presentation including HLA mutations, deletion and down modulation as a means of immunoescape. We will also study immunogenetic predictors of the strength of graft vs. leukemia according to the HLA divergence in the context of relapse, TCR repertoire diversity and HLA mutations.

Project Term: November 1, 2021 - October 31, 2024

Peripheral T-cell lymphomas (PTCLs) are poorly understood and patients with PTCL are underserved by current therapies. The most common subtypes (among >20) are PTCL-not otherwise specific (NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALK- ALCL). Rational treatment strategies for these lymphomas are lacking, largely due to the insufficient characterization of PTCL pathobiology and historic paucity of faithful models. Over the past 4 years, our groups and others have identified recurrent alterations in PTCL subsets, developed targeted agents against PTCL and established an unprecedented repository of PTCL models for in vitro and in vivo interrogation. A clinical trial led by director Dr. Horwitz established a new standard-of-care for upfront treatment of CD30+ PTCLs. Additional trials developed through this SCOR have advanced therapeutics targeting PI3 kinase (duvelisib), JAK1/2 (ruxolitinib) and IDH2 (enasidenib) for relapsed/refractory PTCL. The central goal for the next 5 years of support is to establish informed combination strategies that eradicate resistant populations and thereby extend the duration of meaningful responses.

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

Starting in July 2010, LLS TAP supported a promising University of Michigan research project led by Jolanta Grembecka, PhD, to develop new treatments for patients with a rare and lethal subtype of leukemia. Through TAP, LLS engaged chemists to improve the properties that produced lead compounds that exhibited potent anti-leukemic activity. In 2014, LLS introduced Kura Oncology to the project that ultimately led to Kura Oncology completing a licensing agreement with the University of Michigan to continue to develop these molecules.Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer with a pipeline that consists of small molecule drug candidates that target cancer signaling pathways.Ziftomenib (KO-539) is selective small molecule inhibitor of menin. A Phase 2 registration-directed clinical trial in patients with NPM1-mutant relapsed or refractory AML completed enrollment (NCT04067336). 

Project Term: December 22, 2014 - TBD

In March 2021, LLS made an equity investment in Immune-Onc Therapeutics to support the "Phase 1 Clinical Development of IO-202, An Antibody Targeting LILRB4, for the Treatment of AML with Monocytic Differentiation and CMML." Immune-Onc is a private, clinical-stage cancer immunotherapy company dedicated to the discovery and development of novel myeloid checkpoint inhibitors for cancer patients. The company aims to translate unique scientific insights in myeloid cell biology and immune inhibitory receptors to discover and develop first-in-class biotherapeutics that reverse immune suppression in the tumor microenvironment. Immune-Onc has a differentiated pipeline with a current focus on targeting the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB) of myeloid checkpoints. The company’s work builds on early research by Chengcheng (Alec) Zhang, Ph.D. at the University of Texas Southwestern Medical Center that was also funded by LLS grants. IO-202 is a first-in-class antibody targeting the LILRB4 and has entered a phase 1 cohort expansion clinical trial (NCT0437243) for the treatment of AML (IO-202 in combination with azacitidine and venetoclax) and CMML (IO-202 in combination with azacitidine). 

Project Term: March 5, 2021 - TBD

In August 2017, LLS TAP partnered with Ryvu Therapeutics (formerly known as Selvita) to support "A Phase Ib Study of SEL120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome." Ryvu Therapeutics is a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology using a proprietary discovery engine platform. RVU120 (SEL120) is a highly selective first-in-class CDK8/CDK19 small molecule inhibitor. RVU120 is currently in a Phase I clinical trial in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome (NCT04021368), enrolling in the US and Poland. 

Project Term: August 7, 2017 - December 31, 2023

In March 2020, LLS made an equity investment in Kymera Therapeutics to "Support Key Studies with IRAK4 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-413 is a dual protein degrader of IRAK4 and IMiD substrates. KT-413 is in a Phase 1 clinical trial currently enrolling DLBCL patients (NCT05233033).

Project Term: March 11, 2020 - TBD