Research we fund

In June 2025, LLS made an equity investment in Auron Therapeutics to "Support Clinical Development of AUTX-703 in Relapsed/Refractory AML and MDS."Auron Therapeutics is a platform-powered company targeting cell-state plasticity to improve patient outcomes in oncology and inflammatory disease. Auron pioneered its AURIGIN platform, which uses AI and machine learning to compare cell states and identify novel drug targets, optimal development models, and biomarkers to facilitate proper patient selection, ultimately accelerating the development of effective and durable therapies.  Leveraging its AURIGIN platform, KAT2A/B was identified as a key driver of cell plasticity and disease. AUTX-703 is a first-in-class, oral KAT2A/B degrader and is being evaluated in a Phase 1 dose escalation and dose optimization study in patients with relapsed/refractory AML or MDS (NCT06846606). 

Project Term: June 25, 2025 - TBD

This study will evaluate the effectiveness of two integrated initiatives aimed at enhancing enrollment of minoritized patients in blood cancer clinical trials. The first initiative aims to increase access to trials by utilizing procedures and technology that facilitate referral of patients from community sites of care to an academic cancer center, fostering physician collaboration, and supporting patient navigation. The second initiative seeks to lower trial design-related barriers at the cancer center through equity-focused alterations to the trial development infrastructure and processes combined with a comprehensive staff engagement strategy.

Project Term: July 1, 2025 - June 30, 2030

Cancer clinical trials (CTs) provide high-quality care and are important for advancing treatment options, yet most Veterans Administration (VA) facilities do not have CTs available for veterans with blood cancer and face challenges in enrolling veterans on the CTs that do exist. With an innovative, multi-faceted approach to supporting VA research teams as well as educating and assisting veterans, this study will address barriers at the institutional, clinician, and patient levels to increase enrollment of veterans with blood cancer on CTs.

Project Term: July 1, 2025 - June 30, 2030

Posttransplant lymphoproliferative disorders (PTLD) are a group of lymphomas that arise during immunosuppression following organ transplantation and are a significant source of morbidity and mortality. PTLD remains challenging to treat due to disease heterogeneity, patient comorbidities, the risk of infectious complications, and organ rejection. The goals of this proposal are to (1) study the therapeutic efficacy and safety of dose modified R-EPOCH in High-Risk PTLD patients; (2) determine the utility of ctDNA defined molecular response as a novel risk-stratification biomarker in PTLD; (3) understand the impact of immune-suppression on T cell function, T cell receptor diversity, and the detection of oncoviruses. The overall goal is to reduce morbidity and identify novel biomarkers for personalized precision treatment decisions to improve survival in this devastating disease.

Project Term: February 1, 2025 - January 31, 2028

Primary cutaneous γδ T-cell lymphoma (PCGDTL) is a rare type of lymphoma caused by the rare types of T-cells called γδ T-cells (most T cells in our body in αβ T-cells). The disease usually shows symptoms in the skin, thus it is also considered a rare type of skin cancer. The disease is very aggressive. After diagnosis patients may die within 3 months. Only about 10% patients are alive after 5 years. However, little is known about the disease. For the last two decades, most knowledge has been generated with a handful of patient samples. More research is needed, which may lead to discovery of new treatments for PCGDTL patients.

Project Term: July 1, 2024 - June 30, 2025

AMKL is a rare leukemia that largely affects infants and toddlers. Of the various subtypes of this disease, CBAF2T3-GLIS2 positive AMKL has proven particularly difficult to treat with traditional cytotoxic chemotherapies and bone marrow transplantation with dismal outcomes. The objective of this study is to investigate protein dependencies in CBAFT2T3-GLIS2 fusion positive AMKL to identify new, and desperately needed, drug targets.

Project Term: July 3, 2024 - June 30, 2025

We will conduct a decentralized randomized controlled trial of a high-fiber plant-based dietary intervention among patients with multiple myeloma undergoing induction chemoimmunotherapy. The study will assess whether the intervention (meals and virtual coaching) leads to improved rates of complete response, and quality of life mediated by improvements in weight and insulin resistance. The study is expected to provide rigorous evidence of the effectiveness of this intervention in patients with newly diagnosed multiple myeloma and support the development of low-cost, minimal-risk nutrition as a strategy to improve cancer treatment outcomes.

Project Term: March 1, 2025 - February 29, 2028

To improve the cure rate of patients suffering from acute myeloid leukemia (AML), our study aims to target resistant leukemia stem cells by developing an 'antibody-drug conjugate' (ADC) against CD99, a protein expressed on these cells. Initial tests of two ADC versions have shown promise in combating AML. Our next steps involve refining the anti-CD99 antibody, identifying the optimal drug for conjugation, and testing the ADC on patient-derived leukemia models. Completing these objectives will pave the way for a phase 1 clinical trial, offering a potentially transformative treatment for AML.

Project Term: July 1, 2024 - June 30, 2027

In October 2023, LLS made an equity investment in Vittoria to "Support Clinical Development of VIPER-101, a CAR-T Cell Therapy for T-cell lymphomas."Vittoria Biotherapeutics is developing novel CAR-T cell therapies that transcend the limitations of current cell therapies. Based on technology exclusively licensed from the University of Pennsylvania, Vittoria's proprietary Senza5 platform unlocks the antitumor potential of engineered T cells and utilizes a five-day manufacturing process to maximize stemness, durability, and target cell cytotoxicity. By acting on the fundamental biology of T cells, Senza5 can be used to improve the efficacy of engineered T cell therapies with pipeline applications in oncology and autoimmune diseases.Vittoria aims to conduct a Phase 1 dose escalation clinical trial for its lead program VIPER-101, an autologous, dual population CD5-knockout CAR-T cell therapy for T-cell Lymphoma featuring the novel Senza5 platform technology. The Phase 1 trial is ongoing to assess the safety and efficacy of VIPER-101 in patients with T-cell lymphomas (NCT06420089).

Project Term: October 31, 2023 - TBD

CMML is a universally lethal blood cancer characterized by increased monocytes (a type of white blood cell) in the peripheral blood and abnormal appearing cells within the bone marrow. Most CMML patients are clinically asymptomatic and remain so for weeks to months following diagnosis, with disease progression remaining inevitable. Despite therapeutic advances in similar blood cancers, no specific molecularly targeted therapies currently exist to treat CMML. Our team aims to identify new therapies and repurpose existing therapies to address the emergent unmet need for new treatments that meaningfully improve, and extend, the lives of patients with CMML.

Project Term: November 1, 2023 - October 31, 2027

hypothesize that demonstrating activity of CLL-1 CAR-T (CLL1CART) cell therapy with or without trametinib in pre-clinical models of chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) is the most efficient method to bring cellular therapy to patients with these orphan diseases. In Aim 1, we will determine the in vitro and vivo efficacy of CAR-T cells redirected against CLL-1 using patient-derived xenograft (PDX) models of CMML and JMML. In Aim 2, we will evaluate the role of combining trametinib with CLL1CART cells. Based on our preliminary data, we hypothesize that trametinib will have direct antileukemia activity and will increase the efficacy of CLL1CART by decreasing T-cell exhaustion and augmenting T-cell fitness. 

Project Term: November 1, 2023 - October 31, 2026

We are aiming to bring a new treatment option to patients with chronic myelomonocytic leukemia (CMML) by utilising CCL2-drug conjugates that specifically target and eliminate cancerous cells. Our leading conjugate shows potent and selective efficacy in killing CMML cells. The proposed work will help us understand how this drug works, which patients are most likely to benefit and how it can be combined with current treatments to achieve the greatest patient benefit.

Project Term: November 1, 2023 - October 31, 2026