Research we fund

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

We will test the efficacy of CAR T cell therapy for CMML. We will modify the tumor microenvironment to enhance their efficacy. and we will upscale CAR T cells to the next level in terms of their genetic structure.

Project Term: November 1, 2023 - October 31, 2028

In October 2023, LLS made an equity investment in Enterome to "support the ongoing Phase 2 SIDNEY study of EO2463 in indolent non-Hodgkin B-cell lymphoma."Enterome is a clinical-stage biopharmaceutical company developing breakthrough immunomodulatory drugs for the treatment of cancer and immune diseases. Enterome’s pioneering approach to drug discovery is based on its unique and powerful bacterial Mimicry drug discovery platform, allowing it to analyze and uncover new biological insights from the millions of gut bacterial proteins in constant cross-talk with the human body. Its first-in-class small protein and peptide drug candidates modulate the immune system by closely mimicking the structure, effect or actions of specific antigens, hormones, or cytokines. EO2463 is a clinical-stage off-the-shelf OncoMimics™ peptide-based immunotherapy. It combines four microbial-derived OncoMimics™ peptides that closely mimic specific cytotoxic T cell (CD8+ T cell) epitopes in B cell Tumor-Associated Antigens CD20, CD22, CD37, and CD268 (BAFF receptor), as well as a helper CD4 peptide, UCP2. The SIDNEY trial is a multicenter, Phase 2 trial investigating EO2463 in monotherapy and in combination with standard of care - rituximab and rituximab in combination with lenalidomide – for treatment of patients with indolent NHL (NCT04669171).

Project Term: October 24, 2023 - TBD

T-cell leukemias and lymphomas have devastating outcomes if they recur after or don’t respond to standard treatment, with the only hope of cure being bone marrow transplant (BMT). Unfortunately, many pediatric, adolescent and young adult (AYA) patients are unable to achieve clinical remission (and thus unable to proceed to BMT) with standard salvage therapies, which are often even more toxic than upfront therapies. Available treatment options for patients with relapsed or refractory T-cell malignancies (particularly pediatric and AYA patients) are lacking, thus 3-year survival rates are <15% for these patients. This proposal aims to study a less toxic, targeted approach using patient or donor-derived T-cells engineered to target an antigen expressed on over 90% of T-cell malignancies that affect pediatric and AYA patients (CD7 Chimeric Antigen Receptor T-cells).

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

AML recurrence is a devastating event after allo-HCT. I hypothesize that it could be counteracted through targeting of leukemia-restricted mHAgs via TCR-like CARs. I will identify scFVs recognizing mHAg:HLA complexes using a cell-free nanobody screening platform, and test the anti-leukemia activity and safety of CAR-Ts bearing such scFVs in vitro and in vivo. Through this approach, I will build a library of CAR constructs able to provide population-scale coverage for at-risk allo-HCT patients.

Project Term: July 1, 2024 - June 30, 2026

Relapsed and/or refractory acute myeloid leukemia (AML) display resistance to Venetoclax and Azacitidine (Ven/Aza) with approximately one third of patients demonstrating upregulated protein synthesis. This proposal will investigate the mechanism(s) underlying the dependence of Ven/Aza-resistant AML on protein synthesis as well as the functional consequences of targeting this pathway. Successful completion of these studies will provide novel insights into Ven/Aza resistance mechanisms.

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

Richter’s syndrome (RS) is a critical complication of chronic lymphocytic leukemia. RS patients are refractory to most existing therapies and show a median survival of ~12 months. I aim to dissect the function of a frequently mutated gene in RS (i.e., MGA) through cutting-edge single-cell analyses of patient samples and mouse models. The objective of these studies is to understand transformation biology, unravel novel therapeutic vulnerabilities, and provide the basis for personalized therapy.

Project Term: July 1, 2024 - TBD

Dr. Mendel Goldfinger and collaborators of Einstein have shown in a preliminary trial that weekly low dose decitabine plus one a week venetoclax is highly effective in newly diagnosed patients with MDS or AML. The regimen has reduced toxicity compared to the current dose and schedule of azacitidine plus venetoclax. The proposed new work is attempting to demonstrate in a prospective trial at 3 sites that this data can be replicated and expanded.

Project Term: October 1, 2023 - September 30, 2024