Research we fund

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.

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). 

In August 2021, LLS made an equity investment in Immunitas Therapeutics to support the "Phase 1 Clinical Development of IMT-009, an Antibody Targeting CD161, in Patients With Advanced Solid Tumors or Lymphomas."

Immunitas is committed to discovering and developing novel, differentiated therapeutics for patients with cancer. Their discovery engine combines deep expertise in single-cell genomics with customized machine learning approaches to elucidate immune cell populations that are key actors in immuno-oncology. Immunitas complements this process with bespoke in-house therapeutic discovery rooted in antibody display and immunization. The company was founded by Longwood Fund with leading scientists from Dana-Farber, MGH, the Broad, and MIT.

IMT-009, a first-in-class NK and T cell modulator targeting CD161, is being developed for the treatment of solid tumors and lymphomas and is in a Phase 1 clinical trial (NCT05565417). 

In February 2021, LLS made an equity investment in Caribou Biosciences to support "A Phase 1, Multicenter, Open-Label Study of CB-010, a CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy in Patients With Relapsed/Refractory B Cell Non-Hodgkin Lymphoma."

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-010, Caribou’s lead allogeneic CAR-T cell program, targets CD19 and is being evaluated in a Phase 1 clinical trial expansion cohort for second-line patients with large B cell lymphoma (LBCL). (NCT04637763). It is the first clinical-stage allogeneic CAR-T cell therapy in which PD-1 was genetically disrupted in the CAR-T genome, leading to more durable anti-tumor activity in pre-clinical studies.

The Weill Cornell Medicine (WCM) Meyer Cancer Center (MCC) has an internationally recognized, clinical/translational blood cancer research program focused at its Manhattan campus. Elsewhere in New York City, the borough of Queens has 2.3 million and the borough of Brooklyn has 2.5 million residents. Both are among the most ethnically diverse urban areas in the world, and each separately ranks just behind Los Angeles and Chicago in population. Over 50% of patients diagnosed with blood cancers in New York City live in Brooklyn or Queens, and half of those are non-white. Involvement of academic cancer centers with a hematologic malignancy clinical trials program physically located in Brooklyn or Queens has previously been limited. New York Presbyterian Hospital and WCM have now integrated with New York Presbyterian-Queens (NYP-Q) and New York Presbyterian-Brooklyn Methodist Hospital (NYP-BMH) to provide access to outstanding cancer care and research for these populations. The community outreach and engagement core of the MCC (led by Dr. Erica Phillips) partners with a robust network of affiliated ambulatory care practices in Brooklyn and Queens. The core has hosted roundtables with over 120 stakeholders (cancer advocacy groups, community physicians, social service organizations) around barriers to diagnosis and treatment in solid tumors, and we will capitalize on this program to expand to blood cancer trials. Other workshops will be targeted directly to diverse groups of patients. Additionally, WCM-MCC cross-campus Hematologic Malignancy Disease Management teams are led locally by Dr. Perry Cook (NYP-BMH) and Dr. Gina Villani (NYP-Q). Clinical trials infrastructure and staffing, a joint IRB, training and oversight are being implemented. This foundation is ideal to synergize with this proposal (BRIDGE) to accelerate access and support for clinical trial participation of blood cancer patients in Brooklyn and Queens who have been previously underserved.

TP53 mutations are present in 10% of MDS cases and are associated with reduced survival and poor prognosis. However, the effect(s) of TP53 mutations on MDS pathogenesis is unknown. We discovered that MDS cells with TP53 mutations display significant alterations in pre-mRNA splicing due to increased EZH2 activity. We will investigate the mechanisms by which TP53 mutations drive MDS pathogenesis and determine the impact of inhibition of EZH2 and the spliceosome on MDS cells with TP53 mutations.

We are investigating new interventions that could improve the effectiveness of CAR T-cell therapy for lymphoma. A clinical trial will test radiation immediately followed by CAR-T. Larger lymphoma tumors are less likely to respond to CAR-T and we expect that radiation could reduce the amount of tumor, leading to improvement in responses. We will also conduct a series of trials to determine the effectiveness of vaccinations before and after CAR T cell therapy, and if anti-cancer vaccines could improve outcomes.

My research investigates the heterogeneity of leukemic and pre-leukemic clonal expansion to identify genes associated with leukemia relapse and genesis. Contrary to conventional studies analyzing cell mixtures, my research uniquely probes the specific cells underlying leukemia development. We expect to identify the key cellular and molecular events that drive leukemia onset and relapse. These findings will help improve diagnosis and can serve as new therapeutic targets for treating leukemia.

We want to understand how leukemia inhibits blood production as this is one of the main causes of death in leukemia patients. We use new microscopy techniques developed by our group to image—for the first time—all types of blood cells and how they are eradicated by leukemia cells. Identification of the mechanisms through which leukemia inhibits blood production will be the foundation for new studies to develop drugs to maintain normal blood levels and prevent death in leukemia patients.

Coming soon.

We seek to reduce the adverse cardiac effects of chemotherapy in pediatric AML patients. We are assessing markers of heart function and injury to compare two clinical strategies for prevention of chemotherapy-induced heart injury. We are also developing a tool using these markers of heart function to characterize a child’s risk for cardiac dysfunction, which is critical to guiding safe chemotherapy delivery. By reducing the toxicity of therapy on the heart we hope to optimize delivery of effective chemotherapy and contribute to long-term leukemia cure without the burden of life-threatening heart disease during survivorship.

Coming soon.