Research we fund

This team science program from Washington University will develop new immunotherapy treatments for patients with hard to treat or incurable lymphomas. The team includes physicians and scientists who have developed new ideas in the laboratory for immune-based treatment, and will translate these to clinical trial testing. These include engineered natural kill cells, healthy donors T cell engineered to attack a T cell lymphoma, and lymphoma-patient specific mutations as vaccine targets.

Venetoclax-based regimens are the standard of care for many patients with acute myeloid leukemia (AML) and are highly active therapeutic strategies for this challenging disease. However, some patients do not respond, and most patients who do respond will relapse. We have discovered that resistance to venetoclax may be mediated by the movement patterns of calcium throughout a cell. Furthermore, we have found that mitoxantrone, a conventional chemotherapy agent, can interrupt these calcium fluctuations at very low doses. Therefore we have proposed a clinical trial using lower-dose mitoxantrone for AML patients whose disease has resistance to venetoclax-based regimens.

In November 2022, LLS made an equity investment in Dren Bio to "Support Clinical Development of the DR-01 Program for Rare Leukemia & Lymphoma Indications Including Large Granular Lymphocyte Leukemia (LGLL) and Cytotoxic Lymphomas."

Dren Bio is a clinical-stage biopharmaceutical company focused on developing therapeutic antibodies for the treatment of cancer, autoimmune and other serious diseases. Dren Bio’s pipeline encompasses two distinct programs, the first focusing on the engineering of antibodies with enhanced antibody-dependent cellular cytotoxicity (ADCC) capabilities and the second revolving around its proprietary Targeted Myeloid Engager and Phagocytosis Platform.

DR-01 is a novel antibody targeting CD94 which is known to be upregulated on LGLL cells. DR-01 functions through depletion of target cells via ADCC by means of fratricide, a method in which the same cell type induces ADCC on each other. A Phase 1/2 trial is ongoing to assess the safety and efficacy of DR-01 in previously treated LGLL patients and cytotoxic lymphomas (NCT05475925).

DR-0201 is a first-in-class bispecific antibody capable of engaging tissue-resident and trafficking myeloid cells to induce deep B cell depletion via targeted phagocytosis. DR-0201 is currently being evaluated in a Phase 1 study in B-NHL patients (NCT06392477).

In August 2017, TAP partnered with Ryvu Therapeutics (formerly known as Selvita) to support "A Phase 1b 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. Ryvu is currently enrolling several Phase 2 clinical trials: RVU120 in combination with venetoclax for patients with relapsed/refractory AML (RIVER-81, NCT06191263), RVU120 as monotherapy for patients with low-risk myelodysplastic syndromes (REMARK, NCT06243458) and RVU120 as monotherapy and in combination with ruxolitinib for patients with myelofibrosis (POTAMI-61, NCT06397313).

In August 2017, TAP partnered with Ryvu Therapeutics (formerly known as Selvita) to support "A Phase 1b 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. Ryvu is currently enrolling several Phase 2 clinical trials: RVU120 in combination with venetoclax for patients with relapsed/refractory AML (RIVER-81, NCT06191263), RVU120 as monotherapy for patients with low-risk myelodysplastic syndromes (REMARK, NCT06243458) and RVU120 as monotherapy and in combination with ruxolitinib for patients with myelofibrosis (POTAMI-61, NCT06397313).

In August 2017, TAP partnered with Ryvu Therapeutics (formerly known as Selvita) to support "A Phase 1b 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. Ryvu is currently enrolling several Phase 2 clinical trials: RVU120 in combination with venetoclax for patients with relapsed/refractory AML (RIVER-81, NCT06191263), RVU120 as monotherapy for patients with low-risk myelodysplastic syndromes (REMARK, NCT06243458) and RVU120 as monotherapy and in combination with ruxolitinib for patients with myelofibrosis (POTAMI-61, NCT06397313).

The field of cancer treatment has made remarkable progress with the adoption of targeted therapy; however, small molecule drugs have limitations such as drug resistance and off-target toxicities. To overcome these challenges, we have developed an innovative approach that enhances the potency and precision of small molecule drugs. Our cutting-edge high-precision pretargeted nanoparticles can deliver potent triple inhibitors that effectively combat drug-resistant mantle cell lymphoma and dual proteolysis targeting chimeras (PROTACs) for treatment of transformed follicular lymphoma. Our proposal is supported by extensive preliminary data, and we are excited to be at the forefront of this revolutionary novel treatment strategy.

The goal of our laboratory is to discover, study, and the translate new leukemia therapies to the clinic. In this project, we are studying a signaling pathway, called PI3 kinase gamma, that we believe is important in patients with AML and might lead to new treatments using drugs that target its activity.

CAR-T cells are made from a patient’s own immune cells, altered so that they specifically recognize and kill the patient’s cancer cells. They are effective in many but not all cases of B-acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL), among other blood cancers. In this proposal we seek to better understand ways to select T cells that will make better CAR-T cells as well as to treat CAR T cells them in ways to make them work better in the cancer patient.

Peripheral T-cell lymphomas are highly aggressive blood cancer that have very poor survival rate, highlighting the need for new therapies to improve patient survival. We aim to improve our understanding of the characteristics of the individual cancer cells and their interaction with surrounding cells in the tumor environment with the goal of identifying new drugs that we can validate in preclinical models and move into more efficient treatments for lymphoma patients.

Our goal is to perform high-resolution molecular characterization of human leukemia stem cells (LSCs). We have developed an integrated set of single-cell techniques that will assess transcriptional, genomic, and phenotypic features of primary LSC populations obtained from patients undergoing varying forms of treatment. We expect to create a molecular atlas of primary LSCs that will provide the leukemia research community with a powerful resource for the development of improved therapies.

Multiple myeloma is characterized by severe changes in chromosomes that result in gains or losses of genetic material. Several key events disrupt the genome of myeloma cells and are important in defining poor patient outcome, but the biological mechanisms of how they cause high-risk disease is not known. We will perform comprehensive genomic studies, involving six different cutting-edge techniques, to examine the interactions of these high-risk events and identify the mechanisms leading to them.