This Project Grant award from the National Cancer Institute (CFDA 93.395 Cancer Treatment Research) provides funding to Sonoval LLC to develop a second-generation version of the Treg-depleting immunotherapy ONTAK, called SON-211. The $1,293,505 award aims to characterize SON-211's ability to selectively rebalance Treg subsets in solid tumors towards a more inflammatory, anti-tumor response. Key objectives include determining SON-211's effects on Treg subsets as a monotherapy and in combination...
This Project Grant award from the National Cancer Institute's Cancer Treatment Research program (CFDA 93.395) supports research conducted by the Sloan-Kettering Institute for Cancer Research to develop and translate chimeric antigen receptor (CAR) T-cell therapies for solid tumors. The $1,313,806 award, granted on August 13, 2024, aims to further advance Sloan-Kettering's work on MSLN-targeted CAR T-cell therapies, including exploring mechanisms to enhance cytotoxicity against low-antigen...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $994,859 to Cytoagents Inc. to develop the compound CTO1681 for the prevention and treatment of cytokine release syndrome (CRS) associated with chimeric antigen receptor (CAR) T-cell therapy. Cytoagents is conducting a Phase 1b clinical trial to evaluate the safety, pharmacokinetics, and preliminary efficacy of CTO1681 in reducing CRS and immune effector cell-associated neurotoxicity...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides funding to develop an innovative approach to treat lung cancer, the leading cause of cancer deaths in the U.S. The $635,248 award to Trustees of Boston University aims to create a self-amplifying ribonucleic acid (SARNA) technology encoding a bispecific T cell engager (BiTE) antibody. The key products and services include: Designing modified SARNA constructs encoding BiTE antibodies and...
This Project Grant award from the Defense Health Agency under the Military Medical Research and Development program (CFDA 12.420) provides $1,181,683 to the Dana-Farber Cancer Institute in Boston, MA to conduct research aimed at enhancing immune checkpoint blockade responsiveness and tertiary lymphoid structure formation through CD4+TFHx13 CAR-T cells to achieve cures for clear cell renal cell carcinoma (CCRCC). The research will involve experimental design and computational analysis of...
This $650,450 Project Grant award from the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) to the University of Southern California (USC) aims to advance the development of T cell receptor (TCR)-engineered CD4+ T cell immunotherapy for lung cancer. The key objectives of the award are to: 1) determine the mechanisms by which the novel MIIC4 TCRM50A-STEM2 T cell product eliminates lung cancer cells; 2) produce GMP-grade master cell bank and viral particles, and...
This Project Grant award from the National Cancer Institute (CFDA 93.393 - Cancer Cause and Prevention Research) provides $689,934 to the Dana-Farber Cancer Institute (DFCI) to conduct research on the genetic factors underlying immune-related adverse events (IRAEs) associated with immune checkpoint inhibitor (ICI) cancer treatments. The key objectives are to: 1) Perform the largest genome-wide association study (GWAS) of IRAEs across over 13,000 ICI-treated patients, to identify shared and...
This R01 Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) for $1,419,108 supports research to advance the understanding of how a novel neoadjuvant therapy impacts the immune system in patients with solid tumors, using refractory melanoma as a model. The key objectives are to: Gain insight into how blocking the Semaphorin 4D (SEMA4D) signaling pathway, when combined with immune checkpoint blockade, impacts the infiltration and function of...
This $755,970 Project Grant awarded by the National Institute of Diabetes and Digestive and Kidney Diseases (CFDA 93.847 - Diabetes, Digestive, and Kidney Diseases Extramural Research) supports research to address key challenges in the care of patients who develop immune checkpoint inhibitor-associated acute interstitial nephritis (ICI-AIN). The goals are to: Test the use of the biomarker CXCL9 to accurately diagnose ICI-AIN and predict response to corticosteroid therapy. This will be...
This Project Grant award from the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) provides $215,985 to The Leland Stanford Junior University to conduct a pilot study on using exosome signatures as early biomarkers to predict response to immune checkpoint inhibitor therapy in metastatic renal cell carcinoma patients. The study aims to 1) define an exosome signature of response by analyzing exosomal RNA from blood and urine at baseline and 3/6 weeks after...
IMMUNE BIOMARKER ASSESSMENT AND MANUFACTURING DEVELOPMENT FOR SQ3370-001, A FIRST-IN-HUMAN PHASE I DOSE-ESCALATION CLINICAL TRIAL TO TEST A NOVEL TREATMENT AGAINST ADVANCED SOLID TUMORS - ABSTRACT IN 2018, THE GLOBAL INCIDENCE OF NEW CANCER DIAGNOSES WAS ESTIMATED AT OVER 18 MILLION CASES, AND CANCER- RELATED DEATHS WERE ESTIMATED AT OVER 9.6 MILLION. OF THESE CASES, THE VAST MAJORITY WERE SOLID TUMORS, ACCOUNTING FOR MORE THAN 16 MILLION NEW CASES AND 8 MILLION CANCER DEATHS. THIS INCLUDES SOFT TISSUE SARCOMA (STS), A HETEROGENEOUS GROUP OF AGGRESSIVE MALIGNANT TUMORS THAT HAVE A POOR 5-YEAR SURVIVAL RATE OF ONLY 65%. IN THE U.S., AN ESTIMATED 13,000 PEOPLE WILL BE DIAGNOSED WITH STS IN 2020, AND MORE THAN 5,000 WILL DIE OF THE DISEASE. FOR PATIENTS DIAGNOSED WITH STS, TREATMENT OFTEN INVOLVES CHEMOTHERAPY WITH A CYTOTOXIC AGENT SUCH AS DOXORUBICIN (DOX), AN ANTHRACYCLINE THAT HAS BEEN USED TO INDUCE TUMOR REGRESSION IN A VARIETY OF NEOPLASTIC CONDITIONS. DOX IS ALSO KNOWN TO INDUCE IMMUNOGENIC CELL DEATH AND ENHANCE TUMOR RESPONSIVENESS TO IMMUNE CHECKPOINT BLOCKADE THERAPIES. UNFORTUNATELY, THE EXTENDED USE OF DOX IN PATIENTS IS LIMITED BY SEVERE TOXIC SIDE EFFECTS-MOST NOTABLY IRREVERSIBLE CARDIOTOXICITY AND BONE MARROW SUPPRESSION-WHICH CAN BE LIFE THREATENING. THEREFORE, THERE IS AN IMMEDIATE NEED FOR NEW METHODS TO REDUCE THE SYSTEMIC TOXICITY AND OFF-TARGET EFFECTS OF DOX WHILE MAINTAINING ITS ANTITUMOR EFFICACY SHASQI HAS DEVELOPED SQ3370, A NOVEL DRUG PRODUCT THAT WILL IMPROVE THE TREATMENT OF PATIENTS WITH INJECTABLE SOLID TUMORS UNDERGOING DOXORUBICIN (DOX)-BASED CHEMOTHERAPY. PRECLINICAL STUDIES DONE TO-DATE HAVE SHOWN THAT SQ3370 RESULTS IN SIGNIFICANT INHIBITION OF TUMOR GROWTH (BOTH INJECTED AND NON-INJECTED TUMORS), IMMUNE ACTIVATION, PROLONGED SURVIVAL, AND PROTECTION AGAINST TUMOR RECHALLENGE, WHILE EXHIBITING REDUCED SYSTEMIC SIDE EFFECTS COMPARED TO CONVENTIONAL DOX. EXTENSIVE PRECLINICAL DATA WITH SQ3370 HAS LED TO AN OPEN INVESTIGATIONAL NEW DRUG (IND) APPLICATION WITH THE U.S. FOOD AND DRUG ADMINISTRATION (FDA). A PHASE 1, FIRST-IN-HUMAN, DOSE-ESCALATION STUDY IS CURRENTLY ENROLLING, TO EVALUATE THE SAFETY/TOLERABILITY, PK, AND PRELIMINARY EFFICACY OF SQ3370 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS. THIS DIRECT-TO-PHASE-2 APPLICATION HAS TWO MAIN OBJECTIVES: 1) TO GAIN ADDITIONAL MECHANISTIC INSIGHT OF SQ3370 IMMUNE ACTIVATION TO SUPPORT FURTHER CLINICAL DEVELOPMENT; 2) TO SUPPORT BOTH CLINICAL AND COMMERCIAL DEVELOPMENT THROUGH MANUFACTURING PROCESS OPTIMIZATION AND STABILITY STUDIES, THAT IS FURTHER DESCRIBED IN 5 SPECIFIC AIMS. THESE AIMS WILL ACCELERATE DEVELOPMENT OF SQ3370, A NOVEL THERAPY THAT PROMISES TO ULTIMATELY RESULT IN IMPROVED TREATMENT AND OUTCOMES FOR MILLIONS OF PATIENTS WITH SOLID TUMORS.