This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) to Chapman University will support the development of small molecule selective inhibitors of neuronal nitric oxide synthase (nNOS) for the treatment of melanoma. The key products and services to be delivered under this $610,415 award, which runs from Jun 2025 to May 2030, include: Designing and synthesizing novel nNOS inhibitors with improved potency, selectivity, and pharmacological properties....
The National Cancer Institute (NCI) awarded a $2,000,000 Project Grant (CFDA 93.395 - Cancer Treatment Research) to Sonoval LLC, a for-profit limited liability company located in Baltimore, MD. The purpose of this 2-year grant, which runs from August 2024 to July 2026, is to develop a second-generation version of the TREG-depleting immunotherapy ONTAK, called SON-211. Sonoval aims to eliminate the vascular leak syndrome side effect that led to ONTAK's removal from the market, while retaining its...
This National Science Foundation (NSF) Small Business Innovation Research (SBIR) Phase I project under the NSF Technology, Innovation, and Partnerships (CFDA 47.084) program aims to develop an image-guided intratumoral delivery system for immunotherapies to treat solid tumors. The $305,000 award to Absco Therapeutics, Inc. (dba Abscotx) will fund the research and development of a biomaterial-based platform that can solidify upon injection to localize and sustain the release of biologics within...
This $399,669 federal Project Grant awarded by the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) aims to establish the feasibility of commercializing a personalized and multi-targeted adoptive T cell therapy (ATCT) for glioblastoma (GBM), the most common and deadly primary brain tumor. The key products or services to be delivered under this grant include: Evaluating the ability of the applicant's Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) platform to...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $1,419,108 to Emory University 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 award will fund research to gain insights into how blocking the SEMA4D signaling pathway, when combined with immune checkpoint blockade, enhances the activity of antigen-presenting dendritic...
This $379,981 Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) aims to develop a localized cancer immunotherapy using particle-anchored cytokines for prolonged intratumoral retention. The primary objectives are to: (I) develop liposome-anchored cytokines with extended tumor retention and minimal systemic leakage, and (II) elucidate the mechanisms by which particle-anchored cytokines elicit durable anti-tumor immunity to improve efficacy in poorly...
This SBIR Phase I project, awarded by the National Science Foundation (NSF) under the NSF Technology, Innovation, and Partnerships (TIP) program (CFDA 47.084), aims to develop a method to turn on cancer immunotherapies only at the site of disease. The $275,000 award will support Synsorybio, Inc., a for-profit organization, in creating protein switches that activate immunotherapies in response to disease signals, rather than indiscriminately throughout the body. This approach seeks to improve the...
The University of California, Davis was awarded a $615,399 Project Grant by the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) to develop a transformable nanoparticle (TNP) platform capable of transforming into nanofibrillar networks that can effectively deliver immunomodulatory peptides, small molecules, and proteins to the tumor microenvironment. This 5-year research project aims to optimize the TNP/TCTS therapeutic platform for on-demand modulation of the tumor...
This Project Grant award from the National Cancer Institute (CFDA 93.395 Cancer Treatment Research) provides $400,000 to Senex Biotechnology Inc. to develop a nanoparticle formulation of a mediator kinase inhibitor drug candidate, SNX631-6, for the treatment of peritoneal ovarian cancer metastases. The goal is to optimize the nanoparticle formulation for improved pharmacokinetics and efficacy compared to oral administration when delivered intraperitoneally. The project will assess the...
The National Cancer Institute (NCI) awarded Celdara Medical, LLC a $1,024,967 Project Grant under the Cancer Treatment Research program (CFDA 93.395) to develop CM-HZ01, a novel non-alpha-IL2 therapeutic for the treatment of metastatic melanoma. The goal is to advance CM-HZ01 to Investigational New Drug (IND) status, providing a potentially best-in-class immunotherapy option for patients with limited effective treatments for this deadly form of skin cancer. The project period runs from January...
IN SITU TUMOR VACCINATION WITH A NANO-OLIGO THERAPEUTIC TO INDUCE WHOLE-BODY ANTITUMOR IMMUNE RESPONSE - SIGNIFICANCE/GOAL. ALTHOUGH IMMUNE CHECKPOINT INHIBITORS (ICIS) HAVE SHOWN IMPRESSIVE OUTCOMES IN MELANOMA PATIENTS, THE MAJORITY OF PATIENTS FAIL TO RESPOND, MAINLY DUE TO THE ABSENCE OF TUMOR-INFILTRATING T CELLS. IN ORDER TO BOOST THE ANTI-TUMOR T CELL REPERTOIRE, WE HAVE DEVELOPED A NOVEL IMMUNO-NANOTHERAPEUTIC, CALLED "AUGMENTING IMMUNE RESPONSE AND INHIBITING SUPPRESSIVE ENVIRONMENT OF TUMORS - AIRISE-02", BASED ON OUR PATENT-PENDING NANOPARTICLE (NP) CO-DELIVERING AN IMMUNE-ACTIVATING CPG OLIGO AND SIRNA AGAINST STAT3. AIRISE-02 RELIES ON "IN SITU TUMOR VACCINATION," WHICH EXPLOITS A LOCALLY TREATED TUMOR TO PRIME IMMUNE RESPONSE AGAINST TUMORS THROUGHOUT THE BODY. UNIQUE TO AIRISE-02 IS THE ABILITY TO ENTER BOTH CANCER AND ANTIGEN PRESENTING CELLS (E.G., DC, MACROPHAGE) UPON INTRATUMORAL (I.T.) INJECTION, RESULTING IN CANCER CELL DEATH AND TUMOR ANTIGEN RELEASE, WHILE BEING SAFE TO AND ACTIVATING THE ANTIGEN PRESENTING CELLS. BY KNOCKING DOWN STAT3 WITH SIRNA, AIRISE-02 ALSO MODULATES IMMUNOSUPPRESSIVE ENVIRONMENT OF THE TUMOR. GIVEN I.T. TO ONLY ONE MELANOMA TUMOR, AIRISE-02 CAUSED REGRESSION IN BOTH TREATED AND UNTREATED DISTANT TUMORS, DEMONSTRATING WHOLE-BODY IMMUNOTHERAPEUTIC ACTION. AIRISE-02 WAS AS EFFECTIVE AS TWO ICIS (PD-1 + CTLA- 4, GIVEN I.P.) COMBINED, AND LED TO COMPLETE CURES IN 5 OUT OF 8 MICE WHEN GIVEN WITH THE ICIS. THE MICE HAVE REMAINED TUMOR-FREE FOR AT LEAST 17 MONTHS, WHILE MICE RECEIVING JUST ICIS DID NOT SURVIVE PAST 2 MONTHS. AIRISE-02 WAS ALSO EFFECTIVE IN COLON AND BREAST CANCER MOUSE MODELS AND WAS WELL TOLERATED IN MONKEYS. APPROACH. THIS DIRECT PHASE II SBIR FOCUSES ON IND-ENABLING STUDIES OF AIRISE-02. IN AIM 1, WE WILL ESTABLISH THE MECHANISM OF AIRISE-02 BY IDENTIFYING KEY IMMUNE CELLS REQUIRED FOR THERAPEUTIC ACTION AND CONFIRM EFFICACY IN ANOTHER CLINICALLY RELEVANT MELANOMA MODEL. IN AIM 2, WE WILL PARTNER WITH CMOS FOR MANUFACTURING GMP-COMPLIANT AIRISE-02 (SISTAT3, CPG, AND NP), STERILIZATION, FILL FINISHES, AND STABILITY STUDIES. IN AIM 3, WE WILL WORK WITH CHARLES RIVER TOXICOLOGY TO CONDUCT GLP-COMPLIANT TOXICOLOGY STUDIES OF AIRISE-02 IN MICE AND CYNOMOLGUS MONKEYS. THE MAXIMUM TOLERATED DOSE AND TOXICOKINETIC PROFILE WILL BE ESTABLISHED. POTENTIAL TOXICITY AFTER REPEATED DOSES WILL BE ASSESSED BY MONITORING BODY WEIGHT, GENERAL HEALTH, INJECTION SITE REACTION, HEMATOLOGY, SERUM CHEMISTRY/CYTOKINES, AND HISTOPATHOLOGY OF KEY ORGANS. IN AIM 4, WE WILL PARTNER WITH RTI INTERNATIONAL AND KNIGHT CANCER INSTITUTE'S CENTER OF EXPERIMENTAL THERAPEUTICS TO SUBMIT AN IND APPLICATION TO ENABLE PHASE I CLINICAL TRIAL IN EARLY 2023. NOVELTY AND IMPACT. NANOPARTICLE CO-DELIVERY OF SIRNA AND ADJUVANT FOR IN SITU CANCER VACCINATION HAS NEVER BEEN DONE BEFORE. SUCCESSFUL AIRISE-02 WILL BENEFIT MANY INJECTABLE TUMORS (E.G., MELANOMA, BREAST, LYMPHOMA, HEAD AND NECK) WITH METASTASIS ANYWHERE. FUTURE TARGET DISCOVERY CAN LEAD TO NEW AIRISE PIPELINES UTILIZING OTHER SIRNAS. OUR NANOPARTICLE HAS BEEN EXTENSIVELY EVALUATED AND SYNTHESIZED AT LARGE-SCALE, AND I.T. AIRISE-02 LIMITS SYSTEMIC TOXICITY, TOGETHER FACILITATING RAPID TRANSLATION OF AIRISE-02 TO THE CLINIC.