CELDARA MEDICAL, LLC — Department of Health and Human Services SBIR Phase I: 102

Description

DESCRIPTION provided by applicant The long term aim of this project is to advance BILT for clinical approval which will provide clinicians with a powerful addition to the armamentarium for treating CTCL and cancer immunotherapy through depleting CD Treg Ontak R denileukin diftitox was making great strides in the treatment of CTCL since its FDA approval in until its discontinuation BILT functions analogously to Ontak R but with greater potency The functional parallel between these two therapies provides a clear pre clinical and clinical path forward An ideal cancer therapy would be effective selective permanent and safe The immune system has the ability to specifically recognize and attack tumor cells and their supportive microenvironments while sparing nearby normal cells We have developed a novel therapy that has met these marks through the use of a genetically engineered bivalent human IL fused to a truncated diphtheria toxin BILT In addition we developed a robust scalable and efficient yeast expression system with greatly enhanced purification yields Although Ontak R was an integral part of the treatment regimen for patients with CTCL its discontinuation due to a supply interruption has introduced a gap The work proposed here is a major step toward advancing a next generation therapy that targets CD tumor cells with greater potency than Ontak R In murine models the bivalent fusion toxin was efficacious against CD tumors and effectively depleted CD tumor cells in vivo while exhibiting no overt toxicity BILT has the potential for significant efficacy against human disease safety profile similar to that of an approved product and improve the cliniciansandapos toolkit against CTCL Beyond its initial effect on CTCL BILT is likely to efficacious against other CD tumors and may also impact organ transplantation where targeting CD T cells is a key therapeutic goal In this Phase I SBIR proposal we will determine the anti tumor efficacy of BILT in vivo we will determine the maximum tolerated dose MTD and the mechanism of toxicity and we will develop a fermentation SOP to support clinical development These studies will advance BILT and if successful will position this therapy for large animal preclinical and subsequent clinical development At the end of this Phase I project we will have achieved key goals on the critical path to move this promissing intervention toward the clinic PUBLIC HEALTH RELEVANCE We created a novel biologic named BILT with tremendous potential for the treatment of CTCL and cancer immunotherapy through its ability to deplete cancerous cells as well as certain immune cells that suppress immunity BILT is an improved alternative to Ontak R due to manufacturability and efficacy We developed a robust scalable and efficient production system with greatly enhanced purification yields Herein we propose to advance this technology toward the clinic by determining the optimal dose performing safety studies and developing a large scale production protocol