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CCR4-IL2 Bispecific Immunotoxin for Targeted Therapy of Cutaneous T-Cell Lymphoma

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R42CA261547-02
Agency Tracking Number: R42CA261547
Amount: $1,000,000.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: 102
Solicitation Number: PA20-265
Solicitation Year: 2020
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-02-01
Award End Date (Contract End Date): 2025-01-31
Small Business Information
Denver, CO 80238-3365
United States
DUNS: 117569981
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (303) 724-8732
Business Contact
Phone: (443) 474-1507
Research Institution
AURORA, CO 80045-2571
United States

 Nonprofit College or University

Cutaneous T-cell lymphoma (CTCL) is a type of extra-nodal non-Hodgkin’s lymphoma characterized by skinlesions resulting from infiltration of malignant T lymphocytes. Mycosis fungoides and Sezary syndrome are thetwo most common types of CTCL. Although treatments exist, they are mainly palliative with low response anddurability of response without any cure. The objective response rate remains approximately 30% with the currenttreatment strategies for refractory or recurrent CTCL. Despite CTCL being an indolent, chronic disease in mostcases, some patients experience severe debilitating itchiness, while others have progressive disease with
extensive skin and organ involvement. There is an unmet medical need for more effective treatments withimproved response for refractory or recurrent CTCL patients. The majority of clinically diagnosed CTCL highlyexpress the surface markers CC chemokine receptor 4 (CCR4) and/or CD25. We have generated a promisingdiphtheria toxin based CCR4-IL2 bispecific immunotoxin therapeutic candidate for targeted immunotherapyof CTCL. Our candidate drug is genetically engineered to contain both anti-human CCR4 scFv and human IL2fused to a truncated diphtheria toxin. Our candidate drug has demonstrated promising preclinical efficacy in amouse tumor model showing 106% improvement in survival (69 vs. 33.5 days) compared to an Ontak®
-likehuman IL-2 fusion toxin. Our candidate drug is expressed using a novel, advanced diphtheria toxin-resistantyeast (Pichia pastoris) expression system. Our yeast expression system overcomes expression and purificationproblems encountered with E. coli-based expressions systems to deliver high production levels and excellentpurification quality of our immunotoxin. Importantly, the surface receptors CCR4 and CD25 are also expressedon tumor-infiltrating effector T regulatory cells (Tregs) known to play a role in suppressing anti-tumor immuneresponses. Therefore, a potential follow-on indication for our candidate drug is depletion of tumor infiltratingCCR4+ or/and CD25+ Tregs to boost tumor immunotherapy for a broad spectrum of cancers. In phase I of thisapplication, we will perform pilot non-GLP toxicology, pharmacokinetics, and immunogenicity studies in both ratsand minipigs. In phase II, we will 1) develop a scalable standard operating procedure (SOP) for large-scale goodmanufacturing practice (GMP) production and produce enough GMP grade CCR4-IL2 bispecific immunotoxinfor phase I and II clinical trials, and 2) perform GLP toxicology, pharmacokinetics, and immunogenicity studies
in both rats and minipigs. Our goal is to prepare an IND-ready preclinical data package and then move thisproduct into clinical trials.

* Information listed above is at the time of submission. *

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