GDT-002 (IL12-FHAB-IL15)
GDT-002 is an immunotherapeutic bifunctional drug candidate that links unmodified single-chain human IL-12 and human IL-15 with the albumin-binding domain of the single-chain antibody fragment FHAB, separating the two cytokines with linkers to avoid steric hindrance.
The FHAB single chain was selected to bind well at normal pH, as well as at an acidic pH that is typically found in the tumor microenvironment (TME). The FHAB technology targets tumor and lymphatic tissue, providing lowered dose, enhanced PK, and an opportunity to improve the safety and efficacy profile of not only IL-12 and IL-15, but a variety of other potent immunomodulators using the platform.
Key Details
Indications
Multiple solid tumors
Current Stage
IND-ready and starting Phase I
Market Opportunity
IL-15 alone, co-dosed with BCG vaccine, has proven very effective in non-muscle-invasive bladder cancer. A dual cytokine molecule with Navigated Delivery ™ that is accumulated and retained in the tumor microenvironment has the potential to also treat advanced and metastatic disease, with lower and less frequent dosing, improving potency with fewer side effects.
Mechanism of actions
We believe these dual-targeting cytokines can orchestrate a robust immune response to many cancers and pathogens, particularly when presented together on the same molecule. Given specific proteins induced in the TME that actively accumulate, retain and bind albumin, such as the Secreted Protein and Rich in Cysteine (SPARC) and glycoprotein 60 (GP60), cancers such as bladder cancer, non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant for this approach.
GDT-002 is designed to navigate IL-12 and IL-15 to accumulate in local tumor tissue, with the intention of turning 'cold' tumors 'hot' by stimulating IFNγ, which activates both innate and adaptive immune cells in the TME, as well as increasing the production of Programed Death Ligand 1 (PD-L1) on tumor cells.
Key Advantages
Dose-Sparing and Enhanced PK
GDT-002 is approximately 2X more potent than GDT-001, demonstrated in Mouse B16F10 Melanoma Model. Approximately 35-fold more potent than IL-12 alone at Day 10, using a 1:30 ratio of IL-12, demonstrated in Mouse B16F10 Melanoma Model.
Bifunctional Action
GDT-002 links IL-12 and IL-15 on the same molecule, separated by linkers to avoid steric hindrance, designed to work together to generate a robust immune response in the tumor microenvironment.
Related Programs
Phase 1 | Solid Tumors
GDT-001 (IL12-FHAB)
A IL-12 immunotherapy candidate designed to be best-in-class to turn 'cold' tumors 'hot’ while avoiding systemic immune-activation toxic effects. Currently in Phase 1 for advanced solid tumors and in combination with trabectedin (Yondelis®) for Soft-Tissue Sarcomas .Currently seeking partnership to move this forward into Phase 1B/IIA.
Preclinical | Solid Tumors
GDT-003 (IL- 18BPR
-FHAB-IL12)
A first-in-class IL-12+IL-18 immunotherapy candidate with issued intellectual property delivering dual cytokine action directly to the tumor microenvironment.
Interested in GDT-002?
Guidant BioTherapeutics is actively engaging with potential partners and licensees interested in leveraging the strength of our proprietary FHAB technology platform.