Medicenna Presents Preclinical Data Demonstrating Anti-Tumor Activity of its Anti-PD1-IL-2 BiSKIT and Long-Acting IL-4/IL-13 Super-antagonist at Cytokines 2022
-- Single agent Anti-PD1-IL-2 BiSKIT™ showed superior efficacy compared to a combination of an anti-PD1 antibody with an IL-2 Superkine in murine models of colon, skin, and breast cancer
--IL-4/IL-13 Super-antagonist displayed monotherapy activity in multiple cancer models and in synergy with an IL-2 Superkine, highlighting its potential to treat immunologically “cold” tumors
TORONTO and HOUSTON,
“Our presentations highlight the versatility of our Superkine platform in designing novel, highly selective immune modulators to treat cancer,” said
Poster P110: A Next Generation Bifunctional Superkine for Immunotherapy (BiSKIT) Encompassing the Combined Therapeutic Potency of IL-2 Super-Agonist and Anti-PD1
Poster P110 includes preclinical data from in vitro and in vivo studies of MDNA223, a next generation BiSKIT consisting of an anti-PD1 antibody linked to an IL-2 super-agonist (MDNA109FEAA). Anti-PD1 drugs, such as Keytruda® (pembrolizumab), have been approved for a number of cancer indications.
In vitro data presented at the meeting demonstrated MDNA223’s potency against the PD1/PDL1 checkpoint was similar to that of a control anti-PD1 antibody while displaying increased affinity for IL-2 receptor beta (IL-2Rβ) and no binding to IL-2 receptor alpha (IL-2Rα). This enhanced IL-2Rβ selectivity resulted in potent and preferential stimulation of anti-cancer CD8+ T cells over pro-tumor Treg cells. In vivo murine data showed MDNA223 exhibiting a prolonged pharmacodynamic response extending beyond the duration of pharmacokinetic exposure. In addition, the murine surrogate of MDNA223 showed superior efficacy compared to co-administration of anti-PD1 and long acting MDNA109FEAA in murine models of colon, skin, and breast cancer. These data demonstrate the therapeutic synergy resulting from the BiSKIT’s ability to concurrently target PD1 and the IL-2 receptor on the same immune cells (cis-binding approach).
Poster P69: Fc-MDNA413 is a Novel Long-Acting IL-4/IL-13 Super-Antagonist that
Poster P69 includes preclinical data from in vitro and in vivo studies of Fc-MDNA413, a novel, long-acting IL-4/IL-13 Superkine. Fc-MDNA413 is designed to reverse the immunosuppressive tumor microenvironments (TMEs) of immunologically “cold” tumors by selectively binding to the IL-13 receptor alpha-1 (IL-13Rα1) with high affinity and blocking signaling via the Type II IL-4 receptor (IL-4Rα/IL-13Rα1) expressed on tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs). It consists of an IL-4/IL-13 super-antagonist fused to the Fc domain for half-life extension.
Data presented at Cytokines 2022 showed Fc-MDNA413 blocking the pathways that induce M2a TAMs and MDSCs to promote cancer growth and demonstrated its potential to treat cold tumors. In vitro analyses showed that the Superkine is 300-times more selective for IL-13Rα1 over IL-13Rα2 (a decoy receptor) compared to a fusion protein consisting of Fc domain linked to wild type IL-13. This superior binding profile enabled Fc-MDNA413 to potently inhibit IL-4/IL-13 mediated functions as measured by pSTAT6 signaling, TF-1 cell proliferation, and M2a polarization of macrophages. In murine studies, Fc-MDNA413 demonstrated sustainable serum exposure at a dose that was well tolerated and inhibited tumor growth as a single agent in melanoma and colon cancer models. In addition, Fc-MDNA413 synergized with an IL-2 agonist in a murine melanoma model, highlighting the advantages of co-targeting suppressive and effector immune cells within an otherwise cold TME.
Copies of the two posters are available on Cytokines 2022’s virtual platform. They will also be posted to the “Events and Presentations” page of Medicenna’s website following the conclusion of the meeting.
Medicenna is a clinical stage immunotherapy company focused on the development of novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first in class Empowered Superkines. Medicenna's long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior CD122 (IL-2 receptor beta) binding without CD25 (IL-2 receptor alpha) affinity thereby preferentially stimulating cancer killing effector T cells and NK cells. Medicenna’s early-stage BiSKITs™ program, (Bifunctional SuperKine ImmunoTherapies) is designed to enhance the ability of Superkines to treat immunologically “cold” tumors. Medicenna's IL-4 Empowered Superkine, MDNA55, has been studied in 5 clinical trials including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. MDNA55 has obtained Fast-Track and Orphan Drug status from the FDA and FDA/EMA, respectively.
Forward Looking Statements
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Source: Medicenna Therapeutics Corp.