Medicenna Presents Updated Preclinical Data on MDNA113, a First-in-Class, Targeted and Masked Bi-functional anti-PD1-IL2 Superkine, at the 2024 Annual Meeting of the American Association for Cancer Research (AACR)
09 Abril 2024 - 1:01PM
Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX:
MDNA), a clinical-stage immunotherapy company focused on the
development of Superkines, today announced new preclinical data on
MDNA113, the Company’s novel T-MASK (
Targeted
Metallo/protease
Activated
Super
Kine) candidate, an IL-13R⍺2
(Interleukin-13 receptor alpha2) specific superkine featuring
unique masking and tumor targeting characteristics, were presented
at the 2024 Annual Meeting of the American Association for Cancer
Research (AACR) held in San Diego, CA, on April 9th, 2024.
“We are pleased to show preclinical data
demonstrating the ability of Medicenna’s first T-MASK candidate,
MDNA113 to enhance tumor accumulation and tolerability of our
potent bi-functional immune modulator, anti-PD1-IL-2SK,” said Fahar
Merchant, Ph.D., President and Chief Executive Officer of
Medicenna. “MDNA113 has novel features, including the tunable
blockade of the IL-2R agonism to reduce peripheral immune
stimulation for enhanced tolerability, and tumor targeting to
IL-13R⍺2 which is linked to aggressive cancers that annually affect
over 2 million patients world-wide. The cleavage and release of the
IL-13 tumor-targeting/masking domain by matrix metalloproteases
restores IL-2R signaling within the tumor microenvironment, thereby
benefiting from the simultaneous and synergistic activity of IL-2R
agonism and immune checkpoint blockade at the tumor site.”
The Company selected MDNA113, a novel,
first-in-class tumor-targeted and tumor-activated bi-functional
anti-PD1-IL-2 superkine with high selectivity and affinity for
IL-13Rα2, a tumor associated antigen expressed in many aggressive
solid tumors. The IL-13 Superkine (MDNA213) is a highly specific
tumor-targeting/masking domain which is fused via a protease
sensitive linker to a bi-functional immunotherapy domain (MDNA223)
containing an IL-2 Superkine fused to an anti-PD1 antibody.
Key findings presented at the conference
include:
- When not activated, MDNA113 shows
reduced IL-2R agonism with no change to PD-1/PDL-1 blockade
activity.
- Cleavage and activation of MDNA113
by cancer specific enzymes (metalloproteases) releases the T-MASK
domain (MDNA213), restoring activity of the IL-2 Superkine at the
tumor site.
- MDNA113 shows attenuated systemic
lymphocyte expansion compared to non-masked version (MDNA223),
consistent with design of MDNA113.
- MDNA113 is better tolerated than
non-masked counterpart (MDNA223), supporting higher and more
efficacious dosing schedule.
- MDNA113 selectively binds IL-13R⍺2
positive tumor cells in vitro, and durably accumulates (>7 days)
in IL-13R⍺2 positive tumors in mice.
- Cleavable MDNA113 shows similar
efficacy as non-masked MDNA223 in mouse tumor models by either
localized (intra-tumoral) or systemic (intra-peritoneal) delivery,
consistent with proteolytic activation within TME.
- Single neoadjuvant treatment with
MDNA113 in a highly invasive orthotopic 4T1.2 breast cancer model
significantly increases survival by preventing metastasis.
- In summary, the T-MASK platform
exemplified by MDNA113, facilitates tumor targeting and minimizes
systemic toxicity while maximizing therapeutic activity at the
tumor site.
The poster, “Characterization of MDNA113, a
Tumor-Targeting Anti-PD1-IL-2SK Immunocytokine with Conditional
Activation to Increase Tolerability and Maximize Efficacy” can be
found on the AACR website for conference registrants. It will be
also available on the Scientific Presentations page of Medicenna’s
website following the conclusion of the 2024 Annual Meeting of
AACR.
About the T-MASK Platform
Medicenna’s novel T-MASK
(Targeted Metallo/protease
Activated
SuperKine) platform involves
fusion of a dual tumor-targeting/masking domain to an immune
modulator (such as a Superkine or a BiSKIT) via a matrix
metalloprotease (MMP) sensitive linker to (i) reduce and fine-tune
the potency of the immune modulator, (ii) increase its systemic
tolerability (iii) prolong its retention in the TME and (iv) to
maximize and restore full potency at the intended target site. The
T-MASK platform offers opportunity to target and fine-tune immune
cell stimulation in the TME to improve the therapeutic index of
Medicenna’s Superkine and BiSKIT platforms.
About MDNA113
MDNA113 is a novel, first-in-class
tumor-targeted and tumor-activated bi-functional anti-PD1-IL-2
Superkine with high affinity for IL-13Rα2 without binding to the
functional IL-13R⍺1. IL-13Rα2 is overexpressed in a wide range of
solid tumors, including cold tumors. IL-13Rα2 is a tumor-associated
antigen with minimal to no expression in normal tissues but is
highly expressed by a wide range of tumors including “cold” tumors.
IL-13Rα2 expressing tumors also have abundant MMPs in the TME that
may efficiently activate MDNA113. IL-13Rα2 expression is associated
with poor clinical outcome in multiple tumor types with an annual
world-wide incidence of over 2 million in different tumor types
including prostate cancer, pancreatic cancer, ovarian cancer, liver
cancer, breast cancer and brain cancer, and among others.
About Medicenna
Medicenna is a clinical-stage immunotherapy
company focused on developing 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 affinity toward CD122 (IL-2
receptor beta) and no CD25 (IL-2 receptor alpha) binding, thereby
preferentially stimulating cancer-killing effector T cells and NK
cells. Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly
MDNA55), has been studied in 5 clinical trials enrolling over 130
patients, including a Phase 2b trial for recurrent GBM, the most
common and uniformly fatal form of brain cancer. Bizaxofusp has
obtained FastTrack and Orphan Drug status from the FDA and FDA/EMA,
respectively. Medicenna’s early-stage BiSKITs™ (Bifunctional
SuperKine ImmunoTherapies) and the T-MASK™ (Targeted
Metalloprotease Activated SuperKine) programs are designed to
enhance the ability of Superkines to treat immunologically “cold”
tumors.
For more information, please
visit www.medicenna.com, and follow us
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Forward-Looking Statements
This news release may contain forward-looking
statements within the meaning of applicable securities laws.
Forward-looking statements include, but are not limited to, express
or implied statements regarding the future operations of the
Company, estimates, plans, strategic ambitions, partnership
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forecasts, projections, guidance, outlook or other statements that
are not historical facts, such as statements on the Company’s cash
runway, preclinical and clinical development activities and the
potential benefits of its Superkine platform, clinical trial
designs and results, clinical potential, expectations and beliefs
around safety profiles and upcoming milestones and data reporting,
including with respect to MDNA11, the ABILITY study and its
expansion, bizaxofusp (MDNA55), MDNA113 and MDNA223. Drug
development and commercialization involve a high degree of risk,
and only a small number of research and development programs result
in commercialization of a product. Results in early-stage clinical
studies may not be indicative of full results or results from later
stage or larger scale clinical studies and do not ensure regulatory
approval. You should not place undue reliance on these statements
or the scientific data presented. Forward-looking statements are
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similar expressions. Forward-looking statements are based on a
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the expectations reflected in such forward-looking statements are
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Investor and Media Contact:
Christina CameronInvestor Relations, Medicenna
Therapeuticsir@medicenna.com (647) 953-0673
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