MDNA209 is a first-in-class beta-enhanced IL-2 superantagonist being developed for the potential remedy of autoimmune illnesses, that are attributed to immune system imbalance and have an effect on 5% to 10% of the worldwide inhabitants
MDNA209 restores immune steadiness by selectively blocking IL-2Rβγc, a receptor extremely expressed by effector CD8 T cells and recognized to advertise tissue injury in autoimmune illnesses.
In an aggressive animal mannequin of graft-versus-host illness (GvHD), MDNA209 prolonged total survival by 400%, lowered weight reduction, and improved scientific scores, highlighting its therapeutic potential to deal with GvHD and autoimmune illnesses.
MDNA113 is a BiSKIT (Bifunctional Tremendous Issue for Immunotherapy) focusing on IL-13Rα2 tumors that delivers anti-PD1-IL-2 tremendous issue (anti-PD1-IL-2SK) on to the tumor microenvironment (™E ).
MDNA113’s efficacy was considerably enhanced in mice bearing tumors that overexpressed IL-13Rα2, highlighting its potential to deal with immunologically chilly tumors equivalent to pancreatic, prostate, ovarian, and breast most cancers, which have an effect on greater than 100,000 sufferers worldwide annually. 2 million sufferers
TORONTO and HOUSTON, Sept. 09, 2024 (GLOBE NEWSWIRE) — Medicenna Therapeutics Corp. (Medicenna or the Firm) (TSX: MDNA, OTCQB: MDNAF) is a clinical-stage immunotherapy firm targeted on the event of Superkines Therapeutics, Inc., as we speak introduced that as deliberate and beforehand introduced, new information from two of its preclinical applications have been introduced orally on the Promise of Interleukin-2 convention in Paris, France, September 4-7, 2024.
Fahar Service provider stated: “Impressed by the encouraging Part 1/2 scientific outcomes of MDNA11’s ABILITY-1 scientific trial, we’re leveraging the identical IL-2 Superkine platform to advance our transformative drug pipeline to not solely deal with most cancers but in addition Can deal with autoimmune illnesses. We’re inspired by these preclinical information, which validate the flexibility of our IL-2 superfactor past most cancers as we additional consider MDNA209 in GvHD and different illness fashions. Moreover, our IL-13 Superkines allow us to exactly ship and goal BiSKIT to tumor websites, which can profit sufferers with cancers that don’t reply to at present accredited checkpoint inhibitors, thereby addressing a major unmet want.
MDNA209 and MDNA113 are preclinical belongings primarily based on the MDNA109 platform and are additionally used to develop MDNA11, a long-acting IL-2 superagonist at present within the Part 1/2 ABILITY-1 scientific trial for the remedy of strong tumors. Consider.
- The primary presentation outlined the potential of MDNA209 to deal with autoimmune illnesses, together with high-grade GvHD, for which the 1-year survival fee is simply 40%. Transplant sufferers with GvHD have excessive morbidity and mortality, and remedy choices to lengthen survival are restricted. Preliminary preclinical information introduced on the MDNA209 platform spotlight the potential of the corporate’s long-acting, high-affinity IL-2β-biased IL-2/IL-15 super-antagonist to downregulate the immune system with the potential to deal with GvHD and autoimmune illnesses.
- The second presentation targeted on MDNA113, which is being developed as a novel, focused and bifunctional model of a blockbuster class of anti-PD1 therapies (anti-PD1-IL-2 Superkine fusion) with present annual gross sales exceeding $30 billion , however the loss might be protected by patent from 2028. Though anti-PD-1 checkpoint blockade improves survival outcomes in quite a lot of strong tumors, roughly 70% of most cancers sufferers don’t profit. To additional enhance affected person outcomes, Medicenna designed an anti-PD1-IL-2SK BiSKIT that makes use of IL-13 Superkine to concurrently goal and localize the BiSKIT to™E whereas shielding the IL-2 area throughout peripheral circulation and Cut back its toxicity. In™E, tumor-specific proteases cleave the IL-13 element, releasing BiSKIT to bind to T cells, thereby stimulating T cell exercise by means of the IL-2 area and stopping T cell exhaustion by means of the anti-PD1 area.
The principle highlights of the presentation have been:
MDNA209, a high-affinity IL-2β-biased IL-2/IL-15 superantagonist for the remedy of autoimmune illnesses
- MDNA209 is an IL-2 superantagonist with enhanced affinity for IL-2Rβ however doesn’t bind to the γc subunit, thus performing as a receptor clamp to exclude native IL-2 in addition to native IL-15.
- MDNA209 is fused to an Fc scaffold (MDNA209-Fc) to increase its half-life in vivo and cut back the necessity for frequent dosing.
- MDNA209-Fc inhibits IL-2 and IL-15-induced p-STAT5 signaling, reduces IFNγ launch and slows immune cell proliferation with out lowering Treg numbers.
- In an aggressive animal mannequin of acute GvHD, MDNA209 prolonged total survival by 400%, lowered weight reduction, and improved scientific scores.
MDNA113, an IL-13Rα2 tumor-targeting and conditionally activatable anti-PD1-IL-2SK BiSKIT, demonstrates enhanced security and potent therapeutic efficacy
- MDNA113 (masked model) has a lowered skill to induce IL-2R-mediated pSTAT5 signaling in contrast with anti-PD1-IL-2SK (unmasked model) in cell-based assays and in human CD8+ T cells. Impacts PD1/PDL1 blockade.
- Proteolytic cleavage of MDNA113 releases anti-PD1-IL-2SK and absolutely restores its skill to activate IL-2R signaling.
- As a consequence of masking by IL-13 Superkine, mice handled with MDNA113 exhibited lowered peripheral lymphocyte growth in contrast with anti-PD1-IL-2SK.
- MDNA113 confirmed greater tolerability than anti-PD1-IL-2SK after repeated dosing in mice.
- MDNA113, however not the non-cleavable model, confirmed related efficacy to anti-PD1-IL-2SK within the MC38 colon tumor mannequin, though these tumors lacked IL-13Rα2 expression.
- MDNA113’s efficacy was considerably enhanced when examined in mice bearing MC38 tumors that had been engineered to overexpress IL-13Rα2, leading to full tumor regression in most animals.
- Variants of MDNA113 are additionally designed with adjustable masking of IL-2 Superkine, emphasizing the flexibility of the platform.
Copies of each briefs might be discovered on the Scientific Briefs web page of the Medicenna web site.
About MDNA209
The corporate’s MDNA209 platform consists of IL-2 muteins with focused mutations that allow high-affinity IL-2 receptor antagonism. MDNA209 blocks the formation of the IL-2Rβγc advanced, stopping downstream signaling and blocking effector T cell operate. MDNA209 competes with IL-2 for IL-2Rβ and blocks γc engagement, blocking downstream signaling and inhibiting reactive effector immune cells, thereby offering therapeutic potential for the remedy of inflammatory and autoimmune illnesses.
About MDNA113
MDNA113 is a novel, first-in-class, tumor-targeting and tumor-activating dual-functional anti-PD1-IL2 superfactor with extraordinarily excessive affinity for IL-13Rα2 with out binding to practical IL-13Rº1. IL-13Rα2 is overexpressed in quite a lot of strong tumors, together with chilly tumors with little or no expression in regular tissues. Tumors expressing IL-13Rα2 even have ample matrix metalloproteinases within the tumor microenvironment, which may successfully activate MDNA113. IL-13Rα2 expression is related to antagonistic scientific outcomes in a number of tumor sorts, together with prostate, pancreatic, ovarian, liver, breast, and mind cancers, with an annual incidence of over 2 million worldwide.
About Medicenna Therapeutics
Medicenna is a clinical-stage immunotherapy firm targeted on growing novel, extremely selective IL-2, IL-4 and IL-13 superkinases and first-in-class Empowered Superkines. Medicenna’s long-acting IL-2 Superkine MDNA11 is the subsequent technology of IL-2 with wonderful affinity for CD122 (IL-2 receptor beta) and doesn’t bind to CD25 (IL-2 receptor alpha), thereby preferentially stimulating anti-cancer Effector T cells and NK cells. Medicenna’s IL-4 Empowered Superkine bizaxofusp (previously often known as MDNA55) has been studied in 5 scientific trials enrolling greater than 130 sufferers, together with in recurrent GBM, the most typical and deadly type of mind most cancers. Part 2b trial. Bizaxofusp has acquired FastTrack and Orphan Drug designations from the FDA and FDA/EMA respectively. Medicenna’s early-stage, high-affinity IL-2β-biased IL-2/IL-15 superantagonist from its MDNA209 platform is being evaluated as a possible remedy for autoimmunity and graft-versus-host illness. Medicenna’s early-stage BiSKITs™ (Bifunctional SuperKine Immunotherapy) and T-MASK™ (Focused Metalloproteinase Activating SuperKine) applications are designed to boost Superkine’s skill to deal with immunologically chilly tumors.
For extra info, go to www.medicenna.com and observe us on Twitter and LinkedIn.
forward-looking statements
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Investor/Media Contact Data:
christina cameron
Investor Relations, Medicenna Therapeutics
(647) 953-0673
ir@medicenna.com
Supply: Medicenna Therapeutics Corp.
