Medicenna Presents New Preclinical Results For its IL-2 Superkine Platform, MDNA109
- Category: Proteins and Peptides
- Published on Friday, 21 June 2019 12:47
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-Long Acting MDNA109 provides durable tumor control and strong memory response without further treatment when combined with checkpoint inhibitors
TORONTO, Canada and HOUSTON, TX, USA I June 20, 2019 I Medicenna Therapeutics Corp. ("Medicenna" or "the Company") (TSX: MDNA,OTCQB: MDNAF), a clinical stage immunotherapy company developing first-in-class Superkines and Empowered Cytokines, presented new pre-clinical data on its IL-2 Superkine program, MDNA109. The data was presented in a poster entitled "Engineering a long-acting CD122 biased IL-2 superkine displaying potent anti-tumoral responses" at the Inaugural Immuno-Oncology Pharma Congress, held from June 18-20, 2019 during World Pharma Week in Boston, MA.
"We are excited with the pre-clinical results from our second oncology platform being built around MDNA109, on the back of promising clinical results from our Phase 2b MDNA55 recurrent glioblastoma trial presented this week at the same conference," said Dr. Fahar Merchant, President and CEO of Medicenna. "Unlike other engineered versions of IL-2 under development where both CD25 and, to a lower extent, CD122 activity is masked when compared to recombinant IL-2 (marketed as Proleukin®), our long acting MDNA109 variant has disabled CD25 binding but stimulates potent CD122 activity relative to Proleukin®. Disabled CD25 activity provides a much better safety profile while superior CD122 stimulation ensures potent recruitment of immune cells (Effector T cells and NK cells) responsible for attacking cancer," added Dr. Merchant.
Highlights from the presentation by Dr. Moutih Rafei, Associate Professor in the Department of Pharmacology and Physiology at the Université de Montreal and Head of Discovery at Medicenna, included the following
- Durable Tumor Control With Strong Memory Response: When MDNA109-LA was co-administered with the immune-checkpoint blocker anti-cytotoxic T-Lymphocyte-Associated Protein (CTLA)4 in a colon cancer mouse model, 67% of animals with pre-established tumors remained tumor-free for over 100 days. When these animals received a second and third re-challenge of the tumor without further treatment, 100% and 75% remained tumor free, respectively, demonstrating a strong memory response.
- Blunted Treg Activity But Potent Activation Of Naïve CD8 T Cells: A long-acting variant, MDNA109-LA1, engineered to mitigate Treg activation by abolishing binding to the CD25 had 50-fold decreased Treg activity and 6-fold higher activity towards naïve CD8 T cells for an overall 300-fold preferential activation of cancer killing T cells than recombinant IL-2.
- Absence Of CD25 Binding: In addition, binding affinity studies using surface plasmon resonance confirmed absence of CD25 binding by MDNA109-LA1.
- Potent Effects With Minimal Dosing: To further validate the potency of MDNA109-LA1 mice with pre-established aggressive B16F10 melanoma tumors showed potent tumor control with a weekly dosing schedule.
"These data show that MDNA109 long-acting variants can be expected to drive clinical efficacy beyond that seen with other treatments," states Dr. Rafei, "The use of Proleukin® for the treatment of skin and renal cancer remains limited due to the poor half-life and severe toxicity. Data show that MDNA109-LA1 may not only minimize adverse effects, but could also eliminate immunosuppression caused by Tregs using a dosing schedule that is compatible with immune-checkpoint blockers. It's clear from these recent data that MDNA109 is a highly versatile platform for multiple uses in immuno-oncology without complex manufacturing and lack of immunogenicity as demonstrated by in-silico analysis.
Developed by scientists at Stanford University, MDNA109 is an engineered version of IL-2 that binds up to 200 times more effectively to IL-2Rβ (CD122), thus greatly increasing its ability to activate and proliferate the immune cells needed to fight cancer. MDNA109 is an IL-2 Superkine that preferentially drives the expansion and responses of effector T cells and Natural Killer (NK) cells over Treg cells. It is the only IL-2 in development with a distinct mechanism by virtue of its high affinity towards CD122 allowing it to effectively combat NK cell anergy (exhaustion) which occurs frequently after cancer immunotherapy.
About Medicenna Therapeutics Corp.
Medicenna is a clinical stage immunotherapy company focused on oncology and the development and commercialization of novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first in class Empowered Cytokines™ (ECs) for the treatment of a broad range of cancers. Supported by a US$14.1M non-dilutive grant from CPRIT (Cancer Prevention and Research Institute of Texas), Medicenna's lead IL4-EC, MDNA55, has completed enrolling patients in a Phase 2b clinical trial for rGBM, the most common and uniformly fatal form of brain cancer, at top-ranked brain cancer centres in the US. MDNA55 has been studied in five clinical trials involving 132 patients, including 112 adults with rGBM. MDNA55 has demonstrated compelling efficacy and has obtained Fast-Track and Orphan Drug status from the FDA and FDA/EMA respectively. For more information, please visit www.medicenna.com.
SOURCE: Medicenna Therapeutics