Medicenna Presents Preclinical Data on MDNA11 as First Step to Shrink Tumors Before Surgery and Prevent Metastasis at the 2024 San Antonio Breast Cancer Symposium (SABCS)
Medicenna Therapeutics (MDNAF) presented new preclinical data for MDNA11 at the 2024 San Antonio Breast Cancer Symposium. The data showed that single-agent MDNA11 outperformed combined immune checkpoint inhibitors in preventing metastasis and achieving long-term survival in triple negative breast cancer (TNBC) models.
Key findings demonstrated that a single low dose of MDNA11 as neoadjuvant therapy significantly prevented metastasis, with 6/7 mice at low-dose (2 mg/kg) and 7/8 mice at high-dose (5 mg/kg) surviving over 4 months without metastasis signs. The treatment also enabled memory immune response against tumor rechallenges, while promoting CD8+ T cell infiltration into the tumor microenvironment without affecting Treg cells.
Medicenna Therapeutics (MDNAF) ha presentato nuovi dati preclinici per MDNA11 al Simposio sul Cancro Mammario di San Antonio 2024. I dati hanno mostrato che il MDNA11 come terapia singola ha superato gli inibitori dei checkpoint immunitari combinati nel prevenire la metastasi e nel raggiungere una sopravvivenza a lungo termine nei modelli di carcinoma mammario triplo negativo (TNBC).
Le principali scoperte hanno dimostrato che una bassa dose singola di MDNA11 come terapia neoadiuvante ha significativamente prevenuto la metastasi, con 6/7 topi alla dose bassa (2 mg/kg) e 7/8 topi alla dose alta (5 mg/kg) che sono sopravvissuti per oltre 4 mesi senza segni di metastasi. Il trattamento ha anche abilitato la risposta immunitaria di memoria contro le ri-esposizioni tumorali, promuovendo l'infiltrazione delle cellule T CD8+ nel microambiente tumorale senza influenzare le cellule Treg.
Medicenna Therapeutics (MDNAF) presentó nuevos datos preclínicos para MDNA11 en el Simposio sobre Cáncer de Mama de San Antonio 2024. Los datos mostraron que el MDNA11 como agente único superó a los inhibidores combinados de puntos de control inmune en la prevención de la metástasis y en la obtención de una supervivencia a largo plazo en modelos de cáncer de mama triple negativo (TNBC).
Los hallazgos clave demostraron que una baja dosis única de MDNA11 como terapia neoadyuvante prevenía significativamente la metástasis, con 6/7 ratones a dosis baja (2 mg/kg) y 7/8 ratones a dosis alta (5 mg/kg) sobreviviendo más de 4 meses sin signos de metástasis. El tratamiento también permitió una respuesta inmune de memoria contra los desafíos tumorales, mientras promovía la infiltración de células T CD8+ en el microambiente tumoral sin afectar a las células Treg.
메디센나 테라퓨틱스 (MDNAF)가 2024년 샌안토니오 유방암 심포지엄에서 MDNA11에 대한 새로운 전임상 데이터를 발표했습니다. 데이터는 단일 약제 MDNA11이 삼중 음성 유방암(TNBC) 모델에서 전이 예방 및 장기 생존 달성에 있어 결합 면역 검문소 억제제보다 우수하다는 것을 보여주었습니다.
주요 발견들은 낮은 단일 용량의 MDNA11이 신보조요법으로 전이를 현저히 예방했으며, 낮은 용량(2 mg/kg)의 경우 6/7 마리와 높은 용량(5 mg/kg)의 경우 7/8 마리가 4개월 이상 전이 증상 없이 생존했다는 것을 보여주었습니다. 이 치료는 또한 종양 재도전에 대한 면역 기억 반응을 가능하게 하며, Treg 세포에 영향을 주지 않으면서 종양 미세 환경 내로 CD8+ T 세포의 침투를 촉진했습니다.
Medicenna Therapeutics (MDNAF) a présenté de nouvelles données précliniques concernant MDNA11 lors du Symposium sur le Cancer du Sein de San Antonio 2024. Les données ont montré que le MDNA11 en monothérapie surpassait les inhibiteurs de points de contrôle immunitaire combinés dans la prévention des métastases et dans l'atteinte d'une survie à long terme dans des modèles de cancer du sein triple négatif (TNBC).
Les résultats clés ont démontré qu'une faible dose unique de MDNA11 en tant que thérapie néoadjuvante prévenait significativement les métastases, avec 6/7 souris à faible dose (2 mg/kg) et 7/8 souris à haute dose (5 mg/kg) survivant plus de 4 mois sans signes de métastases. Le traitement a également permis une réponse immunitaire de mémoire contre les rechallenges tumoraux, tout en favorisant l'infiltration des cellules T CD8+ dans le microenvironnement tumoral sans affecter les cellules Treg.
Medicenna Therapeutics (MDNAF) präsentierte neue präklinische Daten zu MDNA11 auf dem San Antonio Breast Cancer Symposium 2024. Die Daten zeigten, dass einzelnes MDNA11 in der Verhinderung von Metastasen und dem Erreichen einer Langzeitüberlebensrate in Modellen von triple negativem Brustkrebs (TNBC) besser abschnitt als kombinierte immuncheckpoint-Inhibitoren.
Schlüsselbefunde zeigten, dass eine einzeldosis MDNA11 in niedriger Dosis als neoadjuvante Therapie die Metastasen signifikant verhinderte, wobei 6/7 Mäuse bei niedriger Dosis (2 mg/kg) und 7/8 Mäuse bei hoher Dosis (5 mg/kg) über 4 Monate ohne Metastasensymptome überlebten. Die Behandlung ermöglichte zudem eine immunologische Gedächtnisreaktion gegen Tumorre-challenges und förderte das Eindringen von CD8+ T-Zellen in die Tumormikroumgebung, ohne die Treg-Zellen zu beeinflussen.
- Single-agent MDNA11 showed superior efficacy compared to combined checkpoint inhibitors
- High survival rates in preclinical trials (87.5% at high dose, 85.7% at low dose)
- Demonstrated effectiveness in preventing metastasis in aggressive TNBC model
- Successful immune memory response against tumor rechallenges
- Results to preclinical stage only
- Effectiveness in human subjects yet to be demonstrated
Single-agent MDNA11 was more effective than a combination of immune checkpoint inhibitors (anti-mPD1 and anti-mCTLA4) in preventing metastasis and achieving long-term survival in an aggressive mouse model of triple negative breast cancer (TNBC)
Mice treated with MDNA11 prior to surgery were able to mount powerful immune and memory response to subsequent tumor rechallenges, demonstrating potential to prevent new tumor growth
TORONTO and HOUSTON, Dec. 13, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, announced that new preclinical data on MDNA11 was presented at the 2024 San Antonio Breast Cancer Symposium (SABCS), the world’s largest breast cancer conference, taking place from December 10-13, 2024, in San Antonio, Texas.
Metastasis is the leading cause of cancer-related deaths worldwide. 1 in 8 women will be diagnosed with breast cancer in the US and 1 in 3 of those will become metastatic resulting in approximately 42,000 breast cancer deaths every year. Of those deaths, it is estimated that 97
Neoadjuvant immunotherapy offers a promising treatment strategy in which patients with advanced but resectable cancer receive immunotherapy before surgery. This approach aims to shrink tumors, making them easier to remove, delay or prevent metastasis, while also targeting cancerous tissue that may not yet be detectable. Additionally, immunotherapy can prime the immune system against tumor antigens, promoting the development of long-lasting anti-cancer T cells. These T cells may help protect against residual tumor cells that could re-emerge and drive metastatic disease.
The presentation at 2024 SABCS highlighted the potential of MDNA11, a long-acting ‘β-enhanced not-α’ IL-2 Superkine, to improve treatment outcomes when administered prior to surgery. New findings demonstrated that a single low dose of MDNA11 as a neoadjuvant therapy significantly prevented metastasis, extended survival, and enabled a memory immune response that protects against tumor rechallenges in a TNBC model.
“We are impressed by MDNA11’s remarkable capability, in the on-going ABILITY-1 clinical trial, to durably control cancer in patients with advanced late-stage metastatic disease in immunotherapy resistant tumors. This naturally encourages us to evaluate the potential of MDNA11 to tackle cancer head-on at the earlier stages of the disease and reverse cancer from a death sentence to a chronic manageable condition,” said Fahar Merchant, PhD, President and CEO of Medicenna. “Our findings show that MDNA11 alone not only prevents metastasis in an aggressive preclinical breast cancer model when administered as a single pre-treatment prior to surgery, but also delivers superior long-term survival by preventing metastasis when compared to combinations of the leading checkpoint inhibitors, such as anti-CTLA4 and anti-PD-1. These data illustrate MDNA11’s potential to redefine traditional immunotherapy by attacking cancer at its earliest stages and efficiently leverage the patient’s healthier immune status to dramatically improve patient outcomes.”
Key findings from presentation of MDNA11 pre-treatment prior to surgery in the aggressive TNBC model included:
- Metastasis Prevention: A single dose of neoadjuvant MDNA11 prevented the spread of tumors, with vast majority of treated mice (7/8 at high-dose of 5 mg MDNA11/kg and 6/7 at low-dose of 2 mg MDNA11/kg) surviving to study end (>4 months) without signs of metastasis despite tumor rechallenges. By contrast, all mice in the control group developed multiple metastasis and died within ~2 months even after tumor resection surgery.
- Superior to Checkpoint Inhibitors: MDNA11 alone, even at the lower dose, was more effective than a combination of immune checkpoint inhibitors (anti-mPD1 and anti-mCTLA4) in preventing metastasis and achieving long-term survival.
- Memory Response Against Tumor Rechallenge: Mice treated with MDNA11 were able to mount strong immune response to subsequent tumor rechallenges by engaging tumor antigen-specific T cells, demonstrating protection against new tumor growth.
- Immune Cell Activation: MDNA11 promoted the infiltration of CD8+ T cells with potent tumor-killing capacity (GrzB+) into the tumor microenvironment (TME) with no impact on immune-suppressive Treg cells, driving a potent and lasting immune response.
A copy of the presentation has been posted on the “Scientific Presentations” page of Medicenna’s website.
About MDNA11
MDNA11 is an intravenously administered, long-acting, ‘beta-enhanced not-alpha’ IL-2 Superkine specifically engineered to overcome the shortcomings of aldesleukin and other next generation IL-2 variants by preferentially activating immune effector cells (CD8+ T and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. These unique proprietary features of the IL-2 Superkine have been achieved by incorporating seven specific mutations and genetically fusing it to a recombinant human albumin scaffold to improve the pharmacokinetic (PK) profile and pharmacological activity of MDNA11 due to albumin’s natural propensity to accumulate in highly vascularized sites, in particular tumor and tumor draining lymph nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both monotherapy and in combination with pembrolizumab.
About Medicenna Therapeutics
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. MDNA11 is being evaluated in the Phase 1/2 ABILITY-1 Study (NCT05086692) as a monotherapy and in combination with pembrolizumab. 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 high-affinity IL-2β biased IL-2/IL-15 Super-antagonists, from its MDNA209 platform, are being evaluated as potential therapies for autoimmune and graft-versus host diseases. 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 on Twitter and LinkedIn.
Forward-Looking Statements
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Investor and Company Contact:
Christina Cameron
Investor Relations
ir@medicenna.com
(647) 953-0673
Daniel Scarr
Investor Relations & Corporate Development
dscarr@medicenna.com
(647) 220-4509
1 Metastatic breast cancer statistics, METAvivor. https://www.metavivor.org/mbc-prep/metastatic-breast-cancer-statistics
FAQ
What were the key results of MDNAF's MDNA11 preclinical trials in December 2024?
How does MDNA11's efficacy compare to existing checkpoint inhibitors for TNBC?
What dosage levels of MDNA11 were tested in the MDNAF preclinical trials?
How long did the MDNA11 survival benefits last in the TNBC model?
