Dr. Fahar Merchant reports
MEDICENNA ANNOUNCES NEW CLINICAL DATA PROVIDING PRELIMINARY EVIDENCE OF MDNA11'S SINGLE AGENT ANTI-CANCER ACTIVITY IN THE PHASE 1/2 ABILITY STUDY
Medicenna Therapeutics Corp. has released new clinical data on safety, pharmacodynamics and anti-tumour activity from the phase 1/2 Ability study of MDNA11, the company's long-acting IL-2 superagonist. The data, which provide preliminary evidence of MDNA11's single-agent anti-cancer activity in patients with advanced solid tumours who have been unresponsive to other treatments, are being featured in an oral presentation taking place at 1 p.m. ET today at the Cytokine Based Drug Development Summit.
"The Ability study's latest data add to a body of clinical evidence we believe supports our view on MDNA11's potential as a best-in-class IL-2 agonist," said Dr. Fahar Merchant, president and chief executive officer of Medicenna. "Data from the trial's initial and mid-stage dose escalation cohorts showed signs of tumour control in four of 10 evaluable patients with hard-to-treat cancers such as sarcomas and pancreatic cancer that are also highly resistant to immunotherapies."
Dr. Merchant continued: "Complementing these early anti-tumour results are pharmacodynamic data that are consistent with MDNA11's novel beta-only mechanism of action and preclinical evidence of tumour localization. Treatment with MDNA11 leads to multifold increases in anti-cancer immune cells without stimulation of cells that cause immunosuppression and toxicity typically associated with native IL-2 and its alpha-binding variants. These early findings continue to fuel our optimism for the outcome of the Ability study based on the evolving data as we escalate from 60 micrograms per kilogram to the 90-microgram-per-kilogram dose."
The Ability study's dose escalation cohorts are evaluating MDNA11 monotherapy administered intravenously once every two weeks to patients with advanced solid tumours. The trial's first two cohorts evaluated MDNA11 doses less than or equal to 10 micrograms per kilogram. The trial's third cohort was administered a dose of 30 micrograms per kilogram. Patients in the fourth and fifth dose escalation cohorts receive two 30-microgram-per-kilogram priming doses of MDNA11 before stepping up to receive fixed doses of 60 micrograms per kilogram and 90 micrograms per kilogram, respectively.
Key data from patients enrolled in the trial's four initial dose escalation cohorts include the following.
Patients enrolled in the study to date (N equals 14) have failed up to four lines of prior systemic therapy.
- Eleven of 14 patients have relapsed or did not respond to at least one prior immunotherapy with a checkpoint inhibitor.
- To date, 10 of the 14 enrolled patients, including two of six patients in cohort 4 have received at least one postbaseline scan and are evaluable for response to the investigational treatment.
MDNA11 treatment in cohort 4 (comprising two step-up doses of 30 micrograms per kilogram followed by fixed doses of 60 micrograms per kilogram every two weeks) was not associated with any dose-limiting toxicities.
- The safety review committee has approved dose escalation for cohort 5 to the 90 micrograms per kilogram dose every two weeks following two priming doses at 30 micrograms per kilogram.
- Significant increases in eosinophil count from baseline were not observed with MDNA11 treatment. Extremely high eosinophil count is associated with vascular leak syndrome, which is a known side effect of high-dose recombinant human IL-2 (Proleukin).
Four of 10 evaluable patients have achieved tumour control as defined in the study with MDNA11 monotherapy, including two patients at the 10-microgram-per-kilogram dose (sarcoma and metastatic melanoma), one sarcoma patient at the 30-microgram-per-kilogram dose and one pancreatic cancer patient in cohort 4 receiving the 60-microgram-per-kilogram dose.
- The first imaging scans in the remaining four patients enrolled at the 60-microgram-per-kilogram dose are expected in September.
MDNA11 preferentially expanded anti-cancer NK and CD8+ T cells without stimulating proliferation of pro-tumour Treg cells.
- MDNA11 treatment potently activated anti-cancer CD8+ T cells as shown by increases in both CD25+ and ICOS+ CD8+ T cells.
- Unlike IL-2, MDNA11 has not induced increases in ICOS+ Treg cells. ICOS+ Treg cells are highly immunosuppressive and associated with lack of response to high-dose IL-2 immunotherapy.
A copy of the Cytokine Based Drug Development Summit presentation, entitled "Co-Stimulation of Adaptive and Innate Immune Cells to Achieve Clinical Benefit with MDNA11, a Long-Acting 'Beta-only' IL-2 Super-Agonist," will be posted to the events and presentations page of Medicenna's website following its conclusion.
About the phase 1/2 Ability study
The Ability (a
beta-only IL-2 immunotherapy) study is designed to assess the safety, pharmacokinetics, pharmacodynamics and anti-tumour activity of various doses of intravenously administered MDNA11 in patients with advanced, relapsed or refractory solid tumours. The trial includes an MDNA11 monotherapy arm as well as a combination arm designed to evaluate MDNA11 with a checkpoint inhibitor. Approximately 100 patients are expected to be enrolled into the Ability study. Following establishment of the recommended phase 2 dose (RP2D) and optimal treatment schedule in the study's dose escalation phase, Medicenna plans to conduct a dose expansion phase that will enroll patients with renal cell carcinoma, melanoma and other solid tumours in monotherapy and combination settings.
About Medicenna Therapeutics Corp.
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 (bifunctional superkine immunotherapies) program is designed to enhance the ability of superkines to treat immunologically cold tumours. Medicenna's IL-4 empowered superkine, MDNA55, has been studied in five clinical trials, including a phase 2b trial for recurrent GBM (glioblastoma), the most common and uniformly fatal form of brain cancer. MDNA55 has obtained fast-track and orphan drug status from the FDA (U.S.) Food and Drug Administration) and FDA/EMA (European Medicines Agency), respectively.
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