Novel drug offers hope for brain cancer patients

MDNA55 covering the rGBM tumor and surrounding margins where relapse is likely to occur.

By Jason Smith

• Glioblastoma multiforme (“GBM”) is uniformly fatal

• A new drug in clinical trials offers hope to patients who have failed other treatments

• Medicenna’s MDNA55 targets tumors and unblinds the immune system by purging the protective tumor micro-environment (“TME”)

Brain cancers will cause nearly 17,000 deaths this year in the U.S. alone, according to the National Brain Tumor Society.
Glioblastoma multiforme or “GBM” is the most aggressive form of brain cancer that tends to strike adults between the ages of 45 and 70. In the past few years, GBM has claimed the lives of U.S. senator, John McCain and Tragically Hip frontman, Gord Downie.
Like other cancers of the brain, GBM is notoriously resistant to treatment. That’s because the brain is sealed by the blood-brain barrier (“BBB”) and GBM is hidden from our immune system by a shield of protective cells known as the tumor micro-environment (TME). As a result, the presence of both the BBB and the TME minimize the effectiveness of potential treatments. Another complication is the cancer’s tendency to spread its tentacles into parts of the brain that are difficult, if not impossible, to reach surgically.

“Because MDNA55 is addressing a huge, unmet need, expedited approval is possible.” — Fahar Merchant, President & CEO, Medicenna Therapeutics Corp.

A new GBM treatment
A new investigational drug, developed by Canadian immunotherapy company, Medicenna (TSX: MDNA, OTCQB: MDNAF), has the potential to improve life expectancy for patients with GBM.
Medicenna’s MDNA55 drug is in the U.S. FDA’s Phase 2b trial phase. The drug is the lead therapy in the company’s library which includes tunable cytokines, the company refers to as Superkines. Cytokines are a broad category of naturally occurring human proteins critical to cell communication via a process called signaling. Medicenna’s library of superkines focuses on interleukin-2 (“IL-2”), interleukin-4 (“IL-4”), and interleukin-13 (“IL-13”).
In the case of MDNA55, the drug is effective because only brain cancer cells have a shuttle service, called the IL4 receptor (IL4R), that delivers MDNA55 into the tumor, whereas healthy brain does not have the IL4R. The IL4R is the gateway for IL-4 to enter tumor cells and since IL-4 is also a nutrient, it makes cancers cells grow faster making brain tumors with IL4R even more aggressive. Using an elegant approach, scientists designed a targeted Molecular Trojan Horse by attaching IL-4 to a tumor-killing payload that is activated only when MDNA55 is inside tumor cells. Because IL4R is only found on tumor cells, MDNA55 ignores healthy brain cells.
Fahar Merchant, Medicenna’s President and CEO, explains that MDNA55 tricks the cancer cell into swallowing IL-4 but also the toxic payload in MDNA55. Furthermore, MDNA55 is so precise and potent that 1 gram can treat 4,000 patients. MDNA55 has the same toxic payload as Astra Zeneca’s Lumoxiti, recently approved by the FDA for treating relapsed Hairy Cell Leukemia. However, Medicenna’s drug targets the IL4R which is found in GBM and 20 other tumors that affect over a million new cancer patients every year.
Getting past the blood-brain barrier
To ensure that the drug goes directly to the tumor cells within the brain, MDNA55 is administered using a technique called convection-enhanced delivery (“CED”).
CED allows clinicians to administer the drug directly to the tumor site using a tiny MRI-guided catheter the size of a biopsy needle. “The process enables the surgeon to bypass the BBB and deliver a maximum amount of the drug to the tumor,” says Merchant. “CED allows MDNA55 to efficiently soak not only the main tumor body but also the adjacent healthy brain invaded by tenacious tumor tentacles that lead to further relapses.
Adding to its effectiveness, MDNA55 has the unique ability to expose the GBM to cancer-killing immune cells by disrupting the TME, which normally acts as a protective “shield” around the tumor. Merchant explains, “Just as the electromagnetic coating on a B-21 stealth bomber hides the aircraft from radar, the TME hides the tumor from the body’s own immune system. Treatment with MDNA55 avoids the BBB, precisely delivers a potent toxin to the tumor and uncloaks the tumor’s defenses, allowing the body’s immune system to also attack the tumor. “We need to use a disruptive approach to fight one of the most resilient tumors as traditional approaches have not made a difference in improving outcomes in GBM.” 
On the fast-track to approval
MDNA55 is in the mid-to-late stages of being launched for commercial use. Since GBM patients typically pass away within 14 months of initial diagnosis, the FDA may consider putting the drug on its fast-track approval process particularly for patients with end-stage recurrent GBM (rGBM).
The drug has already demonstrated impressive results through clinical studies on 66 rGBM patients who had failed surgery, radiation and/or chemotherapy. Of the rGBM patients treated, more than 40 per cent had experienced multiple relapses. For patients who were not candidates for repeat surgery, 68 per cent of the patients experienced disease control, including complete and partial responses or disease stabilization.

Destruction of rGBM tumor following MDNA55 treatment.

Avastin (marketed by Roche), having received accelerated approval by the FDA, consistently shows median survival of 8 months in rGBM patients. Recent interim results in the Phase 2b clinical trial show that MDNA55 is able to improve median survival to nearly 12 months. The results are particularly striking in rGBM patients that carry the IL4R biomarker where the median survival exceeds 15 months. These results are impressive considering that the IL4R makes brain cancers more aggressive.

Moving ahead
Medicenna is in the process of enrolling 52 subjects to participate in a Phase 2b trial of the drug and enrolment is expected to be completed in the next few weeks.
According to Merchant, by the time this trial is completed, over 120 brain cancer patients would have been treated with MDNA55. He adds, “Because MDNA55 is addressing a large, unmet medical need, expedited approval for rGBM patients with the IL4R biomarker is possible.”
The company is also looking at patients who are newly diagnosed with GBM. Medicenna is hopeful to start another trial for new cases, while it pushes through with its rGBM approval. In addition, the company is looking to bring its MDNA109 drug into the clinic, with the hope of triggering new investigational drug studies. MDNA109 has shown promise as an enhanced version of the currently approved IL-2 cytokine, one that can stimulate the immune system’s T cells to attack tumors.
Kumar Raja, director and senior biotechnology analyst for Brookline Capital Markets, sees a bright future for the company. “Medicenna will have a top-line data readout by mid-year,” says Raja. “Between that milestone and MDNA109 possibly moving into clinic later this year, the company will have two potentially major share price catalysts in 2019.”
More importantly, a drug that holds the promise of providing hope to brain cancer patients could be that much closer to full approval.