Glioblastoma kills almost everybody who gets it. Median survival is around 15 months even with the standard regimen of surgery, radiation, and temozolomide.
For the roughly 60% of patients whose tumors are MGMT unmethylated, temozolomide barely works at all. Survival drops further.
Drug development for GBM has been a graveyard. Avastin, Optune, lomustine.
Some marginal benefit, no cures.
Most clinical trials in this space report disappointing data and quietly disappear.
So when something publishes in Nature Communications claiming a survival improvement in MGMT-unmethylated GBM, it’s worth slowing down and reading carefully.
TME Pharma just did exactly that.
The Berlin-based biotech (formerly NOXXON Pharma) published Expansion Arm A data from the Phase 1/2 GLORIA trial. The cohort tested NOX-A12 in combination with radiation therapy and bevacizumab in chemo-resistant, MGMT-unmethylated glioblastoma patients, the hardest population to treat.
The company says median overall survival reached 19.9 months, exceeding what comparable external standard-of-care cohorts have shown.
That’s a meaningful jump in a population where every month matters.
Median OS in MGMT-unmethylated GBM (chemo-resistant)
19.9 months
~12 months
Source: GLORIA Phase 1/2 Expansion Arm A, published in Nature Communications
NOX-A12 is unusual.
It’s a Spiegelmer, a mirror-image L-RNA aptamer that binds and neutralizes CXCL12…yeah, you read that right. It’s an RNA that binds to and quenches a cytokine…
CXCL12 is a chemokine that tumors exploit to recruit immunosuppressive cells and create a protective barrier against immune attack. By blocking CXCL12, NOX-A12 is meant to break down that barrier and let radiation and immune cells do their work.
The mirror-image structure makes it resistant to natural nucleases, so it survives in circulation. This calms my biggest concern.
Spiegelmer technology has been around for two decades but has produced relatively few clinical successes. NOX-A12 might be the breakout.
The company already has FDA Fast Track Designation for this combination, plus Orphan Drug Designation from both FDA and EMA. The IND for a randomized Phase 2 cleared in March 2024. The Nature publication adds the academic validation that often opens doors with regulators and partners.
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It’s worth noting that bevacizumab in GBM has a complicated history.
It improves progression-free survival but not overall survival in most studies. So attributing the OS benefit to NOX-A12 specifically (versus the bevacizumab) requires the controlled trial.
For more on the GBM space, Hemispherian’s oral pill approach is taking a completely different angle on the same indication. Two GBM stories worth tracking in the same week is unusual.
TME Pharma also has a second clinical asset, NOX-E36 (emapticap pegol), targeting CCL2. That program has shifted from oncology to ophthalmic indications including AMD and diabetic retinopathy.
For now, the GLORIA data are the cleanest signal yet that targeting the tumor microenvironment via chemokine inhibition might work in solid tumors where checkpoint inhibitors have failed.
The randomized Phase 2 is what matters next. If the survival benefit holds up under randomization, the conversation about GBM standard of care starts to shift.
That would be the first time anyone has been able to say that in a while.
