IL-2 is one of the most frustrating molecules in oncology.
It was the first cytokine therapy ever approved – some consider it the first IMMUNOTHERAPY ever approved. It performs very well in a small percentage of melanoma and kidney cancer patients outright but, for the most part, its insanely toxic.
It induces a condition called vascular leak syndrome (VLS) — leaky blood vessels? Yeah, not good. So, for the past few decades, its been mostly put on the shelf.
The industry has spent that time coming up with ways to engineer around this problem.
Attenuate the alpha receptor binding.
PEGylate it.
Pre-complex it.
Make it a prodrug.
Fuse it to an antibody.
Nektar’s bempegaldesleukin was supposed to solve it, then the Phase 3s collapsed…in dramatic fashion.
Really, an objective look at the IL-2 field usually leaves you thinking, “just give up and move on.”
But, Medicenna Therapeutics showed up at AACR 2026 with a preclinical package for MDNA113 that takes a different angle. It’s a PD-1 × IL-2 bifunctional. The IL-2 arm only activates when it’s anchored to a PD-1 target. No anchor, no signal, no toxicity.
In non-human primates, MDNA113 was tolerated up to 50 mg/kg with a noticeably wider therapeutic window than comparator PD-1/IL-2 approaches. They showed tumor-localized activity with no systemic immune storm.
Preclinical, yes. But it’s showing promise.
The Biotech Voyager
Early-stage biotech signals, personalized.
The signals that matter to you, contextualized and written directly to you, so you cut through the noise and immediately understand why it matters.
Now the context that matters. MDNA113 is Medicenna’s third shot at this.
Their lead asset bizaxofusp is an IL-4 Empowered Superkine, through Phase 2b in recurrent glioblastoma with FDA agreement on Phase 3 trial design. Median OS of 13.5 months versus 7.2 months in controls. The company got Fast Track and Orphan Drug for this programs.
They’re ready to run a registrational study, but the company is explicitly looking for a partner to help fund it.
MDNA11 is their IL-2 Superkine, in Phase 1/2 ABILITY-1 trials, both as monotherapy and with pembrolizumab. 37% tumor control in evaluable patients. The dose expansion is underway.
MDNA113 is the next wave and they have a IND planned H2 2026.
The company is public on the TSX under MDNA, with RA Capital in the cap table. Per their own disclosures, the cash runway stretches into mid-2026. Which is to say, the Phase 3 partner for bizaxofusp needs to materialize, or the IND filing for MDNA113 needs to get some wind under it, or both.
Cytokine engineering is honestly one of my favorite segments of the industry and they’re having a bit of a moment right now.
Look at Ampersand Biomedicines getting the same tissue-restriction logic to work on IL-22. Look at the steady flow of IL-2 partial agonists and conditional prodrugs from Synthorx (now Sanofi), Asher Bio, Brightpeak, Inhibrx, Xilio (Abbvie), Werewolf, CUE Biopharma, Synthekine.
Everyone’s trying to solve the same problem from a different direction.
Medicenna has been at this longer than most, and they have the rare distinction of already having run an engineered cytokine through Phase 2b with a positive readout.
Whether MDNA113 gets to the clinic on its current cash position is the thing to watch between now and year-end.
