INOVIO, Akeso Form Clinical Collaboration to Evaluate Glioblastoma Combination Therapy
INOVIO Pharmaceuticals (Plymouth Meeting, PA) and Akeso, Inc. (Zhongshan, China) announced a clinical collaboration on March 4, 2026, to evaluate a glioblastoma combination therapy pairing INOVIO's DNA medicine candidate INO-5412 with Akeso's bispecific antibody cadonilimab. The collaboration will assess the combination in a Phase 2 adaptive platform trial in patients with glioblastoma multiforme (GBM), the most common and lethal primary brain malignancy in adults. Financial terms of the Akeso INOVIO collaboration were not disclosed.
What the Deal Covers
The collaboration centers on two distinct immunotherapy assets contributed by each party. INOVIO contributes INO-5412, a combination regimen comprising INOVIO INO-5401, a DNA plasmid encoding three tumor-associated antigens (hTERT, WT1, and PSMA), and INO-9012, a DNA plasmid encoding the pro-inflammatory cytokine interleukin-12. Akeso contributes cadonilimab, also known as AK104, a PD-1/CTLA-4 bispecific antibody designed to achieve dual immune checkpoint blockade with a single molecule.
The combination will be studied within the INSIGhT adaptive platform trial framework. Each company retains ownership of its respective drug candidate. The collaboration is structured as a clinical study agreement rather than a traditional licensing arrangement, with neither party granting commercial rights to the other based on the publicly available terms.
Deal Terms and Financial Structure
The press release did not disclose an upfront payment, milestone structure, royalty rates, territorial rights allocation, or equity investment. The absence of disclosed financial terms is consistent with the deal's characterization as a clinical collaboration, where each party supplies its own compound for evaluation in a joint study, rather than a full-scale licensing or co-development agreement with commercial rights attached.
Additional details may emerge in subsequent SEC filings by INOVIO or Hong Kong Stock Exchange disclosures by Akeso, but as of the announcement date, no economic terms were made public.
Scientific Rationale for the Glioblastoma Combination Therapy Approach
The pairing of INO-5412 with cadonilimab reflects a strategy to address GBM's immunosuppressive tumor microenvironment from multiple angles. INO-5412 is designed to generate antigen-specific cytotoxic T lymphocyte responses against GBM cells expressing hTERT, WT1, and PSMA, while the IL-12 component encoded by INO-9012 is intended to amplify and sustain those responses by promoting a pro-inflammatory milieu at the tumor site. Cadonilimab's simultaneous blockade of PD-1 and CTLA-4 is intended to release the brakes on T cell activity that the tumor microenvironment imposes through checkpoint-mediated suppression.
The rationale for combining these modalities rests on the hypothesis that antigen-directed immune priming (via INO-5412) paired with checkpoint de-repression (via cadonilimab) could produce a more durable anti-tumor response than either approach alone. This is particularly relevant in GBM, where single-agent checkpoint inhibitors have so far failed to demonstrate survival benefits in randomized trials.
INO-5412 Clinical Trial History and Development Status
INOVIO has been developing INO-5412 in GBM for several years. The company previously reported interim survival and progression-free survival data from a Phase 1/2 trial evaluating INO-5401 and INO-9012 in combination with cemiplimab (Regeneron's PD-1 inhibitor) in newly diagnosed GBM patients at the ASCO Annual Meeting in 2022. That trial, conducted at U.S. sites including UCSF, Baylor, UNC, and the University of Pennsylvania, is listed as active but no longer recruiting, with an estimated completion date of December 2026.
The current collaboration with Akeso represents a shift in the checkpoint inhibitor partner from cemiplimab, a monospecific PD-1 antibody, to cadonilimab, a bispecific antibody targeting both PD-1 and CTLA-4. The move to a dual-checkpoint agent reflects the broader oncology field's interest in whether simultaneous PD-1 and CTLA-4 blockade can overcome resistance patterns observed with PD-1 monotherapy in GBM immunotherapy treatment settings.