Johns Hopkins mKRAS Vaccine Trial Strengthens The Case For Elicio's ELI-002

Disclosure: The author holds a beneficial long position in Elicio Therapeutics (NASDAQ: ELTX). This article is provided for informational and educational purposes only and is not financial advice. Although the author is a Medical Doctor, this content represents a personal opinion regarding the science and market potential of the companies mentioned and is not medical advice, a diagnosis, or a treatment recommendation. The author neither works at nor has worked at any centers participating in the studies testing Elicio's candidates and has no involvement in the design, conduct, or analysis of Elicio's clinical trials or scientific programs. The author receives no compensation for this article and has no business relationship with the company. Please see the full "Legal Information and Disclosures" section below.

The central question facing Elicio Therapeutics (NASDAQ: ELTX) ahead of AMPLIFY-7P's readout is whether its mKRAS peptide vaccine can generate T cell immunity that tracks with disease control in pancreatic cancer, or whether the correlation observed in AMPLIFY-201 was a small-sample artifact.

In February 2026, Huff, Haldar et al. at Johns Hopkins published in Nature Communications the results of mKRAS-VAX (NCT04117087), a pooled synthetic long peptide vaccine targeting six KRAS mutations combined with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1), in 12 patients with resected pancreatic cancer. Because the regimen includes one of the most potent immunostimulatory combinations in clinical oncology, clinical outcomes cannot be attributed to the vaccine alone, and any comparison with Elicio's ongoing Phase 2 AMPLIFY-7P trial, which tests a vaccine as monotherapy against observation, must account for this. What the Hopkins trial does offer is immunological depth: CyTOF phenotyping, single-cell TCR sequencing, and functional validation of cross-reactive and public T cell clonotypes characterize the type and breadth of T cell responses that off-the-shelf KRAS vaccines can generate.

The scientific rationale for targeting mutant KRAS in the adjuvant setting is covered in my earlier article on Elicio's therapeutic vaccine ELI-002. In a subsequent article, I used a Monte Carlo simulation of AMPLIFY-7P that converted published survival data to a common time zero at vaccination, estimated control-arm DFS at 16 to 22 months, and modeled how the readout delay maps onto combinations of that baseline and vaccine efficacy. The Hopkins data provide an additional, albeit limited, calibration point for those estimates. I will work through the immunological findings first, then turn to survival outcomes.

The Hopkins investigators enrolled 12 patients between May 2020 and May 2023 after curative-intent surgical resection and standard-of-care therapy. KRAS mutations were G12V (n=6), G12D (n=4), and G12R (n=2). Perioperative chemotherapy was administered to 11 of 12 patients, with regimens including mFOLFIRINOX and gemcitabine-based combinations; some patients also received radiation. Median time from completion of standard-of-care therapy to first vaccination was 4.2 months (range 1.6 to 6.0). The vaccine consisted of six 21-mer synthetic long peptides formulated with poly-ICLC (Hiltonol), administered alongside ipilimumab and nivolumab during the priming phase, followed by nivolumab maintenance.

First, to the immunological findings from both trials.

By IFNγ ELISPOT, 11 of 12 patients generated a significant increase in average mKRAS-specific T cell responses across all six antigens, 10 of 12 responded to their tumor-specific KRAS mutation, seven responded to all six mutations simultaneously, and 11 of 12 responded to at least three. Vaccine-related adverse events were all grade 1-2, with the most common being injection site pain, fatigue, and fever. Dual checkpoint blockade produced four grade 3 immune-related adverse events (pneumonitis, myalgias, arthralgias, and adrenal insufficiency) in 2 of 12 patients, both of whom discontinued ICIs but continued booster vaccines. By comparison, ELI-002 produced no dose-limiting toxicities and no grade 3 or higher treatment-related adverse events.

Elicio's ELI-002 2P in AMPLIFY-201 reached 84% immune response targeting only G12D and G12R without checkpoint inhibitors, and the 7-peptide formulation in AMPLIFY-7P reached 99%. Response definitions and assay formats differ, but Elicio's platform appears to reach comparable response rates as monotherapy. The delivery mechanism may explain this. Conventional subcutaneous peptide vaccines face a pharmacokinetic problem: small immunogens injected into the subcutis are rapidly absorbed into blood capillaries and cleared before reaching the draining lymph nodes, where antigen presentation to T cells occurs. The Hopkins vaccine used poly-ICLC, a TLR3 agonist, as adjuvant, and dual checkpoint blockade may have partly compensated for the limited lymph node delivery inherent in conventional subcutaneous injection. Elicio's AMP platform takes a different approach: both the KRAS peptide antigens and the CpG adjuvant are conjugated to lipophilic tails that bind to endogenous albumin at the injection site. Albumin, at 67 kilodaltons, is too large to cross blood capillary walls and is instead channeled through lymphatic vessels into draining lymph nodes, concentrating the immunogen where antigen-presenting cells reside.

Both trials show predominantly CD4 Th1 responses. Hopkins CyTOF identified activated CD4 central memory and effector memory T cells as the dominant populations, with CD8 effector memory T cells present at lower frequency. Elicio reported dual CD4 and CD8 priming in 85% of Phase 2 AMPLIFY-7P patients, consistent with the earlier AMPLIFY-201 data. Th1 cytokines (IFNγ, IL-2, TNFα) dominated in the Hopkins Luminex analysis, with lower Th2 (IL-5) and detectable Th17 (IL-17A) signals. This phenotype aligns with what Balachandran et al. found in long-term PDAC survivors, where neoantigen quality in combination with T cell infiltration predicted outcomes, and with the AMPLIFY-201 data.

The Hopkins data also reveal differences in immunogenicity across KRAS subtypes. G12V and G12R induced significantly stronger IFNγ responses than G12C, G12D, or G13D. G12D, the most common KRAS mutation in PDAC at roughly 40% prevalence, was among the weakest immunogens, and all four G12D patients in the Hopkins trial recurred.

This matters for AMPLIFY-7P. The AMPLIFY-201 trial enrolled only G12D and G12R patients, meaning part of the efficacy signal was generated from the harder-to-target mutation. The 7-peptide formulation used in AMPLIFY-7P, covering G12D, G12R, G12V, G12C, G12A, G12S, and G13D, includes the more immunogenic variants and may benefit from cross-reactive T cells that compensate for the weaker G12D response.

The Hopkins paper documents this cross-reactivity in detail. In 3 of 4 patients analyzed by TCR sequencing, more than 10% of the enriched repertoire expanded to multiple KRAS peptides, with the most common cross-reactivity between G12C, G12A, and G12V. The investigators also identified public TCR clonotypes shared across patients, including one previously detected in tumor-infiltrating lymphocytes by Levin et al. The existence of public clonotypes supports the core premise of off-the-shelf vaccination: if different patients generate nearly identical T cell receptors against shared KRAS mutations, personalization may be unnecessary. Elicio's Phase 2 AMPLIFY-7P HLA diversity analysis reinforces this point, showing no meaningful association between specific HLA alleles and T cell response across 1,132 unique HLA types.

Elicio reported in December 2025 that 87% of evaluable Phase 2 patients (13 of 15) demonstrated antigen spreading to neoantigens beyond vaccine targets. The Hopkins paper does not report antigen spreading in comparable terms, though the detection of vaccine-induced TCRs within a metastatic lung recurrence biopsy from patient J1994_5 suggests these T cells can traffic to and persist at tumor sites. The investigators found 80 unique mKRAS-specific TCR sequences overlapping within this metastasis, representing almost 20% of the patient's identified mKRAS repertoire, with 55% specific for the patient's tumor mutation (G12V).

Now, to the survival data.

At a median follow-up of 35.8 months from first vaccination, median DFS in the Hopkins trial was 6.35 months and median OS was 29.59 months. Four of 12 patients (33%) remained disease-free, all with G12V or G12R tumors.

A median DFS of 6.35 months from vaccination may appear short for a cohort that underwent curative-intent resection and perioperative chemotherapy, but DFS here is measured from the first vaccine dose, not from end of standard therapy. The median time from completion of standard-of-care therapy to first vaccination was 4.2 months, placing the effective DFS at roughly 10.5 months from end of treatment. The modest DFS likely reflects the disease stage of this cohort: 9 of 12 patients were node-positive (N1 or N2) and 3 were pathologic stage III, all of whom recurred.

All four G12D patients recurred, two in the lowest quartile of immune response, and G12D was among the weakest immunogens in the trial. In a cohort of 12 with 8 events, a cluster of early recurrences in node-positive G12D patients shifts the median considerably. An exploratory analysis stratifying patients above and below the 25th percentile of T cell response magnitude showed median DFS of 18.8 months for the upper three quartiles versus 2.76 months for the lowest quartile (HR 0.19, 95% CI: 0.04 to 0.95, p=0.024).

With 12 patients and 8 events, the confidence interval on the median is too wide to constrain the 16-to-22-month corridor I estimated in the Monte Carlo analysis for AMPLIFY-7P's control arm. The Hopkins cohort was evenly split: 6 of 12 received neoadjuvant mFOLFIRINOX. The paper tested neoadjuvant chemotherapy as a variable and found no correlation with DFS, though 12 patients cannot support that comparison.

The Hopkins median of 6.35 months from vaccination sits below even the lowest of the benchmarks I used for my Monte Carlo simulation, likely explained by the disease stage of this cohort. This may suggest that adjuvant vaccine trials at high-volume academic centers enroll patients with more advanced disease than published benchmarks assume, which would make my 16-to-22-month corridor for the AMPLIFY-7P control arm too optimistic. If the true control median is shorter, however, the observed delay in reaching the event target becomes harder to explain without a treatment effect, as my Monte Carlo simulation showed: shorter control medians paired with no efficacy would have reached the event target before November 2025. Paradoxically, a lower-than-expected control median might be cautiously positive for AMPLIFY-7P.

The correlation between T cell response magnitude and DFS in the Hopkins trial (HR 0.19) parallels what Elicio reported in AMPLIFY-201 (HR 0.12 for high vs. low T cell responders). Neither study can establish causality alone, but the consistency across two independent platforms, adjuvants, and assays, combined with the Hopkins finding that tumor-specific KRAS response tracks with outcome while baseline immunopathological features (CD4, CD8, macrophage density, PD-L1 expression) did not correlate with DFS, suggests that mKRAS-specific immunity may be linked to disease control rather than merely serving as a proxy for general immune fitness. Four disease-free patients maintained mKRAS-specific T cell responses beyond 52 weeks on vaccine alone, after ICIs were stopped, with rapid in vitro re-expansion confirming functional immunological memory.

The AMPLIFY-7P DFS readout remains expected in H1 2026. The Hopkins paper does not materially change my estimate of the probability of success, but it sharpens the answer to the question that opened this article. When two independent research groups arrive at the same biological conclusion, the result starts to look like signal rather than noise.

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