Imunon looks for an IL-12 Ovation

Imunon is pushing into phase 3 with its IL-12 gene therapy IMNN-001, a recent clinicaltrials.gov listing has revealed – although there are questions about how the microcap will fund the study. Imunon had just $5.9m at the end of 2024, only enough to get it into late June.

Still, the group was upbeat during a recent call to discuss the design of its phase 3 trial, Ovation-3, in perioperative ovarian cancer. Imunon reckons it has a “solid plan” to raise cash, “including some potential non-dilutive strategies”, its chief executive, Stacy Lindborg, claimed.

Presumably such funding will have to be secured sooner rather than later, otherwise Imunon would be in the dubious position of beginning a trial it doesn't have the cash to complete. Either way, the company believes that it has found the most cost-effective way forward for Ovation-3, which will test IMNN-001 alongside standard neoadjuvant and adjuvant chemotherapy, versus chemo alone.

The study will initially enrol a planned 250 patients with homologous recombinant deficiency, a group of mutations that include BRCA1 and BRCA2. These patients are eligible for maintenance therapy with PARP inhibitors such as AstraZeneca/Merck & Co’s Lynparza; indeed, Ovation-3 also mandates PARP inhibitor maintenance in these patients.

Imunon then has the option to broaden the trial to encompass 500 all-comers, although this will depend not only on a positive result in HRD-positive patients, but also on the company having sufficient cash, Lindborg noted.

She added that the HRD-positive portion of the trial would cost around 40% less than the all-comers study, and could deliver results as much as two years earlier.

The study design includes two event-driven interim analyses, which could allow Imunon to stop the trial early and seek approval of IMNN-001. The company declined to give concrete timelines, but said the first interim look could come around a year after enrolment was completed.

Ovation-2

Imunon is pushing on following the phase 1/2 Ovation-2 trial, also in the perioperative setting. That study compared IMNN-001 plus neoadjuvant and adjuvant chemo, versus chemo alone, with a primary endpoint of progression-free survival.

According to data presented at last year’s SITC meeting, median PFS was 14.9 months with IMNN-001 plus chemo, versus 11.9 months for chemo alone. Median OS numbers were 40.5 and 29.4 months respectively.

However, there are reasons to be cautious: the trial had an open-label design owing to IMNN-001’s intraperitoneal delivery, and also wasn’t powered to show a statistically significant difference between cohorts.

These caveats notwithstanding, results looked even better in the subgroup of patients who received PARP inhibitors: here mPFS was 33.8 months for IMNN-001 plus chemo, versus 22.1 months for chemo alone; and mOS was not reached versus 37.1 months respectively.

Imunon raised the possibility that, by increasing levels of IL-12, IMNN-001 could be changing the tumour microenvironment, giving PARP inhibitors a better chance of controlling disease in HRD-positive patients.

IMNN-001 is an IL-12 DNA plasma vector encased in a nanoparticle delivery system, designed to transfect host cells and lead to persistent, local secretion of IL-12, a cytokine that spurs antitumour immune responses.

Still, other cytokine-based approaches haven’t gone smoothly. Even if Imunon, which used to be known as Celsion and has a market cap of just $12m, can raise the necessary funds, it’ll have its work cut out.