Aulos Bioscience’s cancer therapy, imneskibart, could enter a registrational study either in melanoma, non-small cell lung cancer (NSCLC) or both, as soon as 2026.
Speaking to Clinical Trials Arena, CEO Aron Knickerbocker said this follows positive early results from the Phase II study (NCT05267626) of imneskibart in advanced solid tumours.
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In the study, six out of 14 patients with melanoma experienced “deep and durable” tumour shrinkage. This effect was observed in those taking imneskibart alongside a low dose of recombinant human IL-2, aldesleukin.
Of these six patients, two achieved partial responses (PRs) of 48% and 58% at the data cutoff period, while one had a target lesion-specific complete response (CR) to treatment.
These three patients also remained on treatment past the one-year mark, with the responders staying on the imneskibart-aldesleukin regimen for 14, 18 and 21 months.
This phenomenon was observed in heavily pretreated melanoma patients, all of whom had progressed after receiving a prior doublet checkpoint inhibitor regimen.
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By GlobalDataMeanwhile, Aulos reported “early signs of anti-tumour activity” in melanoma patients given a combination of imneskibart, aldesleukin and Bristol Myers Squibb’s (BMS) Opdivo (nivolumab) in the safety run-in portion of the trial. The run in used a lower dose of aldesleukin to evaluate the combination’s dose-limiting toxicity potential.
Now that this stage of the trial has been cleared, patients are receiving the recommended Phase II dose of aldesleukin, with three of five remaining on treatment.
The safety profile of imneskibart-aldesleukin was also favourable, as most treatment-emergent adverse events (TEAEs) were classified as Grade 1 or 2. The most common Grade 3 or 4 TEAE was transient lymphopenia.
Meanwhile, the addition of Opdivo resulted in no increase in drug-related TEAEs classified as Grade 3 or 4.
Imneskibart in NSCLC and beyond
Alongside its efficacy in melanoma, imneskibart has demonstrated its early impacts in programmed death ligand 1 (PD-L1)-positive NSCLC.
During the Phase II study, four out of nine patients with NSCLC experienced tumour reductions. Of these four, two who previously progressed on anti-PD-1 therapy experienced 43% and 48% tumour shrinkages.
According to Aulos, imneskibart demonstrated an “initial signal” towards anti-tumour activity alongside aldesleukin or in combination with Merck KGaA’s Bavencio (avelumab).
Meanwhile, two patients with metastatic bladder and nasopharyngeal head and neck cancer achieved CRs through treatment with imneskibart and aldesleukin.
Imneskibart’s unique IL-2 interaction
When aldesleukin got the US Food and Drug Administration (FDA) go-ahead in 1992, it became the first ever marketed cancer drug to target IL-2.
Though it has been seen to drive CRs in patients with melanoma and renal cell carcinoma, Knickerbocker notes there are concerns with associated side effects.
“As there are IL-2 receptors on the lining of our blood vessels, drugs like aldesleukin commonly cause vascular leak syndrome and oedema, as well as a drop in blood pressure,” he said.
According to Knickerbocker, imneskibart overcomes this issue by attaching to the CD25 binding portion of IL-2, meaning the cytokine is less able to bind to CD25-positive receptors expressed in vasculature.
When aldesleukin is continually used, it can also trigger the activation of the regulatory T-cells (Tregs), which then shut off the immune response. This can dampen the anti-tumour effect of the drug.
Imneskibart’s CD25-binding activity also reduces the Treg response, as the drug makes IL-2 unable to bind to trimeric receptors found on Tregs. However, the drug does not prevent IL-2 from binding to T-cells and natural killer (NK) cells, meaning it can reinforce anti-tumour immune effects.
Aulos’ plans for imneskibart
In conversation with Clinical Trials Arena, Knickerbocker noted that he is “excited about the data” thus far, as he believes that imneskibart could be “useful for a wide range of cancers – much like the checkpoint inhibitors”.
If the next data readout for imneskibart is positive, Knickerbocker mentioned that Aulos will look into initiating a registrational study in the second half of 2026, which will be “either in melanoma, NSCLC or both,” depending on the biotech’s interactions with regulatory authorities.
Though the plans for the Phase III trial are still in their infancy, Knickerbocker stated that Aulos may seek accelerated approval through single arm studies. However, the company may also choose to go with the gold-standard randomised, placebo-controlled trial (RCT).
