NEW YORK – After an infusion of new funding this month, Elicio Therapeutics is gearing up to begin human trials for its lead product candidate, a therapeutic vaccine that can potentially treat and prevent recurrence of cancers driven by KRAS mutations.
Days after Elicio raised $73 million in a Series B financing round, the US Food and Drug Administration approved its investigational new drug application for ELI-002, clearing the way for the company's planned Phase I/II trial of the therapeutic vaccine in patients with KRAS-mutated pancreatic cancer and other solid tumors.
With this momentum, Cambridge, Massachusetts-based Elicio is focusing on the development plan for ELI-002. The company has identified a best use-case for the drug in early-stage patients who have undergone surgery or received treatment to remove or shrink their tumor, but still have some remaining disease, said Christopher Haqq, chief medical officer at Elicio.
Patients with detectable minimal residual disease (MRD) can receive ELI-002 after treatment to kill the remaining tumor cells and train their body's T cells to recognize and kill any future growth, potentially preventing recurrence down the road.
The therapeutic vaccine involves injecting patients with a mutated KRAS peptide attached to an adjuvant. The drug travels to the lymph nodes and signals the body's dendritic cells and T cells to target and kill tumor cells with a KRAS mutation.
Elicio's vaccine uses its Amphiphile technology, which allows the drug to "hitchhike" on albumin proteins that shuttle it to the lymph nodes, where it can educate the body's T cells to target KRAS-mutated cells. The technology was originally developed by researchers at the Massachusetts Institute of Technology, including Elicio co-founder Darrell Irvine, who started the company in 2011. This method solves an issue where the drug might "leak out" and end up in the blood stream instead of entering the lymphatic system, Haqq said.
"They could then go to tolerogenic places like the liver, which actually turn off the immune response instead of switching it on," Haqq said. "This technology was invented to solve that problem. They ride on the back of albumin and into the lymph node where they're delivered to the exact right place. No one has before been able to get such a high proportion of the administered material to go into the lymph node."
In animal studies of ELI-002, the researchers found that the vaccine produced a durable complete response in several tumor types, including lung, melanoma, breast, colorectal, head and neck, and glioma. The animals had a 400-fold increase in functional T-cell responses when administered Amphiphile vaccines targeting mutant KRAS relative to conventional soluble vaccines.
The researchers also conducted challenge experiments, where they reintroduced the tumor into the animals and found the remaining T cells, primed by ELI-002, were able to recognize and eliminate the tumor cells again. Haqq compared the response to how the immune system responds to a viral infection and can respond better if it is reinfected with the virus.
"The technology awakens the immune system through the T cell, and that makes a memory response," Haqq said. "Even after the initial elimination of the cancer, a pool of these memory cells remains and they will rapidly expand again if they are needed."
The final benefit Elicio sees in ELI-002 is its ability to target all seven different KRAS amino acid mutations. Typical KRAS inhibitors can only target one of these amino acid mutations. This ability sets up ELI-002 as a potential combination partner with other KRAS inhibitors that would otherwise have a more limited indication. Two specific drugs ELI-002 could be paired with are Amgen's sotorasib, which the company submitted for FDA approval in December, and Mirati's adagrasib, which is still in clinical trials. Both sotorasib and adagrasib specifically target the KRAS G12C mutation.
While the combination of ELI-002 and these other drugs have not been studied yet, Haqq suggested that ELI-002 could be administered after treatment with one of these drugs as an adjuvant to "mop up any remaining tumor cells." Because of the drug's ability to fight off relapse after the initial treatment, ELI-002 could provide a longer response for patients, Haqq said. It could also prevent cancer recurrence if the tumor cells return with a different KRAS mutation. Sotorasib and adagrasib, currently being studied in metastatic settings, target only the KRAS G12C mutation, but cancer cells could also express another type of KRAS mutation.
Because ELI-002 targets all seven KRAS amino acid mutations, it could help prevent other avenues of treatment resistance due to such mutations. "T cells can kill their tumor target the best when the burden of cancer is the smallest," Haqq said. "It would be ideal for us to treat patients after their treatment with either the Amgen or the Mirati drug because their tumor would have shrunk down to the smallest possible burden and that gives the T cells the easiest opportunity to attack."
Elicio has yet to study ELI-002's activity after a KRAS inhibitor. For the moment, the firm is focused on its forthcoming clinical trial investigating ELI-002's activity in early-stage patients with KRAS-mutated cancers who have undergone surgery or chemotherapy but have remaining disease.
In the upcoming clinical trial of ELI-002, Elicio will be evaluating the drug in patients who are MRD-positive by circulating tumor DNA (ctDNA) after surgery or chemotherapy. These patients who have remaining disease after standard treatment are at a high risk of relapse, Haqq said.
The Phase I/II trial will initially focus on patients with KRAS-mutated pancreatic cancer who have undergone standard-of-care surgery and neoadjuvant or adjuvant chemotherapy. The researchers will use Natera's Signatera ctDNA liquid biopsy test to identify those with MRD after initial treatment and at higher risk of recurrence. The liquid biopsy test will also assess whether patients have KRAS mutations in their tumors.
In an expansion stage, after the dose is determined, Elicio will begin to enroll patients with other solid tumors that have KRAS mutations in the study. Haqq expects most patients in the trial will have pancreatic, colorectal, and lung cancer, or GI tumors like bile duct and gallbladder cancer. Trial participants will either receive ELI-002 after standard treatment or will be part of the control group. If patients in the control group relapse, they will be moved to the ELI-002 cohort and their data will be assessed separately to determine the drug's effect on metastatic disease.
"Right now physicians are in the position where they don't have anything available for their patients that can prevent them from having a recurrence, so they're just ordering CAT scans every few months to see when it does come back," Haqq said. "That's what makes it exciting to be given the permission to go ahead with the trial design that can treat so early. We know that the earlier we can give this kind of therapy to patients, the higher the chances that we'll be able to completely eliminate those nests of tumor cells."