Beyond 'Watch-and-Wait': A New Immunotherapy Paradigm for Lymphoma

PARIS, FRANCE – December 09, 2025 – For thousands of individuals diagnosed with slow-growing follicular lymphoma, the initial treatment plan is often a jarring paradox: you have cancer, but we’re going to "watch and wait." This period of active surveillance, while medically sound for asymptomatic, low-tumor-burden disease, places a heavy psychological weight on patients left to wonder when their condition will progress. Now, emerging data on a novel immunotherapy may offer a proactive alternative, potentially shifting the treatment paradigm from passive observation to early, well-tolerated intervention.

At the 67th American Society of Hematology (ASH) meeting, French biotech company Enterome presented highly encouraging interim results for EO2463, its lead immunotherapy. The findings suggest a significant impact for two distinct groups of follicular lymphoma patients, offering a glimpse into a future where the body’s own immune system can be trained to hold this chronic cancer at bay.

Challenging the Anxiety of Active Surveillance

Follicular lymphoma is often described as an indolent or chronic condition, one that patients live with for many years. While this sounds reassuring, the standard approach for those without severe symptoms involves regular check-ups but no active treatment. This leaves patients in a state of limbo, living with visibly swollen lymph nodes and the constant anxiety that their disease is progressing. The unmet need for a safe and effective therapy in this "watch-and-wait" setting is a widespread consensus among leading oncologists.

Enterome’s SIDNEY Phase 2 trial directly addresses this gap. In a cohort of 19 evaluable patients with follicular lymphoma who would typically be in the watch-and-wait phase, treatment with EO2463 as a standalone monotherapy resulted in an objective response rate (ORR) of 52.6%. This means over half the patients saw a measurable reduction in their tumors. For a population currently offered no treatment at all, this result is a significant beacon of hope.

“These new results are encouraging, despite the limited number of patients,” said Dr. Stephen Smith, the study's principal investigator from the Fred Hutchinson Cancer Center, who presented the data at ASH. He emphasized the core scientific principle at play: "The potent and rapid expansion of specific CD8 T-cells induced by EO2463 supports our understanding that OncoMimics™ trigger memory T-cells to generate sustained immune responses." The data points toward a future where an active, yet gentle, therapy could be deployed early, alleviating patient anxiety and potentially altering the natural course of the disease.

The Science of Mimicry: An 'Off-the-Shelf' Revolution

What makes EO2463 particularly innovative is the technology behind it, known as OncoMimics™. This platform represents a new class of immunotherapy that functions like an in vivo therapeutic vaccine. Instead of complex and costly cell engineering outside the body, like CAR-T therapies, OncoMimics™ use synthetically produced peptides derived from gut bacteria. These peptides are designed to closely mimic specific markers found on the surface of malignant B cells—the cancerous cells in follicular lymphoma.

EO2463 combines four such peptides, which mimic the markers CD20, CD22, CD37, and CD268. When injected subcutaneously, these "non-self" peptides are recognized by the immune system, activating a powerful army of memory T-cells that were previously primed by exposure to gut bacteria. These T-cells then cross-react with the cancerous B cells, recognizing them as a threat and destroying them. By targeting four different markers simultaneously, this approach aims to prevent the cancer from escaping the immune attack, a common challenge in cancer therapy.

This "off-the-shelf" nature is a critical differentiator. Unlike personalized CAR-T therapies that require harvesting a patient's own cells, shipping them to a lab for genetic modification, and then reinfusing them—a process that can take weeks and carries risks of severe side effects like cytokine release syndrome—EO2463 is a standardized product. It can be manufactured at scale, stored easily, and administered via a simple subcutaneous injection in an outpatient setting. This dramatically improves accessibility, reduces logistical complexity, and, based on data from over 230 patients across Enterome's programs, comes with a benign safety profile. It’s a powerful example of how sophisticated biotechnology can be harnessed to create a user-friendly, patient-centric solution.

Powerful Results Signal a Path to Registrational Trials

The potential of EO2463 was further underscored by stunning results in another patient group: previously untreated individuals with low tumor-burden follicular lymphoma who were in need of treatment. In this cohort, EO2463 was given in combination with rituximab, a widely used monoclonal antibody. The outcome was a 100% objective response rate in all six patients evaluated. Of those six, five achieved a complete response, meaning all signs of their cancer disappeared.

The responses were not only deep but also rapid, with a median time to a complete response of just 18 weeks. This potent efficacy in the first-line setting suggests that the therapy could become a foundational part of initial treatment, potentially replacing or augmenting harsher chemotherapy regimens. The combination appears to synergize well, using rituximab to target the B cells directly while EO2463 simultaneously marshals a durable T-cell response against them.

These robust clinical findings have already captured the attention of regulators. In October 2025, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to EO2463 for follicular lymphoma. This status is reserved for therapies that address serious conditions and fill an unmet medical need, and it is designed to expedite the development and review process.

Buoyed by this regulatory validation and the strong clinical data, Enterome is moving forward with confidence. "These new data with EO2463 contribute more compelling evidence and further strengthen our belief in the potential of our OncoMimics™ multi-targeted in vivo immune therapies for blood cancers," stated Pierre Belichard, CEO of Enterome. He confirmed the company's ambitious next step: "I’m looking forward to initiating Phase 3 testing of EO2463 in patients in the watch-and-wait setting in 2026."

While the journey from Phase 2 data to a widely available therapy is long, these results represent more than just promising statistics. They signal a potential paradigm shift in how chronic cancers are managed, moving away from a reactive model to one of proactive, intelligent, and tolerable immune engagement. For patients living with the uncertainty of follicular lymphoma, that is a profoundly meaningful development.