By Melane Sampson
AIM ImmunoTech (NYSE American: AIM) is developing Ampligen, an immune modulator with potential applications across oncology, immune disorders, and viral diseases. The company is currently focused on developing Ampligen for late-stage pancreatic cancer, where AIM believes the therapy’s apparent ability to alter the tumor microenvironment could help address a significant unmet medical need.
“Late-stage metastatic pancreatic cancer is one of the most painful and difficult patient experiences. It is our primary focus for Ampligen’s development given the lethal malignancy’s high unmet need, the large potential market, our U.S. patent for Ampligen in combination with checkpoint inhibitors for the treatment of cancers, and our pancreatic cancer orphan drug designation in the EU and U.S.,” Thomas Equels, CEO of AIM, says in an interview with BioTuesdays.
Ampligen is a double-stranded RNA selective TLR3 agonist immunomodulator that has demonstrated broad-spectrum activity in human clinical studies. In oncology, the company believes its mechanism of action could help address one of the fundamental challenges of cancer immunotherapy: “cold” tumors.
Mr. Equels explains that cold tumors are in an immunosuppressed state because the microenvironment is imbalanced. It contains myeloid-derived suppressor cells and T regulatory cells, which hinder the immune response and inhibit T effector cells—commonly called “killer” T cells—from entering the tumor to fight the cancer. Conversely, “hot” tumors show signs of inflammation that trigger T-cell infiltration, enabling immune cells to attack cancer cells. As a result, hot tumors are generally more responsive to immunotherapy with checkpoint inhibitors.
“Pancreatic cancer is the archetypal cold tumor,” he contends. “The impact of the imbalanced microenvironment is that the tumor cannot be seen by the immune system, and if the immune system can’t see the tumor, neither can checkpoint inhibitors.”
AIM believes Ampligen can alter the imbalanced microenvironment and help convert cold tumors into a more immunologically active state, potentially creating an environment in which checkpoint inhibitors can work more effectively. “We believe Ampligen has the ability to turn cold tumors hot,” Mr. Equels says. “Our understanding of the mechanism has been strengthened through research conducted with the University of Pittsburgh and Erasmus Medical Center.”
He emphasizes that this approach is currently being evaluated in DURIPANC, a Phase 1/2 study of Ampligen in combination with AstraZeneca’s (NYSE: AZN) checkpoint inhibitor durvalumab in pancreatic cancer. DURIPANC grew out of a Named Patient Program at Erasmus Medical Center in the Netherlands, where Ampligen as a monotherapy was made available to more than 50 patients with late-stage pancreatic cancer with remarkable reports of extended overall survival and improved quality of life.
According to Mr. Equels, observations from the Named Patient Program provided an important signal for further clinical development, although he notes that the program was not a controlled clinical trial and therefore did not have the statistical rigor of a Phase 2 or Phase 3 study.
“The overall survival and progression-free survival data from the Named Patient Program were encouraging,” he adds. “What is especially significant is that these patients consistently reported improved quality of life.”
Mr. Equels points out that pancreatic cancer is particularly painful because, as the tumor grows, it compresses and infiltrates the surrounding nerve bundle. Ampligen’s ability to stabilize the tumor may reduce pain by limiting compression and infiltration. “Moreover, because Ampligen is also a powerful antiviral, we believe it may help reduce viral complications, including infections that can contribute to pneumonia, which often plagues patients with late-stage pancreatic cancer.”
The company’s exploratory analysis of the Named Patient Program suggested particularly notable outcomes among patients identified by certain immune and tumor biomarkers. In patients with a neutrophil-to-lymphocyte ratio below 4.5—a measure of the balance between two types of white blood cells that can provide an indication of inflammation and immune system activity—progression-free survival was 17.7 months compared with 8.6 months for historical controls, while overall survival was 34.8 months compared with 12.5 months. Among patients with CA 19-9 levels below 1,000—a blood-based tumor marker commonly used in assessing pancreatic cancer—progression-free survival was 13.1 months compared with 8.6 months, while overall survival was 24.1 months compared with 12.5 months.
AIM is using these observations to inform the development of biomarker strategies for its clinical program. Mr. Equels notes the company believes the biomarkers may identify patients whose immune systems remain sufficiently intact following first-line chemotherapy and therefore may be more likely to respond to Ampligen. “The important thing is that we understand how Ampligen is working.”
The Phase 1/2 DURIPANC trial is designed to evaluate Ampligen as a maintenance therapy following standard first-line treatment. Mr. Equels highlights that approximately 80% of patients receiving FOLFIRINOX experience disease progression within roughly three months, creating a substantial unmet need for effective maintenance approaches.
“We’re stepping in trying to develop a maintenance therapy,” he says. “We take patients who are within that first four-month period who are still stable, and we begin treating them with Ampligen and add the checkpoint inhibitor afterwards—Ampligen paves the way for the immunotherapy.”
AIM has completed enrollment in DURIPANC, with the final patient having received their last dose of Ampligen. The company expects primary endpoint data toward the end of 2026, with an overall survival analysis expected in the third quarter of 2027. Mr. Equels says the study is progressing ahead of schedule, which he attributes in part to patient access and enrollment opportunities in Europe.
The company is also building a broader oncology portfolio around Ampligen. Clinical programs have evaluated the therapy in several solid tumors, including advanced recurrent ovarian cancer and stage IV triple-negative breast cancer. A Phase 2 study in advanced recurrent ovarian cancer, conducted in collaboration with the University of Pittsburgh Medical Center’s Magee Women’s Health Center and supported by a Merck (NYSE: MRK) grant, demonstrated what AIM describes as a significant therapeutic impact and synergy between Ampligen and Merck’s checkpoint inhibitor Keytruda.
“There are a lot of therapies on the market for ovarian cancer that work really well for many patients—Ampligen is for those patients for whom nothing works,” Mr. Equels asserts.
In addition to oncology, Ampligen has been approved in Argentina for the treatment of severe chronic fatigue syndrome and has received orphan drug designation for Ebola. The company is also evaluating Ampligen in various aspects of SARS-CoV-2/COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID conditions.
Mr. Equels maintains that the pancreatic cancer program represents the company’s most immediate value-creation opportunity for potential investors and pharmaceutical partners. AIM believes the combination of clinical data, a defined mechanism of action, biomarker development, intellectual property, and regulatory exclusivity could provide the foundation for a commercially viable product.
“We have rigorously developed our IP portfolio and we have a number of different patents that have been issued to Ampligen in oncology in combination with checkpoint inhibitors,” Mr. Equels says. “Additionally, in pancreatic cancer, we have orphan drug designations from the FDA and the EMA.”
AIM is positioning Ampligen as a potential maintenance therapy in late-stage pancreatic cancer, a substantial patient population with limited treatment options after first-line therapy. Mr. Equels says the company intends to advance the program toward a pivotal Phase 3 study, either through additional financing or with a pharmaceutical partner capable of supporting late-stage development and commercialization.
“The reality is we are an immunology research and development company, and what we’re doing in pancreatic cancer is within a very large patient population,” Mr. Equels says. “It requires a partner that has the ability to move forward. Alternatively, we will raise the funding required ourselves because one way or another we are going to move forward with Ampligen.”
With its lead program supported by clinical data, biomarker research, intellectual property, orphan drug designations, and collaborations with major academic and pharmaceutical organizations, AIM believes Ampligen has the potential to address significant unmet medical needs across multiple disease areas while creating a path toward meaningful commercial potential.
“Our ongoing intention is to unlock the value of Ampligen with the current priority goal of new drug approval in pancreatic cancer,” Mr. Equels concludes. “Our mission is to extend overall survival and improve quality of life—to give hope to those who currently have no hope.”
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