Ampligen (rintatolimod) / AIM ImmunoTech - LARVOL DELTA

AIM ImmunoTech…detailed a recent abstract containing data from the completed Phase 2 advanced recurrent ovarian cancer clinical study utilizing Ampligen (rintatolimod), which was presented at the 40th Annual SITC Meeting… (GlobeNewswire) - "Platinum-sensitive patients with measurable peritoneal disease were eligible for combination therapy with up to six treatment cycles at 3-week intervals of intraperitoneal cisplatin, intravenous pembrolizumab (also known as Merck’s Keytruda) and intraperitoneal Ampligen. Of the 27 patients included in the trial, 24 were evaluable for response and of those 24 there were 5 patients with complete response and 7 patients with partial response, for an Objective Response Rate ('ORR') of 50%....These new ovarian cancer study results are consistent with AIM’s belief that Ampligen can act as a synergistic agent when combined with checkpoint inhibitors."

P2 data • Platinum sensitive • Ovarian Cancer

A Phase II Trial of Combination Locoregional Chemoimmunotherapy in Recurrent Platinum-Sensitive Ovarian Cancer Triggers a T Lymphotactic Response Correlating with Clinical Outcomes (SITC 2025) - P1/2 | "Platinum sensitive patients with measurable peritoneal disease were eligible for combination therapy with up to six treatment cycles at 3-week intervals of IP cisplatin, IV Pembrolizumab and IP TLR3 ligand Rintatolimod. Digital spatial profiling revealed a higher fraction of CD3+, CD8+, GZMYB+, cells within the tumor area within responders compared to nonresponders with no significant difference observed in regions outside of the tumor (figure 2).Conclusions Combination locoregional chemoimmunotherapy was well tolerated and demonstrated clinical benefit with a 50% ORR, locoregional T cell activation signals, and several EOC patients with durable treatment responses. Correlative biologic studies suggest treatment response is associated with localized enrichment of cytotoxic and memory T cell populations within the TME.Acknowledgements This trial receives support from both Merck and AIM Immunotech."

Clinical • Clinical data • IO biomarker • Late-breaking abstract • P2 data • Platinum sensitive • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD8 • TLR3

AIM ImmunoTech…announced that data from the completed Phase 2 cisplatin-resistant advanced recurrent ovarian cancer clinical study utilizing Ampligen (rintatolimod) was accepted in a late-breaking abstract at the 40th Annual SITC Meeting… (GlobeNewswire)

Late-breaking abstract • P2 data • Platinum resistant • Ovarian Cancer

Ampligen Combined With SOC Versus SOC Alone Following First-Line Therapy in Subjects With LAPC (clinicaltrials.gov) - P2 | N=90 | Suspended | Sponsor: AIM ImmunoTech Inc. | Trial completion date: Oct 2028 ➔ Jan 2030 | Trial primary completion date: Sep 2028 ➔ Dec 2029

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

AIM ImmunoTech Secures Patent in Japan Through 2039 for Novel Cancer Therapy Combining Ampligen (Rintatolimod) with Checkpoint Inhibitors (GlobeNewswire) - "The claims are broad, encompassing multiple cancer types, including pancreatic cancer, skin cancer, colorectal cancer, ovarian cancer, melanoma, breast cancer/triple negative breast cancer, head and neck tumors, bladder cancer, renal cell carcinoma, and lung cancer."

Patent • Bladder Cancer • Colorectal Cancer • Head and Neck Cancer • Melanoma • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Cancer • Renal Cell Carcinoma • Skin Cancer • Triple Negative Breast Cancer

AIM ImmunoTech Announces Publication of Journal Article On the Positive Effect of Ampligen and Interferon-Alpha on Tumor Growth (GlobeNewswire) - "The paper concluded that the ability of systemic chemokine modulation to eliminate the PD-1-resistance of cold tumors indicates that intratumoral cytotoxic t-lymphocyte accumulation, rather than tumor immunogenicity, is the key factor limiting the therapeutic effectiveness of immune checkpoint inhibitors."

Preclinical • Solid Tumor

Synergy between TLR3-ligand and IFN-α in the transient sensitization of "Cold" tumors to PD-1 blockade and the induction of systemic immunity. (PubMed, J Immunother Cancer) - "The ability of systemic CKM to eliminate the PD-1-resistance of cold tumors indicates that intratumoral CTL accumulation, rather than tumor immunogenicity, is the key factor limiting the therapeutic effectiveness of ICI. These data suggest a broad therapeutic potential of TME-reprogramming strategies."

IO biomarker • Journal • Colorectal Cancer • Immunology • Oncology • Solid Tumor • BATF3 • CD8 • CXCL10 • CXCL9 • CXCR3 • IFNA1 • TLR3

AIM ImmunoTech Highlights Growing Body of Compelling Data of Ampligen for the Treatment of Pancreatic Cancer at Conference in Poland (GlobeNewswire) - "AIM CEO Thomas K. Equels provided an overview of data from AIM’s pancreatic cancer Early Access Program and the latest advancements in the Phase 2 DURIPANC pancreatic cancer clinical trial currently underway at Erasmus University Medical Center in the Netherlands."

Clinical • Pancreatic Cancer

NCI-2019-01192: Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Roswell Park Cancer Institute | Recruiting ➔ Active, not recruiting | N=30 ➔ 12 | Trial primary completion date: Nov 2026 ➔ Jun 2025

Biomarker • Enrollment change • Enrollment closed • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: Roswell Park Cancer Institute | Trial completion date: Dec 2025 ➔ Jun 2025 | Active, not recruiting ➔ Terminated; Funding ended

Trial completion date • Trial termination • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

AIM ImmunoTech Reports Positive Mid-year Safety and Efficacy Data from Phase 2 Study Evaluating Ampligen (rintatolimod) in Combination with AstraZeneca’s Imfinzi (durvalumab) for the Treatment of Pancreatic Cancer (GlobeNewswire) - P1/2 | N=43 | DURIPANC (NCT05927142) | "AIM ImmunoTech Inc...today reported positive data in a mid-year update from the ongoing Phase 2 clinical study evaluating AIM’s drug Ampligen (rintatolimod) combined with AstraZeneca’s anti-PD-L1 immune checkpoint inhibitor Imfinzi (durvalumab) in the treatment of metastatic pancreatic cancer patients with stable disease post-FOLFIRINOX (the 'DURIPANC' study)...A total of 14 subjects have been enrolled in DURIPANC as of the mid-year report....Compared to these data, the DURIPANC study mid-year report shows continuing promising early signs of both no significant toxicity and superior PFS and OS: No significant toxicity, an encouraging safety profile for a post-chemo setting; ~21% of patients have PFS >6 months (3/14), with an additional 21% not yet progressed; and OS >6 months in the majority (64%) of eligible patients—better than expected in this setting."

P2 data • Pancreatic Cancer

Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov) - P2 | N=1 | Terminated | Sponsor: Roswell Park Cancer Institute | Trial completion date: Apr 2026 ➔ Jun 2025 | Active, not recruiting ➔ Terminated; Funding completed

Trial completion date • Trial termination • Melanoma • Oncology • Solid Tumor

Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines (clinicaltrials.gov) - P1/2 | N=25 | Terminated | Sponsor: Roswell Park Cancer Institute | Trial completion date: Jun 2026 ➔ Jun 2025 | Suspended ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Jun 2025; lack of funding

Trial completion date • Trial primary completion date • Trial termination • Oncology • Ovarian Cancer • Solid Tumor

AIM ImmunoTech Granted U.S. Patent Covering Methods of Manufacturing Therapeutic dsRNA, Including Ampligen (GlobeNewswire) - "AIM ImmunoTech...announced the United States Patent and Trademark Office has granted U.S. patent No. 12312376, titled 'Therapeutic Double Stranded RNA and Methods for Producing the Same.' The patent expires January 25, 2041. The new patent covers methods involving the manufacture of a range of therapeutic double-stranded RNA (dsRNA) products, of which Ampligen is included. Combined with AIM’s multiple compositions and methods patents involving Ampligen, this manufacturing patent, along with AIM’s other issued patents, further secures the Company’s control over the synthesis and use of the first-in-class drug, and provides patent protection for manufacturing until 2041. The new patent significantly extends the potential development runway for the drug, securing AIM additional time to safely and confidently develop its drug program as it seeks U.S. Food and Drug Administration ('FDA') approval for Ampligen in any of a series of indications."

Patent • Oncology

Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer (clinicaltrials.gov) - P1/2 | N=24 | Active, not recruiting | Sponsor: Robert Edwards | Recruiting ➔ Active, not recruiting | N=45 ➔ 24 | Trial primary completion date: Dec 2026 ➔ Jul 2024

Checkpoint inhibition • Enrollment change • Enrollment closed • Platinum sensitive • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov) - P2 | N=1 | Active, not recruiting | Sponsor: Roswell Park Cancer Institute | Recruiting ➔ Active, not recruiting | N=24 ➔ 1 | Trial completion date: Nov 2027 ➔ Apr 2026 | Trial primary completion date: Nov 2027 ➔ Apr 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Systemic Infusion of dsRNA (Rintatolimod) plus IFNa Selectively Enhances Intratumoral CTL Influx in Cancer Patients (IMMUNOLOGY 2025) - P1, P1/2, P2, P2a | "It showed very good tolerability, average 10.3-fold increase in intratumoral CTL markers and preliminary signals of clinical activity (1 objective response, 50% survival of >4 years), when followed by pembrolizumab. Analogous CTL increases were also seen on study NCT04081389 (neoadjuvant CKM/chemotherapy in TNBC) and NCT03403634 (liver-metastatic colon cancer). Ongoing studies NCT04093323 (PD1-resistant solid tumors), NCT02432378 (advanced ovarian cancer), test the clinical efficacy of concomitant application of CKM with PD1 blockade and/or DC vaccines.Keywords: Animals Human; Cells T Cells; Molecules Chemokines; Processes Cell Trafficking Chemotaxis"

Clinical • IO biomarker • Breast Cancer • Colon Cancer • Colorectal Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • TLR3

Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=5 | Active, not recruiting | Sponsor: Roswell Park Cancer Institute | Recruiting ➔ Active, not recruiting | N=15 ➔ 5 | Trial completion date: Jun 2025 ➔ Dec 2025

Enrollment change • Enrollment closed • Trial completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

NCI-2019-01192: Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Roswell Park Cancer Institute | Suspended ➔ Recruiting | Trial completion date: May 2026 ➔ Nov 2026 | Trial primary completion date: May 2026 ➔ Nov 2026

Biomarker • Enrollment open • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Expected Upcoming, Value-Driving Milestones (GlobeNewswire) - "Phase 1/2a Study of Ampligen, Celecoxib and Interferon Alpha 2b with Pembrolizumab for the Treatment of Patients with Metastatic or Unresectable Triple Negative Breast Cancer (NCT05756166); Grant funded by Merck and National Cancer Institute: Q2 2026: Expected completion of enrollment....Phase 2 Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer (NCT03734692); Grant funded by Merck: H1 2025: Completion of study, publication of data."

P2 data • Trial status • Ovarian Cancer • Triple Negative Breast Cancer

Expected Upcoming, Value-Driving Milestones (GlobeNewswire) - "Phase 1b/2 Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab with TLR-3 Agonist Ampligen in Patients with Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy (DURIPANC) (NCT05927142); Funded through collaboration of AstraZeneca and Erasmus Medical Center: Q2/Q3 2026: Last patient enrolled in Phase 2...Phase 2 Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Ampligen, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (NCT04093323); Grant funded by National Cancer Institute: H1 2025: First patient dosed."

Trial status • Melanoma • Pancreatic Ductal Adenocarcinoma

AIM ImmunoTech Inc. Participates in the Virtual Investor “Top 5 for ‘25” On-Demand Conference (GlobeNewswire) - "As part of the event, AIM CEO Thomas K. Equels presented his...reasons why he believes the investment community and industry colleagues should pay attention to the Company in 2025: Progress in late-stage pancreatic cancer treatment with significant advancements in the Phase 1b/2 DURIPANC trial at Erasmus Medical Center in the Netherland...Rapid advancement across oncology pipeline with multiple key trials reaching or approaching major milestones....Ampligen’s overall potential as a broad-spectrum immunotherapy."

Pipeline update • Trial status • Pancreatic Cancer

AIM ImmunoTech Inc. Participates in the Virtual Investor “Top 5 for ‘25” On-Demand Conference (GlobeNewswire) - "AIM ImmunoTech Inc...announced its participation in the Virtual Investor “Top 5 for ‘25” On-Demand Conference...investment community and industry colleagues should pay attention to the Company in 2025...Expanding research in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) research and post-COVID conditions, including the Company’s early recognition of the link between COVID-19 and ME/CFS-like conditions....Plans to advance Ampligen as a vaccine adjuvant for the growing and serious threat of bird flu as part of the Company’s antiviral priority development pipeline."

Pipeline update • Infectious Disease • Novel Coronavirus Disease

Ampligen Combined With SOC Versus SOC Alone Following First-Line Therapy in Subjects With LAPC (clinicaltrials.gov) - P2 | N=90 | Suspended | Sponsor: AIM ImmunoTech Inc. | Recruiting ➔ Suspended

Trial suspension • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Nov 2025 ➔ Nov 2027 | Trial primary completion date: Nov 2025 ➔ Nov 2027

IO biomarker • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • CD8