Immune Fx (IFx) Personalized Cancer Vaccines

Overcomes Resistance to Checkpoint Inhibitors

Immunotherapies, such as checkpoint inhibitors (CPI), recruit a patient’s immune response to target tumor cells and have revolutionized the treatment of cancer for a number of patients. However, with as many as 60%-80% of patients not responding to checkpoint inhibitor therapy, there is room for significant improvement. A primary obstacle that limits the effectiveness of immunotherapies in targeting cancer is primary or innate resistance related to tumor intrinsic factors associated with insufficient tumor immunogenicity, allowing tumors to escape immune recognition and immune attack.

IFx Primes the Activation of Immune Response to Target Cancer Cells

Our IFx Personalized Cancer Vaccine technology is designed to overcome primary resistance to CPIs by making cancer cells look like bacteria, triggering an innate immune response.

Some personalized cancer vaccines being developed by others require tumor tissue from each individual patient, followed by extensive molecular processing and computational modeling in an attempt to predict which foreign or neoantigens are important to activate an immune response. Typically, only 30 or 40 neoantigens, among the tens of thousands in each patient’s tumor, are targeted using an mRNA construct that is specific to an individual patient. This complex process is expensive, time consuming and does not take full advantage of all of the neoantigens in a patient’s tumor.

In contrast, our IFx technology involves a simple injection into the patient’s tumor of a proprietary gene that encodes for emm55, an immunogenic bacterial protein that is then expressed on the surface of the tumor cell. Recognizing the bacterial protein as being foreign, the patient’s immune system is activated, “ingesting” the tumor cell. This process educates the immune system to all the patient’s tumor’s neoantigens, not just a few dozen predicted to be important.

Directly injecting IFx-Hu2.0 into the tumor ensures that emm55 is expressed by tumor cells, initiating an immune response directed against the tumor antigens contained within the patient’s tumor cells.

Our approach provides a potent, multivalent, and systemic response against all of the patient’s tumor sites, not just the ones that were injected, through a process called primary epitope spreading.

Our IFx personalized cancer vaccine can be used across a number of cancer indications and is initially being developed as a first line treatment for metastatic Merkel Cell Carcinoma.

Primary Epitope Spreading Provides Potent, Multivalent Systemic Response Against All of the Patient’s Tumors

Diagram showing spread and response of IFX-HU2.0 process

IFx-Hu2.0: Personalized Cancer Vaccine

Entering Expected Single Phase 2/3 Registration Trial as First Line Treatment for Metastatic Merkel Cell Carcinoma

Program Highlights:

  • Demonstrated 80% systemic objective response rate in advanced Merkel Cell Carcinoma
  • Excellent safety profile including combination with checkpoint inhibitors
  • Developing under Accelerated Approval pathway for treatment of advanced Merkel Cell Carcinoma
  • Granted Orphan Drug Designation

Demonstrated Ability to Overcome CPI Resistance Across Multiple Tumor Types in Phase 1/1b Study

Phase 1/1b Trials in Advanced Merkel Cell, Squamous Cell, Melanoma

In our Phase 1 trial among patients with treatment refractory advanced malignant Melanoma, after intralesional delivery of IFx-Hu2.0, correlative transcriptomic studies confirm the systemic nature of the ensuing innate and adaptive immune responses. Gene signatures consistent with an innate immune response are demonstrated in the injected tumor, while gene signatures consistent with an adaptive immune response are seen in the un-injected tumors. Both injected and un-injected tumors demonstrated substantial reduction in tumor size and a marked downregulation of genes encoding multiple melanoma antigens. Production of tumor-specific antibodies recognizing hundreds of previously unrecognized melanoma tumor epitopes similarly confirmed activation of a systemic immune response.

In our Phase 1/1b dose and schedule finding study, IFx-Hu2.0 demonstrated an ability to overcome checkpoint inhibitor resistance across multiple tumor types including metastatic Merkel Cell Carcinoma and other advanced malignant skin cancers.

In the Phase 1b portion of the study, the five patients with advanced metastatic Merkel Cell Carcinoma exhibited primary resistance to first line treatment with a checkpoint inhibitor (all having disease progression within three months of initiating checkpoint inhibitor therapy). These patients were then treated with IFx-Hu2.0, followed by re-administration of a checkpoint inhibitor. Four patients achieved a major objective systemic anti-tumor response, including one complete response, one near complete response, and two partial responses documented on restaging CT or MRI evaluation.