- The presented data show ELI-005 elicits strong and long-lasting cellular and humoral immune responses that were maintained at significantly higher levels than comparator vaccines over 32 weeks in mice.
- ELI-005, containing the lymph node-targeted Amphiphile vaccine adjuvant AMP-CpG, induced potent, comprehensive and persistent innate immune responses in draining lymph nodes in mice.
- Animals treated with AMP-CpG showed a significantly higher percentage of CD8+ T cells with central memory phenotype, which resulted in more robust recall responses one week after antigen challenge in mice.
- ELI-005 rapidly induced potent cellular and antibody responses in non-human primates up to 5,000-fold over baseline which exhibited cross-reactive neutralization activity specific to Beta, Delta and Omicron SAR-CoV-2 variants of concern.
BOSTON, July 6, 2022 – Elicio Therapeutics, a clinical-stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer and other diseases, today announced the presentation of preclinical data on ELI-005, a protein subunit vaccine containing the spike receptor-binding domain (RBD) protein of SARS-CoV-2, and Elicio’s lymph node-targeted CpG TLR-9 agonist, Amphiphile-CpG (AMP-CpG), demonstrating they induce potent cross-reactive antibody and T cell responses in mice and non-human primates. ELI-005 yielded robust and durable cross-reactive serum IgG responses specific to several SARS-CoV-2 variants of concern alongside potent and cross-reactive peripheral T cell responses. The data were presented in three posters at the 2022 Keystone Symposia on Viral Immunity: Basic Mechanisms and Therapeutic Applications virtually and in-person at the Keystone Resort in Keystone, CO from June 29-July 2, 2022. The electronic presentations are accessible here.
While currently authorized vaccines have shown success in the reduction of severe disease risk from COVID-19, rapidly emerging viral variants continue to drive substantial pandemic waves of infection, resulting in numerous global public health challenges. Future advances in prophylactic vaccine activity will play a critical role in the resolution of the current pandemic and preparation for future pandemics driven by similar coronavirus pathogens. The robust immune responses generated by ELI-005 suggest that it may enhance broad protection against new variants of concern.
“We are pleased to present updated data from ongoing preclinical work in mice and non-human primates with ELI-005, our lymph node-targeting AMP-vaccine against SARS-CoV-2. The truly exciting component of the data is that we are seeing an immune response that is very broad in its ability to recognize variants of concern that did not exist at the point when we were developing the approach. This potential to address many variants is critically important for any future coronavirus outbreaks,” said Peter DeMuth, Ph.D., Chief Scientific Officer at Elicio. “Overall, ELI-005 generated robust and durable responses from the two arms of adaptive immunity—cellular and humoral. These parallel responses are critical to providing optimal immune protection against pathogens like SARS-CoV-2 and support the differentiation of ELI-005 from existing COVID-19 vaccines.”
Christopher Haqq, MD, Ph.D., Executive Vice President, Head of Research and Development and Chief Medical Officer added, “These data sets validate our ability to deliver therapeutic payloads with the Amphiphile platform, driven by our Amphiphile modified TLR-9 agonist ELI-004, directly into the lymph nodes, the ‘schoolhouse of the immune system.’ This approach allows us to educate the T cells in the lymph nodes to recognize the antigen and develop persistent, broad immune specificity for a pathogen.”
Poster Presentation Highlights
Title: A lymph node targeted protein subunit vaccine induces robust cellular and humoral immunity to SARS-CoV-2 in non-human primatesHighlights from the Presentation:
- ELI-005, containing the Amphiphile vaccine adjuvant AMP-CpG and WH-01 Spike receptor binding domain (RBD), induced polyfunctional antigen-specific CD8+ and CD4+ T cells in the peripheral blood of non-human primates.
- ELI-005 rapidly induced potent antibody responses in non-human primates up to 5,000-fold over baseline (reaching 104 binding antibody units/mL) which were cross-reactive to Beta, Delta and Omicron SAR-CoV-2 variants of concern.
- ELI-005 vaccination with AMP-CpG was safe and well tolerated with no observation of local reactogenicity, or abnormal changes in blood chemistry, hematocrit, body weight, body temperature or serum cytokine levels following each immunization.
Title: A lymph node targeted protein subunit vaccine generates strong cellular and cross-reactive humoral immunity against SARS-CoV-2 with potent long-term recall responses
Highlights from the Presentation:
- ELI-005 elicits strong and long-lasting cellular and humoral immune responses.
- Acute immune responses to ELI-005, one week after boost immunization, resulted in >60% of circulating and lung-resident CD8+ T cells, as well as nearly 10% of lung-resident CD4+ T cells to be reactive to RBD.
- Over 32 weeks, these responses were maintained at significantly higher levels than comparator vaccines, with 6% of circulating CD8+ T cells having maintained a cytokine+ status at 32 weeks.
- Animals treated with ELI-005 showed a significantly higher percentage of CD8+ T cells with central memory phenotype, which resulted in more robust recall responses one week after antigen challenge.
- Strong antibody responses, that were cross-reactive towards RBD variants, were generated and maintained throughout the course of the study.
Title: A lymph node targeted CpG, TLR-9 agonist induces potent and persistent activation of lymphatic innate immune responses resulting in robust cellular and humoral immunity to SARS-CoV-2
Highlights from the Presentation:
- ELI-005, containing the lymph node-targeted Amphiphile vaccine adjuvant AMP-CpG, induced potent, comprehensive and persistent innate immune responses in draining lymph nodes.
- AMP-CpG induced increased numbers of all innate cell lineages in the lymph nodes, as well as increased numbers of innate cells expressing co-stimulatory molecules and producing key cytokines.
- In the lymph nodes, AMP-CpG upregulated numerous pro-inflammatory immune mediators associated with multiple axes of immune activation, including hematopoietic growth factors, cytokines and chemokines.
ELI-004 (AMP-CpG) is an Amphiphile modified TLR-9 agonist that is included in ELI-005. ELI-004 “hitchhikes” on endogenous albumin until it reaches antigen presenting cells in the draining lymph nodes to potently stimulate immune activation and support expansion of adaptive immune responses. ELI-004 has previously demonstrated at least 10-fold improved lymph node delivery, leading to substantially enhanced immune cell delivery and immune responses versus conventional CpG and other benchmark adjuvants. ELI-004 has demonstrated eradication and cures in multiple preclinical cancer models and activity against infectious diseases and, in this study, COVID-19. When the IND was approved for ELI-002 last year, IND approval for ELI-004 was automatically gained as well as it is 1 of 8 components in the asset.
About the Amphiphile Platform
Our proprietary Amphiphile, or AMP, platform delivers investigational immunotherapeutics directly to the “brain center” of the immune system – the lymph nodes. We believe this site-specific delivery of disease-specific antigens, adjuvants and other immunomodulators may efficiently educate, activate and amplify critical immune cells, potentially resulting in induction and persistence of potent adaptive immunity required to treat many diseases. In preclinical models, we have observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability. We believe our AMP lymph node-targeted approach will produce superior clinical benefits compared to immunotherapies that do not engage the lymph nodes.
Our AMP platform, originally developed at the Massachusetts Institute of Technology, or MIT, has broad potential across cancers, infectious diseases and other disease indications to advance a number of development initiatives through internal activities, in-licensing arrangements or development collaborations and partnerships.
The Amphiphile platform has been shown to deliver immunotherapeutics directly to the lymph nodes by latching on to the protein albumin, found in the bloodstream, as it travels to lymphatic tissue. In preclinical models, we have observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability.
About Elicio Therapeutics
Elicio Therapeutics is a clinical-stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer and other diseases. By combining expertise in immunology and immunotherapy, Elicio is engineering investigational Amphiphile immunotherapies that are intended to precisely target and fully engage the lymph nodes, the site in our bodies where the immune response is orchestrated. Elicio is engineering lymph node-targeted AMPlifiers, immunomodulators, adjuvants and vaccines for an array of aggressive cancers and infectious diseases.
Elicio began dosing subjects in AMPLIFY-201, its Phase 1/2 clinical trial in solid tumor subjects for its lead Amphiphile vaccine, ELI-002, targeting KRAS-driven cancers in October 2021. The Amphiphile platform emerged from the laboratories of Darrell Irvine, Howard Hughes Investigator and Professor of Biomedical Engineering in the Koch Institute of Integrative Cancer Research at MIT. For more information, please visit https://elicio.com/.
Cautionary Note on Forward-Looking Statements
This press release includes forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties, assumptions and other important factors that could cause our actual results, performance or achievements to differ materially from historical results or any future results, performance or achievements expressed, suggested or implied by such forward-looking statements. Forward-looking statements include, but are not limited to, statements regarding or expectations for our lymph node-targeted approach to treating cancer and infectious diseases, our interpretation that the strong T cell responses generated by ELI-005 could enhance broad protection against new variants of COVID-19 and the general ability and potential of our proprietary Amphiphile, or AMP, platform, to deliver investigational immunotherapeutics directly to the lymph nodes, including across indications, our expectation that advances in prophylactic vaccine activity will play a critical role in the resolution of the current pandemic and preparation for future pandemics driven by similar coronavirus pathogens.
Applicable risks and uncertainties that could cause our actual results, performance or achievements to differ materially from historical results or any future results, performance or achievements expressed, suggested or implied by our forward-looking statements include, among others: the potential that we experience slower than expected enrollment in our clinical trials, we identify serious side effects or other safety issues, we do not have clinical supply of our product candidate that is adequate in amount and quality and supplied in a timely fashion, and the inherent risks of clinical development; the results of our clinical trials do not continue to support our approach and expectation of lymph node targeting for the enhanced treatment of cancer and infectious diseases or that the results do not continue to support that the AMP platform enhances TCR-T clinical responses in solid tumors; our limited operating history and historical losses; our need to raise capital to fund our research and development programs; the early stage nature of the development of our product candidates; our ability to obtain orphan drug designation from the FDA; competition from various competitors in the markets targeted by our product candidates, including from competitors with substantially greater resources than us; our general dependence on third parties in connection with manufacturing, clinical trials and preclinical studies; the potential complexity of the manufacturing process for our product candidates; our ability to protect our intellectual property; our dependence on the patents we license from the Massachusetts Institute of Technology, or MIT; our compliance with healthcare laws and regulations; and risks relating to the impact on of COVID-19 or other infectious diseases on our business. The forward-looking statements contained in this press release reflect our current views with respect to future events, and we do not undertake and specifically disclaim any obligation to update any forward-looking statements, except as required by law.