Shots: 

• Robert Connelly, CEO of Elicio Therapeutics, shared his views on the aftermath of the merger between Elicio Therapeutics & Angion Biomedica Corp. The strategic merger is instrumental to further advance Elicio’s product candidates with a focus on advancing its proprietary lymph node targeting Amphiphile (AMP) technology to develop immunotherapies 

• Robert recapitulates data presented at ASCO from the ongoing Ph 1 (AMPLIFY-201) study of ELI-002 2P, a 2-peptide formulation designed to treat cancers driven by G12D and G12R mutations in KRAS 

• While eloquently explaining the mechanism of Amphiphile technology, Robert stresses more on AMP technology to develop immunotherapies, with ELI-002, an investigational cancer vaccine targeting mKRAS-driven tumors, as the lead candidate 

Saurabh: To begin with, can you provide an overview, financial disclosures, and advisors of the recently completed merger between Elicio Therapeutics and Angion Biomedica Corp.? 

Robert: In January 2023, we announced that Elicio entered a definitive merger agreement with Angion Biomedica, which closed in June. The combined company operates under the name Elicio Therapeutics, and its shares commenced trading on a 1-10 reverse split-adjusted basis on June 2nd, on the Nasdaq Global Market under the ticker symbol “ELTX”.  

We focus on advancing our proprietary lymph node-targeting Amphiphile (AMP) technology to develop immunotherapies. Our lead candidate is ELI-002, an investigational cancer vaccine targeting mutant KRAS (mKRAS)-driven tumors. ELI-002 is being evaluated in the AMPLIFY-201 Phase 1 trial (NCT04853017) and the AMPLIFY-7P Phase 1/2 study (NCT05726864) in patients with mKRAS-driven solid tumors. 

The management team of Elicio has become the management team of the combined company, led by Robert Connelly as Chief Executive Officer. The board of directors is comprised of nine directors including Mr. Connelly and Angion’s former President and Chief Executive Officer, Jay Venkatesan, MD, MBA. We currently have approximately 9.7 million shares of common stock outstanding on a fully diluted basis, with prior Elicio shareholders owning approximately 65.2% and prior Angion shareholders owning 34.8%.   

Oppenheimer & Co., Inc. served as financial advisor and Cooley LLP provided legal counsel to Angion. Mintz, Levin, Cohn, Ferris, Glovsky, and Popeo, P.C., and Goulston & Storrs PC provided legal counsel to Elicio. 

Saurabh: Can you elaborate on the reasons for the merger between Elicio and Angion? What were the synergies? 

Robert: Angion was looking for strategic alternatives to preserve and increase shareholder value, including potential mergers, while Elicio was looking to go public and raise funds to further advance ELI-002 through the clinic. The reverse merger with Angion provided Elicio an opportunity to assume the $30M of cash held by Angion and a Nasdaq listing to help further advance Elicio’s product candidates. 

Saurabh: Please elaborate on the study (AMPLIFY-201), study design, results, and the technology it is utilizing. 

Robert: ELI-002 is an investigational cancer vaccine developed with our proprietary lymph node-targeting Amphiphile, or AMP, technology, which delivers therapeutic payloads directly to the lymph nodes, the “brain center” of the immune system. ELI-002 is comprised of AMP-modified mutant KRAS peptide antigens and ELI-004, an AMP-modified immune-stimulatory oligonucleotide CpG adjuvant, or AMP CpG. The AMP mKRAS peptides and AMP CpG are targeted to the lymph node where they are designed to enhance the response of key immune cells able to specifically recognize and eliminate mutant KRAS-expressing cancer cells. 

AMPLIFY-201 is a multicenter Phase 1 trial assessing the safety, immunogenicity, and antitumor activity of an initial 2-peptide formulation of ELI-002, ELI-002 2P, as a monotherapy in patients with mutant KRAS-driven tumors who are at high risk for relapse due to detection of minimal residual disease following standard surgery and chemotherapy. This formulation is designed to treat cancers driven by G12D and G12R mutations in KRAS. There were five cohorts of patients who received a 1.4 mg fixed dose of the two mutant KRAS peptide antigens and escalating doses of AMP CpG (0.1 mg, 0.5 mg, 2.5 mg, 5.0 mg, or 10.0 mg). 

Interim results from the AMPLIFY-201 study presented at ASCO showed that ELI-002 2P was well-tolerated with no Grade ≥3 related adverse events, no cytokine release syndrome, and no dose-limiting toxicities. A high proportion of ELI-002 2P patients had tumor biomarker reduction (77%) with a subset achieving clearance (32%). Notable mutant KRAS-specific T cell responses were induced by vaccination with 87% of patients developing increased mutant KRAS-specific T cell responses in direct ex vivo assays; 100% of patients responded at the two highest dose levels, with an average of a 56-fold [range 2-423-fold] increase over baseline. In a subset of patients where radiographic findings on the study led to biopsy of new lesions, T cell infiltration was 10 to 29-fold higher than literature-reported values for pancreatic tumors. The recommended Phase 2 dose (RP2D) is 10 mg of AMP CpG. 

We have also developed a 7-peptide formulation, ELI-002 7P, which is currently being studied in AMPLIFY-7P, a Phase 1/2 trial in patients with high relapse risk mKRAS-driven solid tumors. The ELI-002 7P formulation is designed to provide immune response coverage against seven of the most common KRAS mutations that drive 25% of solid tumors, thereby increasing the potential patient population for ELI-002 and potentially reducing the chance of bypass resistance mechanisms. 

Saurabh: What are the next steps for Elicio Therapeutics in terms of its clinical development program and the advancement of ELI-002? Is Elicio's team planning for any potential collaboration or licensing agreement? 

Robert: Our clinical development program is focused on ELI-002, our lead asset, and the ongoing clinical trials, AMPLIFY-201 and AMPLIFY-7P. While we can’t speak to any ongoing discussions, we can point to a clinical supply agreement we have with Regeneron to evaluate the safety and efficacy of ELI-002 in combination with Regeneron’s Libtayo® (cemiplimab), a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells, in patients with mutant KRAS-driven tumors.   

Saurabh: As the press release mentions the potential clinical utility of ELI-002 in patients with high relapse risk mKRAS-driven solid tumors, can you highlight more details about the interim data that will be presented at ASCO supporting ELI-002’s potential? 

Robert: We recently announced positive interim clinical data from the ongoing Phase 1 (AMPLIFY-201) study of our lead asset, ELI-002, an investigational cancer vaccine at the 2023 American Society of Clinical Oncology (ASCO). This study evaluated ELI-002 2P, a 2-peptide formulation designed to treat cancers driven by G12D and G12R mutations in KRAS. ELI-002 was studied as a monotherapy in patients with mutant KRAS-driven tumors who are at high risk for relapse due to detection of minimal residual disease (MRD) following standard surgery and chemotherapy (NCT04853017). 

The data showed that ELI-002 2P was well-tolerated, with no dose-limiting toxicity or cytokine release syndrome across 5 cohorts that evaluated ascending doses from 0.1 to 10.0 mg of the adjuvant AMP CpG. Responses were observed at all dose levels, with a high proportion of patients having tumor biomarker reduction including a subset with clearance. Robust mKRAS-specific T-cell responses were induced in 87% of patients with an average of a 56-fold [range 2-423-fold] increase directly ex vivo. 

Saurabh: Could you please list out the solid tumor indications for which Elicio is focused on developing immunotherapies? 

Robert: The focus of the ELI-002 program is on mutant KRAS-driven cancers, particularly pancreatic ductal adenocarcinoma (PDAC), colorectal cancers (CRC), and non-small cell lung cancers.  

Saurabh: Please let us know the mechanism of the Amphiphile platform, and how it improves the therapeutic utility of currently approved immunotherapies. 

Robert: We believe the therapeutic utility of many immunotherapy approaches is limited because while they have been designed to modulate the biology of immune cells against disease, they are not effectively delivered to lymph nodes where these critical immune cells coordinate the build-up of anti-tumor immunity.  Instead, after administration, they are quickly flushed away into the systemic circulation and delivered to irrelevant sites throughout the body. Our AMP platform is designed to reprogram this delivery process to target immune therapeutic payloads directly to the lymph nodes where they can potently stimulate the immunity needed to fight disease.  To accomplish this, AMP binds to albumin, a common protein found in tissues, which serves as a shuttle bus traveling to lymphatic tissue. In preclinical models, Elicio has observed lymph node-specific engagement driving immune responses of increased magnitude, function, and durability. We believe the smart delivery of disease-specific antigens, adjuvants, and other immunomodulators directly to the lymph nodes may efficiently educate, activate, and amplify critical immune cells, potentially resulting in the induction and persistence of potent adaptive immunity required to treat many diseases.   

We believe our AMP lymph node-targeted approach has the potential to produce superior clinical benefits compared to immunotherapies that do not engage the lymph nodes based on the evidence from these preclinical studies. 

Saurabh: What are the plans for the new molecules added from this merger? And how compatible are these molecules with the existing pipeline? 

Robert: At this point in time, we don’t have any plans to develop these programs further. However, we are open to exploring options to see whether there are interested parties who could license these programs from us.  

Saurabh: Give us a glimpse into the preclinical programs. What is your plan of action for their development? 

Robert: At this point in time, we don’t have any plans to develop these programs further. Our focus is on advancing our proprietary lymph node-targeting AMP technology to develop immunotherapies, with ELI-002, an investigational cancer vaccine targeting mKRAS-driven tumors, as our lead candidate. 

Image Source: Canva 

About the Author:

Robert Connelly

Bob joined Elicio as CEO in October 2018. He is a prolific entrepreneur and company builder/leader with 30+ years of experience in the Life Sciences sector. Since 2000, Bob has been the CEO and/or Chairman of startup or early-stage novel therapeutic companies, in the US and EU, including as founding CEO and first employee of Domantis (sold to GSK in 2007 for $454 million, the largest all-cash purchase of a preclinical company at that time), CEO of Pulmatrix (NASDAQ:PULM) and Axcella Health (NASDAQ:ALXA). 

Bob also served as a Venture Partner with Flagship Pioneering from 2013 to October 2018, working on the creation and management of 5 portfolio companies, including as a CEO of Axcella, Board member of Kaleido (NASDAQ:KLDO) and Kintai, Chairman of Aero Designs and Founding CEO of WikiCell Designs (Aero and Wiki merged into Incredible Foods in 2013). He raised over $400 million in financing and led partnering transactions for his companies, including product and platform license, government and foundation funding and M&A transactions, while launching innovative platforms and products across disease areas. 

Bob began his career with Abbott Laboratories, spending over 11+ years in sales, sales-management, marketing, and strategic marketing positions of increasing responsibility. He then spent 6 years with BioVeris (acquired by Roche for $1.6 billion) as SVP of Sales and Marketing and General Manager of the Life Sciences Business Unit, taking on lead marketing and investor communication roles in the company’s public financings of over $300 million. 

Bob and his wife Marlen are part of an exceptionally large, thriving multi-ethnic family, with siblings, cousins, nieces, and nephews in every US time zone, including three children of their own, PLUS two beautiful little granddaughters. So much family leaves little spare time, but Marlen and Bob both grew up in the Miami-Ft. Lauderdale area, so getting on the water, anyway possible, is a priority. 

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