Shots: 

• Purnanand spoke about the preclinical results of lead candidate in oncology and how its identifies IL-38 as a target to treat cancer
• Purnanand also talked about Immunome’s collaboration with Fox Chase Cancer Center for the further development of its prime product
• The interview gives a understanding of Immunome’s goal of developing therapeutics to treat oncology and infectious diseases

Smriti: How does Immunome’s discovery engine work and how did you identify IL-38 as a relevant target in cancer treatment? 

Purnanand: Immunome’s discovery engine is designed to interrogate human memory B cells. B cells are the part of the immune system that makes antibodies. When the immune system sees a foreign substance (antigen), many different B cells are produced, each making a different antibody. Memory B cells, as their name implies, are the ones the body prioritizes and stores, or remembers. They produce high quality antibodies that bind to the antigens they have encountered and react immediately when they encounter the same antigens again in the future. We believe that by viewing disease through the lens of memory B cells and understanding how they act and react with other cells, we may be able to identify previously unknown therapeutic targets for cancer and infectious diseases.

Our discovery engine can capture thousands of patient-derived memory B cells and convert them into stable hybridomas which are specialized cells that can produce large quantities of antibodies. We then conduct function-based screening of antibodies produced by memory B cells within these hybridomas – screening up to 20,000 antibodies in a single experiment – to identify those antibodies which exhibit interesting patterns of binding and that we believe will be most effective. We identified IL-38 as a novel target by isolating the memory B cells of a head and neck cancer patient. Since this initial discovery, recognition of IL-38’s role in cancer has grown and IL-38 is increasingly being regarded as a key cytokine in inflammatory disease. 

Smriti: Please tell us more about the details (MOA, ROA, formulations, etc.) of IMM-ONC-01. 

Purnanand: IMM-ONC-01 is an antibody therapeutic targeting IL-38, a negative regulator of inflammation. Research suggests that expression of IL-38 reduces immune cell infiltration of the tumor microenvironment, creating a strong anti-inflammatory effect. When left unchecked, we believe IL-38 prevents our immune system from targeting tumor cells and allows for the proliferation of cancer cells.

Immunome’s data suggests IL-38 could be an important target in multiple cancer indications. We are still in the pre-clinical phase, but it is our intention to submit an Investigational New Drug (IND) application which will allow for IMM-ONC-01 to serve as an effective treatment for cancers that have a high expression of IL-38.

Smriti: Can you please share the preclinical results of IMM-ONC-01 in detail?

Purnanand: During our extensive preclinical testing we have gained a broad understanding of the relevance of IL-38 in cancer. First, we built on previously published literature that demonstrated that lung adenocarcinoma patients, whose tumors expressed high levels of IL-38, had poorer outcomes. This finding drove us to find out more about what other cancer subtypes express IL-38. 

In our most recent preclinical studies, we used a proprietary commercial database of over 60 cancer subtypes established by Tempus Labs to conduct an extensive expression profile assessment of IL-38 mRNA and learned that IL-38 is highly expressed in multiple cancer types with high unmet need, including Gastroesophageal Squamous Carcinoma, Head and Neck Squamous Carcinoma and Lung Squamous cancer. Additional preclinical testing has shown that treatment with our IL-38-targeting antibody, IMM-ONC-01, could lead to reduced tumor growth. IMM-ONC-01 also appeared to induce anti-tumor memory in a subset of animals and may therefore be able to restore and sustain an immune response in patients with these hard-to-treat cancers. 

Smriti: Shed some light on your collaboration with Fox Chase Cancer Center. How will this collaboration support the next steps in the development of IMM-ONC-01?

Purnanand: Our collaboration with Fox Chase Cancer Center is expected to allow us to build on our preclinical results by directly measuring IL-38 protein in patient tumors to confirm its prevalence in specific cancer types. The results will allow us to better identify the patient populations most likely to respond to treatment with IMM-ONC-01 so that cancer patients who stand to benefit most can receive our treatment faster.  

Smriti: Give our readers a brief overview of Immunome’s plans to proceed with its IND application and clinical trials of IMM-ONC-01. 

Purnanand: We are completing the safety, pharmacology and manufacturing data required to submit an IND to the FDA. As previously mentioned, the tumor data we are generating through our strategic partnerships has allowed us to refine our initial clinical testing plans in specific cancer subtypes. Based on that data and the results of our Phase 1 study, we will identify the relevant patient populations for our later stage clinical trials. We look forward to providing further information as the program progresses.  

Smriti: What other targets is Immunome pursuing in oncology and how do you plan to use Immunome’s  technology platform to identify future treatment options? 

Purnanand: Our pipeline of oncology treatments is continually evolving and includes multiple undisclosed targets that could be addressed through antibody therapeutics and/or antibody-drug conjugates (ADCs), an area that has gained renewed attention in oncology research. We are continually conducting function-based screening of memory B cells derived from patients and expect to identify additional antibody-antigen pairs that could lead to new treatments for people with a broad array of difficult-to-treat cancers. 

In parallel with our oncology pipeline, we are developing a COVID-19 antibody cocktail, IMM-BCP-01. IMM-BCP-01 consists of three antibodies, each with a different mechanism of action, and is designed to target distinct, non-overlapping epitopes of SARS-CoV-2 to neutralize the virus and initiate multiple viral clearance mechanisms simultaneously. We recently published research in Science Immunology describing how the antibodies in our cocktail stand up to current variants and were identified by interrogating the memory B cells of recovering COVID-19 patients. IMM-BCP-01 is being evaluated in a Phase 1b trial with topline data expected by the end of this year. 

Source: Canva

About the Author:

Purnanand Sarma serves as the President and CEO of Immunome. Dr. Sarma has 25+ yrs of experience in pharmaceutical industry business across multiple R&D platforms, ranging from venture-backed biotechnology start-ups to large cap pharmaceutical companies. He earned his PhD in Pharmaceutics from the University of Minnesota and B. Pharm from Andhra University, Visakhapatnam, India. Sarma also serves as an independent Board member at Vaxess Technologies Inc.

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