In this interview, we speak with Carter Keller, CEO at GigaGen, about their innovative recombinant polyclonal antibody therapy, GIGA-2339, and its potential impact on treating chronic Hepatitis B Virus (HBV). They delve into the unique mechanism of action, the design of the upcoming Phase 1 trial, potential challenges, and future applications of GigaGen’s platform.
Moe Alsumidaie: Can you explain the unique mechanism of action of GIGA-2339 and how it differs from existing HBV therapies?
Carter Keller: GIGA-2339 is the first recombinant polyclonal antibody therapy for the hepatitis B virus surface antigen. Unlike existing therapies, our mechanism of action is entirely different. We have a mixture of over 1,000 antibodies, each targeting the hepatitis B virus. This diversity is enabled by a proprietary platform we’ve developed over the last 13 years, combining microfluidics, genomics, molecular engineering, and manufacturing know-how. Our therapy is more than 2,000 times more potent than polyclonals derived from human plasma, offering hope for meeting the high unmet needs of patients with chronic hepatitis B.
Traditional monoclonal antibodies involve trillions of copies of a single clone, whereas our approach uses thousands of clones. This polyclonal mixture is derived from the best responders to the hepatitis B vaccine, ensuring a robust and diverse immune response. This novel approach sets us apart from current HBV therapies and represents a new way to treat diseases in general.
Moe Alsumidaie: Can you describe the design of the upcoming Phase 1 trial? What’s the primary objective?
Carter Keller: Our Phase 1 trial, the first for a recombinant polyclonal for HBV, focuses on safety and tolerability, as well as pharmacokinetics. Unlike many Phase 1 trials, we will move directly into patients with chronic hepatitis B. This allows us to observe markers of chronic infection and assess how our potent polyclonal therapy impacts these patients. We aim to see dramatic decreases in virus levels and surface antigens.
Specifically, the trial will include single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. By working closely with the FDA, we have designed the trial to ensure we gather comprehensive data on how the therapy behaves in the human body. This approach accelerates the development process and provides early insights into the therapy’s efficacy in real-world conditions.
Moe Alsumidaie: What potential challenges might you see in the clinical trial phase, and how does GigaGen plan to address them?
Carter Keller: One challenge is the immune system’s response in patients with chronic infections, which can be compromised. We are exploring combination strategies to support the immune system if needed. However, based on our observed potency, we hope our therapy will show significant results as a single agent. Chronic HBV patients often have a “tired” immune system due to the prolonged infection, which could potentially impact the effectiveness of our therapy. We are considering combination therapies that could enhance the immune response to address this. However, our preclinical data showing more than 2,000 times greater potency than plasma-derived polyclonals gives us confidence that GIGA-2339 can make a significant impact.
We’ve been working with the FDA since 2016, addressing concerns and ensuring our product’s safety and efficacy. Our collaborative approach has led to the FDA granting us the go-ahead for clinical trials. The FDA has been open to understanding our control over product and manufacturing processes, which has been crucial for our progress. Our ongoing dialogue with the FDA has allowed us to address potential concerns early on. This proactive approach has been instrumental in gaining regulatory approval for our clinical trials. By demonstrating the quality and consistency of our manufacturing process, we have built a strong foundation for future regulatory interactions.
Moe Alsumidaie: How does the potency of GIGA-2339 translate into clinical efficacy, and what specific biomarkers or clinical outcomes are you focusing on in your trial?
Carter Keller: The potency of Gigagen GIGA-2339 has been demonstrated both in vitro and in vivo. We’ve seen significant reductions in surface antigen levels and virus in preclinical models, giving us hope for achieving functional cures. We aim to differentiate ourselves from nucleoside analogs and other current HBV treatments by achieving higher functional cure rates. In our preclinical studies, GIGA-2339 has shown the ability to significantly reduce HBV surface antigen levels, a key marker of chronic infection. By targeting multiple epitopes on the virus, our polyclonal therapy can potentially prevent the virus from escaping immune detection, leading to more effective and durable responses.
We have extensive experience with antibody therapies. We start with low doses and increase slowly, monitoring for any off-target effects. We are paying close attention to all markers to ensure the safety of our product. Our phased dosing approach allows us to monitor patients carefully for adverse reactions. We can identify and address potential safety concerns early by starting with low doses and gradually increasing them. This methodical approach ensures that we prioritize patient safety while gathering valuable data on the therapy’s effects.
Moe Alsumidaie: How do you plan to scale up manufacturing if you progress into later stages, and what steps are you taking to ensure consistency and cost-effectiveness in large-scale production?
Carter Keller: Our expertise in manufacturing is a key strength. We’ve shown that a controlled, scalable process for thousands of antibodies is possible. We use CDMOs familiar with monoclonal processes and make necessary adjustments for polyclonal production. We are confident in our ability to scale up to meet the needs of the 300 million patients with chronic HBV. Our manufacturing process leverages existing monoclonal antibody infrastructure, making it easier to scale up production. Working with experienced CDMOs ensures that our process remains consistent and cost-effective, even at larger scales. This approach not only streamlines production but also ensures that we can meet the high demand for our therapy.
Moe Alsumidaie: What factors are you considering for payer reimbursement to ensure your product is covered by CMS, private payers, and patients?
Carter Keller: Hepatitis B is an urgent situation with significant patient needs. If we achieve functional cures, the value we provide will be clear. Given the large patient population and unmet needs, we are looking at precedents in other medical advances and believe there is space for us to play from a value perspective. The success of hepatitis C treatments has shown that payers are willing to cover therapies that offer significant clinical benefits. By demonstrating the efficacy and long-term benefits of GIGA-2339, we aim to build a strong case for reimbursement. Our focus on addressing a high unmet need and improving patient outcomes will be key factors in our discussions with payers.
Moe Alsumidaie: Besides HBV, are there other infectious diseases or conditions that GigaGen’s recombinant polyclonal platform targets for future development?
Carter Keller: Yes, infectious diseases are a primary focus at GigaGen. We’ve announced a partnership with the DoD for botulinum toxin and aim to be the go-to platform for pandemics and biothreats. We’re also developing therapies for primary and secondary immune deficiencies, targeting threats like Haemophilus, Streptococcus pneumoniae, and antibiotic-resistant bacteria. Beyond infectious diseases, we’re exploring autoimmune issues, immune dysregulation, and oncology.
During the COVID-19 pandemic, monoclonal antibodies faced challenges due to genetic and antigenic escape. Our polyclonal approach, which mimics the body’s natural response to infections, could offer a more robust and adaptable solution. Additionally, our work with the Department of Defense on botulinum toxin showcases the platform’s versatility and potential for addressing various biothreats.
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.
