GigaGen Inc has announced the dosing of its first patient in a Phase 1 clinical trial investigating GIGA-2339, a recombinant polyclonal antibody for the treatment of chronic hepatitis B virus (HBV) infection. The trial will assess the safety and tolerability of the drug, which holds a potential functional cure for chronic HBV.
Current treatments for chronic HBV can suppress viral replication but do not offer a cure. It remains a global health threat, affecting over 296 million people worldwide and causing more than 800,000 deaths each year. GIGA-2339 is designed to target the Hepatitis B surface antigen (HBsAg), a key protein that facilitates viral replication, potentially allowing for viral clearance and long-term immune system activation.
Developed using GigaGen’s innovative recombinant polyclonal antibody platform, GIGA-2339 combines over 1,000 fully human antibodies targeting HBV, providing a highly potent and diverse treatment option. The drug is over 2,000 times more potent than existing therapies and aims to tackle a broad range of circulating HBV variants, including potential escape mutations.
In an exclusive interview, Carter Keller, senior vice president at Grifols and Head of GigaGen, shared his excitement about the trial’s launch and the drug’s potential to address the challenges of chronic HBV.
“We’re really excited. We just announced that we’ve dosed our first patient in our Hepatitis B trial,” Keller said. “The Hepatitis B trial is for a product called GIGA-2339. This is a mixture of thousands of different antibodies made recombinantly. They’re human antibodies, all targeted towards the Hepatitis B surface antigen, and it really represents a new way to treat the disease. We’re really excited to see how it performs in the clinic.”
GIGA-2339 is unique in that it uses a polyclonal approach, meaning it includes multiple antibodies that target different parts of the virus. Keller explained how this could offer advantages over existing therapies.
“We have a unique platform that allows us to take the best human immune systems, extract the genetic components of those immune systems, and recombinantly reproduce them,” he said. “We can then select the antibodies that are directed towards the virus or viral target we’re interested in. This is a very unique way to treat disease, nobody’s ever done it like this before.”
The approach allows for a diverse and multifaceted immune response. “The fact that we have thousands of different antibodies against Hepatitis B antigens means we can target multiple epitopes of the HBV. By coating the surface of the virus and viral particles, we can mount a highly efficient immune response to clear the virus,” Keller added.
Moreover, this diversity of antibodies allows GIGA-2339 to target all HBV genotypes and tackle potential escape mutations that can arise during treatment. “Having thousands of antibodies against different epitopes allows us to target all genotypes of the virus. This means we won’t miss patients with different or diverse genotypes. It also helps us address any potential escape mutations that might arise during treatment.”
Focus on Safety and Efficacy in Phase 1 Trial
The Phase 1 clinical trial is primarily focused on determining the safety and tolerability of GIGA-2339 in individuals with chronic HBV who have not responded to previous nucleoside analog therapy. Keller explained that this study differs from typical Phase 1 trials, which are often conducted in healthy volunteers.
“We’re definitely interested in determining what dose is safe and tolerable for different patients. But many safety and tolerability studies are conducted in healthy volunteers. In contrast, this Phase 1 study is being done in individuals with chronic HBV. This gives us an opportunity to find a safe dose that also optimally depletes the Hepatitis B surface antigen in these patients,” Keller noted.
The goal of the trial is to find the optimal dose that can effectively reduce the levels of HBsAg, which could lead to better outcomes in later trials. “Finding the dose that optimally depletes the surface antigen will allow us to move into Phase Two clinical trials, where we can expand the patient population at that dose and better assess the drug’s efficacy in a statistically significant way,” he said.
The Path Toward a Functional Cure for HBV
A key objective for GigaGen is to explore the possibility of a functional cure for HBV. Keller explained that GIGA-2339 could offer something beyond just viral suppression.
“We have a hypothesis that if we can downregulate the Hepatitis B surface antigen, an antigen that’s known to suppress the immune system, we might be able to not only clear the virus but also reactivate the immune system,” Keller explained. “This could potentially lead to what we call a functional cure. We’re very interested to see how this plays out in our clinical trial.”
By reducing HBsAg levels, the drug could help restore the body’s natural immune response to the virus, which may lead to a sustained immune-mediated clearance of the infection. Keller referred to this as a “virtuous cycle”: “There’s this kind of ‘virtuous cycle’ where we efficiently deplete the virus, reactivate the immune system, and then the immune system helps to clear the virus.”
Keller highlighted the importance of this innovation in the context of HBV treatment and beyond. “Our platform allows us to create these incredibly diverse therapies. It’s the only platform that can do this at scale while maintaining manufacturing consistency. This gives us the ability to treat as many patients as needed,” Keller said.
As GigaGen’s clinical trials progress, the company remains hopeful that GIGA-2339 will offer a novel solution to the millions living with chronic HBV. With its unique combination of potent, broad-acting antibodies and a potential to reactivate the immune system, GIGA-2339 could play a key role in advancing the treatment landscape for chronic hepatitis B.
“We’re really excited to see where this takes us. If we’re successful in targeting the surface antigen and reactivating the immune system, we could see significant improvements for people living with chronic HBV,” Keller concluded.
Watch our previous interview with Keller to gain additional background and insights into the developments that led to this milestone: HBV Antibody GIGA-2339 Cleared for Clinical Trials to Address Hepatitis B Cure Gap
