Exploring the Human Body’s Own Drug Library

In the bustling labs of Infinimmune east of San Francisco, a revolutionary idea has taken shape: that within each human lies a treasure trove of potential antibody drugs waiting to be discovered. Every day, within our own bodies, nature orchestrates the equivalent of 100 billion antibody clinical trials, showcasing the ingenuity of our immune system’s response to potential threats. Infinimmune is harnessing this phenomenon in research to unlock and deploy protective antibodies as antibody therapeutics, with AVITI™ emerging as an indispensable tool in this quest.

“We started Infinimmune because we saw a huge opportunity to develop drugs that have already been validated for their safety and efficacy inside the human body,” said Wyatt McDonnell, a co-founder of Infinimmune and the company's CEO.

Humans have known about the power of the immune system since the time of the ancient Greeks, when Thucydides wrote about the plague in Athens. Since the discovery of antibodies over a century ago, antibody-based drugs have emerged as formidable weapons in the fight against diseases, notably cancer. Yet, despite this wealth of knowledge, the process of discovering effective therapeutic antibodies remains inefficient—and the drug discovery process contains many traps that can waylay a promising antibody drug candidate. Animal models—the workhorse of developing antibodies and other therapies—often do not provide a clear path to successful drug discovery, due to complex differences in how animals process proteins and other molecules.

In the current approach to antibody research and development, scientists test drugs that bind to a target without necessarily knowing if the target is a good one. Then, even if the target turns out to be relevant, the drugs themselves may not be effective in humans, even if they work in animal models of a given disease. Moreover, today’s technologies frequently produce antibody drugs for humans from transgenic animals or microbial systems.

Infinimmune wants to bring safer and more effective antibody medicines to the clinic by using completely human-derived antibodies, which would bring multiple advantages. These antibodies are less likely to trigger immune reactions when given to patients because the immune system already recognizes them as ‘self’. This reduces the risk of adverse reactions and improves safety and efficacy by minimizing damage to healthy cells and tissues—in part because these antibodies have already been “tested” inside a human body already. This approach also has potential to help discover novel, biologically important targets and improve matching of patient populations to immunotherapies.

“We believe that every company should be screening human antibodies to find new medicines for humans,” McDonnell.

Enter AVITI—a critical component of Infinimmune’s discovery research workflow.

“This is our bread and butter of how we find drug candidates every single day,” McDonnell said. “AVITI is, in one word, incredible. AVITI gives us NovaSeq-level pricing at NextSeq-level throughput, with an excellent yield of ultra-high-quality reads.”

For a company focused on sequencing only the cells that matter the most, affordable sequencing no longer must come at huge scale. The higher quality of avidity base chemistry is already helping Infinimmune researchers get farther with fewer reads.

“We are able to get more cells onto the instrument, we are able to recover more antibodies, and we are able to run our platform on larger numbers of samples,” McDonnell said. “That’s all hugely helpful in making our sequencing operations and our discovery campaigns more efficient.”

The team has already discovered new protein sequences in the Fc region (the antibody’s tail section that connects with cellular receptors and confers functional activity) that are relevant to engineering better antibody drugs, as the technology they’ve developed analyzes antibodies from the body directly rather than from a display library or a transgenic mouse.

“We found a massive amount of diversity in the Fc region. We are sitting on thousands of new coding, protein sequences of Fc. Wow!” McDonnell said. “We can observe this variation even with relatively shallow sequencing of a small number of humans. And sequencing the antibody regions with AVITI helped us identify this diversity.”

Infinimmune announced a partnership with Grid Therapeutics earlier this year to identify new drug candidates for non-small cell lung cancer using Infinimmune's Anthrobody™ drug-discovery platform and its Complete Human™ immunosequencing technology.

What inspires the team at Infinimmune is a combination of personal experiences and a profound sense of purpose. McDonnell and his fellow antibody drug hunters met while working at 10x Genomics. Having witnessed the toll of aggressive pediatric lymphoma, Huntington’s disease, rheumatoid arthritis, and chronic viral infections within his own family, McDonnell was driven by a determination to alleviate suffering and pave the way for a brighter future. The team also saw a clear opportunity to apply high-quality technology that traditional pharma and biotech companies have been slow to adopt.

“The reason people don’t develop autoimmune disease and cancer more often,” he said, “is that our immune systems do a wonderful job keeping these things at bay for decades at a time. And we need to learn what antibodies are responsible and then bring them to others.”

“Over time, we should be able to read out patients' immune systems as part of how you match the patient to the immunotherapy they receive, while ensuring that they receive extremely safe and extremely potent antibody therapy. That is the long-term future we would love to see.”