Beyond Engineered Antibodies: Harnessing The Natural Human Repertoire
A conversation with Srikanth Pendyala, MD, chief medical officer, Infinimmune
Every person generates 100 billion antibodies per day, continuously stress-tested against the environment and refined by evolution. Each human performs 1,000x more discovery throughput than the most advanced biotech platforms today.
Rather than engineering antibodies from scratch, Infinimmune starts with antibodies already produced naturally by the human immune system, using its platform to identify highly functional human-native antibodies directly from memory B cells.
In this Q&A, Life Science Connect’s Morgan Kohler caught up Srikanth Pendyala, MD, chief medical officer of Infinimmune, to discuss the importance of learning directly from the human immune system itself in antibody research.
Why might the future of immunology depend on more human-native antibody discovery approaches?
The human immune system is arguably the most powerful drug discovery engine ever created. It has been refining antibodies through natural selection for hundreds of millions of years, generating molecules with exceptional specificity, potency, and safety characteristics.
Historically, the industry has relied heavily on animal models, synthetic libraries, and engineered systems to discover antibodies. Those approaches have delivered important medicines, but they only capture a fraction of what human biology is capable of producing.
At Infinimmune, we start with antibodies discovered directly from humans. By studying millions of memory B cells and naturally occurring immune responses, we're able to uncover antibodies and biological mechanisms that traditional approaches may never find.
We believe the future of immunology will increasingly involve learning directly from the human immune system itself. Human biology has already solved many of the problems we're trying to address therapeutically. Our job is to identify those solutions and translate them into medicines.
You've worked extensively on inflammatory disease therapies over the course of your career. What are the most important and surprising things you've learned and witnessed during those 25 years?
The biggest lesson is that biology is always more complex, and more interesting, than we expect it to be.
When I entered the field, many people believed we would eventually pin down a handful of key inflammatory pathways and effectively solve most immune-mediated diseases. Instead, we've learned that diseases such as atopic dermatitis, inflammatory bowel disease, and rheumatoid arthritis are highly heterogeneous, involving multiple overlapping biological mechanisms.
That leads us to the second lesson: patient biology matters enormously. Some of the most successful therapies have come from following human biology rather than forcing the data to fit a preconceived hypothesis.
Perhaps the most surprising realization is how much biology remains unexplored. Even after decades of progress, we're still discovering entirely new immune pathways, antibody architectures, and mechanisms of disease. That gives me tremendous optimism for what the next 25 years will bring.
Can you tell me about the evolution from engineered antibodies to naturally occurring human antibodies?
The field has evolved through several generations. The first generation involved mouse-derived antibodies that required significant engineering to be clinically useful. The next generation focused on fully human antibodies generated through display technologies and transgenic platforms.
Today, we're entering what I view as the next chapter in antibody development: discovering antibodies that already exist within the human population and have been naturally optimized through immune selection and maturation.
What's exciting is that advances in single-cell sequencing, computational biology, and AI now allow us to interrogate human immune repertoires at unprecedented scale. Infinimmune has analyzed millions of human memory B cells and observed millions of naturally occurring antibodies, revealing forms of antibody diversity that were previously unknown.
Instead of asking what antibody we can engineer, we're increasingly asking what antibodies human biology has already discovered.
How is antibody discovery changing in the AI and computational biology era?
AI is fundamentally changing how we understand and navigate biological complexity.
The current challenge in antibody discovery is extracting meaningful insights from enormous biological data sets. AI allows us to identify patterns across millions of antibody sequences, predict functional properties, and optimize molecules far more efficiently than was previously possible.
At Infinimmune, we've built an antibody language model trained on proprietary human antibody data sets. We use it to improve potency, manufacturability, formulation characteristics, and developability while preserving the advantages of human-native biology.
Importantly, AI doesn't replace biology. The most powerful combination is human biology plus computational intelligence. The future belongs to companies that can unite unique biological data sets with advanced AI capabilities to discover medicines that would otherwise remain hidden.
What differentiates next-generation immunology companies in an increasingly crowded landscape?
The next generation of immunology companies won't be defined by any single drug candidate. They'll be defined by something harder to replicate: the ability to uncover novel biology repeatedly and to translate it reliably into therapeutics. In my view that comes down to three capabilities:
- access to unique biological data
- the computational tools to make sense of it
- the discipline to execute in the clinic.
At Infinimmune, our differentiation starts upstream of all of that, with a human-first discovery engine. We discover antibodies directly from human immune systems, which lets us see biology that platforms built on animal models or synthetic libraries simply can't access. We then pair those insights with AI-driven optimization through our platform and focus the pipeline on high-value inflammatory and immunology targets.
The clearest signal that the approach works is the interest it's drawing from partners. Earlier this year we announced a multi-target antibody discovery collaboration with Merck. This indicates to us the industry's growing conviction in human-native antibody discovery. But the goal was never to develop a handful of medicines. It's to build a discovery engine that can generate a continuous pipeline of differentiated therapeutics.
Ultimately, the companies that lead the next era of immunology will be the ones that can see biology others can't and turn what they see into real benefit for patients.
About The Expert
Srikanth Pendyala, MD, is chief medical officer of Infinimmune, where he leads clinical development and regulatory strategy across the company’s pipeline, including the advancement of IFX-101 and IFX-201 into the clinic. He brings more than 25 years of experience developing therapies for immunology, inflammation, fibrosis, respiratory, dermatology, and rare diseases. Prior to Infinimmune, Pendyala served as chief medical officer at several biotechnology companies, including Endeavor Biomedicines, and held senior clinical development roles at BridgeBio, Theravance Biopharma, Merck, and Roche/Genentech. He completed fellowships in allergy and immunology at Johns Hopkins University and The Ohio State University and has authored more than 30 peer-reviewed publications.