Axial Podcast – Details, episodes & analysis

Doug Chapnick is the Co-Founder and CEO of BioLoomics. A platform company using directed evolution to discover antibody therapeutics. Combining cell line engineering, machine learning, and imaging.

At the core of BioLoomics' technology is directed evolution, a process that mimics natural evolution in the lab. The company uses this to create biologics for a given property like target engagement or stability. Traditional directed evolution relies on displaying proteins on the surface of cells or viruses and using binding or activity assays to isolate variants with enhanced characteristics. However, this approach has limitations, especially when evolving complex proteins like antibodies that require proper folding and post-translational modifications found in human cells.

BioLoomics circumvents these issues by using human cell libraries that naturally produce fully human antibodies. Their key innovation is an advanced imaging and computer vision system that can track millions of individual cells in these libraries and quantify cellular phenotypes using fluorescent biosensors. This allows them to precisely identify rare cells producing antibodies with the desired activity.

For example, BioLoomics might engineer biosensor cell lines where a fluorescent protein reports on the degradation of a specific target protein. They can then screen human antibody libraries in these cells, using computer vision to pick out the few cells that show enhanced degradation of the target compared to typical antibodies. By isolating the genetic sequences encoding these rare antibodies, they can rapidly iterate and evolve highly specific protein degraders or other therapeutic antibodies.

This live cell-based directed evolution approach has several key advantages. First, by working in human cells, BioLoomics ensures their engineered antibodies are naturally folded, glycosylated, and trafficked properly for optimal therapeutic activity. Second, the use of biosensors allows them to select for very specific mechanisms of action, rather than just binding - enabling development of precisely targeted degraders or modulators. Finally, the high-throughput nature of their platform facilitates rapid exploration of vast protein sequence landscapes to find optimal solutions.

In our conversation, we also talk about Doug’s work that set up BioLoomics. His PhD work at the University of Colorado Boulder focused on understanding cellular signaling networks and mechanisms through multi-omics approaches like proteomics and metabolomics. After, he was part of the DARPA Rapid Threat Assessment program, where he built out high-throughput microscopy workflows. Where the core idea behind BioLoomics emerged from this DARPA project. Chapnick co-founded BioLoomics in 2019 to bring directed evolution to therapeutic antibody development.

A key focus area for BioLoomics is developing novel antibody degraders that can precisely remove target proteins from cells by marking them for lysosomal degradation. While a few companies have developed degraders based on binding to specific E3 ligase enzymes, BioLoomics' platform allows them to evolve degraders that act through diverse and unexplored mechanisms not limited to any single pathway. For example, they could evolve antibodies that traffick target proteins to lysosomes through interactions with sorting receptors or endocytic adaptor proteins. Or create antibody fusions that oligomerize targets and induce their proteasomal degradation. The diversity of potential mechanisms enabled by their platform could lead to a whole new class of highly specific protein degraders for tackling undruggable targets across multiple disease areas. By combining human cell libraries, advanced imaging, computer vision, and directed evolution, BioLoomics is pioneering a new path for antibody discovery.

Evan Zimmerman is the Co-Founder and CEO of Edge, that helps patent attorneys, patent agents, and inventors make the patent process less painful and more effective.

He earned a Juris Doctor (JD) degree from the UC Berkeley Law School, where he specialized in IP law. Seeing the potential of AI to transform the patent system, Zimmerman teamed up with Len Boyette, an early employee at Okta. Together, they went through the Y Combinator accelerator program in 2022 to build Edge.

Edge's AI-powered patent assistant aims to automate and streamline every step of the patent process, from recreating patent claims from basic technology descriptions to suggesting improvements and identifying relevant prior art. This approach removes the grunt work for attorneys and patent agents while making high-quality patents more accessible for inventors and companies.

The patent system is critical for protecting inventions and stimulating innovation, but is often cumbersome for all involved. For attorneys and patent agents, the system involves painstaking hours poring over documents, extracting key technical details, and translating those details into watertight patent claims. For inventors and companies, the costs and complexities of patents can be prohibitive.

Edge aims to change all that by using AI to automate and streamline every step of the patent process. Evan describes Edge as "the ultimate patent assistant", able to recreate patent claims from basic technology descriptions, suggest areas for improvement, and more. This removes grunt work for practitioners while making high-quality patents more accessible for innovators.

Edge's product offering is centered on a patent editor and assistant app. For example, Edge generated claims mimicking those from the famous PageRank patent solely from a description of the technology, capturing nuances an inventor might have missed. Its AI also suggests ways to strengthen claims, identifies relevant prior art, and more.

Evan sees Edge as revolutionizing how patents are created and managed. For attorneys and agents, it removes the drudgery of claim drafting and prior art searching. For inventors and companies, it makes robust patents far more accessible. He sees patents as a rising tide that can lift all boats when done right. By using technology to democratize access to effective patents, Edge seeks to empower inventors.

Just as the Kitty Hawk Flyer gave rise to modern aviation, robust yet accessible patents can spur the next wave of human ingenuity.

Vikas Goyal has one of the best records in biotech having spent over 8 years at SR One partnering with companies like Nimbus and Morphic Therapeutic before joining Pandion Therapeutics (acquired by Merck) full-time after investing in it as well. Now starting Trekk Venture Parners, Vikas' story uniquely blends success across investing, operations, and company building.

Starting off his career at McKinsey, Vikas went on to work with dozens of start-ups and early-stage companies as a consultant at Extera Partners then went off to earn his MBA in healthcare management from Wharton. He started work in business development at Infinity Pharmaceuticals before joining SR One full-time after an internship there during business school.

Max Jamilly is the Co-Founder and CEO of Hoxton Farms, a London-based startup develop cultivated fat as an ingredient for the meat alternatives industry. We discuss his journey from scientist to founder starting at Oxford where Max earned his PhD in synthetic biology. Along with his work at Microsoft Research, Gen9, and in venture capital. Leading up to founding Hoxton with his childhood friend.

Rishi Bedi is the Co-Founder and CEO of Y-Trap a biotech company developing multifunctional fusion proteins for cancer immunotherapy. We discuss the founding story of Y-Trap, the current status of protein engineering and computational biology, along with his career leading up to Y-Trap. Rishi's experience spans machine learning, immuno-oncology, and drug development.

Previously, Rishi built the machine learning team at Herophilus (fka System1 Biosciences), leading the analysis of multi-omics and imaging datasets to identify deep phenotypes of neuropsychiatric diseases in cerebral organoids. Before that, he studied computer science at Stanford, where he developed machine learning methods for structural biology in Ron Dror's group.

Eric Ward is the Co-Founder and Co-CEO of AgBiome, an agtech company that analyzes crop microbiomes to develop crop protection products & traits. Founded in 2012, AgBiome has no managers; rather, the company uses committees of employees to handle core functions like business development and financials. AgBiome has built a wide-ranging platform, called Genesis, integrating plant genomics with breeding and gene editing to characterize the plant microbiome to do this. On the tools side, AgBiome has more scalable plant screening methods and a growing database of plant microbiomes. AgBiome’s work creates a pretty large database of microbes (>80K, growing by 10Ks annually) & their effects on crops. On the products side, AgBiome uses these tools to hone in on microbes with a particular activity. Leading to 2 major products: Howler and Theia (both fungicides). With this platform and a series of products, AgBiome is helping growers protect their crops from insects, fungal infections, nematodes, and disease in general.

Eric discusses his career that spans over 3 decades from serving as president of the Two Blades Foundation, a non-profit dedicated to promoting the development of durable disease resistance in crops. Prior to that he was CEO and Co-Founder of Cropsolution, an agriculture chemical discovery company focused on novel fungicides. Eric began his career at Ciba-Geigy (later Novartis, now Syngenta), where he held various positions in research management, ultimately serving as co-president of Novartis Agribusiness Biotechnology Research.

Anand Muthusamy is a graduate student at Caltech working in the Lester Lab at the intersection of chemistry and neuroscience. In our conversation we discuss his journey starting at Penn where he studied biochemistry with a strong grounding in philosophy. Working in the Petersson lab, focused on unnatural amino acid mutagenesis to control enzyme function and organic synthesis for the development of fluorescent probes, set up Anand to work under Luke Lavis at Janelia.

While at Janelia, Anand used synthetic organic chemistry to make molecular probes often having application for imaging in neuroscience. We talk about his current work in the Lester lab as well as his entrepreneurial ambitions and more.

Melih Yilmaz is a PhD student at the University of Washington. Where he focuses on computational biology and develop machine learning tools. Advised by William Noble and Sewoong Oh, Melih's current research interests are around proteomics, particularly building deep learning methods to analyze mass spectrometry data.

We start off the conversation talking about his journey to biology and consequently the United States. Around 2016-2017, deep learning had began to gain pace, drawing Melih in. Around the same time, peers of his were going to the US. Slightly influencing Melih to land a research internship at Stanford with Tina Hernandez in the biomedical informatics department.

He then entered a PhD program at Washington after several other internships. We go into various experiences of Melih's as an engineer in biology. Expanding on his work in protein sequencing.

Peter Turnbaugh is a professor at UCSF studying the human microbiome’s effect on pharmacology and nutrition. In our conversation, we discuss his journey to become a scientist and help pioneer the microbiome field starting in graduate school. We talk about his research as a fellow at Harvard then professor at UCSF, and his lab’s current work. A key theme across the conversation is learning by doing.
Peter’s work has been anchored around predicting and controlling the metabolism of complex microbial communities. Going to a liberal arts college, Whitman College, Peter gravitated more to science because the grades seemed more objective. An experience in a stem cell lab helped Peter learn that science is not just a series of facts and helped spark him to apply to a PhD program. He applied to a bunch of schools, getting rejected by many of them like UCSF, and got into 2 programs. Peter ultimately chose to attend WUSTL. This might have been one of the best, and luckiest, decisions Peter made.

Washington University in St. Louis was an epicenter for the Human Genome Project and is a hotbed of genomics/bioinformatics talent. Going in his rotations, Peter was excited about genomics and wanted to work on more computational problems. He ended up joining Jeffrey Gordon’s lab, a legend in genomics. Jeff gave Peter the nickname, “Professor,” almost foretelling his future. Ruth Ley had also just joined the lab as a postdoctoral fellow after working with Norman Pace and wanted to study microbes across mammals. She had gone to the St. Louis Zoo to collect samples. On Peter’s first day in the lab, the fridge was full of wild animal poop to study. At the time metagenomics was not widely accepted - many genome scientists thought microbial communities would be impossible to understand.

This is around 2004 and there wasn’t a checklist to follow. Peter, Ruth, and the lab had to not be shy to ask for help in order to pioneer a new field of the human microbiome. This ultimately led to 2 papers in 2006 that established gut microbes associated with obesity.
After writing up his thesis, Peter wanted to “keep going as far as he can go” with science. He became a Bauer Fellow at Harvard, rejected by UCSF again during this process, and was excited to start his own lab. Similar to his grad school research, Peter learned by doing to build a lab. The lab’s initial idea was to switch from studying host-associated microbes' role in diet to pharmacology. Xenobiotics seemed “really weird” and an open field to study. A 2013 paper showed how diet can alter the human microbiome, where the lab had to run the trial themselves - feeding participants a veggie or meat-only diet over 5 days. This type of work helped Peter finally get into UCSF and become a professor.
The next skill he had to learn while doing was grant writing. Up until then, Peter had only written grad school applications and a 3-page proposal to Harvard that gave him 5 years of guaranteed funding. At UCSF, he’s built a highly successful group leading the way on the study of the human microbiome and how it intersects with diet & pharmacology. He’s expanded to work on CRISPR/phage research now, and excited to see how that thread grows over the next few years. Looking back, Peter has gained a greater appreciation for the community, something his grad school mentor, Jeffrey Gordon had emphasized. Just as much as multiple genes affect something like height or a disease, it’s important to go beyond a single microbe causing a phenotype.

In our conversation with Wyatt McDonnell, the Co-Founder and CEO of Infinimmune, we discuss his journey to 10X Genomics, his work there, and the founding of Infinimmune. Wyatt is a world-class inventor & immunologist working across a wide range of projects at 10X from launching BEAM (barcode-enabled antigen mapping), working on the Immune Profiling v2 product, and developing various immune repertoire technologies. After making a significant impact on 10X, Wyatt along with 4 other colleagues that had worked together founded Infinimmune to transform human antibodies into drugs.

A key theme of the conversation is that tool users greatly outnumber tool builders. This creates an opportunity for the latter to build applications before others. Infinimmune is hiring across business, engineering, and biology roles. And is a home for tool builders. Please get in touch via founders@infinimmune.com if you're interested in applying your expertise to the next generation of antibody therapeutics.

Wyatt got his first exposure to science from a Breaking Bad consultant that showed him a redox reaction. To Wyatt, it was like “watching alchemy unfold.” He went to Hillsdale, a small college in Michigan where the largest science class had 60 people. This intimacy played a key role in Wyatt’s development and allowed him to speed up his education. He thrived in organic chemistry as a freshman and worked with Frank Steiner, taking 4 of his classes and working in his lab where Wyatt caught the research bug. He had been thinking about medical school but decided to go to Vanderbilt for a PhD program focusing on immunology & precision genomics.

While in graduate school, Wyatt saw 10X Genomics’ Chromium products taking off. People were coming back to use their instruments, something that is pretty rare in scientific research. This motivated him to apply to 10X and end up joining them to build solutions on top of Chromium. Coming on board in the summer of 2019, the first 90 days were spent figuring things out. Wyatt worked on a wide range of projects, and a key reason was his immunology expertise. He had a strong knowledgebase on TCRs, which was pretty rare at 10X at the time, allowing Wyatt to work across divisions. For example, he got to work with David Jaffe, a co-founder of Infinimmune, on the Enclone project. For Wyatt, working at a market leader like 10X was the perfect example to follow when he built his own startup.
After leaving 10X Genomics in the summer of 2022, Wyatt started Infinimmune with people he had worked with at 10X. The company is built with a strong conviction around 3 pillars:

1. We still don’t understand immunology that well

2. Adoption of immunology tools has been too slow

3. The best antibodies come from humans

The platform is centered on analyzing healthy & disease samples to uncover rare, human antibodies. This requires deep analytical expertise, at the raw sequence read level, to maximize the value from sequencing samples. Infinimmume is building the toolkit to discover effective antibodies from patients that might have survived cancer or have protective genes against Alzheimer’s. On this point, for Wyatt, “platforms are only as good as the assets they produce.” Wyatt and the founding team are setting the foundation of the company right now to scale up partnerships and drug development over the next 2 years. Excited to get the update from Wyatt then.