Today we are launching Ormoni Biosciences to industrialize peptides. Ormoni started with a question: what would it take to accelerate peptide drug development 100X, to a single design cycle? That is, what if we could investigate thousands upon thousands of drugs in vivo all at once, train machine learning models on the outcomes, and then generate therapeutic peptides ready for human trials? My cofounder Brad Pentelute and I have spent the past year building the answer.
I began my career as a peptide engineer, designing de novo peptides during my doctorate at MIT. I then spent a decade at Flagship Pioneering learning a different craft - how to transform biotechnology innovations into groundbreaking companies like Inari Agriculture and Sail Biomedicines. The biggest opportunities arise when divergent scientific breakthroughs become integrated and engineerable. When I joined Pillar VC, I was looking for exactly that scientific intersection. When I met Brad, I found it.
Brad is the pioneer for peptides, an MIT chemistry professor with over 150 peer-reviewed papers and over 10,000 citations across peptide chemistry, analytics, drug development, and machine learning. While the impact of peptide therapies is now clear in the wake of drugs such as Ozempic and Mounjaro, the development of such molecules has historically been a slow, artisanal process. Brad and I jointly recognized that the tools to industrialize peptide development – pooled chemistry, in vivo analytics at scale, and machine learning fueled by millions of data points – already existed. Integrating them was the opportunity.
And so we built Ormoni, to industrialize peptides.
A trillion-dollar bottleneck
In the summer of 1983, Graeme Bell published a string of thirty-one letters destined to upend the healthcare industry. Bell and colleagues defined a small family of endocrine peptides – shortish strings of amino acids – and included the sequence of a molecule they named Glucagon-Like Peptide 1, or GLP-1. In the decades that followed, thousands of biochemical doppelgangers were synthesized, tested, and iterated upon to “drug-ify” this molecule. GLP-1 analogues became more stable, circulated longer, and eventually demonstrated levels of weight-loss that would change the lives of millions of patients. In 2022, nearly forty years after Bell’s publication, the FDA approved tirzepatide – as Mounjaro and then Zepbound – now the best-selling pharmaceutical product in history. Ormoni stands on the foundation of such extraordinary chemistry from Novo Nordisk, Eli Lilly, and other laboratories around the world.
But why are there not more peptide therapies? Why did tirzepatide take nearly forty years? And what is Ormoni doing differently?
Drug development is fundamentally a multi-property optimization exercise. Chemists develop peptides stepwise, empirically, starting with the easier properties such as target binding and saving the hardest problems for last. Eventually the properties require animal experiments, and the cycle slows severely. Many programs die at the in vivo stage. Any peptide that succeeds in this setting, that is successfully optimized across the litany of required properties, represents many years of trial-and-error across thousands of individual chemical syntheses of peptide candidates.
Peptide therapies, industrialized
And so after those forty years, tirzepatide was approved, the 7,023rd peptide molecule in Eli Lilly’s GLP-1 portfolio.
In our first year of operation, Ormoni has synthesized and assayed over 250,000 unique peptides. We have built an engine to solve the myriad properties critical for drug success – in months, rather than decades. And we are doing so for diverse disease areas where peptides promise to help millions upon millions of patients.
Ormoni’s unique approach to developing peptides is built on three principles:
- We optimize drug properties in parallel, from the start. We define a product profile and test all key properties upfront, rather than saving the harder (more valuable) properties for last.
- We experiment where it matters. For some drug properties, that’s a highly precise in vitro measurement. But the most important properties require costly animal experiments. Circulation half-life, oral uptake, biodistribution – these have no shortcut. And so every peptide we make, we make for in vivo experiments, again from day one.
- We operate at scale, at pace. Experiments are conducted at a 1,000-plus peptide throughput, a number that will continue to grow. Furthermore, Ormoni executes a 30 day cycle time, from start-of-synthesis to a full drug profile for a set of thousands of peptides.
We have established a fundamentally different process for developing peptide therapies, akin to deploying the first highly parallelized GPUs while the rest of the industry remains reliant on serial-processing CPUs.
Ormoni’s novel pooled capability yields exponentially growing datasets to train our proprietary ML models. With this approach, we can tune key PK/PD properties by several orders of magnitude each. This is where scale and pace of data generation enable rapid design-ability, and where the platform flywheel compounds our advantages iteration by iteration. Every program teaches the next: our vision is blockbuster after blockbuster, each one accelerating the program that follows.
The Inflection Point
Returning to the GLP-1 analogues offers key lessons for those of us designing the next wave of therapies.
- Market sizes will cross $100B when a therapy improves chronic conditions that millions of people feel on a day-to-day basis. And customers will eagerly pay $1000 or more a month out-of-pocket when the molecule works well, for both FDA-approved and “grey market” peptides.
- Peptides are a uniquely potent therapeutic technology. They evolved as agonists, turning biology on. The antibodies and small molecule inhibitors which comprise the large majority of today’s drug landscape are antagonists, meaning they merely slow biology instead. Peptides can easily be designed for agonism or antagonism.
- Pharmacokinetics is underappreciated. The first GLP-1 drug approved was exenatide, which improved the half-life of native human GLP-1 from two minutes to two hours, but still required two injections per day. The peak sales for exenatide were a little over $1B. When semaglutide extended that half-life to ~168 hours, or a full week, not only did it enable a more convenient therapy. It dramatically, non-linearly increased efficacy and 100X’d the market for the drug class.
We are at a historic inflection point in drug development and for the broader health economy. The GLP-1 analogues demonstrated the tremendous value a carefully crafted peptide therapy can achieve, and many more peptides are filling pipelines from discovery to commercialization.
- The hottest (literally) oncology drugs are peptide radioligand therapies, such as Novartis’ Lutathera. And in the years to come, peptide-drug conjugates will replace antibody-drug conjugates, the oncology darlings of recent years with tens of billions of dollars in deal value.
- Protagonist and J&J recently launched Icotyde, a peptide that blocks IL-23 signaling, similar to antibodies Skyrizi and Tremfya (>$20B annual sales cumulatively). But as a peptide Icotyde can be given as a pill, whereas the antibodies require an injection.
- Merck’s enlicitide, which blocks PCSK9 for high cholesterol, similarly offers a massively high-upside daily pill to replace injected biologics already selling billions annually.
- Heart failure and hypertension also have revolutionary peptide drugs in clinical trials, as does neurodegeneration.
Obesity, cancer, cardiology, neurodegeneration: across the most foundational areas of health and disease, peptides will transform patients’ lives. These are each markets measured in the $100Bs, and markets Ormoni’s platform is uniquely suited to address. We are catalyzing the peptide industrial revolution by transitioning from one-by-one chemical craftsmanship to speed, scale, and precision. And it’s working: already we can go from idea to development candidate-quality molecules in months.
Forty years ago, Bell handed us thirty-one letters. We have read out millions in our first year, just the start of our quest to create better peptides, faster. We will have more to say about each of these areas in the weeks and months ahead. If you are an investor, a partner, or a scientist who wants to help build the industrial era of peptide medicines, we want to hear from you. This is just the beginning and we hope you will join us.