Investing in Stipple Bio
a16z invests in Stipple Bio
America | Tech | Opinion | Culture | Charts
We must search for magic bullets…We must learn how to aim chemically.
- Paul Ehrlich (1908)
Paul Ehrlich’s dream was not merely to kill disease, but to “aim chemically”: to separate efficacy from collateral damage, and in doing so define the earliest intuition behind what we now call “therapeutic index” in drug development. More than a century later, oncology therapeutics have made that aspiration real in waves: from blunt cytotoxics, to targeted small molecules, to antibodies and now CAR-Ts, T-cell engagers, radiopharmaceuticals, and antibody-drug conjugates. Each modality aims to concentrate potency where it belongs and spare healthy tissue where it does not. They are modern descendants of Ehrlich’s “magic bullet” concept, pairing tumor specificity with powerful cell-killing.
But hard problems in oncology have not disappeared; they now just demand even more precision. Many biologic drugs for cancer have delivered groundbreaking clinical wins (from Herceptin to Enhertu in HER2+ breast cancer, for example), but dose-limiting “on-target, off-tumor” toxicities still too often limit how much drug can actually be delivered to a patient. And while we rejoice upon seeing tumor shrinkage in our cancer patients, we also ask them to endure a painfully wide range of adverse effects to achieve this goal: cytopenias, immunosuppression, neuropathy, pneumonitis, ocular inflammation, skin toxicity…to name a few. In the real world, these toxicities cause dose interruptions, discontinuations, even unfortunate deaths. And these are just the drugs we approve; for every drug approved, many others have failed in clinical trials – often due to a therapeutic window that simply proved too narrow.
This is why we got excited about Stipple Bio. From the very beginning, scientific co-founders Aaron Ring and Aashish Manglik said they wanted to go after novel tumor biology — not something most seed-stage biotechs say. And they framed novelty at the level of epitope resolution. With the right tools for inquiry, they proposed, tumor-specificity could be defined not just at the RNA level, not just at the protein expression level, but at the level of specific epitopes. They wanted to ask: what are the epitopes that are uniquely presented on tumor cells, in unique tumor-specific conformations, or via unique post-translational modifications? Over the last few years, the Stipple team has built a high-throughput, experimental “epitomics” platform (dubbed ‘Pointillist’) to do exactly this: discover cell-specific pathological epitopes, as well as therapeutically useful binders against them, at an ambitious scale.
Pointillist is creating a whole new map of tumor biology that hasn’t been built before — and one that could guide the development of a new wave of epitope-targeted biologic therapies for cancer and perhaps even other diseases. As Stipple Bio is now at the cusp of becoming a clinical-stage biotech company with our first lead drug candidate, we are proud to be doubling down on this team. Jeff, Michelle, Andi, Aaron, Aashish, and the entire Stipple team and board: we look forward to painting this tapestry of epitopes, binders, and insights with you. And we are eager to see the impact that new Stipple medicines – our own magic bullets – might have one day on patients.
This newsletter is provided for informational purposes only, and should not be relied upon as legal, business, investment, or tax advice. Furthermore, this content is not investment advice, nor is it intended for use by any investors or prospective investors in any a16z funds. This newsletter may link to other websites or contain other information obtained from third-party sources - a16z has not independently verified nor makes any representations about the current or enduring accuracy of such information. If this content includes third-party advertisements, a16z has not reviewed such advertisements and does not endorse any advertising content or related companies contained therein. Any investments or portfolio companies mentioned, referred to, or described are not representative of all investments in vehicles managed by a16z; visit https://a16z.com/investment-list/ for a full list of investments. Other important information can be found at a16z.com/disclosures. You’re receiving this newsletter since you opted in earlier; if you would like to opt out of future newsletters you may unsubscribe immediately.