Smash Notes
Thrive Capital's Bet on Neuralink, OpenAI & the Future of Medicine
Dr. Nworah Ayogu, MD, MBA, Partner at Thrive Capital, joins Sourcery to discuss how AI is transforming drug discovery, medicine, and the economics of healthcare. A Harvard-trained physician, founding team member of Cityblock Health, former General Manager of Amazon Clinic and first Chief Medical Officer of Amazon Pharmacy, Nworah is now a partner at Thrive…
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Notes
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Nworah Ayogu said that, more so than at maybe any other time in history, the frontier of science and the frontier of what has been accomplished is moving faster than ever. The explosion of artificial intelligence and drug discovery is changing the way drugs will be delivered and made, and the change will also run through the entire value chain.
Artificial intelligence labs already sent needs around compute, memory, and energy through the entire supply chain. Biotech will follow the same path, and the path is not just drug discovery. It will be manufacturing, development, how clinical trials are done, and commercialization. N of 1 medicine is the ability to create a customized treatment for an individual and to treat conditions that could not be treated before. Customized treatments have already occurred and have already had an effect, with more of them still to come. The remaining marker is an intersection between hardware and biotech that unlocks treatments people could not unlock before. Neuralink and Fortel are two of the companies named, and the problems they are solving, plus the capabilities they allow, are almost biblical in proportion.
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Drug discovery models have gotten better and better at the first job: choosing a molecule that binds a chosen target well. Nworah Ayogu said the work after a bind still has room to grow. The next models have to predict what the body does once a molecule binds, and which unwanted effects come with it.
People often point to companies like Isomorphic and Chai. A target is a molecule in the body, and hitting it changes something. Biological risk is whether the target is the right one. Upregulate it or downregulate it, and the open questions are whether a person gets sleepier, more awake, or loses weight. Off-target effects are the side effects to avoid, including nausea, a higher heart rate, and liver toxicity. The aim is the intended change without the rest. A molecule still has to be made to bind the target, and some molecules are easier to make than others. Undruggable means the pocket is small. The shapes are three-dimensional, so Nworah Ayogu said the molecule itself may move when part of it is bound and let something else bind, which is why people talk about hidden pockets. A model has to predict the shape in real time and how the shape changes over time.
Step one is the best thing to make so it binds. Step two is what happens after the bind. Step three is the unwanted effects. Binding well is the step the field has improved.
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Nworah Ayogu said healthcare often does a very good job of extending life and does not do a very good job of improving quality of life or giving people life back. Neuralink created an implantable device so people can interact with the world again. The device lets them control a computer with their minds. Motorized arms let them control a robotic arm to pick things and grab things. In another trial, Neuralink implanted the device in the vocal cortex so someone who was not able to speak could speak.
Neuralink now focuses on a lot of populations. One of the first was people with ALS or paralysis, whether through a disease or a car accident. A lot are veterans who served the country and no longer have usage of their arms and legs. Nworah Ayogu said they maybe were hit with an IED. Often they are young, 30 or 40, and no longer able to work, because work often needs hands and legs. They also cannot be outside playing with their children.
He said the core of Neuralink is using the implant so people can manipulate the outside world again. He added that Neuralink may not replace the arms and legs someone has lost, and states the implant can still give that functionality back.
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Nworah Ayogu called Neuralink a more interesting company than SpaceX, because the brain is vaster than space. "A $3 trillion company?" is a scoff at that scale of thinking, capped with "What are we thinking?" People do not reach space, and people do not invent silicon chips, without the brain. The brain is the fundamental substrate that unlocked all of it. The brain is still a more efficient engine of compute than every chip NVIDIA has ever made.
Neuralink's president leads much of Neuralink and is a compelling leader. Passion is contagious, and excellence and talent density are contagious too. People who are truly N of 1 want to work with other N of 1 people. The team works on an important problem and was category defining. When Neuralink first did the work, no one else was doing it. Neuralink created the category and brought in everyone who cared about the space. As the work went forward, the lead only compounded.
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Nworah Ayogu said Keytruda, one Merck drug, had 2025 revenue larger than the revenue of all the major labs combined. Biotech is already big business. Companies keep finding new uses for medications like Keytruda. Keytruda is a checkpoint inhibitor, an immune booster that can boost the immune system.
Nworah Ayogu said he thinks Merck and Moderna's new cancer vaccine is an example of amazing frontier science. Moderna are the COVID goats of mRNA. For melanoma, a specific type of skin cancer, surgery takes the tumor out. Each tumor is unique because tumors mutate and change in different ways. Nworah Ayogu said a mother's cancer is likely different in a lot of ways from the cancer of someone else. The tumor is sequenced to find the parts of the tumor's expression and the tumor's own genome that make it unique, and an mRNA vaccine is created to target that exact cancer.
The vaccine is then injected, and Keytruda is given at the same time for an immune boost, so the immune system can recognize the cancer more easily. Any microscopic pieces of the cancer still floating around in the body are wiped out by the boosted immune system.
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Nworah Ayogu said OpenEvidence spread because doctors wanted it. Nworah Ayogu said he had never heard doctors rave about a clinical tool. Clinics normally force software on physicians, the way someone forces a pager or an enterprise tool, then monitors the work and flogs people for using it. The old thesis said doctors just do not like technology. He rejected the thesis: doctors have iPhones and Macs at home and simply hate the bad technology they are forced to use.
Friends from residency were the first to mention OpenEvidence, one of Nworah Ayogu's companies, and they did it with joy. He tried the product, called it differentiated, emailed a college friend behind it, drove to the house, and met that day. A clinician sees right away why OpenEvidence is an N of one product. Two thirds of physicians in America use OpenEvidence. Epic, called the behemoth in health care, took 40 years to reach today's scale and still has less than 50 percent of physicians using the product. OpenEvidence got to two thirds after three years.
He said the speed is the kind of scale now possible with a user population that is notoriously hard to gain adoption for.
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Nworah Ayogu said medicine can now treat rare genetic problems one patient at a time, and said a million and a half dollars to make and deliver a treatment is worth it so a child lives. The answer given is yes: raise taxes or cut spending somewhere else if that is the way to pay.
The fight is over the total bill. Cancer care, a transplant, and gene therapy are each life or death, so a health system keeps deciding what to fund, what to leave unpaid, and where values sit. Underneath sits the price of a life, including the life of a child. The same push is to stop leaving development at a million and a half dollars. Infrastructure has to make the work scalable, repeatable, and cheaper, with manufacturing that holds up and a way to pay.
The frontier is exciting because the science can now do work people had dreamed about for a long time, with massive impact. As more of the work shows up, and shows up faster, the rest of the system has to be ready across the whole supply chain.
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Oscar Health, the first company Thrive ever invested in, fell 95% from its peak value in December 22. It then climbed back above its IPO price. Nworah Ayogu said Oscar increased 100% year over year, while health insurers as a group had a hard last year and a half.
Nworah Ayogu remembered arguing as a know-it-all med student that a new health insurer was a bad idea. The last health insurer created was United Healthcare in 1977, before the internet. A new insurer was not something people did, because it is too hard and takes too much scale and too much capital. He was glad to be proven wrong. Oscar's plan was to use the ACA to build a consumer-centric health insurer, and the plan worked. Oscar built a tech-first infrastructure a decade ago, including its own claim stack and its own claims processing.
The infrastructure from a decade ago is what has let Oscar move fast with AI, because Oscar already had a modern tech stack.
Related notes
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