Weekly Dose of Optimism #93

AlphaFold 3, CRISPR Eyes, Ear Genes, MDMA, Societal Collapse

Hi friends 👋,

Happy Friday and welcome back to our 93rd Weekly Dose of Optimism.

In lieu of sharing our perspective on Apple’s latest marketing campaign, we’ll focus this week’s edition on covering some major recent breakthroughs in biotech: a model that predicts the structures of all molecules, CRISPR enabled vision, gene edited ears, and an MDMA-based therapy on the cusp of a FDA review. Packy spent the week at SynBioBeta and reports that the bio renaissance is just getting started.

Let’s get to it.

---

(1) AlphaFold 3 predicts the structure and interactions of all of life’s molecules

From Alphabet

In a paper published in Nature, we introduce AlphaFold 3, a revolutionary model that can predict the structure and interactions of all life’s molecules with unprecedented accuracy. For the interactions of proteins with other molecule types we see at least a 50% improvement compared with existing prediction methods, and for some important categories of interaction we have doubled prediction accuracy.

Google is so weird. The same company that blew its lead on Transformers and released an AI that Pirate Wires called “an Anti-White Lunatic” is also behind Waymo, which is objectively incredible, and AlphaFold, which may be AI’s greatest contribution to humanity to date.

And it keeps getting better. Earlier this week, Google DeepMind unveiled AlpaFold 3, its AI model that predicts the structure and interactions of all types of biomolecules — and by “all types” we literally mean “all types.” AlphaFold3 is designed to predict the behaviors of “all of life’s molecules.” Earlier versions of DeepMind’s protein structure models have been available for a couple of years now and have contributed to breakthroughs in vaccines and cancer treatments, but AlphaFold 3 is significantly more accurate and models how proteins interact with other key molecules like DNA, RNA, and potential drugs.

This is a big breakthrough. Scientists can now gain valuable insights into protein function without relying solely on lab experiments. It will speed up the already accelerating progress happening in bio to understand the body in order to eradicate disease.

Google DeepMind is making AlphaFold 3 free and available to access (for non-commercial use) via the AlphaFold Server and partnering with Isomorphic Labs on applying the model to real world drug discovery efforts. We hope to see them fully open source it like they did with AlphaFold 2.

Chatbots are the least interesting application of AI. Google DeepMind is leading the pack where it counts.

(2) Gene Editing Improves Vision in Some People With Inherited Blindness

From Harvard Medical School

Results from a small proof-of-concept study indicate that CRISPR gene editing is safe and can improve vision in some people with inherited blindness. In the multicenter clinical trial, 11 of the 14 individuals treated had measurable improvements on at least one key vision test, while six people experienced improvement on two or more vision outcomes.

From molecule unfolding to gene editing, biotech was on a heater this week. A new clinical trial successfully demonstrated that CRISPR could be safely used directly in the human body to edit genes and improve vision in individuals with inherited blindness.

One more time: humans are editing genes to cure blindness.

This is amazing in the abstract, but it’s even cooler when you hear the stories of the people behind the numbers, like Olivia Cook who CNN profiled this week. Cook received the surgery in her left eye, and months later, around Christmas, realized that she could see her friends’ faces: “With my right eye, I was not able to see their facial features. I was only able to see their silhouette. With my left eye, I could see everything on their face – so, significant difference, especially in the dim lighting,”

CRISPR is still very early. Only about 250 people worldwide have received any CRISPR-based therapies. But as each new study proves safety and shows promise on efficacy, researchers will be able to expand study sizes and target new conditions.

You love to see it.

(3) Latest DB-OTO Results Show Dramatically Improved Hearing to Normal Levels in a Child with Profound Genetic Deafness

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the investigational gene therapy DB-OTO improved hearing to normal levels in one child (dosed at 11 months of age) within 24 weeks, and initial hearing improvements were observed in a second child (dosed at 4 years of age) at a 6-week assessment.

Anotha one.

Regeneron announced that their gene therapy DB-OTO significantly improved hearing in children with profound genetic deafness caused by otoferlin gene variants. The therapy, currently in Phase 1/2 CHORD trials, demonstrated normalization of hearing levels in one child and initial improvements in another.

The otoferlin gene is essential for sound signal transmission from the inner ear to the brain. Defective otoferlin genes leads to impaired transmission which leads to deafness. Regeneron’s DB-OTO delivers a working copy of the otoferlin gene directly into the inner ear, helping to restore hearing. Specifically for children, the idea is that if you can intervene early enough with a treatment to restore hearing, you can also improve speech development outcomes.

Can you imagine if you went back in time told your great grandparents that humans made significant progress towards curing blindness and deafness in one week? We are living in an age of miracles.

(4) Lykos Therapeutics Announces FDA Advisory Committee Meeting to Review Investigational MDMA-Assisted Therapy for PTSD

“This will be the first MDMA-assisted therapy and psychedelic-assisted therapy to be reviewed by the Psychopharmacologic Drugs Advisory Committee, a significant milestone in the field of psychedelic medicine, resulting from decades of clinical research and advocacy," said Amy Emerson, Chief Executive Officer of Lykos Therapeutics.

One small step for Lykos Therapeutics, one giant step for psychedelics. Lykos, formerly known as MAPS Public Benefit Corporation, announced this week that the FDA is planning to review data on the company’s “MDMA-assisted therapy" as a treatment for PTSD. This is the first time in 25 years that the FDA is meeting to review any potential treatment for PTSD and the first time ever the FDA has convened to review any MDMA-assisted therapy.

Earlier this year, the FDA accepted Lykos’ NDA (New Drug Application) for MDMA-assisted therapy and granted the application Priority Review, with a scheduled action date of August 11th 2024. Data from the two Phase 3 trials showed significant improvements among MDMA recipients, including a substantial percentage of patients who no longer met the criteria for PTSD at the end of the study. The trials also showed that the treatments were safe, with normal-sounding side effects like mild to moderate muscle tightness, nausea, decreased appetite, and sweating. Nothing weird, just normal boring drug side effects.

Things are certainly moving in the right direction for psychedelic treatments, which is a good thing, because they uhh actually work and help people.

(5) Idaho Strategic Announces MOU with Radiant Industries Frontier Program

From Yahoo! Finance

Mass-producible, transportable by air, sea, road or rail and roughly the size of a shipping container, Radiant's Kaleidos unit is designed to replace diesel generators with clean, cost-effective base-load power in remote and hard-to-reach locations.

Radiant is one of the coolest companies out there. Founded by ex-SpaceX engineer Doug Bernauer, it’s building nuclear reactors that are small and safe enough to be put on the back of a truck and delivered to remote locations.

This week, it signed an MOU with Idaho Strategic, Idaho’s largest gold producer, to aid in the development and deployment of its Kaleidos reactor. As part of the agreement, Idaho Strategic will be able to operate one of the first five Kaleidos reactors at one of its sites.

While most of us think of large, utility-scale reactors when we think of nuclear, the nuclear renaissance will largely be driven by customers with specific needs that nuclear fits best. Mining — which often requires setting up your own infrastructure — is a great application. Instead of having to bring in more and more fuel, you can drive a reactor out with all of the fuel it will need for years. Power hungry data centers will be another big adopter. Ultimately, nuclear will win by offering a product that buyers need in a way that no other power source can.

Pulling power from atoms to pull metals from the ground. What a world.

---

Bonus: NYC Tech Week is happening from June 3rd though June 9th. We’re hosting a happy hour with Tamarack Global: ROBOT ROCK for the people building and investing in hard things (sponsored by our friends at Antimetal, Fuse Energy, and Create). We’d love to see some of you there. Spots are limited. Apply here.

Double Bonus: Eight Sleep Announces Pod 4 Ultra

Packy here with a quick one. Eight Sleep announced its Pod 4 Ultra this week, and as a very happy Eight Sleep customer (but sadly, not investor), I’m excited. I have a lot of redeeming qualities, but sleep isn’t one of them. I snore. I wake up in the middle of the night. And when I do, I get tired and noticeably less energetic and creative.

This mattress detects snoring and adjusts automatically to stop it. If it works, I can’t imagine a higher-ROI investment. Do you know how many thousands and thousands of words I could write if I just slept a little bit better? We’re about to find out.

---

We’ll be back in your inbox on Tuesday.

Thanks for reading,

Packy + Dan