Shane Lofgren

Really great collaboration between @ManifoldBio and @nvidia to test 1M de novo designed binders against 127 targets, measuring over 100 million potential protein-protein interactions! This was a great collaboration with some very exciting results. NVIDIA's new Proteina-Complexa method is SOTA for de novo minibinder design. If you're interested in designing minibinders to targets you couldn't hit with other methods, try it out! I'm particularly excited about what this large scale data enables. As we generate 1000s of experimentally validated structures, this data becomes the input to training new protein design models. At Manifold, we are generating datasets of this size continuously, and have experimentally validated thousands of de novo designed binders across many formats (VHH, minibinders, peptides, etc). New models will open up new hard to hit targets, paired with our large scale in vivo measurement, will enable us to create previously impossible therapeutics. Up next is training new models on this and other data we have generated, stay tuned! And thanks to NVIDIA for setting up such a great collaboration, its been fun and fruitful!

What you’re seeing at @ManifoldBio is what happens when two exponentials begin to resonate–the evolution of AI and the evolution of massively parallel molecular measurement and design. When we started Manifold Bio with @PierceOgdenJ , @geochurch , and @slofgren, we set out to do something bold: to build an AI-first biopharma company that could map the astronomic space of molecular design against the complexity of human biology. We had already become world leaders in the secret art of combining Machine Learning and Multiplexed Libraries, or ML². We believed this approach could be transformative to drug discovery. AI in drug discovery has always faced one fundamental barrier: the translational gap between what works in a petri dish and what will work in a patient. We believed that closing that gap required a way to power AI models with massive-scale experimental feedback directly from living organisms. Such a platform would be positioned to solve grand challenges in human health, including creating medicines that could cross the blood-brain barrier. To succeed in such a challenge, it not only takes a culture of scientific boldness, but also bold partners. The boldness of the Roche team was clear from the moment we started mapping out this collaboration, both in their rigor in evaluation of the Manifold platform and the ambition we both shared in how to best leverage our approach. This is the company that has literally integrated the Genentech DNA, and charted many firsts along the way, including some of the most compelling brain-shuttling clinical data to date. It’s a privilege to combine forces to advance the frontier of brain delivery together. This deal is fantastic validation of the power of our approach. And we’re just getting started.

It's been amazing to see the progress in generative AI mAb design, by both our team and others (Chai, Germinal, etc)

@PierceOgdenJ Awesome progress!

Excited to announce mBER, our fully open AI tool for de novo design of epitope-specific antibodies. To validate, we ran the largest de novo antibody experiment to date: >1M designs tested against 145 targets, measuring >100M interactions. We found specific binders for nearly half the targets, with up to 40% hit rates. Thread below:

@glebkuz @ManifoldBio @ElliotHershberg Really exciting to see the progress laid out like this!

We're stil writing the @ManifoldBio story, but @ElliotHershberg just dropped a fantastic piece capturing the journey so far on his blog Century of Biology.

Really proud of the work that went into winning the Harvard President's Innovation Challenge. Excited to keep building!

.@manifoldbio won the grand prize in this year's @Harvard President's Innovation Challenge. The transformative company builds technology that exponentially increases measurement throughput at all stages of drug development. bit.ly/3tqa8DZ

Great podcast from our CSO @PierceOgdenJ on the design of synthetic proteins!

We're looking for creative bioengineers (Scientists and RAs) to join us in building @ManifoldBio Here's why we're building Manifold: manifold.bio/blog/introduci… If this resonates with you or someone you know, please reach out directly or email careers@manifold.bio

Extremely excited to get to work bringing multiplexing to all stages of the biologics development pipeline.

Excited to share our seed raise @ManifoldBio to build multiplexed tech for protein therapeutics dev with @PierceOgdenJ, @slofgren, @geochurch and a talented team! Huge support from @Playground_VC and @fiftyyears. Thanks @FierceBiotech for the nice piece! fiercebiotech.com/biotech/could-…

Hey @slrobinet, @MikeNGladstone any idea where to get the minutes / recording of the FDA Advisory Committee discussion today?

@purveshkhatri Haha dang, that is actually very cool. We should include it in our presentations (seriously).

@MikeNGladstone Curious what makes ON safer than OFF? Docs start with lower initial cell dose, titrate up after assessing safety?

Great inside look at how seed stage VCs think about company formation from academic inventions. They do much of company formation leg-work. twitter.com/LifeSciVC/stat…

@slrobinet Very interesting. Any data suggest that patients w/ prior treatment w/ dna damaging chemo respond better to later line anti PD1?

@slrobinet Love animal model predictive power eval, seen any other work like this? Side note: NSG seems strange model for immunotherapy?

@slrobinet @Deliniabio wow, 2-3 week dosing, IV for a cytokine. Does look like PEG blocks IL2Ra interface. Wonder how SAEs comp w/ WT IL2?

@MauriceOnTW excellent, thank you @slrobinet