Shane Lofgren

Head of Strategy at Manifold Bio

[Pierce @PierceOgdenJ]

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!

[Gleb Kuznetsov @glebkuz]

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.

[Shane Lofgren @slofgren]

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

[Pierce @PierceOgdenJ]

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:

[Shane Lofgren @slofgren]

@PierceOgdenJ Awesome progress!

[Shane Lofgren @slofgren]

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

[Gleb Kuznetsov @glebkuz]

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.

[Shane Lofgren @slofgren]

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

[Manifold Bio @ManifoldBio]

@manifoldbio wins the Life Lab track of the 2021 Harvard President's Innovation Challenge! We were born in the @geochurch lab and have been enabled by the @innovationlab community and staff since the start. So much progress in just one year at @harvardlifelab and more to come!

[Playground Global @Playground_VC]

.@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. https://t.co/R0dgrL3oIh

[Shane Lofgren @slofgren]

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

[Seth Bannon @sethbannon]

On Translation #3, we talk with @PierceOgdenJ, lead author on the paper that forms the basis of @Dyno_Tx!

We talk AAV design, the need for synthetic proteins, & more! And hint at what's to come w/ his newco @manifoldbio.

With special guest hosts @dbgoodman & @vram142!

Links 👇

[Shane Lofgren @slofgren]

We're looking for creative bioengineers (Scientists and RAs) to join us in building
@ManifoldBio

Here's why we're building Manifold: https://t.co/lRB0jaxV47

If this resonates with you or someone you know, please reach out directly or email [email protected]

[Shane Lofgren @slofgren]

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

[Gleb Kuznetsov @glebkuz]

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! https://t.co/VSdsmxV8BX

[Gleb Kuznetsov @glebkuz]

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! https://t.co/VSdsmxV8BX

[Shane Lofgren @slofgren]

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

[Shane Lofgren @slofgren]

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

[Shane Lofgren @slofgren]

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

[Shane Lofgren @slofgren]

Great inside look at how seed stage VCs think about company formation from academic inventions. They do much of company formation leg-work. https://t.co/mbgCTBtKBX

[Bruce Booth @LifeSciVC]

Watch @MikeNGladstone share the @atlasventure startup approach! https://t.co/uDuJVl1LbV

[Shane Lofgren @slofgren]

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

[Shane Lofgren @slofgren]

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

[Shane Lofgren @slofgren]

@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?

[Shane Lofgren @slofgren]

@MauriceOnTW excellent, thank you @slrobinet