David K. Yang
@davidkmyang
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Life sciences @Lux_Capital . Prev: Co-founder of Latus Bio, Investor at 8VC, Comp bio at Broad Institute
San Francisco, CA
Joined September 2018
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In biotech, a common pitfall in target selection is not that the target doesn’t work. It’s that the target is too late.
By the time a target is “validated”, it’s a crowded space and the most advanced drug is years ahead. And rarely do 5th-in-class+ drugs get handsomely rewarded.
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I got curious how big pharmas today grew from once fledging biotechs.
Here’s 7 of the times it happened and the iconic blockbuster drugs that came along for the ride 👇
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Thrilled to share that I’ve joined the Lux Capital team! Looking forward to continue backing and building transformational life sciences companies
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In biotech, we often hear that decisions should always be driven by the science & data. But in reality, there’s always more data to be gathered while time is of the essence.
Hallmark of great management teams is knowing when data is "enough" and making the right call.
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Unlike small molecules and antibodies which have decades-refined design strategies, new modalities lack a playbook.
This may be where AI can be particularly valuable today.
Some companies exemplifying this strategy 🧵
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Fun fact of revisionist history: many platform biotechs didn’t actually get their lead drug from their platform. It was a med chemist getting lucky with a screen or a design.
Often, serendipity >> value of a single tech
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I see induced proximity as one of the most exciting paradigms in drug discovery today.
Thrilled to share the debut of Photys Tx, launching with 75M Series A to pioneer a new class of small molecules capable of controlling protein phosphorylation. A 🧵:
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Every new therapeutic modality is like an ecosystem.
Blockbuster drugs are the apps and often get most of the attention.
But the infrastructure companies that provide manufacturing, discovery, and IP are giants too.
I've been researching notable players, and why they won👇
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A couple additional thoughts:
I see this often with platform cos picking a “derisked target,” but it can expose them to far more market risk. Yes the potential of best-in-class is there, but that's hard to know a priori. And preclinical improvements may not translate to
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Biotech dinner in NYC 🗽
Was great to be with old friends and new. Excited to be spending more time here
I'll be hosting these regularly - dm to join next one!
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For biotechs developing complex therapies, management teams face some of the toughest decisions around manufacturing & CMC.
For example - should you delay the Ph1 trial to first optimize the manufacturing process, or move ahead with a less efficient process for a faster readout?
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Many TechBio companies from the 2018-2021 vintage have now raised Series Bs.
Successful rounds seem to follow one of two patterns:
1. Transition into a biotech, primarily valued by lead drug
2. Mega-round from mostly TechBio investors
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Wonder if there will ever be another new big pharma?
Many of the giants today started as biotechs that commercialized large blockbuster drugs. But now, the same biotechs positioned for commercial success get snapped up pretty quickly by existing pharmas that absorb the upside
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Biotech bowling night in SF 🎳
Lot of fun bringing folks together from VC, pharmas, and biotechs in the ecosystem. Couldn't have asked for a better venue
@presidiobowl
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Pharmas typically acquire drugs they know how to commercialize.
This means assets that are trickier to commercialize, e.g. drug+device combos, can be overlooked due to low M&A interest.
What are other therapeutics classes with similar dynamics, but nonetheless promising?
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Great article on "next-gen acquirers" in biopharma from Endpoints.
Amgen and Gilead would've been on this list years ago as they were buying Immunex and Pharmasset.
Every commercial-stage biotech is one great acquisition away from becoming the next major pharma.
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Always impressive how quickly the zeitgeist shifts among biotech investors.
The recent boom in T-cell engagers for autoimmune is a good example of this, which has accelerated from the early Blincyto data in refractory RA from late April. Many unannounced cos already on its way.
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Great writeup from
@ElliotHershberg
on the Bio-IT Fellowship. It's been an incredible 3 months working with and learning from these 6 fellows - keep an eye out on these superstars
@ElliotHershberg
@JamesADiao
@kristinali
@chloehsu0
@saigourisankar
@SRsrivatsan
This was the last week of the epic
@8vc
Bio-IT Fellowship that I was very fortunate to be a part of 🧬
I wrote an essay reflecting on what I've learned...
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Applications are now open for the 8VC Fellowship! If you're a graduate student / postdoc with an entrepreneurial interest, you'd be hard pressed to find a better opportunity to learn about biotech and starting your next company. Read our recap here:
If you're a graduate student in the life sciences with an entrepreneurial interest, join us this Spring to learn everything about biotech and help invest in & start companies with us. Read our recap of the program at and apply here
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@ElliotHershberg
@JamesADiao
@Kristinali
@chloehsu0
@saigourisankar
@SRsrivatsan
Highlight was bringing together this group as well as the 5 fellows from last year into SF. Excited for the next cohort - if you're a PhD student or postdoc with an entrepreneurial interest, be on the lookout for our application cycle / DM me to get on the mailing list!
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Another interesting q is how the pharmas deploy the cash from their blockbusters. Gilead spent their Sovaldi cash on large acquisitions to enter inflamm and onc, Vertex put a large bet into cell & gene therapy, while Regeneron doubled down on internal R&D
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A couple additional thoughts:
There’s always tradeoffs. In the above example, the latter decision indeed achieves a faster readout. But you'll eventually need to do PD while also ensuring it's comparable to the Ph1 product & run a bridge study group. This can be expensive and
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A few observations:
• Independent commercialization of a blockbuster drug is the necessary ingredient
• The defining blockbuster is rarely the first approved product, and often developed much later or acquired
• These cos were mostly founded in the 80s
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Rate of pharma M&A has remained strikingly consistent over the years.
Much of the biotech game is finding a way to get on this shopping list.
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Induced proximity
Glues & heterobifunctionals are exciting approaches that modulate proteins in new ways, e.g. degradation, phosphorylation, and stabilization, but the design rules remain inscrutable. VantAI is advancing AI e.g. PPI prediction to better optimize this drug class
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Targeting RNA with small molecules is a compelling paradigm to expand the druggable universe. Atomic AI's unique ability to generate structures at scale is massively unlocking for the field, and we're excited to support
@raphaeljlt
and the incredible team to push this forward
We’re excited to announce the close of our $35M Series A financing! Atomic AI is fusing artificial intelligence and structural biology to unlock RNA drug discovery, designing RNA-targeted and RNA-based medicines to treat undruggable diseases.
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RNA targeting small molecules
This could substantially expand the druggable space, but designing specific & functional binders to RNA is difficult, as we lack quality RNA structures. Atomic AI has built a ML model to predict RNA tertiary structure to guide small molecule design
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Oral pill for sickle cell anemia - awesome work from the NIBR team.
Molecular glues are perhaps the most exciting modality today, but much of the translational efforts have focused on oncology. Great to see advances in additional important therapeutic areas
Today in
@ScienceMagazine
, together with my former colleagues at NIBR, we report the discovery and characterization of first molecular glue degraders of the WIZ transcription factor (TF) for fetal hemoglobin derepression and therapeutic consideration in Sickle Cell Disease. 1/10
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Impressive to see Twist continue scaling revenue, while cutting back on both R&D and SG&A expense last year.
Currently trading 8x EV/Rev, highest among specialty tool companies
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Applications are open until 2/4! We're so excited to bring on the next batch of Bio-IT fellows, please join us this spring to dream all things biotech together. Learn more on our website: and apply here
The
@8VC
Bio-IT fellowship is back. Which means another chance to learn from the incredible
@davidkmyang
.
✅ Develop a thesis in cutting-edge science
✅ Review potential investment opportunities
✅ Survey new tech
Due Feb 4, rolling. It's paid.
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Brain delivery
BBB-penetrating antibodies can dramatically improve protein drugs for the CNS, but we lack good shuttles especially for the newer BBB-transport targets. Manifold Bio combines ML with an in-vivo screen to identify new designs for next-gen brain shuttles
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Regeneron
Founded in 1988 with an initial focus on neurodegenerative disorders ("regenerate neuron"), their big break was the Eylea approval in '11 which sold $9.6bn in ‘22. The company is still operated by its original founders George Yancopoulos and Len Schleifer
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Amgen
Founded in 1980 to commercialize recombinant DNA technology, their first big win was in recombinant EPOs for anemia. The breakthrough moment was the 2001 Immunex acquisition that brought on Enbrel, which went on to bring $70bn+ in revenue with $7bn in peak sales
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Point 2 means that commercial biotechs of today can grow into a large pharma through a clever acquisition or development. It's why cos like Exelexis and Incyte are actively looking for their next major product, internally and externally, partly for LOE but also for the next leap
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Exciting new platform for multiplexed nucleic acid detection from
@sabeti_lab
. Proud to have been part of this work
Delighted to share with you our latest publication describing CARMEN: a massively multiplexed, Cas13-based technology for nucleic acid detection, out this morning in
@nature
[1/8]
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🔥Hot off the press: Cas7-11 can target RNA without any of the collateral activity, expanding the RNA-targeting toolbox and opening up new therapeutic applications. Huge congrats to
@jgooten
and
@omarabudayyeh
for this amazing work
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Monoclonal Antibody
Adimab stood out as a one-stop shop for antibody discovery service, importantly with FTO during a litigious time. They have been a chosen partner to discover more than 500 therapeutic antibodies, with 74 programs in the clinic.
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Vertex
Founded in 1989 to realize the vision of rational drug design, Vertex built an empire in cystic fibrosis starting with the approval of Kalydeco in '12. The major milestone was Trikafta that boasted profound efficacy in CF, which brought in $9bn in '23
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Genetic medicines
Manufacturing of genetic medicines - AAV, lentis, or mRNA - all start with a plasmid DNA. Aldevron has become the standard for plasmid DNA manufacturing and powers the ecosystem with an infra built over 25+ years.
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Gilead
Founded in 1987 to focus on antiviral medicines, they found early success in HIV and Influenza. The defining decision was the 2011 acquisition of Pharmasset which brought on Sovaldi for HepC. The Hep C drugs alone generated $19bn sales in the 2nd year of launch
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@AlfredoAndere
Software for commercialization is a coveted space and hope to see more there.
Part of why there's much more software in R&D is that it's straightforward to understand for founders, but software needs in pharma commercialization is far more tacit & obtuse
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So excited to see all the science and medicines that are sure to come from this bold initiative. Congrats
@pdhsu
and team!
Delighted to announce the Arc Institute
@arcinstitute
, a new, independent scientific institution dedicated to the study of complex human disease. Working with our partners
@UCBerkeley
@Stanford
@UCSF
, our mission is to accelerate progress in biomedical research and therapeutics.
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Check out this cool work by
@dawnchenx
! Using Cas9 nickase & helicase + editor for endogenous long range mutagenesis
We are happy to share our latest long-range, programmable mutagenesis toolbox - the Helicase-Assisted Continous Editing (HACE) system - to achieve target-specific mutagenesis of the endogenous genome. (1/11)
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Genentech
Founded in 1976 and regarded as the first biotech, they developed multiple foundational protein drugs including Rituxan (approved '97, peak. $9bn), Herceptin (approved '98, peak $7bn), Avastin (approved '04, peak $7bn). Ultimately acquired by Roche in '09 for $47bn
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@MartinBJensen
True, but I'll highlight that Gilead was incubated by Menlo Ventures and Amgen by Bill Bowes which is lesser known history today. Genentech was more of a seed rather than incubation by Kleiner Perkins
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Macrocycles
They have the promise of achieving antibody-like specificity and small molecule-like convenience, but designing them to be selective and permeable is difficult. Unnatural Products is using ML to iterate and optimize macrocycle drugs and solve these key challenges
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mRNA Therapy
mRNA vaccines and therapies have quickly entered the zeitgeist, and Maravai is a leading provider in manufacturing supplies & raw materials. They notably commercialize CleanCap, the leading capping tech incorporated in over 350 programs
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Let me know if I’ve missed other companies in this theme!
Excited to track the progress of all of these players
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Congrats to the Tidal team on the Sanofi acquisition. mRNA therapies have huge potentials beyond vaccines, and Tidal's tech exemplifies this. Compelling implications for improved logistics, safety, and re-dosing - excited to see clinical data on this one.
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Can't imagine a more fun place to be than Sanjay's lab! Excited for all the magic that will ensue
Thrilled to announce the opening of the Srivatsan Lab () at the
@fredhutch
. The lab will be building new sequencing technologies to understand how our cells and bodies form over the course of development.
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Broadly, I think there's a huge opportunity for these alt-TACs to modulate biology in totally new ways. Some other interesting applications of this are control of acetylation, methylation, or glycosylation, as well as RNA modulation via degradation or editing
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Gene editing
Recombinases have the potential to be the ultimate platform for gene insertion as therapeutics, but endogenous ones lack in efficiency in specificity. Stylus Medicine is leveraging AI to engineer recombinases for improved targeting and precision for gene therapy
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I’ll also highlight that though small molecules and mAbs have a head start given existing discovery platforms, there’s still substantial room for AI to help. Companies like BigHat, LabGenius, Anagenex, and Iambic continue pushing the envelope
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What’s interesting is that these companies also innovate heavily on the experimental side.
It makes sense - they’re optimizing for the productivity of the combination of AI and internal experiments, and that involves tinkering with not just one, but both sides of the equation
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"Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design"
Very cool work in an important area. Loving fig4b
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Excited to see all of what Photys accomplishes for patients and this scientific field. In the meantime, I'm looking forward to continue betting on companies advancing these modalities and building enabling infrastructure for the space
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Alloy is democratizing foundational drug discovery platforms and will help birth more drugs than any other entity in the next few years. Proud to be supporting the team and their mission - may the best drug win!
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Lipid nanoparticles
LNP is a foundational modality that underlies siRNA, in vivo CAR-T, gene editing, and mRNA. Arbutus & Genevant have built important know-how and IP in the space, and several players today license from Genevant for their LNP IP.
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Cell Therapy
CAR-Ts have yet to translate their transformative success in liquid tumors into solid tumors, but we've since identified areas of needed improvement. Outpace Bio is using ML-guided protein engineering to superpower cell therapies across the many different axes
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Folks at NeurIPS, looking for something to do after the poster session tomorrow? Come check out my friend
@tonyyikeyang
's recital tomorrow evening!
#VANCOUVER
FRIENDS 🇨🇦
Looking forward to returning to the
@VAMSchool
for a recital after my first time there three years ago!
Get your tickets here:
Programme includes sonata selections by Mozart, Beethoven, and Chopin.
@tomleemusic
@SteinwayAndSons
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“Found data is not enough.”
Generating the right, appropriate data is key to building better models, can’t agree more
@DaphneKoller
@insitro
@lmrl_bio
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Celgene
Founded in 1986 as a spinoff of Celanese, their first win was in repurposing then controversial thalidomide for leprosy. This work led to the development of Revlimid for heme onc with peak sales of $13bn. Ultimately acquired by BMS in ‘19 for $74bn
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Congrats to Vaibhav! Really excited for his work in the coming years - one to watch
Incredibly thankful to be selected as a 2023
@HertzFoundation
Fellow! With the
@PDSoros
Fellowship, the Hertz will fund my PhD at
@HarvardMITmdphd
/
@HarvardGSAS
.
So thankful to my parents, family, Anna, professors, mentors, and friends for their support of my scientific endeavors.
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Just finalized itinerary for
#NeurIPS2019
! Excited to meet everyone at
#LMRL
and
#MLCB
. I will be presenting some preliminary work on using generative models for codon optimization
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AAV gene therapy
RegenxBio had a near monopoly over AAV capsid IP that originated from Penn & GSK. Their initial licensing-based business model powered dozens of new gene therapy companies and programs, including Avexis & Zolgensma.
They've since transitioned into a pipeline co
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Work with us this spring through the Bio-IT Fellowship! This is a chance for grad students to learn about investing and identify opportunities in emerging areas of science. All grad students and postdocs encouraged to apply at
Applications for the 8VC Bio-IT Fellowship are now open! Calling all graduate students in the life sciences to apply. Fellows have a chance to work with the bio team at 8VC to learn about venture and identify new investment opportunities. Apply today at
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Incredible work by
@haydenmetsky
. ADAPT designs optimal probe sets for viral diagnostic and surveillance, with an emphasis on computational efficiency and guarantees. Important, and much needed work.
I'm excited to share ADAPT, which designs optimal activity-informed viral diagnostic assays. We developed new algorithms and ML models focused on CRISPR dx — and applied them to ~2K viruses. ADAPT's designs outperform standard techniques. Thread 👇
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Gene therapy
Novel AAV capsids can unlock transduction in tissues we can’t access today, improving therapeutic window to access new indications. Dyno Therapeutics is coupling in-vivo capsid variant screens with AI to discover & optimize potent capsids for different tissues
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Biogen
Founded in 1978 by (later) Nobel-prize winning scientists, Biogen’s major success was in multiple sclerosis with Avonex (approved ‘96, peak $3bn), Tysabri (approved ‘04, peak $2bn), and Tecfidera (approved ‘13, peak $4.4bn)
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In that sense, investments into a modality-specific infra company is akin to getting an index in the entire modality. You take a risk that one of the programs in the modality will generate exciting data, and hopefully get rewarded for it.
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Congrats
@joshpetepeters
!! Excited to see what you're up to next 👀
Congratulations Dr.
@joshpetepeters
aka Mr Macrophage. Not enough space in a tweet to say how you’ve changed my thinking about science and my life personally, but thank you. Very proud of you!
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Overall, these infra cos are the unsung heroes of new modalities. They play a key role in amortizing the cost of development & manufacturing, making it easier for the next therapeutic program to get started
Hope to see continued innovation and new companies in this space.
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Signal extraction for in vivo voltage imaging. Elegant work by
@MichaelEXie1
Excited to share my first first author paper!
We developed a signal extraction method for in vivo voltage imaging data sets and validated with simultaneous in vivo patch + voltage imaging recordings (courtesy of the Svoboda lab!)
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@Banana_Oncology
Agree, also BCR-ABL, PARP, and other countless examples. Second generation drugs that's meaningfully informed by Ph2 data has been value accretive.
But if the story is to be a fast-follower within that first generation, better make sure you're fast enough.
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@varma_ashwin97
Current structure does work pretty well. Couple potential pitfalls IMO: (1) pharmas further consolidate and M&A market becomes less efficient, and (2) underinvestment in areas that pharmas don't have an existing franchise or don't know how to commercialize (e.g. drug+device)
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Phosphorylation is the most ubiquitous PTM and is involved in several diseases, which is why I'm so excited about Photys's work on advancing PHICS, bifunctional molecules that can phosphorylate proteins. PHICS can potentially access many of the undruggables with this approach:
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@ASchulz888
argenx has real potential to be a giant - Vyvgart sold $1.2bn it’s 2nd yr of launch. And any of the $5-20bn market cap commercial biotechs could scale too, as long as they develop or acquire the next big drug. We’ll see who pulls this off!
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Simultaneously, there are new enabling technologies that serve as tailwinds: DELs have been increasingly effective for binder discovery, especially thanks to expansion of compatible chemistry and increased sequencing depth, and improved methods to profile on / off-target PTMs
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Some thoughts:
When a new modality generates exciting clinical data, it handsomely rewards the underlying infra companies.
That success can rapidly expand the market size of these infra cos by increasing the # of new programs being started, who are all potential customers.
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Important for founders & mgmt teams to be mindful of broad sentiment, but the tricky part is knowing whether the trend is durable vs. a short-term fad
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@glebkuz
Illumina's ratio is great, with consumables doing ~80% of revenue (excluding services). That number has been consistent since 2016.
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And the recent acquisitions of Seagen and Alpine mean several executive talent have just freed up.
As new operational leaders and innovative science come together, I anticipate a cycle of strong biotech companies in Seattle.
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🎉🎉🎉
Huge congratulations to my advisor
@PardisSabeti
who was just elected to the
@theNAMedicine
today! I couldn't be more proud to be a member of
@sabeti_lab
😁
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so cool. wonder what other organisms might have pressure to keep a compact Cas enzyme
Hey friends, excited to share my 💥🚨New Paper 🚨💥‼ with co-first author
@patrick_pausch
, out now
@ScienceMagazine
! Proudly presenting the teeny tiny 🤏 but mighty💪CRISPR-CasΦ system we found in giant bacterial viruses aka huge phages!
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Patients see their pharmacists much more frequently than their physicians, and these touchpoints are incredible opportunities to improve outcomes. Really excited to see Docstation lead the way in empowering pharmacists to better actively engage in patient care.
Pharmacists can do more than just dispense medication - let's get the red tape out of the way and empower them to practice at top of license + become fully-fledged members of a care team.
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I spent the last few days meeting with academics at UW, Fred Hutch, and Seattle Children’s.
The science here is incredible. Exciting advances across cell therapy, nanopores, and of course, protein engineering.
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Traditional drugs have often relied on inhibition of proteins, but nature has evolved a complex machinery of protein control through post-translational modifications (PTM). PTMs clearly drive a significant portion of biology - how can we harness this mechanism to treat disease?
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🙏
There is a trend for huge Transformers. We went the other way: decreasing the size! 🤗
Introducing DistilBERT: a smaller, faster, cheaper, lighter BERT trained w/ distillation!
95% of BERT's GLUE perf w/ 66M parameters.
📃:
💻:
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Resolving RNA tertiary structure is massively enabling for developing RNA-targeting small molecules. Really exciting work by
@raphaeljlt
, trained on just 18 known structures!
AlphaFold for RNA? Excited to share our
@StanfordAILab
work on deep learning for predicting 3D RNA structure, out today on the cover of
@ScienceMagazine
!
Sound interesting? Join us at to bring this work to life! More news soon!
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@GenomicsCow
Would say majority of investments are still underwritten to M&A than IPO. It's still quite rare for tools consolidators to buy companies before they're well into revenue, which contrasts with biopharmas often purchasing pre efficacy PoC assets
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Another exciting addition to the generative model + protein design set of works
Proudly present our work on AI designed functional proteins! fantastic collaboration with
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