Decoding Bio Snapshot 2023 - Release!
The Decoding Bio Snapshot 2023 is a multi-month and multi-contributor effort to contextualize the underpinning shifts in culture, scale + automation, AI/ML, and data accessibility and what these mean for the broader therapeutic and synthetic biology verticals. (Link to the full report here.) The snapshot aggregates learnings around areas such as AI-driven design, Infra for Bio, Extreme Biology, Target Discovery, Screening, Biomanufacturing and provides contextual examples of companies building in those verticals. Over forty companies generously contributed their own companies overviews, info on pipelines, and commercial traction. Some companies featured include Spaero Bio, PostEra, Eigen Therapeutics, Prime Medicine, Synonym Bio, Dyno Therapeutics and other industry leaders.
Amee Kapadia and Pablo Lubroth are the fearless leaders of the Decoding Bio Snapshot and also produce a weekly newsletter of bio events, called Decoding Bio. They do a fantastic job in summarizing the industry on a weekly basis and see this Snapshot as a landmark contribution to the bio community.
I contributed to this project by decoding biomanufacturing. Biomanufacturing is hard and doesn’t follow chemical scaling trajectories due to the constraints of cells and proteins which frequently have small temperature, pH, and pressure functioning ranges. However, using cells (and/or proteins) is sometimes the only way to produce the target product. Maybe there’s no possible way of chemical retrosynthesis of a small molecule so a cellular chassis is needed or maybe the chemical means of manufacturing has harsh reagents that are detrimental the planet. Regardless of the reason, better biomanufacturing increases our option space of solving important problems but consistently runs into issues at the ‘scaling’ level. Biomanufacturing leader, Bolt Threads, recently paused production of their sustainable leather line Mylo after having difficulty in fundraising. News like this reminds us that laser focus on economies of scale, shortening design, build, test, learn (DBTL) cycles, and matching products with the platform (as well as with the market) are of paramount importance. I’ve included some of the text below and was fortunate to have biomanufacturing leaders Bit.Bio, Synonym Bio, and Kano Therapeutics contribute company deepdives to the report.
Why biomanufacturing matters
Advances in genome/metabolome mining and transgenic expression haven’t been complemented (as many*) by breakthroughs in large-scale bioproduction of goods. However, driving factors such as parallelization, condition optimization, cloning tech, and automation are pushing the industry forward. Bits are easier to optimize but new tech is coming to atoms too.
What’s changed
The bottlenecks of biomanufacturing (scale-up, downstream process and digitization and automation) are being addressed with better data and tools which will lead to better optimizations leading to significantly increased economies of scale.
Scale-up: involved in the scale-up are condition and organism optimization. Companies have typically focused on one or the other (condition - Bioraptor, Officinae, Melonfrost, Boston Bioworks; organism - EV Biotech, Cradle Bio, Eden Bio). Orthogonal to scale-up is scaling-out. Instead of having 1000L+ reactions, keeping the smaller reactions vessels and distributing those around places where they’re needed is another biomanufacturing angle, with strides being made in GMP distributed manufacturing too (Ori Biotech, Unicorn Bio, BioNTech - BioNTainer, Nuclear, DNAScript).
Downstream processing: with the emergence of new production
organisms ranging from non-model bacteria (Wild Bioscience) to
plants (Nobell, Tiamat, ORF Genetics), to insects (Future Fields) -
new downstream processes have to be developed. Cell-free systems
(Solugen, Enginzyme, Zymtronix, Cascade Biocatalysts) or hybrid
fermentation + cell-free (Debut Bio) attempt to address those
aspects. Other companies such as Opera Bio uses new secretion
tech to increase ease of product capture while reducing risk of
endotoxin.
Digitization/automation: Ideally bioproduction would
work like many industrial production facilities which are highly
automated. Many large companies help in Stage initial digitization
Metronik, Metastorm, Veeva. Invert Bio, Seeq, Ganymede, Falkonry
help companies undertake more sophisticated automation, leading
to more data collection which can be used to optimize experiments.
How new biomanufacturing companies are different
The types of products being produced with bio is much larger than we have ever seen before (70+ companies that engineer organisms to produce anything from soap to drugs). The types of products being produced puts much more pressure on unit economics. When you don’t have the pricing power of a therapeutic (43% of the prescription drug spend in biologics of drug approvals but only 2% of the prescription drugs prescribed are biologics) but have freedom to experiment with conditions - it leads to many optimization possibilities.
Space and knowledge constraints become massive opportunities for value creation:
Space constraints - Synonym Bio is working to address an upcoming shortage of bioreactor capacity. Other initiatives such as Singapore’s ScaleUp Bio and The Cultivated B. Unlikely players such as Anheuser-Busch have orchestrated BioBrew to use their understanding of fermentation for beer to a much wider suite of products.
Knowledge constraints - very few people know how to scale-up production. The people originating ideas around microbial production of goods typically don’t have the chemical engineering experience to understand fluid dynamics and the difficulties of shearing force in 100L+ bioreactors. This gives players such as Planetary Systems and Boston Bioworks an interesting mote. Moreover, it gives early stage start-ups a suite of knowledge that they need in order to bring products to market. What is normally a service model by these systems could have more relevance if they’re able to capture unique data and exploit that by furthering their own products (e.g. an Amazon basics for biology.)
A lot is happening in bio all at once and the Decoding Bio Snapshot is an effort to contextualize it all. I hope you enjoy reading. Link to the full report here.