Platform & Pipeline
Realizing the Promise of Miniproteins
Imagine an Ideal Next-Generation Therapeutic Modality
Specificity
selective binding to the target; no non-specific tissue binding
Safety
no harmful breakdown products; non-immunogenic
Developability
well behaved in vitro and in vivo; simple to formulate and administer
Patentability
protect from potential competitors, fast followers and biosimilars
Versatility
high tissue penetration, and ability to precisely control serum half life and in-tissue residency
Modularity
plug-and-play multivalent constructs or chemical conjugation
Stability
able to withstand high temperature, solvent, acid, proteolysis, denaturants, etc.
Affordability
low cost manufacturing using existing infrastructure
Miniproteins:
Combining the Best Features of Small Molecules and Biologics
peptide that folds into a highly stable structure
optional disulfide bonds
protein surface confers high solubility, no deamidation, and resists oxidation
multivalent constructs via
genetic fusion to the termini
comprised of canonical amino acids and without post-translational modifications
entirely novel
composition of matter
negatively charged to reduce
off-target tissue binding
ability to synthesize chemically or through fermentation
low molecular weight leads to improved tissue penetration and lack of immunogenicity
Miniproteins:
Combining the Best Features of Small Molecules and Biologics
peptide that folds into a highly stable structure
optional disulfide bonds
protein surface confers high solubility, no deamidation, and resists oxidation
multivalent constructs via genetic fusion to the termini
comprised of canonical amino acids and without post-translational modifications
entirely novel
composition of matter
negatively charged to reduce
off-target tissue binding
ability to synthesize chemically
or through fermentation
low molecular weight leads to improved tissue penetration and lack of immunogenicity
From Concept to Candidate
Our proprietary platform has enabled us to repeatedly engineer miniproteins ready for preclinical development in 3-12 weeks.
de novo design of miniprotein binders
yeast & phage
display
automated production
& biophysics
“AWESSM”
deep saturation mutagenesis
in silico design
de novo design of miniprotein binders
- Unique “pre-designed” libraries accelerate discovery of hits with ideal drug-like properties
- Targeted design enables conformationally selective binding to a desired epitope; especially helpful for GPCRs
Screening & Discovery
yeast & phage display
- Because our miniproteins are genetically encodable, we’re able to use yeast and/or phage display to screen libraries >109
- Yeast display allows for more precise selection campaigns, while our automated phage method enables massive parallel screening capacity
Characterization
automated production & biophysics
- Our highly-automated protein production and purification platform has the capability to make ≤ 1,000 miniproteins per week
- We perform biophysical characterization in high-throughput, including circular dichroism spectroscopy to measure structure and stability, and surface plasmon resonance to measure binding activity
Optimization
“AWESSM” deep saturation mutagenesis
- The ability to optimize hits into leads is a longstanding challenge in drug development, as it requires the ability to predict and test many variants, often empirically
- We solved this challenge in a novel way by combining artificial intelligence and synthetic biology, creating a highly differentiated method that rapidly yields optimized miniproteins while also producing vast amounts of useful data
Lead Molecules
- We have the ability to design, discover and optimize miniproteins for multiple targets in parallel
- Because drug-like properties are designed into the miniproteins from the start, every molecule with optimized activity is ready to begin pre-clinical studies
Advancing a Broad and Deep Pipeline
Our proprietary drug discovery engine has already enabled us to validate hits against ~90 targets with unparalleled speed. With initial proof of concept in inflammatory, oncology, and metabolic diseases, we are currently advancing our own pipeline while also exploring partnerships to realize the full value of our innovations.
