Cure
Applications & Impact.
The combination of expanded chemistry and scalable peptide and protein manufacturing opens territory that conventional biologics development cannot enter. Here are some therapeutic categories where Constructive’s platform creates the clearest clinical and commercial advantage — the molecules that become manufacturable when the constraints of conventional chemistry no longer apply.
Medicine is our proving ground. Everything we make here demonstrates what expanded biology can do.
Pipeline and therapeutic programs
Traditional antibody-drug conjugation (ADC) creates heterogeneous mixtures — variable drug-to-antibody ratios, inconsistent potency, and toxicity associated with over-loaded antibodies. Defined, site-specific conjugation handles installed through BioForge eliminate that heterogeneity. The result is homogeneous ADCs and other peptide and protein conjugates with exact conjugation ratios, reproducible manufacturing, and an optimised therapeutic window — improving both patient outcomes and the consistency of clinical development.
Cytokines are powerful therapeutic agents with a fundamental problem: systemic toxicity at effective doses. Site-specific incorporation of non-canonical amino acids addresses this directly. By placing chemical modifications — conjugations, masking groups, half-life extenders — at defined positions within the cytokine sequence, it becomes possible to engineer molecules with improved selectivity, controlled activation, and more favourable pharmacokinetic profiles. The result is a new class of engineered interleukins and cytokines for a broad range of diseases.
Most biologics bind their targets reversibly, requiring sustained high drug concentrations to maintain therapeutic effect. Covalent binding chemistry — reactive warheads installed at precise positions in a protein sequence — enables controllable target engagement, prolonged pharmacological effect, and reduced dosing frequency. Constructive installs covalent chemistry into biologics architecturally, not through post-synthesis conjugation. The warhead is where it needs to be, from the first production run.
Many of today’s most valuable peptide drugs must be administered by injection. Oral peptides that survive the gastrointestinal environment face a second barrier: poor membrane permeability limits absorption into systemic circulation. Constructive is developing a pipeline of peptides engineered with non-canonical amino acids with novel membrane-penetrating properties, opening a path to oral bioavailability for molecules that have historically required injection.
Use case:
Antibody-Drug Conjugates
THE CHALLENGE
Traditional ADC conjugation creates mixtures with 0-8 drugs per antibody. This heterogeneity leads to:
- Batch-to-batch variability
- Inconsistent efficacy
- Increased toxicity from over-loaded antibodies
THE SOLUTION
Install click chemistry handles (e.g., azide or tetrazine) at precise positions for:
- Defined drug-antibody ratio (e.g., exactly 2-4 drugs)
- Reproducible manufacturing
- Optimal therapeutic window
CLINICAL IMPACT
Improved patient outcomes through consistent dosing and reduced side effects
Use case:
Covalent Biologics
THE CHALLENGE
Most biologics bind reversibly, requiring sustained high concentrations. This leads to:
- Frequent dosing requirements
- Limited duration of action
- Off-target effects from high systemic exposure
THE SOLUTION
Install reactive warheads at specific positions adjacent to binding sites for:
- Irreversible covalent bond formation with target
- Prolonged pharmacological effect
- Reduced dosing frequency
CLINICAL IMPACT
Long-lasting therapeutic effect with lower systemic exposure and improved patient compliance
The manufacturing advantage, applied.
Every programme in the Cure portfolio is enabled by BioForge. The molecules described above are not new concepts. Precision ADCs, covalent biologics, protease-resistant oral peptides: these ideas have been in development for years. What has been missing is a manufacturing platform capable of producing them reliably, at scale, and economically.
BioForge is that platform. It is why Constructive’s pipeline programs can advance on molecules that other development approaches have been forced to abandon or simplify.
Beyond pharma: medicine as proof of concept.
Biology is the most sophisticated manufacturing system on Earth. The same capabilities that allow BioForge to produce a site-specific ADC also allow it to produce sequence-defined biopolymers, functional protein-based materials, and advanced sustainable chemicals.
Medicines are where Constructive proves the platform. The bioeconomy is where it scales. Advanced materials, agricultural biologics, and industrial biomanufacturing each represent applications of the same fundamental capability: programmable production of proteins with chemistries beyond those found in nature.
As the platform matures, Constructive’s expanded chemistry becomes a foundation for manufacturing categories that don’t yet fully exist.
We welcome partnerships to drive forward your therapeutic programmes and to co-develop assets within our internal pipeline.
REFERENCES
Synthesis of site-specific antibody–drug conjugates using unnatural amino acids
PNAS 109, 16101–16106 (2012)
Demonstrates that genetically encoded unnatural amino acids enable homogeneous ADCs with precise conjugation site and stoichiometry control, producing conjugates with superior pharmacokinetics and complete tumour regression in preclinical models.
Angewandte Chemie International Edition 57, 2831–2834 (2018)
From the Chin Lab at MRC-LMB: describes site-specific incorporation of a cyclopropene-lysine derivative into trastuzumab using genetic code expansion, enabling rapid, homogeneous ADC conjugation, the approach directly applicable to Constructive’s ADC programme.
Scientific Reports 11, 22521 (2021)
Illustrates how substituting protease-vulnerable sites in GLP-1 with modified amino acids enables oral delivery with meaningful bioavailability, the scientific basis for both the GLP-1 analogue and oral peptide therapeutic programmes in Constructive’s pipeline.
Total synthesis of Escherichia coli with a recoded genome
Nature 569, 514–518 (2019)
The foundational Syn61 paper.
