Pipeline
Small molecules against intrinsically disordered proteins, advancing from discovery toward the clinic
One Product Engine, many disordered targets
Peptone's Product Engine generates small-molecule drug candidates against intrinsically disordered proteins. It measures protein dynamics, builds experimentally grounded ensemble models, designs binders against transient pockets, and returns candidates to the laboratory for biological validation across oncology, CNS disease, immunology and inflammation, and longevity.
Programs
Each program advances across six development stages, from discovery to the clinic. Select a program to expand its target, approach, and development detail.
AR-NTD antagonist
AR-NTD antagonist
Target
The androgen receptor N-terminal domain (AR-NTD) carries the receptor's main transcriptional activation function and stays intrinsically disordered in isolation. Because approved antiandrogens bind the ligand-binding domain, splice variants and ligand-independent signalling through the NTD remain a driver of resistance in castration-resistant disease.
Approach
Peptone maps the transient pockets that appear across the AR-NTD ensemble using HDX-MS and GPU-accelerated modelling, then designs binders that stabilise a conformation which cannot recruit the transcriptional machinery. The result is a fully synthetic small molecule rather than a biologic.
Preclinical
Preclinical work shows target-dependent suppression of AR-driven transcription in cell lines that no longer respond to ligand-binding-domain inhibitors, with activity retained against common AR splice variants. Mechanism-of-action studies are advanced with academic partners at IOR and The Royal Marsden.
Development Plan
The program is at the development candidate stage, where candidate characterisation and development planning precede IND-enabling studies. Collaborations continue to deepen disease biology and MoA understanding.
c-Myc antagonist
c-Myc antagonist
Target
c-Myc is a transcription factor that is disordered outside of its complex with MAX and is deregulated across a broad range of cancers. Direct pharmacological control of c-Myc has been considered undruggable because it presents no classical binding pocket.
Approach
Peptone applies its Product Engine to characterise the conformational ensemble of c-Myc and to search for binders that disrupt its productive interactions. This extends the same disorder-first discovery work beyond aggregation targets into transcriptional biology.
Preclinical
Lead optimization work focuses on improving the emerging chemical series against defined disordered regions. Mechanism-of-action studies are advanced with Prof. Marc Mansour at UCL Cancer Institute in MYC-driven leukaemia and transcriptional models.
Development Plan
The program is in lead optimization, where chemical series are pressure-tested in disease models to support later candidate selection.
TDP-43 aggregation modulator
TDP-43 aggregation modulator
Target
TDP-43 is an RNA-binding protein with a long intrinsically disordered low-complexity domain. In disease it mislocalises from the nucleus and assembles into cytoplasmic aggregates, a pathology shared across most amyotrophic lateral sclerosis and a large fraction of frontotemporal dementia cases, which makes the disordered domain itself the object of therapeutic design.
Approach
Peptone profiles the transient contacts within the low-complexity domain that drive phase separation and aggregation, then designs binders that favour soluble, assembly-incompetent states while preserving the protein's normal RNA-processing role.
Preclinical
Biophysical and cellular assays confirm target engagement and read out reduced aggregation, guiding selection of a chemical series. Disease biology and mechanism-of-action studies are advanced with Prof. Leonard Petrucelli at Mayo Clinic.
Development Plan
The program is in lead optimization, where the chemical series is being refined using collaboration-backed proteinopathy models ahead of candidate selection.
Alpha-synuclein aggregation modulator
Alpha-synuclein aggregation modulator
Target
Alpha-synuclein is a small intrinsically disordered protein whose misfolding and aggregation into oligomers and fibrils is a hallmark of Parkinson's disease and other synucleinopathies. Its lack of a stable fold has made it a classic undruggable target for conventional structure-based design.
Approach
Rather than chasing a fixed pocket, Peptone measures the transient contacts that precede aggregation and designs binders that stabilise non-amyloidogenic states of the monomer, lowering the population of aggregation-prone conformers.
Preclinical
Illustrative biophysical and cellular assays show reduced aggregation and preserved physiological behaviour of the target, supporting progression of the chemical series.
Development Plan
This example program is at hit to lead, where confirmed hits are evaluated for potency, selectivity, and central nervous system exposure before lead series selection.
IRF-5 antagonist
IRF-5 antagonist
Target
Interferon regulatory factor 5 (IRF-5) is a transcription factor with intrinsically disordered regions that switch its activity on downstream of innate immune signalling. Common IRF-5 variants are among the strongest genetic links to systemic lupus erythematosus and related autoimmune conditions, yet the protein presents no classical binding pocket for conventional design.
Approach
Peptone applies its Product Engine to characterise the conformational ensemble of IRF-5 and to search for binders that block the interactions it needs to activate inflammatory gene programmes. This extends the same disorder-first discovery work into immunology and inflammation.
Preclinical
Hit-to-lead work is focused on confirming and triaging hits against defined disordered regions of the protein.
Development Plan
This example program is at hit to lead, where confirmed hits are evaluated before progression into a dedicated chemical series.
Partnering and Collaborations
Peptone actively partners with leading academic hospitals and research institutes to deepen mechanism-of-action understanding and disease biology for its compounds. The goal is first-in-class drug candidates built on access to cutting-edge models, patient-derived insight, and translational biology ahead of the field.
Deepening AR-NTD mechanism of action with prostate cancer resistance biology at IOR in Bellinzona.
Collaboration AR-NTD Royal Marsden London, United Kingdom Prof. Johann de Bono Regius Professor of Cancer ResearchAdvancing AR-NTD disease biology with clinical prostate cancer leadership at The Royal Marsden and ICR.
Collaboration c-Myc UCL London, United Kingdom Prof. Marc Mansour Professor of Haematology, UCL Cancer InstituteMapping c-Myc mechanism of action with leukaemia biology and MYC-driven disease models at UCL.
Collaboration TDP-43 Mayo Clinic Jacksonville, United States Prof. Leonard Petrucelli Chair, Department of NeuroscienceAdvancing TDP-43 mechanism of action and proteinopathy biology with Mayo Clinic neurodegeneration research.
Collaboration Protein modeling UCPH Copenhagen N, Denmark Prof. Kresten Lindorff-Larsen Professor of Computational Protein Biophysics, Department of BiologyRevealing rare, transiently structured states in disordered proteins through multithermal simulation and experimental reweighting.
Collaboration AR-NTD PCCTC New York, United States Jake Vinson CEOPreparing AR-NTD programs for clinical development through trial design, endpoint strategy, U.S. site, regulatory, and operational planning.
Collaboration