TECHNOLOGY

 
 
 
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Nimble is using its unique maskless chemical synthesis platform to synthesize and systematically discover novel medicines in a variety of therapeutic areas.

Nimble harnesses the power of photolithography and an extensive library of photoprotected amino acids to enable the design, synthesis, and screening of millions of diverse macrocycles at unprecedented speed.

Lead peptides are systematically engineered using the vast scale and chemical diversity of our amino acid library. Our catalog of photoprotected amino acids span both natural and non-natural amino acids including L-, D-, beta, gamma, and N-methyl monomers. We incorporate additional chemical reactions and orthogonal protecting groups to access unique molecular architectures . Nimble libraries are systematically designed using chemical matter that is either discovered or designed specifically with a target's profile in mind.

Accelerating Hit Discovery And Lead Optimization To Preclinical Phase

Nimble has designed a core technology that is powered by a massively parallel chemical synthesis platform. We’ve paired this with a variety of molecule enhancing assay capabilities and robust chemo-informatics to enable rapid discovery and optimization of peptidic compounds with optimal drug-like properties.

Offering Intelligent Libraries With Limitless Possibilities

Our synthesis platform enables intelligent library designs containing millions of peptidic molecules. Our custom amino acid library contains over 350 different amino acids (L-, D-, beta, gamma, non-natural, cyclic backbone modifiers, linkers, etc.) including access to thousands of N-alkyl variants and carboxylic acid capping possibilities. This diverse amino acid catalog coupled with the incorporation of orthogonal protection chemistry enables the systematic discovery of novel linear, macrocyclic and branched molecules.

Integrating Drug Like Properties Into Discovery & Optimization Campaigns

We’ve developed highly parallelized assays that help precisely and efficiently navigate a massive chemical space through rapid structure–activity relationship (SAR) analysis paired with molecule enhancing assays designed to incorporate optimal drug-like properties in the earliest stage of hit discovery to lead optimization.

Proven To Systematically Unlock Novel Chemical Matter

Nimble’s core capabilities have been applied in various studies and have helped unlock new learnings and discoveries.

Publications

  1. Lo KC, et al. "Comprehensive Profiling of Rheumatoid Arthritis Antibody Repertoire." Arthritis Rheumatol. 2019 Aug 26 [Epub ahead of print]. doi: 10.1002/art.41089

  2. Mishra N, et al. (2019) "Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis." mBio. 10(4). pii: e01903-19. doi: 10.1128/mBio.01903-19

  3. Zhou AE, et al. (2019) "Antibodies to Peptides in Semiconserved Domains of RIFINs and STEVORs Correlate with Malaria Exposure." mSphere. 4(2). pii: e00097-19. doi: 10.1128/mSphere.00097-19

  4. Reindl-Schwaighofer R, et al. (2019) "Contribution of non-HLA incompatibility between donor and recipient to kidney allograft survival: genome-wide analysis in a prospective cohort." Lancet. 393(10174): 910-917. doi: 10.1016/S0140-6736(18)32473-5

  5. Yan Y, et al. "Whole genome-derived tiled peptide arrays detect pre-diagnostic autoantibody signatures in non-small cell lung cancer." Cancer Res. 2019 Feb 5 [Epub ahead of print]. doi: 10.1158/0008-5472.CAN-18-1536

  6. Steen J, et al. (2019) "Recognition of Amino Acid Motifs, Rather Than Specific Proteins, by Human Plasma Cell–Derived Monoclonal Antibodies to Posttranslationally Modified Proteins in Rheumatoid Arthritis." Arthritis Rheumatol. 271(2): 196-209. doi: 10.1002/art.40699

  7. Heffron AS, et al. (2018) "Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques." PLoS NTD. 12(11): e0006903. doi: 10.1371/journal.pntd.0006903

  8. Mishra N, et al. (2018) "Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay." MBio. 9(2): e00095-18. doi: 10.1128/mBio.00095-18

  9. Tokarz R, et al. (2018) "A multiplex serologic platform for diagnosis of tick-borne diseases." Scientific Reports. 8: 3158. doi: 10.1038/s41598-018-21349-2

  10. Bailey A, et al. (2017) "Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection." PLoS Pathogens. 13(10): e1006692. doi: 10.1371/journal.ppat.1006692

  11. Steffen W, et al. (2017) "Discovery of a microbial transglutaminase enabling highly site-specific labeling of proteins." J Biol Chem. 292(28): 15622-35. doi: 10.1074/jbc.M117.797811

  12. Lyamichev, V. I., Goodrich, L. E., Sullivan, E. H., Bannen, R. M., Benz, J., Albert, T. J., & Patel, J. J. (2017). Stepwise evolution improves identification of diverse peptides binding to a protein target. Scientific reports, 7(1), 12116. https://www.nature.com/articles/s41598-017-12440-1

  13. Zandian A, et al. (2017) "Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy." J Proteome Res. 16(3): 1300-13. doi: 10.1021/acs.jproteome.6b00916

  14. Ch-ng JH, et al. (2017) "Epitopes of anti-RIFIN antibodies and characterization of rif-expressing Plasmodium falciparum parasites by RNA sequencing." Scientific Reports. 7: 43190. doi: 10.1038/srep43190

  15. Häggmark-Månberg A, et al. (2016) "Autoantibody targets in vaccine-associated narcolepsy." Autoimmunity. 49(6): 421-433. doi: 10.1080/08916934.2016.1183655

  16. Engmark M, et al. (2016) "High-throughput immuno-profiling of mamba (Dendroaspis) venom toxin epitopes using high-density peptide microarrays." Scientific Reports. 6: 36629. doi: 10.1038/srep36629

  17. Hansen CS, et al. (2016) "Linear epitope mapping of peanut allergens demonstrates individualized and persistent antibody binding patterns." J Allergy Clin Immunol. 138: 1728-30. doi: 10.1016/j.jaci.2016.06.019

  18. Qundos U, et al. (2016) "Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients." Proteomics Clin Appl. 10: 681-90. doi: 10.1002/prca.201400167

  19. Christiansen A, et al. (2015) "High-throughput sequencing enhanced phage display enables the identification of patient-specific epitope motifs in serum." Scientific Reports. 5: 12913. doi: 10.1038/srep12913

  20. Edqvist PH, et al. (2015) "Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma." Gynecol Oncol. 137(3): 529-37. doi: 10.1016/j.ygyno.2015.03.055

  21. Edfors F, et al. (2014) "Immunoproteomics using polyclonal antibodies and stable isotope-labeled affinity-purified recombinant proteins." Mol Cell Proteomics. 13(6): 1611-24. doi: 10.1074/mcp.M113.034140

  22. Forsström B, et al. (2014) "Proteome-wide epitope mapping of antibodies using ultra-dense peptide arrays." Mol Cell Proteomics. 13(6): 1585-97. doi: 10.1074/mcp.M113.033308