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Pipeline

FGF21: TODD-B-001

Structure-based design of TODD-B-001 with enhanced
potency & heating-mediated purification

5.27-fold

higher potency

Modified HEK293 cells used for reporting FGFR1c/f3-Klotho activity was treated with the wild type htFGF21 (htWT), htM2, htM3, and htM5 at the indicated concentration for 6 h.

  • TODD proprietary FGF21 point-mutations
  • High affinity for β-Klotho and enhanced FGFR1c activiation
  • Better translation to human pharmacology

High affinity for β-Klotho and enhanced FGFR1c activiation

Enhanced β-Klotho affinity

Kinetic rate constants for β-Klotho by Surface Plasmon Resonance

Cell-based activity tests of htM2, htM3, and htM5

M2: Q201H/A208T
M3: S195G/P199G/S200G
M5: S195G/P199G/S200G/Q201H/A208T

Reference: Jung, YE., Lee, K.W., Cho, J.H. et al. Heating-mediated purification of active FGF21 and structure-based design of its variant with enhanced potency. Sci Rep 13, 1005 (2023). https://doi.org/10.1038/s41598-023-27717-x

High affinity for β-Klotho and enhanced FGFR1c activiation

In vivo activity tests of FGF21 variants

HFD-fed mice were injected with the wild type htFGF21 (htWT) or htM5 intraperitoneally at doses of 0.1 or 0.5 mg/kg once daily for 14 days.

In silico immunogenicity prediction

Immunogenicity for T cell epitope by TepiTool

Immunogenicity for B cell epitope by Kolaskar and Tongaonkar antigenicity prediction

Better translation to human pharmacology

In silico immunogenicity prediction

2000-fold minimum effective concentration

* There were no unscheduled deaths and clinical abnormality in all study animals

In silico immunogenicity prediction

Results of cell test

Reference: Jung, YE., Lee, K.W., Cho, J.H. et al. Heating-mediated purification of active FGF21 and structure-based design of its variant with enhanced potency. Sci Rep 13, 1005 (2023). https://doi.org/10.1038/s41598-023-27717-x

Temperature-reversibility of FGF21 and Proprietary heating mediated purification

Reversibility of FGF21

Heat treated FGF21 is active in vitro

DLS analysis

Reference: Jung, YE., Lee, K.W., Cho, J.H. et al. Heating-mediated purification of active FGF21 and structure-based design of its variant with enhanced potency. Sci Rep 13, 1005 (2023). https://doi.org/10.1038/s41598-023-27717-x

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