Oruka Therapeutics : March 6, 2025 AAD 2025 — Characterization of ORKA 002
ORKA
#64919
Characterization of ORKA-002, a Novel Extended Half-life Monoclonal Antibody Targeting IL-17A/F for the Treatment of Psoriasis and Other Indications
1Paragon Therapeutics, Waltham, MA, United States; 2Departments of Dermatology and Medicine, Division of Rheumatology, UT Southwestern Medical Center, Dallas, TX, USA; 3Blauvelt Consulting, LLC, Portland, OR, USA; 4Oruka Therapeutics, Menlo Park, CA, and Waltham, MA, USA
Introduction
ORKA-002: A novel highly specific extended half-life monoclonal antibody targeting IL-17A and F
'YTE' amino acid substitutions increase the pH-dependent affinity of the Fc region for FcRn, extending antibody half-life
• M252Y/S254T/T256E
("YTE") substitution to the
Fc region of antibodies increases the pH-dependent binding affinity to FcRn
• YTE substitution results in increased antibody recycling, causing less lysosomal degradation and thus a prolonged half-life
©2024 FigureO r ukadapteda TfromherApogeeapeuticTherapeuticss
Fig. 1: ORKA-002 binds IL-17A and F at a similar epitope as bimekizumab with similar affinity
Fig. 2: ORKA-002 shows similar potency to bimekizumab across multiple in vitro assays
IL-17A surface
ORKA-002
epitope
Bimekizumab
epitope
ORKA-002
IL-17A
IL-6 secretion from NHDF
NFκB activation in reporter cell line
0.01
0.1
1
IC50 (nM)
B
100
κNF
80
fo
60
Inhibition%
40
20
0
0.00010.001
0.01
0.1
1
10
[Ab] (nM)
Bimekizumab
IL-17F
0.1
1
10
100
IC50 (nM)
0 .1
1
1 0
1 0 0
1 0 0 0
[A b ] (n M )
Abbreviations: NHDF, normal human dermal fibroblasts
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Fig. 3: ORKA-002 demonstrates a significantly extended half-life
in non-human primates (NHP) compared to bimekizumab
Pharmacokinetics of ORKA-002 vs. bimekizumab in NHPs
Plasma concentration (µg/mL)
1000
100
10
0
10
20
30
40
50
Time Post-Injection (days)
Half-life (d)
ORKA-002
(IV)
31
ORKA-002
(SC)
32
Bimekizumab (IV)
9
Bimekizumab (SC)
10
ORKA-002 has a >3-fold longer half-life than bimekizumab in NHPs
Notes: Study completed at Day 49
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Fig. 4: Predictive simulations of ORKA-002 PK in humans
support dosing every four to six months
Projected exposure of illustrative ORKA-002 regimens vs. approved bimekizumab regimens
ORKA-002 (~50d half-life):
ORKA-002 (~75d half-life):
Bimekizumab: 320 mg
320 mg W0, 4 then Q4M
320 mg W0, 4 then Q6M
W0, 4, 8, 12, 16 then Q8W
50
Cmax bimekizumab
40
Q4W maintenance
g/mL)μ(
30
[Ab]
20
10
Ctrough bimekizumab
Q8W maintenance
0
0
8
16
24
32
40
48
56
64
72
0
8
16 24 32 40 48 56 64 72 80
Weeks
Weeks
Notes: Bimekizumab modeling, Cmax, and Ctrough are based on published PK parameters from FDA and EMA review documents
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Conclusions
Disclosures: BK, GF, JM, JM, DR, JO, and HS are employees and stockholders of Paragon Therapeutics; CF, EV, and JS are employees of Oruka Therapeutics;
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AB, CF, EV, JS are stockholders of Oruka Therapeutics
Disclaimer
Oruka Therapeutics Inc. published this content on March 06, 2025, and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on March 07, 2025 at 13:52:40.761.