Slide 1: A New In Vivo Platform for Discovery of Novel Mini-Proteins and Structured Peptides
1 A New In Vivo Platform for Discovery of Novel Mini-Proteins and Structured Peptides AETC: Monday, December 15, 2025 Scientific Briefing #6: 12:15-1:15pm
Slide 2: OmniAb Enables Innovative Antibody Therapeutics
2 OmniAb Enables Innovative Antibody Therapeutics AS OF 9/30/2025 Overview Clinical and Commercial-Stage Partner Pipeline(1) Phase Phase 1 Phase 1 1/1b Phase 1/2 1/2 Phase 2 Phase 3 Registration Approved 1/1b 104 Zhikang Hongyi Cessation Zhikang Hongyi Gloria Merck KGaA Genmab Hanall, Harbour, Immun
Slide 3: OmniAb Technologies
3 OmniAb Technologies TECHNOLOGY OFFERINGS ADDRESSES THE MOST CRITICAL CHALLENGES OF ANTIBODY DISCOVERY Create Screen Deliver Create Diverse Repertoires of Screen Millions of Cells to Find Further Characterize, Select and Optimize High-Quality Antibodies Potential Therapeutic Candidates the Right Th
Slide 4: Introducing OmniUltra
4 Introducing OmniUltra Leveraging evolutionary A new in vivo platform distance for discovery of for discovery of novel ultralong CDRH3 antibodies with mini-proteins and broad epitope coverage structured peptides Christine Vuong, Ph.D. Yasmina Abdiche, Ph.D. Tuesday, December 16, 2025 Monday, Decemb
Slide 5: Overview
5 Overview • Therapeutic Peptides: An Emerging Drug Class ‒ High specificity, low toxicity, and structural adaptability to target diverse biological interfaces ‒ Enhanced drug-like properties of structured vs linear peptides • Nature as a Blueprint ‒ Across the biosphere, convergent structural motif
Slide 6: Importance of Therapeutic Peptides as a Drug Class
6 Importance of Therapeutic Peptides as a Drug Class PEPTIDE DRUGS FULFILL A UNIQUE ROLE IN THE PHARMACEUTICAL INDUSTRY Peptide Drugs Approved by the FDA (2004-2023) 25 • Peptides are a distinct and growing class of drugs approved peptide drugs 21 20 blending properties of small molecules and antibo
Slide 7: Advantages of Structured Peptides for Drug Discovery
7 Advantages of Structured Peptides for Drug Discovery enhanced drug-like properties • Peptides are structurally adaptable • Structured peptides can be engineered using nature-inspired and synthetic approaches • Techniques include constrained peptides (cyclic, stapled, knotted) and CDR-grafting into
Slide 8: Convergent Structural Motifs in the Biosphere
8 Convergent Structural Motifs in the Biosphere Cow antibody ‘knob’ ShK peptide (potent Kv1.3 inhibitor) RSCIDTIPKSRCTAFQCKHSMKYRLSFCRKTCGTC Pohl et al, Lett Pept Sci 1995 Wang et al, Cell 2013 Ultralong CDRH3 antibodies potentially combine biological potency with high target specificity
Slide 9: Alternative Antibody Binding Modes to Kv1.3 Ion Channel
9 Alternative Antibody Binding Modes to Kv1.3 Ion Channel CRYO-EM STRUCTURES REVEAL HOW CDRH3 LENGTH IMPACTS BINDING MODE Fusing the ShK peptide (from sea anemone) *Nanobodies (~15kDa) bind turret onto a human Fab mimics an UL CDRH3 loops atop (not within) pore antibody and binds within pore Selvaku
Slide 10: Ultralong CDRH3: Cow vs. Human
10 Ultralong CDRH3: Cow vs. Human glycans CDRH3 knob HIV gp120 One protomer stalk (gp120+gp41) of the HIV envelope trimer VL BG505 SOSIP.664 VH knob CH1 CL VL VH Human Fab Cow Fab Cows can generate antibodies with knob-defined paratopes Vadnais et al, Curr Opin Struct Biol 2016 Stanfield et al, Sci
Slide 11: OmniUltra
11 OmniUltra NEW IN VIVO TECHNOLOGY FOR PEPTIDE DRUG DISCOVERY Uses in vivo optimization of ultralong CDRH3 ‘knob’ sequences expressed in the context of a human variable (V) framework Generates structured peptides that autonomously bind to human drug targets Leverages a divergent host species to evo
Slide 12: Traditional Methods for Peptide Drug Discovery
12 Traditional Methods for Peptide Drug Discovery COMBINATORIAL CHEMISTRY & RATIONAL DESIGN: CONCEPTUALLY DISTINCT YET COMPLEMENTARY Phage Display of Combinatorial Libraries Rationally-Designed Libraries Discovery-oriented Optimization-focused Cyclization Substituting non-natural AAs Phage C-term pa
Slide 13: Complementary Peptide Discovery Approaches
13 Complementary Peptide Discovery Approaches Method Pros Cons Combinatorial Chemistry Fixed libraries Synthesizes libraries of diverse compounds to Chemical diversity Limited by synthesis 'cast a wide net' and then screens for activity Display Technologies Screens millions of variants Fixed librari
Slide 14: Advantages of OmniUltra vs. Cow
14 Advantages of OmniUltra vs. Cow • Only 10% of cow antibodies contain the UL CDRH3 feature, and all rely on a bovine framework • Knob domain structures vary, and not all cysteine patterns enable independent binding • Discovery campaigns generally use one or two cows instead of standard laboratory
Slide 15: OmniUltra Workflow: From Knobs to Picobodies
15 OmniUltra Workflow: From Knobs to Picobodies REDEFINING PEPTIDE INNOVATION: PRECISION PEPTIDES OPTIMIZED IN VIVO Hit ID Hit Confirmation Peptide production Native VH+VL Native VH Native stalk + knob Native knob Picobodies 4 kDa Chemical Synthesis 6 kDa Cleaved from Germline VL Germline VH + Germl
Slide 16: OmniUltra Clones with Knob-Restricted Paratopes
16 OmniUltra Clones with Knob-Restricted Paratopes SPR BINDING KINETICS CONFIRM HIGH AFFINITY BINDERS TO MULTIPLE TARGETS Native VH Native stalk-knob on germline VH Native knob on germline VH
Slide 17: OmniUltra Clones with Knob-Restricted Paratopes
17 OmniUltra Clones with Knob-Restricted Paratopes SPR BINDING KINETICS CONFIRM HIGH AFFINITY BINDERS TO MULTIPLE TARGETS Native VH Native stalk-knob on germline VH Native knob on germline VH Specific to B7-H3: Clone 1 Clone 2 Clone 3 Clone 4 Clone 5 Knobs that retain high affinity within a fully ge
Slide 18: Tethering OmniUltra Stalk-Knobs for Bispecifics: EGFR
18 Tethering OmniUltra Stalk-Knobs for Bispecifics: EGFR OmniUltra IgG (EGFR) Stalk-knob (EGFR) Stalk-knob <3-fold (EGFR) affinity loss Trastuzumab IgG Trastuzumab IgG (HER2) (HER2) Native VH Stalk-knob-IgG N-term Heavy Chain Stalk-knob-IgG N-term Light Chain KD = 9.3 nM KD = 38 nM KD = 35 nM #1 Omn
Slide 19: Isolating Knobs as Autonomous Binding Units: EGFR
19 Isolating Knobs as Autonomous Binding Units: EGFR CONVERTING OMNIULTRA ANTIBODIES INTO SYNTHETIC PEPTIDES WHILE PRESERVING AFFINITY Anti-EGFR picobody (monovalent analyte) Recombinant Cleavage and stalk-knob isolation peptide Chemically synthesized EGFR-Fc (ligand) (6 kDa) Stalk-knob knob peptide
Slide 20: Nature-Inspired Peptide Innovation
20 Nature-Inspired Peptide Innovation Key Advantages • Proprietary In Vivo Platform – A breakthrough approach for peptide discovery that’s potentially more dynamic and efficient than traditional methods or cow-based immunization • Knob-Derived Peptides – Deliver antibody-like binding precision with
Slide 21: OmniUltra: Leveraging evolutionary distance for the discovery of ultralong CDRH3 antibodies
21 Tuesday, December 16th 12:35 p.m. – 1:05 p.m. Pacific Ballroom 15 OmniUltra : Leveraging evolutionary distance for the discovery of ultralong CDRH3 antibodies with broad epitope coverage Poster 126: Development of OmniUltra : A transgenic chicken system for the generation of ultralong CDRH3 antib