Slide 1: Role of MRGPRX2 in Migraine
Role of MRGPRX2 in Migraine April 13, 2026
Slide 2: Forward-Looking Statements
Forward-Looking Statements © Evommune, Inc. This presentation has been prepared by Evommune, Inc. (“we”, “us” or “our”). Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation
Slide 3: Agenda and Speakers
Agenda and Speakers 3 © Evommune, Inc. Luis Peña Evommune President & CEO Jeegar Patel, PhD Evommune CSO Greg Dussor, PhD Professor, UT Dallas EVMN Speakers Stewart Tepper, MD VP, NEINH Professor of Neurology, Dartmouth Introduction Luis Peña Overview of Migraine Stewart Tepper, MD Role of Mast Cell
Slide 4: Our Inflammation Portfolio
Our Inflammation Portfolio © Evommune, Inc. Program / Target Indication Preclinical Phase 1 Phase 2 Phase 3 Next Anticipated Milestone EVO756 MRGPRX2 Chronic Spontaneous Urticaria Phase 2b Data (Q2 2026) Atopic Dermatitis Phase 2b Data (H2 2026) Migraine Phase 2 Trial Initiation (mid-2026) Other Ind
Slide 5: EVO756: Broad Spectrum Oral Anti-Inflammatory Potential
EVO756: Broad Spectrum Oral Anti-Inflammatory Potential MRGPRX2 Expressed on Both Mast Cells and Sensory Neurons Potent and highly selective small molecule Oral convenience could drive adoption across multiple indications Anticipate favorable safety and tolerability profile Potential First-Line Oral
Slide 6: EVO756 Development Roadmap: Demonstrate Proof-of-Concept and Expand into Additional Indications
EVO756 Development Roadmap: Demonstrate Proof-of-Concept and Expand into Additional Indications Initially pursue inflammatory diseases with: Underserved patient population Economic viability Well-defined clinical and regulatory development pathway Cutaneous Neurological Respiratory Other EVO756 Deve
Slide 7: MRGPRX2 is a Novel Migraine Target
MRGPRX2 is a Novel Migraine Target with Potential to Address Neuroinflammatory and Mast Cell Drivers of Migraine Strong Scientific Rationale for EVO756 in Migraine © Evommune, Inc. MRGPRX2 is expressed in human trigeminal neurons and meningeal mast cells Disease-Relevant Expression in vivo headache
Slide 8: High Demand for Preventative Migraine Therapy
High Demand for Preventative Migraine Therapy © Evommune, Inc. Source: Clarivate “Migraine: Disease Landscape and Forecast” (February 2026). Note: Sales represent 7 Major Markets (US, EU5, Japan); Percent of patients by therapy type exceeds 100% due to co-prescribing; % patient numbers by therapy re
Slide 9: Innovation in Migraine Prevention Has Been Limited to CGRPs
Advanced Treatments Class Route of Administration CGRP Oral QD Oral EOD IV SC SC SC Neurotoxin IM Innovation in Migraine Prevention Has Been Limited to CGRPs © Evommune, Inc. Source: Qulipta Prescribing Information from pivotal trial in chronic migraine patients. Limited Therapeutic Diversity Only C
Slide 10: Overview of Migraine
Overview of Migraine Stewart Tepper, MD Vice President, The New England Institute for Neurology and Headache Professor of Neurology, Geisel School of Medicine at Dartmouth
Slide 11: Migraine is Highly Prevalent and Disproportionately Affects Women
Migraine is Highly Prevalent and Disproportionately Affects Women Population-Based Studies Show Consistent Prevalence 4 20 18% 18% say, ~3x higher prevalence in women vs. men 154 12% 13% 12% 7% Migraine Prevalence (%) Ss 6% 6% ; ao | 0 Total Females Males 1989 mmm 1999 Mmmm 2007 Sources: Stewart et
Slide 12: High Prevalence Impacts Patients and Communities
High Prevalence Impacts Patients and Communities Scale of Disease = ~25% of the population has migrainous illness = ~12% episodic, ~2-4% chronic = Additional 10-20% meet criteria for probable migraine! = ~40M migraineurs in the U.S. (>75M globally) = Prevalence peaks during prime working-age years C
Slide 13: Migraine is a Leading Cause of Disability Worldwide
Migraine is a Leading Cause of Disability Worldwide Global burden of disease study across 328 conditions YLD = Years Lived with Disability. Source: The Lancet (2017, PMID28919117). Age-Standardized YLD Rate per 100,000 in 2016 Annualized Rate of Change in Age-Standardized YLD Rate (2006-2016) 0.03 0
Slide 14: Frequent Attacks Drive Meaningful Functional Impairment
Frequent Attacks Drive Meaningful Functional Impairment Burden exceeding many chronic systemic conditions Sources: Lanteri-Minet et al. (2024, PMID:39160483). Lipton et al. (2001, PMID11554951); Stang and Osterhaus (1993, PMID8436495); Cull et al. (1992). Note: impact metrics pertain to U.S. Attack
Slide 15: Interictal Burden is the Primary Driver of Treatment-Seeking in Migraine
Interictal Burden is the Primary Driver of Treatment-Seeking in Migraine Note: The OVERCOME study evaluated ~100,000 participants with migraine in the US, EU, and Japan. Sources: Ashina S et al. (2024; PMID38785227); Pascual et al. 18th Biennial MTIS 2022; Sep 8 – 11, 2022. MTIS22-EP-018. What Bring
Slide 16: Treatment Paradigm is Shifting Away from Step Therapy
Treatment Paradigm is Shifting Away from Step Therapy Legacy Preventives Lack Efficacy and are Rarely Sustained Step Therapy Fails Patients with Migraine New AHS guidelines recommends removal of non-specific step therapy Charles et al, (2024). Calcitonin gene-related peptide targeting therapies are
Slide 17: Modifications Reflect Instability in Disease Control
Modifications Reflect Instability in Disease Control 50% of Patients Modify Preventive Therapy without Physician Consultation Self-adjustment of these medications poses the potential for serious health effects1 Treatment modifications primarily driven by lack of efficacy and adverse events Patients
Slide 18: CGRP: Scientifically and Clinically Proven, Yet Substantial Room for Improvement
Response Rate (%) 100 mg1 300 mg1 PBO1 70 mg2 140 mg2 PBO2 70 mg2 PBO2 225 mg2 675 mg2 PBO2 120 mg2 PBO2 120 mg2 PBO2 75 mg3 PBO3 10 mg4 30 mg4 60 mg4 PBO4 CGRP: Scientifically and Clinically Proven — Yet Substantial Room for Improvement, Especially for Oral Options Clinical data from pivotal trials
Slide 19: The opportunity for a more fulfilling migraine-free life
“The opportunity for a more fulfilling migraine-free life, with potential impact on society as a whole” The goal should be migraine freedom in prevention, and even with anti-CGRP therapies, we are not there yet!
Slide 20: Key Clinical Insights
Key Clinical Insights Migraine is the most common neurologic illness and a leading cause of disability, with profound impact on patients, families, and society Interictal burden—the pervasive impact between attacks—is a primary driver of treatment-seeking Older non-specific preventive therapies are
Slide 21: Role of Mast Cells and MRGPRX2 in Migraine
© Evommune, Inc. Role of Mast Cells and MRGPRX2 in Migraine Greg Dussor, PhD Professor, Department of Neuroscience The University of Texas at Dallas
Slide 22: Migraine Pain Arises from Activation of the Trigeminovascular System
Migraine Pain Arises from Activation of the Trigeminovascular System © Evommune, Inc. Migraine involves heightened sensitivity of sensory pathways Pain arises from activation of trigeminal afferents that innervate the meninges Activated trigeminal neurons release neuropeptides — CGRP, PACAP, VIP, Su
Slide 23: Trigeminal Neurons and Meningeal Mast Cells as Key Components of Migraine Biology
Trigeminal Neurons and Meningeal Mast Cells Increasingly Recognized as Key Components of Migraine Biology © Evommune, Inc. Right Time, Right Place Abundant in meninges and perivascular spaces – regions innervated by trigeminal neurons Neuroimmune Communication Trigeminal neuropeptides (CGRP, PACAP,
Slide 24: MRGPRX2: Positioned to Address Neuronal and Mast Cell Drivers of Migraine
MRGPRX2: Positioned to Address Neuronal and Mast Cell Drivers of Migraine © Evommune, Inc. Source: Evommune internal data (trigeminal neurons; in situ hybridization on human tissue samples), PMID40712576 (meningeal mast cells) Expression Confirmed in Disease-Relevant Tissues MRGPRX2 nuclei Trigemina
Slide 25: PACAP Triggers Migraine via MRGPRX2 as Primary Receptor in vivo
PACAP Triggers Migraine via MRGPRX21 as Primary Receptor in vivo © Evommune, Inc. 1. Mrgprb2 is rodent homologue. 2. In grams, measured via Orbital von Frey assessment. Source: Internal Evommune data. Confirms data published in PMID37516794. Facial withdrawal threshold2 in vivo data support function
Slide 26: MRGPRX2 Ligands Induce Migraine in Humans
MRGPRX2 Ligands Induce Migraine in Humans PACAP, VIP, Substance P are Known MRGPRX2 Agonists © Evommune, Inc. Note: Data shown from PACAP-38; PACAP-27 also induces migraine. Sources: Adapted from PMID19052139, PMID34357396, PMID37009867, Al-Khazali et al., (2026). Note that there have been multiple
Slide 27: PACAP Likely Induces Migraine in Humans Through MRGPRX2
PACAP Likely Induces Migraine in Humans Through MRGPRX2 as Primary Receptor © Evommune, Inc. 1. Trigeminal sensory neurons, brainstem pain circuits, hypothalamus, cortex, thalamus. Note: In addition to MRGPRX2 PACAP binds PAC1, VPAC1, VPAC2, but PAC1 inhibition (Amgen’s AMG301: PAC1 blocking mAb.) d
Slide 28: PACAP Inhibition Achieves CGRP-Like Efficacy in Migraine Prophylaxis
PACAP Inhibition Achieves CGRP-Like Efficacy in Migraine Prophylaxis © Evommune, Inc. Note: Lundbeck’s bocunebart is a humanized mAb that neutralizes PACAP. Results above from Phase 2 a study in migraine prophylaxis (HOPE; N=237; single IV administration of bocunebart in patients that were a mix of
Slide 29: EVO756 Migraine Development Program
© Evommune, Inc. EVO756 Migraine Development Program Jeegar Patel, PhD Evommune CSO
Slide 30: Neuropeptides that Trigger Migraine Signal Through MRGPRX2
3 Neuropeptides that Trigger Migraine Signal Through MRGPRX2 Neuropeptide Preclinical Evidence Induced Headache in Humans Clinical Validation PACAP VIP TBD Substance P TBD MRGPRX2 Inhibition May Offer Broader Migraine Benefit than Targeting PACAP Alone © Evommune, Inc. Note that PACAP also binds PAC
Slide 31: EVO756 Potently Inhibits PACAP, Substance P and VIP-Induced MRGPRX2 Activation in vitro
EVO756 Potently (low nM) Inhibits PACAP, Substance P and VIP-Induced MRGPRX2 Activation in vitro © Evommune, Inc. All assays (agonists) run at ≥EC80. Primary skin MC: CD63; similar experiment run on primary skin mast cells with CD107a with similar results. EVO756 Inhibits PACAP and SP-Induced Primar
Slide 32: EVO756 has Front-Line Therapy Potential in Migraine
EVO756 has Front-Line Therapy Potential in Migraine EVO756 Positioned for Broader Efficacy Than Single-Ligand Strategies © Evommune, Inc. Dual Action MOA Dampens neuroinflammatory signaling and attenuates neuronal sensitization Multi-Neuropeptide Coverage Blocks multiple migraine-triggering pathways
Slide 33: Phase 2b Dose-Ranging Trial in Migraine Prophylaxis
Phase 2b Dose-Ranging Trial in Migraine Prophylaxis Initiation Expected Mid-2026 © Evommune, Inc. BL = Baseline; CFB = change from baseline; MMD = monthly migraine days; MHD = monthly headache days; QoL = quality of life BL Adults with Refractory Migraine ≥6 Days/Month (N ≈ 330) Screening Enrollment
Slide 34: Closing Remarks
© Evommune, Inc. Closing Remarks Luis Peña Evommune President & CEO
Slide 35: EVO756 Well-Positioned to be Meaningful Potential New Therapy in Migraine Prophylaxis
EVO756 Well-Positioned to be Meaningful Potential New Therapy in Migraine Prophylaxis © Evommune, Inc. Evommune internal estimation from DRG, Evaluate Pharma and KOL interviews; Biohaven Market Research 2021. Novel dual mechanism may address broad population with potential for efficacy comparable or
Slide 36: Role of MRGPRX2 in Migraine
Role of MRGPRX2 in Migraine April 13, 2026