Targeting Chronic Inflammation Driven by Mast Cells and Eosinophils with Lirentelimab (AK002) 2 Lirentelimab (AK002) Clinical Summary

• Lirentelimab, an anti-Siglec-8 mAb, has demonstrated activity in several inflammatory diseases – Eosinophilic Gastrointestinal Disorders: Eosinophilic gastritis (EG), duodenitis (EoD), esophagitis (EoE) – Mast Cell Gastrointestinal Diseases (MGIDs) – Chronic urticaria – Indolent systemic mastocytosis – Severe allergic conjunctivitis/atopic diseases

• Strong scientific rationale for development of AK002 in additional indications – Asthma, atopic dermatitis, ulcerative colitis, and other diseases • Studies initiated in 2020 – Phase 3 study in eosinophilic gastritis and/or duodenitis – Phase 2/3 study in eosinophilic esophagitis – EGID/MGID prevalence study – AK002 subcutaneous PK/PD/safety study 3 Confidential Lirentelimab (AK002) Targets Siglec-8 on Mast Cells and Eosinophils 4 Mast Cells and Eosinophils Are Key Drivers of Inflammatory Disease

Allergens

Epithelium

IL-33 CTIVATION AND ECRUITMENT OF THER TSLP A R O IMMUNE CELLS AND TISSUE INFLAMMATION IL- 4 IL-13 NGF, Histamine Histamine IL-5 IL-8 IL-6, TNFa

T Cell B Cell Sub P

IL- 4 IL-13 Sub P

Neuron Smooth Muscle Eosinophil Neutrophil Macrophage Mast Cell ECP, MBP, elastase, MMP, Activated IgE TNFa , IL-1b, TGFb

B Cell Histamine, LTC4, PGD2 and Bronchoconstriction, Tissue damage, fibrosis proteases increased GI motility, pain, itch

SENSITIZATION ACUTE AND CHRONIC INFLAMMATION 5 Mast Cells and Eosinophils Contribute to Allergic and Non-Allergic Inflammation

Mast Cell

Eosinophil

ALLERGEN-MEDIATED MIXED NON-ALLERGEN-MEDIATED

Severe Allergic Conjunctivitis Eosinophilic Gastrointestinal Chronic Urticaria (PAC, VKC) Diseases (EoE, EG, EoD, EC) Indolent Systemic Mastocytosis

Atopic Dermatitis IBD

Severe Allergic Conjunctivitis IBS (AKC) Idiopathic MCAS

Asthma IPF 6 Clinical Program Highlights MOA and MC / Eosinophil role in Disease

Key Findings Eosinophilic • Positive Phase 2 EG/EoD study: significant histological and clinical improvements Gastrointestinal • Strong EoE signal Diseases

• High response rates in multiple forms of antihistamine-resistant chronic urticaria, Chronic Urticaria including omalizumab-refractory and inducible urticaria

Indolent Systemic • Substantial symptom and quality of life improvement Mastocytosis

• Substantial reduction of patient reported ocular symptoms and physician assessed signs Severe Allergic and symptoms Conjunctivitis • Improvements observed in comorbid atopic dermatitis, asthma and rhinitis

• Rapid depletion of eosinophils Healthy Volunteers • Dose-dependent duration of eosinophil depletion 7

Characterizing Eosinophilic Gastrointestinal Disorders (EGIDs) 8 Eosinophilic Gastrointestinal Disorders (EGIDs)

EOSINOPHIL THRESHOLD1

Eosinophilic Esophagitis (EoE) ≥15 / hpf

Eosinophilic Gastritis (EG) ≥30 / hpf

Eosinophilic Duodenitis (EoD) ≥30 / hpf

Many patients with EGIDs remain undiagnosed for years4,5, suggesting a high underdiagnosis rate

1. Collins et al., 2014. 43(1):257-268 and FDA-accepted diagnostic thresholds defined as number of eosinophils (eos) per high powered field (hpf); 2. Jensen et al., 2016; 62(1):36-42; 3. Dellon and Hirano 2018; 154(2):319-332; 4. Chehade et al., 2018; 6(5):1534-1544; 5. Pineton de Chambrun, et al., 2011; 9(11):950-956 9 EG/EoD Patients Endure a Tortuous Path to Diagnosis

Average time from presentation Common alternative diagnoses prior to EG/EoD diagnosis to confirmed EG/EoD diagnosis

50% All patients 47.2 (3.9 years) 40% * Children 36.8 * (3.1 years) 30%

Adolescents 36.8 * (3.1 years) 20% * 10% * * Adults 53.6 (4.5 years) * Proportion of patients 0% 0 20 40 60 Unspecified Gastric/peptic Functional Irritable bowel Months non-infectious ulcer dyspepsia syndrome gastroenteritis and colitis Factors contributing to diagnostic delay: • Delayed GI referral and endoscopy All patients Children Adolescents Adults • Failure to diagnose on first endoscopy • Lack of histopathology evaluation of biopsy samples

Source: Chehade et al., EAACI 2019 and data on file; *P < 0.01 comparing children or adolescents vs adults 10 Mast Cell and Eosinophil Numbers are Elevated in EGIDs

Allergen Eosinophil Mast Cell HEALTHY EGIDs

Lumen Mucosa

Sub- mucosa

Blood Vessel

SOURCE:Youngblood BA, et al. JCI Insights 2019; Collins MH, et al. Frontiers in Medicine. 2018; Dellon ES, et al. DDW 2019. 11 EGID Biopsies Have Elevated Eosinophils & Mast Cells

Esophageal Tissue Gastric Tissue Eosinophils Mast Cells Eosinophils Mast Cells 20 12 15 ** 15 *** ** *** Cells Cells 15 8 10 10 Viable Viable

+ + 10

5 5 4

CD45 5 of CD45 of % % 0 0 0 0 Normal EoE Normal EoE Normal EG/EoD Normal EG/EoD

** p<0.01; *** p<0.001

Increased numbers of eosinophils and mast cells are found across EGIDs

Source: Butuci M, et al. DDW 2020. 12 Eos and Mast Cells Are Activated in EGID Biopsies

Eosinophils Mast Cells

CD49d CD11b CD63 IgE 8000 150000 60000 3000 6000 40000 2000 100000 4000

20000 1000 50000 2000 Expression (MFI) Expression

0 0 0 0 Normal EG Normal EG Normal EG Normal EG *p<0.05

Eosinophils and mast cells both appear to play a pathogenic role

Source: Youngblood B, et al. JCI Insights. 2019 13

ENIGMA Study: AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis 14 ENIGMA Phase 2 Study

Study Design • Randomized, double-blind, placebo-controlled study in EG/EoD with 4 monthly infusions of AK002 or placebo • Active moderate to severe symptoms • Biopsy confirmed EG/EoD – Stomach: ≥30 eos/high powered field (hpf) in 5 hpfs – Duodenum: ≥30 eos/hpf in 3 hpfs • 65 Patients – 3 arms – 22 patients 0.3, 1.0, 1.0, 1.0 mg/kg AK002 – 21 patients 0.3, 1.0, 3.0, 3.0 mg/kg AK002 – 22 patients placebo • 4 monthly doses • Endpoints assessed two weeks after last dose

SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 15 Symptoms Assessed Using Validated Patient-Reported Outcome (PRO) EG/EoD Questionnaire©

• Developed in accordance with FDA guidance on PRO development • Captures the symptoms of EG/EoD patients on a daily basis • Measures 8 symptoms each on a scale of 0-10 (Total Symptom Score 80 points):

- Abdominal pain - Loss of appetite - Nausea - Abdominal cramping - Vomiting - Bloating - Early satiety - Diarrhea

This is the only validated PRO tool for Eosinophilic Gastritis and Eosinophilic Duodenitis

SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 16 Prespecified Hierarchical Analysis Per Protocol

Primary Endpoint • Mean percent change in gastrointestinal eosinophil counts from baseline Responder Secondary Endpoint • Proportion of patients who have: - >75% decrease in tissue eosinophils AND >30% benefit in Total Symptom Score (TSS) Symptoms Secondary Endpoint • Mean percent change in TSS from baseline

Endpoints designed to show (1) tissue eosinophil depletion, (2) symptom improvement, and (3) that these effects occur in the same individuals

SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 17 Confidential Primary Endpoint Met for All AK002 Groups

Baseline Mean %∆ in Eosinophil Eosinophil p - value Treatment Arm Counts / hpf Counts High Dose AK002 76 -97% <0.0001 (n=20) Low Dose AK002 80 -92% <0.0001 (n=19) Combined AK002 78 -95% <0.0001 (n=39) Placebo 75 +10% - (n=20)

SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 18 Confidential AK002 Demonstrates Potent Tissue Eosinophil Depletion

Stomach/Duodenal Eos ≤ 6/HPF

95%* 100% (37/39)

75%

50%

% ofPatients% 25% 0% (0/20) 0% * p <0.0001 AK002 Placebo

37 of 39 AK002 patients had ≤6 eos/hpf & 31 of 39 patients had 0 eos/hpf No placebo patients had ≤6 eos/hpf

SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 19 Confidential AK002 Met Treatment Responder Secondary Endpoint

Treatment p - value Treatment Arm Responders* High Dose AK002 (n=20) 70% 0.0009

Low Dose AK002 (n=19) 68% 0.0019

Combined AK002 (n=39) 69% 0.0008

Placebo (n=20) 5% -

*Treatment responder defined as: >75% reduction in tissue eosinophil counts AND >30% reduction in symptoms (TSS)

SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 20 Confidential AK002 Met Patient Reported Symptoms Secondary Endpoint

Baseline Mean % Total Symptom Change in p - value Treatment Arm Score (TSS) TSS High Dose AK002 34 -58% 0.0012 (n=20) Low Dose AK002 35 -49% 0.0150 (n=19) Combined AK002 34 -53% 0.0012 (n=39) Placebo 30 -24% - (n=20)

SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 21 Confidential Improvement Across All Symptoms Measured on AK002

EG/EoD-PRO Symptom Scores AK002 (n=39)

7 Baseline 6 End of Tx 5 -47% 4 -65% -59% -57% 3 -61% -79% 2 -55% Median Score Median 1 0 -100% -1 Abdominal Nausea Vomiting Early Loss of Abdominal Bloating Diarrhea Pain Satiety Appetite Cramping

SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 22 Response in Concomitant EoE1

Esophageal Eos ≤ 6/hpf2 Severity of Dysphagia3 AK002 Placebo (n=12) (n=8) 0% 93%* 100% (13/14) -17% -25% 75%

50% -50% 11% % ofPatients% 25% -53% (1/9) Mean%∆ from BL 0% -75% AK002 Placebo * p <0.001†

1 25 patients with concomitant EoE (≥15 eos/hpf or history of EoE) and baseline dysphagia 2 Excludes patients with eos < 6/hpf at baseline. At end of treatment, 10/14 AK002 patients had 0 eos/hpf; 2/14 AK002 patients had 1 eos/hpf; 1/14 AK002 patients had 3 eos/hpf; 1/14 AK002 patients had 105 eos/hpf (biopsy occurred 6 weeks post last dose instead of 2 weeks per protocol); 1/9 placebo patients had 2 eos/hpf; 8/9 placebo patients had 19 – 200 eos/hpf 3 All EoE patients with end of treatment dysphagia scores † p = 0.00015 SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 23 Safety Summary

Treatment-Emergent AEs in ≥5% of Patients

AK002 Placebo % of Patients, (n) (n=43) (n=22) • Generally well tolerated Infusion related reaction 60% (26) 23% (5) • Most common Adverse Event (AE) was Headache 9% (4) 9% (2) mild to moderate infusion related Upper respiratory tract infection 9% (4) 9% (2) reactions (IRR) Urinary tract infection 9% (4) 5% (1) Nausea 7% (3) 14% (3) – 93% mild to moderate (flushing, feeling of Fatigue 7% (3) 9% (2) warmth, headache, nausea, dizziness) Diarrhea 5% (2) 9% (2) – Mostly on first infusion, greatly reduced or Nasopharyngitis 5% (2) 9% (2) does not occur on subsequent infusions Abdominal pain 2% (1) 9% (2) – 1 drug-related serious adverse event, an IRR Dehydration 2% (1) 9% (2) which recovered within 24 hours with no Gastroenteritis viral 2% (1) 9% (2) further sequelae Pyrexia 2% (1) 9% (2) • Treatment-emergent serious AEs: Sinusitis 2% (1) 9% (2) Cough 0% (0) 9% (2) 9% on AK002, 14% on Placebo Influenza 0% (0) 9% (2) • No other significant AEs White blood cell count increased 0% (0) 9% (2)

SOURCE:Dellon ES, et al. N Engl J Med. 2020. In Press 24 ENIGMA Summary

• This was the first randomized study in eosinophilic gastritis and duodenitis • Study met all primary and secondary endpoints, demonstrating significant histologic and symptom improvements in EG/EoD • Strong histologic and symptom improvement in EoE • Generally well-tolerated • These results build on clinical activity of AK002 observed in chronic urticaria, severe allergic conjunctivitis, asthma, atopic dermatitis, and indolent systemic mastocytosis 25

Patients with EG/EoD Endure a Tortuous Path to Diagnosis 26 Confidential Steps Required for Diagnosis of EG/EoD

Endoscopy Histopathologic Diagnosis of Presentation with biopsies evaluation EG/EoD

• Nonspecific symptoms • EGD • Standard H&E • ≥30 eosinophils and signs • Multiple biopsies • Quantification of per hpf • History of EoE, allergic from stomach and eosinophils • Rule out other disease, and/or duodenum causes of tissue peripheral eosinophilia eosinophilia (e.g. increase clinical parasitic infection) suspicion

Unlike for EoE, there are no standardized diagnostic guidelines for eosinophilic gastritis (EG) or eosinophilic duodenitis (EoD) 27 Confidential EG/EoD Patients Endured a Diagnostic Delay of ~4 Years

Presentation Diagnosis

All Patients 43.7 (3.7 years)

Adults 48.6 (4.1 years)

Adolescents 33.9 (2.8 years)

Children 36.4 (3.0 years)

0 12 24 36 48 60 Mean months SOURCE:Chehade M. EAACI 2019 28 Confidential Substantial Delay Between Required Diagnostic Steps

Presentation Gastroenterologist Index EGD Diagnosis

All Patients 8.1 12.9 22.8 43.7 (3.7 years)

Adults 9.5 12.8 26.3 48.6 (4.1 years)

Adolescents 4.8 11.9 17.1 33.9 (2.8 years)

Children 6.0 13.3 17.1 36.4 (3.0 years)

0 12 24 36 48 60 EGD, esophagogastroduodenoscopy Mean months SOURCE:Chehade M. EAACI 2019 29 Confidential About 40% of Patients Were Not Diagnosed on Index EGD

80%

70%

60%

50%

40%

30% 62% 62% 64% 62%

20% PercentagePatientsof 38% 38% 36% 38% 10%

0% All patients Adults Adolescents Children

Diagnosed on index EGD Diagnosed on repeat EGD

EGD, esophagogastroduodenoscopy SOURCE:Chehade M. EAACI 2019 30 Confidential Patients Requiring Repeat EGD Endured Longer Dx Delay

6 +1.7 +1.6 +1.6 5 +1.4

4

3 5.1 4.6 Meanyears 2 4.0 3.4 3.7 3.0 1 2.3 2.4

0 All Patients Adults Adolescents Children

Diagnosed on index EGD Diagnosed on repeat EGD

EGD, esophagogastroduodenoscopy SOURCE:Chehade M. EAACI 2019 31 Confidential Patients Do Not Always Undergo Biopsy and Histopathology

Subset of patients (N=1,569) who were not diagnosed on initial EGD

100%

80%

60% 97% 98% 92% 88% 89% 40% 86% 74% 64%

PercentagePatientsof 20%

0% Biopsy Histopathology

All Patients Adults Adolescents Children EGD, esophagogastroduodenoscopy SOURCE:Chehade M. EAACI 2019 32 Confidential EG/EoD Patients Present With Nonspecific GI Symptoms

100% 90% 80% 70% 60% 50% 40% 30%

PercentagePatientsof 20% 10% 0% Abdominal Pain Vomiting Diarrhea Nausea Weight Gastrointestinal Gas/Bloating Loss/Failure to Bleeding Thrive

All Patients Adults Adolescents Children

SOURCE:Chehade M. EAACI 2019 33 About Half of Patients Received Alternative Diagnoses Prior Confidential to Diagnosis of EG/EoD

60%

50%

40%

30%

20%

10% PercentagePatientsof

0% Any Alternative Other Functional Peptic Ulcer Irritable Bowel Diagnosis Gastroenteritis Dyspepsia Syndrome

All Patients Adults Adolescents Children

SOURCE:Chehade M. EAACI 2019 34 This Study Identified Several Reasons for Diagnostic Delay Confidential and Provides Tools to Aid in Prompt Diagnosis

Endoscopy Histopathologic Diagnosis of Presentation X X X with biopsies evaluation EG/EoD

• Non-specific • EGD • Standard H&E • ≥30 eosinophils symptoms and signs • Multiple biopsies • Quantification of per hpf • History of EoE, allergic from stomach and eosinophils • Rule out other disease, and/or duodenum causes of tissue peripheral eosinophilia eosinophilia (e.g. increase clinical parasitic infection) suspicion • Delayed referral to • No collection of • No quantification of eosinophils gastroenterologist biopsies • Number and location of biopsies • Lack of thorough • Biopsy samples not insufficient to capture elevated diagnostic workup sent to pathology lab eosinophilic infiltration due to • Colonoscopy only patchy nature

SOURCE:Chehade M. EAACI 2019 35 Conclusions

• The journey to diagnosis for EG/EoD patients is long and tortuous

• Factors leading to delay in diagnosis – Lack of diagnostic criteria – Delay in referral to a gastroenterologist – Failure to diagnose on first endoscopy – Lack of routine histopathology evaluation

• Heightened disease awareness and standardized EG/EoD diagnostic criteria are needed Allakos is conducting two clinical studies to test the safety and efficacy of experimental drug AK002 for eosinophilic gastrointestinal diseases (EGIDs)

EOSINOPHILIC GASTRITIS AND/OR EOSINOPHILIC DUODENITIS (EG/EOD)

Eosinophilic gastritis (EG) and/or eosinophilic duodenitis (EoD), sometimes referred to as eosinophilic gastroenteritis or EGE, are chronic, inflammatory diseases characterized by high levels of mast cells and eosinophils (two types of immune system cells) in the stomach (gastritis) and/or the upper part of the small intestines known as the duodenum (duodenitis). This study will test whether AK002 can reduce eosinophils in the blood and the tissue of the stomach and/or duodenum and help improve symptoms. If you have been diagnosed with, or think you may have EG and/or EoD, you may be eligible forthis study.

If you experience persistent gastrointestinal symptoms like: WHO IS ELIGIBLE

Abdominal pain Females and males, age 18 to 80 years old who have a confirmed diagnosis of Nausea/Vomiting EG and/or EoD AND/OR have ongoing gastrointestinal symptoms

Diarrhea Early fullness when eating PARTICIPATION DETAILS Cramping Bloating • There is no cost to participate • Qualified participants will receive drugs, lab tests and medical care related to Loss of appetite the study at no cost • Participants are eligible for compensation to cover the cost of timeand travel You may have Eosinophilic Gastritis • Learn more at www.clinicaltrials.gov –NCT#04322604 and/or Eosinophilic Duodenitis (EG and/or EoD)

TO LEARN MORE ABOUT THESE STUDIES, OR TO LOCATE YOUR NEAREST STUDY CENTER, CALL: 1.833.209.8331

EOSINOPHILIC ESOPHAGITIS (EoE) Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease characterized by high levels of mast cells and eosinophils (two types of immune system cells) in the esophagus (muscular tube connecting the mouth to the stomach).This study will test whetherAK002 can reduce eosinophils in the blood and the tissue of the esophagus and help improve symptoms. If youhave been diagnosed with, or think you may have EoE, you may be eligible for this study.

WHO IS ELIGIBLE If youexperience Females and males, age 12 to 80 years old who have a confirmed diagnosis of symptoms like: EoE AND/OR have difficulty swallowing or discomfort when swallowing Difficulty swallowing Painful swallowing PARTICIPATION DETAILS Feeling like food isstuck • There is no cost to participate after swallowing • Qualified participants will receive drugs, lab tests and medical care related to You may have the study at no cost • Participants are eligible for compensation to cover the cost of timeand travel Eosinophilic Esophagitis • Learn more at www.clinicaltrials.gov –NCT#04322708 (EoE)

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