Corporate Update January 2024 Developing Therapeutic Antibodies Targeting Allergic, Inflammatory and Proliferative Disease Exhibit 99.1
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Agenda Robert Alexander, CEO Introduction Craig Paterson, CMO Results of ATLAS and MAVERICK Phase 2 Studies Baird Radford, CFO Restructuring and Financial Implications Robert Alexander, CEO AK006 Program Update Q&A
ATLAS: Phase 2 Study of Lirentelimab in Atopic Dermatitis
Phase 2 Atopic Dermatitis Study Design Multi-center, randomized, DB, placebo-controlled Chronic disease that has been present ≥3 years EASI score ≥16 Involvement of ≥10% of body surface area IGA score ≥3 Inadequate control by topical treatments Includes patients with prior biologics treatment 131 adult patients (1:1 randomization) 300 mg Q2W subcutaneous lirentelimab Placebo Enrolled from 53 Sites in the US and Germany Primary Endpoint Proportion of patients who achieve eczema area and severity index (EASI)-75 at week 14 Key Secondary Endpoints Percent change in EASI from baseline to week 14 Proportion of patients who achieve an IGA score of 0 or 1 AND a ≥2-point improvement in Investigator Global Assessment (IGA) at week 14 Study Design Endpoints
ATLAS: Baseline Demographics & Patient Characteristics Baseline Characteristics (mITT population) Phase 2 ATLAS (AD) Patient Characteristics Lirentelimab n=61 Placebo n=61 All n=122 Age (years), median (IQR) 39 (31-54) 35 (26-49) 37 (26-53) Female sex, n (%) 32 (52.5%) 34 (55.7%) 66 (54.1%) White, n (%) 39 (63.9%) 33 (54.1%) 72 (59.0%) From US Sites, n (%) 49 (80.3%) 49 (80.3%) 98 (80.3%) BMI (kg/m2), median (IQR) 27.5 (24.1-34.3) 29.3 (24.0-31.9) 28.1 (24.0-33.3) Duration of AD diagnosis (years), median (IQR) 22.4 (7.7-32.3) 21.9 (11.9-29.4) 22.0 (10.2-29.6) Prior biologic use for AD, n (%) 10 (16.4%) 12 (19.7%) 22 (18.0%) Peripheral blood eosinophils (cells/µL), median 180 290 230 IgE (kU/L), median 250.0 391.0 355.8 Baseline EASI [0-72], median (IQR) 26.8 (23.6-30.6) 26.9 (23.7-33.4) 26.9 (23.6-32.1) Baseline IGA=4, n (%) 32 (52.5%) 31 (50.8%) 63 (51.6%) Baseline BSA [0-100%], median (IQR) 42.0 (31.0-57.3) 46.6 (39.0-58.9) 46.0 (33.5-58.9) Baseline SCORAD [0-103], median (IQR) 66.2 (59.7-73.2) 69.6 (59.4-75.5) 68.7 (59.5-74.3) Baseline ppNRS [0-10], median (IQR) 7.8 (6.9-8.6) 7.2 (6.3-8.1) 7.5 (6.3-8.3) Baseline DLQI [0-30], median (IQR) 15 (10-21) 14 (10-20) 14 (10-21)
ATLAS Primary Efficacy Endpoint Proportion of EASI-75 Responders at Week 14 (mITT) % of Subjects (11/61) (14/61) Lirentelimab Placebo *ns
Secondary Endpoint: Change in EASI Score Change in EASI Score from Baseline to Week 14 (mITT) Percent Change EASI LS Mean Change from BL Absolute Change Lirentelimab (n=61) Placebo (n= 61) 26.9 26.8 Median BL = Lirentelimab (n=61) Placebo (n= 61) EASI LS Mean % Change from BL *ns *ns
Significant Change in EASI Scores in Patients with Higher Inflammatory Disease Burden Percent Change in EASI Score from Baseline to Week 14 (mITT) Baseline IGA-4 Difference from placebo p-values derived using MMRM Baseline IGA-3 Lirentelimab (n=29) Placebo (n= 30) 24.0 Median BL = Lirentelimab (n=32) Placebo (n= 31) EASI LS Mean % Change from BL 31.9 29.7 Median BL = *ns p=0.0476 24.2 EASI LS Mean % Change from BL
Exploratory Endpoint: Improvement in ppNRS (Itch) Proportion of ppNRS Responders at Week 14 (mITT) Difference from placebo p-values derived using Cochran-Mantel-Haenszel (CMH) Includes all subjects regardless of baseline ppNRS. No minimum ppNRS required for study entry. % of Subjects (14/61) (7/61) Lirentelimab Placebo (12/61) (5/61) Lirentelimab Placebo % of Subjects p=0.0903 p=0.0696 Achieving ≥3-Point Improvement Achieving ≥4-Point Improvement
MAVERICK: Phase 2b Study of Lirentelimab in Chronic Spontaneous Urticaria
Phase 2b Chronic Spontaneous Urticaria Study Multi-center, randomized, DB, placebo-controlled Active moderate-to-severe symptoms CSU diagnosis with onset ≥6 months prior to screening Diagnosis of CSU refractory to antihistamines Presence of itch and hives despite current use of antihistamines UAS7 score ≥16 and HSS7 score ≥8 at baseline Includes patients with prior biologics treatment 127 adult patients (1:1 randomization) 300 mg Q2W subcutaneous lirentelimab Placebo Enrolled from 56 Sites in the US, Germany, and Poland Primary Endpoint Change from baseline in UAS7 at week 12 Key Secondary Endpoints Absolute change in ISS7 Absolute change in HSS7 Proportion of patients who achieve UAS7=0 Study Design Endpoints
MAVERICK: Baseline Demographics & Patient Characteristics Baseline Characteristics (mITT population) Phase 2 MAVERICK (CSU) Patient Characteristics Lirentelimab n=64 Placebo n=59 All n=123 Age, mean ± SD 42 ± 14 46 ± 16 44 ± 15 Female sex, n (%) 48 (75.0%) 55 (93.2%) 103 (83.7%) White, n (%) 52 (81.3%) 42 (71.2%) 94 (76.4%) From US Sites, n (%) 55 (85.9%) 53 (89.8%) 108 (87.8%) BMI (kg/m2), mean ± SD 29.7 ± 7.1 30.8 ± 6.3 30.2 ± 6.8 Duration of CSU diagnosis (years), median (range) 4.8 (0.5-47.3) 4.4 (0.5-53.3) 4.5 (0.5-53.3) History of CSU-associated Angioedema, n (%) 23 (35.9%) 25 (42.4%) 48 (39.0%) Prior omalizumab use, n (%) 22 (34.4%) 18 (30.5%) 40 (32.5%) Peripheral blood eosinophils (cells/µL), median 130 120 120 IgE (kU/L), median 105 58.1 77.3 Baseline UAS7 [0-42], mean ± SD 31.4 ± 7.2 32.4 ± 7.4 31.9 ± 7.3 Baseline UAS7 28-42, n (%) 40 (62.5%) 43 (72.9%) 83 (67.5%) Baseline HSS7 [0-21], mean ± SD 15.1 ± 4.1 16.0 ± 3.9 15.6 ± 4.0 Baseline ISS7 [0-21], mean ± SD 16.3 ± 4.4 16.3 ± 4.2 16.3 ± 4.3 Baseline UCT [0-16], mean ± SD 3 ± 2 3 ± 3 3 ± 3 Baseline DLQI [0-30], mean ± SD 16 ± 8 15 ± 8 16 ± 8
MAVERICK Primary Efficacy Endpoint Change in UAS7 from Baseline to Week 12 (mITT) Percent Change Absolute Change 32.4 UAS7 LS Mean % Change from BL UAS7 LS Mean Change from BL Lirentelimab (n=64) Placebo (n=59) Lirentelimab (n=64) Placebo (n=59) 31.4 BL = *ns *ns
UAS7 Response vs. Placebo Proportion of Subjects Achieving UAS7 ≤6 and UAS7 =0 at Week 12 (mITT) Lirentelimab (n=64) Placebo (n=59) % of Subjects (9/64) (7/59) (0/59) UAS7 ≤6 UAS7 =0 *ns (4/64) *ns
Complete Response in Hives and Itch % of Subjects (2/59) (4/64) Lirentelimab Placebo Lirentelimab (1/59) (6/64) Placebo % of Subjects *ns *ns Proportion of Complete Responders in Hives and Itch at Week 12 (mITT) Achieving HSS7=0 Achieving ISS7=0
Robust Depletion of Blood Eosinophils with SC Lirentelimab Blood Eosinophils over Time (mITT) Study Weeks Dose Median Blood Eos (cells/µL) BL ATLAS Lirentelimab (n=61) ATLAS PBO (n=61) Dose Median Blood Eos (cells/µL) BL Study Weeks ATLAS (AD) MAVERICK (CSU) MAVERICK Lirentelimab (n=64) MAVERICK PBO (n=59)
Safety
Overall Safety Summary Safety profile of SC lirentelimab was consistent with previously reported lirentelimab studies Most common adverse events were injection-related reactions (IRRs) ATLAS (AD): 18.5% lirentelimab experienced IRRs vs. 6.2% placebo MAVERICK (CSU): 18.2% lirentelimab experienced IRRs vs 8.2% placebo Common IRR symptoms included Headache, Chills, Nausea, Dizziness, and Flushing
Financial Update
Expected Cash Runway into Middle of 2026 Estimated 2024 Net Cash Used in Operating Activities Estimated net cash used in operating activities (GAAP) $85 to $90 million Less: estimated lirentelimab closeout, severance and other costs ($30 million) Adjusted net cash used in operating activities (non-GAAP) $55 to $60 million The Company will halt lirentelimab-related activities across clinical, manufacturing, research and administrative functions Reduce our workforce by almost 50% The Company anticipates that the significant majority of the restructuring expenditures will be paid in the first half of 2024 Restructuring Actions
AK006 Development Plans and Update
Siglec-6 is a more potent inhibitory receptor than Siglec-8 Siglec-6 regulates more cellular processes than Siglec-8: Signal Transduction Transcription Translation Cellular metabolism Degranulation AK006 has two key attributes Long residence time on the cell surface which correlates to increased inhibitory activity Antibody Dependent Cellular Phagocytosis (ADCP) AK006 Targets a Different Receptor with Different Underlying Biology Siglec-6 Biology and AK006
Siglec-6 and Siglec-8 Differentially Interact with Proteins that Regulate Mast Cell Activity Gray lines represent direct interaction Cytokine Signaling Protein Processing (Translation) TGFb Signaling Interferon-Related Cytoplasmic Transport Mitochondrial Translocation Ubiquitin Activity (Protein Degradation) Pyrophosphate Metabolism (Cellular Metabolism/ATP) Serine/Threonine Phosphatases (Signal Transduction) Pyruvate Metabolism (Cellular Metabolism) SOURCE: Korver, W. et al Allergy 2024.
AK006 was Designed to Drive Maximal Mast Cell Inhibition AK002 AK006 Mast cell inhibition for AK002 and AK006 requires Fc-Fc𝛾 receptor interaction Binding of AK002 induces Siglec-8 internalization, limiting mast cell inhibition AK006 displays a high residence time on mast cells which is associated with optimal inhibition AK006 induces antibody dependent cellular phagocytosis
AK006 Displays Significantly Stronger MC Inhibition than AK002 in Preclinical Studies IgE Activation AK006 inhibits IgE-dependent and –independent modes of MC activation better than AK002 n=3 human donors SOURCE: Korver, W. et al Allergy 2024. KIT Activation Peritoneal Mast Cells MRGPRX2 Activation Lesional Monocytes
AK006 Reduces Human Mast Cells via Antibody-Dependent Cellular Phagocytosis in Preclinical Studies AK006 can reduce mast cell numbers and mediate broad inhibition Ex Vivo Human Tissue Mast Cells - IFN𝞬 Activated Macrophages + IFN𝞬 Activated Macrophages Mast Cells in Tissue * p < 0.01; n=3 human donors In Vitro ADCP Assay SOURCE: Schanin, J et al. Communications Biology, 2022
AK006 Inhibits Mast Cell Activation in Human Tissues IgE-Activated Human Tissue Mast Cells AK006 inhibits IgE-mediated mast cell activation Human Mast Cell Activation Assay n=3 human donors SOURCE: Schanin J, et al. EAACI 2022 Presentation.
AK006 Protects Against Systemic Anaphylaxis in Humanized Mice Humanized Model of Anaphylactic Death Systemic Anaphylaxis AK006 inhibits IgE-mediated mast cell activation in vivo Humanized Mouse Model of Anaphylaxis Anaphylactic Death SOURCE: Schanin, J et al. Communications Biology 2022
AK006 Reduces Allergic Enteritis in Siglec-6 Transgenic Mice AK006 reduces allergen-mediated GI inflammation via mast cell inhibition in vivo SOURCE: Allakos Data on File. Stomach Mast Cells p < 0.05, n=6 mice/group Transcriptional Profiling of Stomach Mast Cells Corporate
AK006 Phase 1 Study Design Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Cohorts in Healthy Volunteers Randomized, double-blind, placebo-controlled Intravenous AK006 SAD: 5, 20, 80, 240, 720 mg MAD: 80, 240, 720 mg monthly Subcutaneous AK006 150 and 720 mg Planned CSU Cohort Randomized, double-blind, placebo-controlled Moderate-to-severe antihistamine refractory CSU UAS7 score ≥16 and HSS7 score ≥8 at baseline Four doses of AK006 IV given monthly SAD and MAD Cohort Safety and tolerability Pharmacokinetics Pharmacodynamics Target receptor engagement in skin biopsies SC Bioavailability CSU Cohort Therapeutic activity assessed by changes in UAS7 at week 14 Trial Cohorts Endpoints
AK006 Clinical Development Plan LOW/MOD 2023 2024 2025 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Part C: CSU Patients Data Availability (n=30) Part B: MAD in HVs (3 Cohorts) Part A: SAD in HVs (5 Cohorts) Ph1 First-in-Human Study Today Bioavailability Ph1b Study in TBD Indication Part D: SC in HVs (2 Cohorts) CSU, chronic spontaneous urticaria; HVs, healthy volunteers; MAD, multiple ascending dose; SAD, single ascending dose; SC, subcutaneous 1 = Phase 2 Study for timing purposes only, potential future investment for Phase 2 study not currently in budget 2026 Q1 Q2 Q3 Q4 IV SC Formulation Ph2 Study in TBD Indication1
Upcoming AK006 Milestones Q1 2024: Complete SAD and MAD dosing with Intravenous (IV) AK006 in healthy volunteers. Q1 2024: Initiate the randomized, double-blind, placebo-controlled subcutaneous (SC) AK006 cohort in healthy volunteers. Q2 2024: Report SAD and MAD safety, pharmacokinetics (PK), and pharmacodynamic (PD) results from the Phase 1 IV AK006 trial in healthy volunteers, including data to confirm Siglec-6 receptor occupancy in skin biopsy samples. Q2 2024: Initiate the randomized, double-blind, placebo-controlled Phase 1 trial of IV AK006 in patients with chronic spontaneous urticaria (CSU). Q3 2024: Report subcutaneous (SC) AK006 safety, PK, and PD results from the Phase 1 trial in healthy volunteers, including data to confirm Siglec-6 receptor occupancy in skin biopsy samples. Year End 2024: Report topline data from the Phase 1 trial of IV AK006 in patients with CSU.
Q&A
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