Spearheading Immunotherapies ESMO 2023 – HPN328 Investor webcast october 23, 2023 Exhibit 99.1
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Harpoon Therapeutics HPN328 Major Value Driver and Additional Opportunity in HPN217/601/Platform HPN217 (BCMA) – Clinically active and differentiated tolerability profile HPN601 (EpCAM) – IND ready conditionally activated T-cell engager with large market potential Multiple next-gen T-cell engager platforms – TriTAC®, ProTriTACTM, TriTAC-XRTM Potential for best-in-class efficacy in small cell lung cancer and neuroendocrine tumors Confirmed response rate 35% across 1mg priming dose cohorts* Generally well tolerated at 1mg priming and target doses Large markets with high unmet needs across various tumor types and lines of therapy offer opportunity for multiple products Completion of monotherapy dose optimization enrollment in October 2023 RP2D identification YE 2023 Phase 2/3 registrational studies to begin in 2H 2024 Supported by top-tier investor syndicate with cash runway into 2026 ADDITIONAL VALUE DRIVERS LEAD ASSET HPN328 (DLL3 T-CELL ENGAGER) HPN328 NEAR-TERM CATALYSTS WELL FUNDED *Based on unaudited database cutoff as of 9/12/2023, subject to change
Large Addressable Population in SCLC and Other High Grade NENs with Significant Unmet Need 7 Major Market Incidence1 5-yr Survival DLL3 Expression (>1%) Small Cell Lung Cancer ~90,000 7%2 82%3 Neuroendocrine Prostate Cancer (NEPC) ~20,0004 14%5,6 77%7 NET, High Grade ~11,500 mOS 10 months8 Highly expressed Extrapulmonary NEC, except NEPC ~2,600 Stomach 9%9 Rectum 11%9 Colon 15%9 Pancreas 20%9 Small Intestine 43%9 Appendix 65%9 Cervix 81%10 Gastroentero-pancreatic 77%11 Pancreas 19-50%12 Bladder 68%13 LCNEC, Lung ~1,300 21%2 82%3 High grade NENs have an estimated annual incidence >120K across 7 major markets, mostly with high DLL3 expression 1. GlobalData Forecast 2023 incidence, 7 major markets (7MM) - US, Japan, France, Germany, Italy, Spain, UK; 2. SEER; 3. Lima et al. Cancer Res (2022); 4. Aparicio et al. Cancer Discov (2011); 5. Alabi et al. Pharmacology & Therapeutics (2022); 6. Bhagirath et al. Sci Rep (2021); 7. Puca et al. Sci. Transl Med. (2019); 8. Dasari, JAMA Oncol. (2017); 9. White, Lancet (2018); 10. Cimic, Appl Immunohistochem Mol Morphol (2021); 11. Liverani, Endocr Onc (2021); 12. Yao, Oncologist (2022); 13. Koshin, Clin Cancer Res (2019)
Unaudited database as of 9/12/2023 Data subject to change HPN328 Phase 1 Interim Update
Figure 1. HPN328 Mechanism of Action HPN328 Mechanism of Action T cell receptor complex DLL3 HPN328 Tumor Cell T cell Anti CD3 domain Anti albumin domain Anti DLL3 domain DLL3 is significantly expressed in SCLC and other neuroendocrine tumor types HPN328 is a DLL3-targeting T cell engager built on the TriTAC platform Redirects T cells to kill DLL3-expressing cancer cells Small protein (~50kDa) to potentially enable efficient solid tumor penetration with prolonged half-life Designed to minimize non-specific T cell activation and Fc receptor engagement, intended to increase therapeutic window HPN328: A DLL3-Targeted T Cell Engager
HPN328 Phase 1 Trial YE 2022 Planned Targets: patients enrolled Optimization of priming dose for step-dosing regimens: 1 – 6 mg step-dose cohort opened Planned 2023 Events: Q1 2023: Start enrollment in atezolizumab combo cohorts Start enrollment in Q2W dosing cohorts for HPN328 monotherapy Mid-2023: Complete enrollment in monotherapy and combination therapy dose escalation cohorts: ~100 patients enrolled (including backfill) by End of Q2 Planned interim data update with potential data maturity at: End of Q1: anticipate up to 30 pts with ≥1 scan End of Q2: anticipate up to 70 pts with ≥1 scan 2H 2023: Complete total study enrollment of ~130 patients Target Population Extensive stage SCLC relapsed after platinum chemotherapy Neuroendocrine prostate cancer and other DLL3 expressing tumors with high grade neuroendocrine features relapsed/refractory to standard therapy Trial Design Assess safety and tolerability at increasing dose levels PK and pharmacodynamic data Evaluate preliminary anti-tumor activity Dosing & Administration IV infusion with weekly and Q2W administration schedules Monotherapy cohorts for all tumor types, and combination cohorts with atezolizumab for SCLC Premedication and step dosing to manage cytokine release syndrome (CRS)
Dose Escalation and Optimization Enrollment Nearing Completion Monotherapy Cohorts - Q4’23; Combination Cohorts - 1H’24 Unaudited database cutoff as of 9/12/2023, subject to change Dose Escalation 3+3 Design Including Fixed & Step Dose Cohorts and Dose Optimization (N=71) 0.015-3.6 mg N = 11 3.6à 7.2 mg N = 4 2à 12 mg N = 5 2à 24 mg N = 4 1à12 mg N = 6‡ 1à12à24 mg* N = 9‡ Q2W 1à12 mg 1à12à24 mg* 1à12 mg N = 8‡ Q1W 1à12à24 mg* N = 8‡ Fixed-dose Escalation 1à6 mg N = 16 HPN328: Q2W + Atezo Q4W De-escalation to 1 mg prime Ongoing 1 mg priming Step-dose Escalation and Optimization Cohorts Early Fixed Dose & Step dose Escalation Cohorts Early Dose Escalation Cohorts Current 1mg Priming Cohorts Planned Cohorts Early Step-dose Escalation Cohorts † * 1 mg to 24 mg cohorts use a 12 mg intermediate step up prior to moving to 24 mg target † Atezo combination cohorts recently opened; data to be presented at later date ‡ Still enrolling: protocol allows for cohorts of up to 17 patients, depending on cohort
Phase 1 Population Includes Heavily Pre-treated Refractory Patients Age (Years) Median 64 Range 41-81 Sex Female 29 (40.8%) Male 42 (59.2%) Race n (%) White 65 (91.5%) Asian 3 (4.2%) American Indian or Alaska Native 1 (1.4%) Multiple 1 (1.4%) Unknown 1 (1.4%) # Prior Therapies n (%) Median 2.5 Range 1-8 PD(L)-1 Inhibitors 56 (78.9%) Diagnosis SCLC 46 (64.8%) NEPC 11 (15.5%) Other NENs 14 (19.7%) Sites of Metastases Brain 29 (40.8%) Liver 37 (52.1%) ECOG n (%) 0 29 (40.8%) 1 42 (59.2%) Baseline Characteristics (N=71) Unaudited database cutoff as of 9/12/2023, subject to change
Adverse Events Manageable with No DLTs at Target Doses No Grade 3 CRS with 1 mg Priming Regimens Unaudited database cutoff as of 9/12/2023, subject to change ICANS=Immune effector cell-associated neurotoxicity syndrome a Grading per CTCAE v5.0, except cytokine release syndrome (grading per ASTCT 2019) b Includes both neutropenia and neutrophil count decreased c Two Grade 3 CRS events were DLTs at 2 mg priming dose (above current priming dose) d Immune effector cell encephalopathy (ICE) score for ICANS assessment performed at Screening and 6 times during Cycle 1; All events of ICANS were transient; none resulted in dose reduction Adverse Events Grade 1 Grade 2 Grade 3 CRS 21 (29.6%) 19 (26.8%) 2 c (2.8%) ICANS d 4 (5.6%) 1 (1.4%) 0 Adverse Events All Grades, n (%) Grade ≥3, n (%) Any treatment-emergent AE 70 (98.6%) 33 (46.5%) Any treatment-related AE 67 (94.4%) 18 (25.4%) Treatment-Related AEs in ≥10% of patients Cytokine release syndrome (CRS) 42 (59.2%) 2 c (2.8%) Dysgeusia 24 (33.8%) 0 Fatigue 24 (33.8%) 1 (1.4%) Nausea 12 (16.9%) 0 Vomiting 11 (15.5%) 0 Diarrhea 10 (14.1%) 1 (1.4%) Decreased appetite 8 (11.3%) 0 Neutropenia b 7 (9.9%) 4 (5.6%) Pruritus 7 (9.9%) 0 Pyrexia 7 (9.9%) 0 Treatment-Related Adverse Events (TRAEs) Incidence ≥10% Patients by Grade a (N=71) No DLTs Observed at Target Doses; Target dose MTD Not Reached Note: Post 9/12/2023 data cut-off, 1 Gr5 SAE (pneumonitis)
SCLC NEN NEPC PD PD PD PD PD PD PD SD PD SD PR PR c PR PR PR c PR PR PR c CR c PD PR c PR c PR c CR CR* c PD SD PR PR PR 1-6 mg QW 1-12 mg QW 1-12 mg Q2W 1-12-24 mg QW 1-12-24 mg Q2W SD PR c c SD PD PR Axis capped at 100% although largest changes were >100.0% * Includes RECIST-based normalization of lymph node size. Patient achieved cPR prior to CR, so considered confirmed response † In patients with opportunity to have 2 scans or discontinued prior to confirmatory scan due to AE or PD ‡ Patients on study with only 1 imaging assessment to date Response In 1 mg Priming Dose Optimization Cohorts with ≥1 Post-baseline Assessment (N=35) Additional SCLC responses were seen in earlier dose escalation cohorts, including 1 unconfirmed response (0.405 mg), 2 confirmed responses (1.215 escalated to 3.6 mg and 2 mg/12 mg), and 1 additional EC-PR (3.6 mg/7.2 mg) ‡ ‡ ‡ ‡ Best Overall Response Rate (confirmed + unconfirmed) 11/23 (48%) Confirmed Response Rate (in patients with an opportunity to confirm)† 6/19 (32%) DCR 14/23 (61%) Best Overall Response Rate (confirmed + unconfirmed) 19/35 (54%) Confirmed Response Rate (in patients with an opportunity to confirm)† 11/31 (35%) DCR 24/35 (69%) SCLC NEPC NEN Other Partial Response (PR) Complete Response (CR) Confirmed Response Best Overall response BOR c c c All Patients SCLC Best Overall Response Rate (confirmed + unconfirmed) 8/12 (67%) Confirmed Response Rate (in patients with an opportunity to confirm)† 5/12 (42%) DCR 10/12 (83%) NEN + NEPC Unaudited database cutoff as of 9/12/2023, subject to change 1 mg Priming Dose Regimens: Responses Across Tumor-Types Cohorts will Inform Dose Optimization and Selection of RP2D Once Data Matures
Prolonged Confirmed Responses Ongoing; Durability Data Maturing Time on Treatment: Patients Treated With 1 mg Priming Dose (N=47) Unaudited database cutoff as of 9/12/2023, subject to change Ongoing SCLC NEPC NEN Other Partial Response (PR) Confirmed PR Complete Response (CR) Confirmed CR c c c c c Cervical c c c c ◆ ✷ Large Cell Lung & SCLC c c c c Esophageal Esophageal c c Small Cell Bladder c Lung adenocarcinoma w/ neuroendocrine features c c c c NEN Lung, NOS c c c ✷ 1.0 – 6.0 QW 1.0 – 12.0 QW 1.0 – 12.0 – 24.0 QW 1.0 – 12.0 Q2W 1.0 – 12.0 – 24.0 Q2W † Small Cell Bladder Treatment duration across all dose levels ranged from 1 to 71 weeks, including 3 patients in early dose escalation cohorts on treatment for >1 year (0.405 mg N=1, 3.6 mg/7.2 mg N=2) Off treatment for PD unless indicated otherwise; ✷Off treatment for withdrawal of consent. ◆ Withdrawal by Investigator for reasons other than an AE. † Patient continued treatment post PD for clinical benefit. Time on Treatment: Dose Optimization Cohorts (N=47)
HPN328 Patient Case: Relapsed ES-SCLC Complete Response Patient History 61-year-old male Diagnosed in June 2021 with extensive-stage SCLC 60% cells positive for DLL3 Location of metastases TLs: lymph nodes x2 Non-TLs: Lymph nodes x4 Prior systemic treatment Cisplatin + Etoposide Carboplatin + Etoposide + Atezolizumab Investigational CCR-8 treatment Time on most recent prior systemic treatment 4 weeks Upon study entry, refractory was best response to most recent prior systemic treatment Results HPN328: started on 1mg prime and 12 mg target dose /week Well tolerated Complete Response at week 8, confirmed at week 12 RECIST v1.1: Target Lesions: CR Remains on HPN328 treatment with ongoing response at week 28, as of Sept 11, 2023 Wk 8 On Treatment 100% reduction at wk 8 Unaudited database cutoff, subject to change
Pre-Treatment Wk 9 On Treatment Wk 27 On Treatment HPN328: started on 1mg prime and 6 mg target dose /week Well tolerated Complete Response at week 9, confirmed at week 13 RECIST v1.1: Target Lesion: CR 100% cells positive for DLL3 Ongoing response Remains on HPN328 treatment as of Sept 27, 2023 Patient History 44-year-old female diagnosed in October 2021 with stage IV cervical small cell carcinoma Location of metastases TL: Pelvis x1 Non-TLs: Lung x1 Prior surgery, external beam radiation, and intracavitary brachytherapy x 3 Prior systemic treatment Carboplatin + Etoposide + Atezolizumab → Atezolizumab maintenance Time on most recent prior systemic treatment 16 weeks Upon study entry, refractory was best response to most recent prior systemic treatment HPN328 Patient Case: Relapsed Response Baseline (23Mar2023) Week 9 (25May2023) Week 27 (25Sep2023) Pelvic Recurrence Results Unaudited database cutoff as of 9/12/2023, subject to change
HPN328 - 1mg Priming Dose Cohorts Clinically Active and Well Tolerated in Ongoing Dose Escalation Study Active agent at 1mg priming dose cohorts at interim update 54% (19/35) overall response rate across all tumor types (SCLC, NEPC, other NENs) 32% (6/19) confirmed response rate in SCLC patients 5 of 7 confirmed responders in patients with other NENs 69% (24/35) disease control rate across all tumor types Potentially Best-in-class Efficacy Generally well tolerated at 1mg priming cohorts CRS events most common with initial priming dose administration Only Grade 1 and 2 CRS seen at 1mg priming cohorts No Grade 3+ ICANS Phase 1 monotherapy dose optimization enrollment anticipated to complete in October 2023 Monotherapy RP2D selection expected by YE 2023 Upcoming Anticipated Milestones Unaudited database as of 9/12/2023 (subject to change) Manageable Tolerability Profiles