EX-99.2
Spearheading Immunotherapies Ash 2022
review and business update December 12, 2022 Nasdaq: HARP Exhibit 99.2
This presentation and accompanying oral
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Agenda Introduction and Overview Julie
Eastland Chief Executive Officer Review of HPN217 Interim Data Presented at ASH andLuke Walker, M.D. HPN328 Progress UpdateChief Medical Officer Summary and Q&AJulie Eastland
Clinical-Stage Immuno-Oncology Company
Directing T Cells to Kill Tumors Strong Capabilities Industry veterans developing novel TCEs Deep expertise in oncology, T cell engagement, and protein engineering Cash runway expected to fund operations through end of 2023 $66.1M in cash, cash
equivalents & short-term marketable securities* Strong patent protection across platforms and programs Clinical-stage T cell engagers across multiple indications Clinical benefit seen in hematological and solid tumor settings: Confirmed
responses, tumor lesion reductions deepening over time Emerging clinical data validate TriTAC platform designed to maximize the therapeutic window Clinical Pipeline Addressing broad patient populations Novel TCE Platforms Solid and hematological
tumors Platform technologies allowing for “off-the-shelf” T cell therapies Treating broad patient populations with unmet needs Addressing solid and hematologic malignancies Each platform designed to maximize the therapeutic window
Advancing a Portfolio of Novel T Cell Engagers (TCEs) *As of September 30, 2022
Broad Pipeline of Immuno-Oncology
Programs Clinical-Stage TriTAC® Programs, Novel TCE Platforms TriTAC/ProTriTAC Oncology TriTAC-XR Oncology / Non-Oncology Program Stage of Development Preclinical Phase 1 Phase 2 HPN2171 (BCMA) Multiple Myeloma HPN3282 (DLL3) Small Cell Lung
Cancer / Other Solid Tumors HPN601 (EpCAM) Multiple Solid Tumors Phase 3 TriTAC Indication(s) Preclinical Candidates ProTriTAC TriTAC-XR AbbVie retains an option to worldwide exclusive rights (HPN217) Roche supply agreement established for the use
of atezolizumab in combination with HPN328 AbbVie entered in a discovery platform collaboration to select a fixed number of targets from these platforms Partner atezolizumab Supply Agreement 3 1
HPN217 Targeting BCMA TriTAC®
Interim Data Presented at ASH 2022
Multiple Myeloma: High Unmet Need
Remains Multiple Development Opportunities in a Rapidly Evolving Landscape 1 Over time period 2012 and 2018 Cancer stats Facts: Myeloma https://seer.cancer.gov/statfacts/html/mulmy.html BCMA means B-cell Maturation Antigen; RRMM means
Relapsed/Refractory Multiple Myeloma, SCT means Stem Cell Transplant (Accessed Oct 2022); Global Data, 2019; Strassel L; Schreder, M, 2021; KOL Interviews SCT Eligible (young / fit) SCT Ineligible (elderly / frail) Newly Diagnosed Multiple Myeloma
(34k patients in the U.S. in 2022) Doublets/Triplets ASCT + Triplets Relapsed Refractory MM New MOAs BCMA Agents: T cell engagers; Cellular Therapies, ADCs NEI, HDAC Inhibitors, Novel Agents Multiple Combinations of PIs, IMIDs, CD38s 50 – 60%
40 – 50% 58% overall 5-year survival rate in U.S. increasing over time1, creating need for multiple lines of therapy BCMA agents beginning to redefine RRMM treatment, with opportunities to improve upon tolerability, efficacy, and accessibility
BCMA agents with improved tolerability have future potential to be developed in the early line setting Lines of Therapy 1L 2L-3L 4L+
HPN217-3001 Phase 1/2 Trial Design
Relapsed/Refractory Multiple Myeloma Dose Escalation 3+3 Design 0.005-1.62 mg 2.15 mg 2.86 mg 3.24* mg 6* mg 12* mg 24* mg Q1W (n=11) Q1W (n=17) Q1W (n=6) Q1W (n=7) Q1W (n=12) Q1W (n=3) Fixed- and Step-Dose Escalation Cohorts: 3-6 patients per dose
level; Backfilling permitted; * Step-Dose Regimen Key Eligibility Criteria Relapsed/refractory multiple myeloma ≥3 prior therapies, including PI, IMID, and anti-CD38 Prior BCMA-targeted therapies allowed Trial Design Primary Objectives:
Safety, PK, Establish MTD or RP2D Secondary Objectives: Clinical Activity per IMWG Criteria Dosing & Administration HPN217 administered by 1-hour IV infusion as flat dose Premedication for Cytokine Release Syndrome (CRS) prophylaxis Next Steps
Currently enrolling initial bi-weekly dosing cohort Dose optimization and backfill ongoing, with final cohort plans to be based upon emerging data Q2W (n=2), enrolling 24* mg Q2W Q1W (n=4) ASH 2021 25 additional patients dosed since ASH 2021 As of
17 Oct ’22
HPN217: Study Patient Population
Represents Real-World, Late-Line Population with High-Risk Features Baseline Characteristics Total N = 62 Age (yr), Median (range) Age > 75 years, n (%) 70 (38 – 83) 12 (19%) Time Since Initial MM Diagnosis (yr), Median (range) 8 (1 –
20) Baseline sBCMA (ng/mL), Median (range) 240 (27– 2444) ECOG, n (%) 0 1 Missing 14 (23%) 46 (74%) 1 (2%) Revised ISS Stage at Study Entry, n (%) I II III Missing 16 (26%) 17 (27%) 26 (42%) 3 (5%) Prior Systemic Therapies Prior Cancer Therapy
Total N = 62 Prior Systemic Therapies, Median (range) 6 (2-19) Prior Transplantation, n (%) 46 (74%) Exposure Status, n (%) Triple-classa exposed Penta-drugb exposed BCMA exposed 58 (94%) 41 (66%) 13 (21%) Relapsed/Refractory Status, n (%)
Triple-classa refractoryc Penta-classb refractoryc BCMA refractoryc 47 (76%) 26 (42%) 11 (18%) aIMiD, PI, and anti-CD38; bAt least 2 Pis, at least 2 IMiDs, and at least 1 anti-CD38 antibody; c No response to regimen or discontinued regimen due to
progression, adapted from Rajkumar et al (Blood 2011) Note: Unaudited patient data are based on entries provided in open clinical database as of 10/17/2022 Baseline Characteristics and Demographics
HPN217: Safety Summary Common
Treatment-Emergent Adverse Events (Regardless of Relationship), >15% Note: Unaudited patient data are based on entries provided in open clinical database as of 10/17/2022 AE Preferred Term All Grades (N=62)a > Grade 3 (N=62)a Anemia 27
(44%) 21 (34%) Fatigue 20 (32%) 2 (3%) Cytokine release syndromeb 17 (27%) 0 (0%) Headache 15 (24%) 0 (0%) Hypokalemia 13 (21%) 2 (3%) Nausea 13 (21%) 0 (0%) Back Pain 11 (18%) 1 (2%) Diarrhea 11 (18%) 1 (2%) Hypophosphatemia 11 (18%) 4 (7%) AST
increased 11 (18%) 5 (8%) Cough 11 (18%) 0 (%) Arthralgia 10 (16%) 1 (2%) Neutrophil count decreased 10 (16%) 8 (13%) Dyspnea 10 (16%) 2 (3.%) ALT increased 9 (15%) 4 (7%) Constipation 9 (15%) 0 (%) Hypercalcemia 9 (15%) 1 (2%) Dose Limiting
Toxicity Fixed Dose: 2 patients at 2.86 mg/week, reversible transaminitis (Gr 3, n=1; Gr 4, n=1), no clinical sequelae Step Dose: No DLTs; MTD not reached Neurologic/Psych Eventsc Treatment related events reported in 10 patients All events
Grade 1 - 2 Most common: Headache (n=6) and Confusion (n=2) No ICANS events reported Infectionsd Reported in 28 (45%) patients (Gr 3/4, 16%) Most common: Pneumonia (n=6), upper respiratory tract infection (n=5) and urinary tract infection
(n=5) No treatment related Grade 5 AEs a Grading per CTCAE v5.0; b Grading per ASTCT 2019 Criteria; c SOC nervous system disorders and psychiatric disorders; d SOC infections and infestations
ASH 2021 CRS Current Data HPN217:
ORR and CRS Rates Suggest Potentially Differentiated Profile with Widened Therapeutic Index *Note: Unaudited patient data based on entries provided in open clinical database as of 10/17/2022. Responses per Investigator Assessment (subject to
change) 1Highest 2 dose levels with disease-evaluable patients at each timepoint Q1W; 2Highest 2 dose levels with patients who received >1 dose Q1W or Q2W Current Data Total: 47% Total: 29% 2.15 and 2.86 mg (n=17) 12 and 24 mg2 (n=17)
Grading per ASTCT 2019 Criteria All patients shown who received >1 dose HPN217 ORR 54% (7/13) >VGPR 23% ORR 77% (10/13) >VGPR 46% Confirmed and Unconfirmed Responses per Investigator Assessment Disease-evaluable patients shown with at least
1 post-baseline assessment 2.15 and 2.86 mg (n=13) 12 and 24 mg1 (n=13) Maximum CRS Grade by Dose Group ASH 2021 Compared to ASH 2022* Overall Response Rate ASH 2021 Compared to ASH 2022* ORR ASH 2021 Highest 2 Target Dose Levels at Each Timepoint
Highest 2 Target Dose Levels at Each Timepoint Grade 1 Grade 2 PR VGPR >CR
HPN217: Time on Treatment at Target
Doses > 2.15mg Deep Early Responses Observed at Highest Exposures Median overall responder time on treatment 7 months (range 1.6 - 18+) Early and Deep Responses across Highest Dose Levels Response Rate 77% (10/13) 6 of 7 responders
from ASH ‘21 remain on tx for an additional 11+ months For 2.15 - 6mg Cohorts: All Patients with at least 9 Months of Follow up Median Responder Time on Tx: 12 months (6 - 18+) For 12 & 24 mg Step Cohorts Enrollment Ongoing Median
Responder Time on Tx: 3 months (1.6 - 7+) 2.15 mg through 6 mg dose levels Q1W 12 mg and 24 mg dose levels Q1W* * All patients Q1W schedule with exception of patients denoted Note: Based on available data in unaudited patient database as of
10/17/2022; confirmed and unconfirmed responses per Investigator Assessment (subject to change) MONTHS
HPN217: Summary 77% (10/13) ORR
observed across highest step-dose levels (12 and 24 mg) Responses occurred early and were durable; for patients with at least 9 months follow up, the median responder time on treatment is 12 months 18 of 21 responders remain on study treatment with
sustained response, with many responses deepening over time HPN328 is active Interim data update from ongoing Phase 1 presented at ASH 2022 Study enrollment anticipated to complete in 1H 2023, with up to potentially 94 patients, based on data from
dose escalation cohorts Next steps Low incidence of CRS and serious adverse events Transient and predictable low-grade CRS in 29% of patients across highest step-dose levels (12 and 24mg) No > Grade 3 CRS events No ICANS2 No DLTs observed across
all step dose cohorts Well Tolerated to Date Active Agent1 Anticipated Near-Term Milestones 1 Relative to other BCMA-targeted TCEs in heavily pretreated patients across the highest step-dose cohorts 2 ICANS means Immune effector cell-associated
neurotoxicity syndrome Note: Unaudited patient data based on entries provided in open clinical database as of 10/17/2022 (subject to change) Profile Emerging with Opportunity to be Best-in-Class T Cell Engager Targeting BCMA
HPN328 Targeting DLL3 TriTAC®
Small Cell Lung Cancer Standard of
Care Limited effective options available in the relapsed/refractory setting 1 Atezolizumab and Durvalumab approved for 1L ES-SCLC in combination with platinum-doublet chemo and continued in maintenance for patients with ≥SD; 2 Lurbinectedin
has accelerated approval in the U.S. only. Source: NCCN Guidance; Physician Interviews 2021 Limited Stage Extensive Stage Newly Diagnosed Small Cell Lung Cancer Platinum + Etoposide + anti-PDL11 Platinum + Etoposide + Radiotherapy Relapsed
Refractory SCLC ~65% ~35% Lines of Therapy 1L 1L-Maintenance 2L 3L+ anti-PDL11 Platinum + Etoposide Clinical Trial Recurs in > 6 m Recurs in ≤ 6 m Topotecan Lurbinectedin2 No approved agents in 3L+
HPN328: Trial Design and
Demographics A Phase 1/2 Open-Label, Multi-Center, Dose Escalation / Expansion, Safety & PK Study Target population SCLC relapsed after platinum chemotherapy Other high-grade neuroendocrine cancers R/R to standard of care (SOC) or no SOC
available Trial objectives Assess safety and tolerability at increasing dose levels Characterize PK and PD Evaluate preliminary anti-tumor activity Dosing and administration Weekly IV infusion Status 22 patients enrolled Currently enrolling 1mg - 6
mg cohort, with dose escalation and optimization cohorts ongoing Baseline Characteristics Total N = 22 Age (yr), Median (range) 61 (43 – 73) ECOG performance status 0-1, n (%) 22 (100) Brain / Liver metastases, n (%) 8 (36) / 11 (50) Disease n
(%) Small Cell Lung Cancer 15 (68) Neuroendocrine Prostate Cancer 2 (9) Other Neuroendocrine Neoplasm 5 (23) Prior Lines of Therapy n (%) 1 5 (23) 2 5 (23) ≥3 12 (54) Median (range) 3 (1-6) Prior immune checkpoint inhibitor
(αPD-1/αCTLA4, αPD-L1) 18 (82) Unaudited patient data based on entries provided in open clinical database as of 10/10/2022 (subject to change)
HPN328: Safety Summary Recent
priming dose DLTs inform optimization of priming dose to support further escalation of target dose1 TriTAC platform designed to minimize CRS risk and allow for greater escalation of target dose, and re-escalation of target dose is underway No ICANS
No DLTs at target dose Target dose MTD not yet reached 1 as reported in Harpoon press release dated November 14, 2022 Unaudited patient data based on entries provided in open clinical database as of 10/10/2022 (subject to change)
HPN328: Clinical Summary Anti-tumor
Activity Seen in Small Cell Lung Cancer at Higher Doses HPN328 is active; 71% SCLC patients had target tumor responses, including 1 confirmed partial response1, 2 25% (3/12) with >30% Target Lesion Shrinkage across all doses 1 Confirmed Partial
Response – Durable Beyond 6 Months Treatment duration ≥ 5 months was observed in 7 of 20 (35%) patients Median half-life of 71 hours, with linear pharmacokinetics 1 Unaudited patient data based on entries provided in open clinical
database as of 10/10/2022 (subject to change), 2 SCLC treated at ≥1.215mg (5/7 patients), including 1 partial response per RECISTv1.1
61-year-old female Diagnosed Jan
2021 with extensive-stage SCLC Location of metastases: TLs: lung, liver x2, lymph nodes x2 Non-TLs: lung x2, liver Prior systemic treatment: carboplatin + etoposide + atezolizumab Time on most recent prior systemic treatment: 20.1 weeks Upon study
entry, stable disease as best response to most recent prior systemic treatment HPN328 Patient Case 1: Relapsed ES-SCLC 53% Reduction in Sum of Target Lesion Diameters at Week 10: Confirmed PR Patient History Results Initiated HPN328 at 1.215mg/week,
later dose escalated Confirmed PR at week 10 Continued treatment with HPN328 for 33 weeks 53% reduction at wk 10 Lymph Node Lung Liver Pre-Treatment Week 10 On Treatment CONFIDENTIAL Unaudited patient data based on entries provided in open clinical
database as of 10/10/2022 (subject to change) Data as of October 10, 2022
HPN328 Patient Case 2: Relapsed
ES-SCLC 72% Reduction in Sum of Target Lesion Diameters Deepening of response over time continuing beyond ASCO 2022 data Data as of October 10, 2022 >99% decrease Durable >99% decrease in CTCs Baseline Week 9 On Treatment Response in
peri-portal lymph node Patient History 67-year-old male Diagnosed in April 2020 with extensive-stage SCLC Location of metastases TLs: liver x2, lymph nodes x2 Non-TLs: liver, lymph nodes x2, spleen, bone, brain Prior systemic treatment Carboplatin +
Etoposide + Toripalimab Cisplatin + Etoposide Lurbinectedin Time on most recent prior systemic treatment 10.9 weeks Upon study entry, partial response as best response to most recent prior systemic treatment but unable to tolerate further treatment
Results HPN328 3.6 à 7.2 mg/week (increased to 12 mg/week) Well tolerated 72% reduction in sum of target lesion diameters Asymptomatic brain metastasis identified at week 2 Systemic disease responding to HPN328 RECIST v1.1: Target Lesions: PR;
Overall: PD 60% cells positive for DLL3 Deepening of radiographic target lesion response over time Remains on HPN328 treatment beyond 54 weeks At ASCO 2022 (April 21, 2022 data) was at 27 weeks Current data: ongoing clinical benefit beyond 1 year
Deep, durable target lesion shrinkage 72% decrease = Dose Increase
HPN328: Anticipated Next Steps
HPN328 is active Continue enrollment in the Phase 1 dose exploration study Monotherapy cohorts: 1 mg – 6 mg step dose cohort opened Optimization of priming dose for step-dosing regimens ongoing 27 patients planned to be enrolled by year end
2022 Start enrollment in Q2W dosing cohorts for HPN328 monotherapy Combination cohorts: Begin enrollment of additional cohorts in the Phase 1 dose escalation study evaluating HPN328 in combination with atezolizumab in SCLC Provide Phase 1 interim
data in mid-2023 for the highest target doses studied Anticipate up to potentially 70 patients with ≥1 on-treatment scan by end of Q2 ’23* Anticipate enrollment of up to 100 patients in monotherapy and combination therapy dose cohorts
(including backfill) by mid-2023* Complete Phase 1 enrollment of potentially up to 130 patients in monotherapy and combination cohorts in 2H 2023 * Next steps Milestones & next steps * Enrollment projections dependent on data from ongoing dose
escalation cohorts
Summary and Anticipated Milestones
Advancing pipeline of next-generation T cell engagers address broad patient populations with high unmet needs Strategic prioritization to focus resources on ongoing clinical programs in or nearing the clinic Clinically meaningful activity in
hematology and solid tumor Phase 1 studies Current cash and equivalents of $66.1 million* expected to fund operations to the end of 2023 YE 2022 1H 2023 HPN217 (BCMA): Updated interim data presented at ASH 2022 (Dec. 11) HPN328 (DLL3): Continue
enrollment in the Phase 1/2 study exploring dose regimens at tolerable and active dose levels through year end HPN217 (BCMA): Ongoing patient enrollment in the Phase 1 trial; expected to reach enrollment completion in 1H-2023 HPN328 (DLL3): Identify
an initial dose for expansion and dose optimization in 1H-2023 Provide interim data for the highest target doses studied in mid-2023 Begin enrolling additional cohorts in the Phase 1 dose escalation study evaluating HPN328 in combination with
atezolizumab in SCLC in 1H-2023 HPN601 (EpCAM): Harpoon expects to be ready to file an IND in 1H-2023 to enable a Phase 1 dose exploration study, pending available resources *Cash, cash equivalents and short-term marketable securities as of
September 30, 2022
