Harpoon Therapeutics : ESMO 2023 Virtual Investor Webcast Presentation – October 2023

Spearheading Immunotherapies

ESMO 2023 - HPN328

INVESTOR WEBCAST OCTOBER 23, 2023

Forward-looking Statements

This presentation and accompanying oral commentary contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "target," "goal," "estimate" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Harpoon's expectations and assumptions as of the date of this presentation. Each of these forward-looking statements involves risks and uncertainties that could cause Harpoon's clinical development programs, future results or performance to differ significantly from those expressed or implied by the forward-looking statements. Forward-looking statements contained in this presentation and accompanying oral commentary include, but are not limited to, statements about the progress, timing, scope, design and anticipated results of clinical trials, the timing of the presentation of data, the association of data with potential treatment outcomes, the development and advancement of platforms and product candidates, the timing of development milestones for platforms and product candidates and Harpoon's cash sufficiency and runway. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during clinical studies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, our ability to enter into strategic arrangements and collaborations and uncertainties in the success of such arrangements, changes in the regulatory environment, the uncertainties and timing of the regulatory approval process, the risk that initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials, the risk that trials may be delayed and may not have satisfactory outcomes, and unexpected litigation or other disputes that impede clinical trial progress. Other factors that may cause Harpoon's actual results to differ from those expressed or implied in the forward-looking statements in this presentation and accompanying oral commentary are discussed in Harpoon's filings with the U.S. Securities and Exchange Commission (SEC) including under "Risk Factors" in Harpoon Therapeutics' quarterly report on Form 10-Q for the quarter ended June 30, 2023, filed with the SEC on August 9, 2023 and our other filings from time to time. Except as required by law, Harpoon assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Certain information contained in this presentation and statements made orally during this presentation relate to or are based on studies, publications, surveys and other data obtained from third-party sources and Harpoon's own internal estimates and research. While Harpoon believes these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, it has not independently verified, and makes no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of Harpoon's internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research.

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Harpoon Therapeutics

HPN328 Major Value Driver and Additional Opportunity in HPN217/601/Platform

LEAD ASSET

HPN328

(DLL3 T-CELL ENGAGER)

HPN328

NEAR-TERM CATALYSTS

ADDITIONAL VALUE

DRIVERS

• 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
• HPN217 (BCMA) - Clinically active and differentiated tolerability profile
• HPN601 (EpCAM) - IND ready conditionally activated T-cell engager with large market potential
• Multiple next-genT-cell engager platforms - TriTAC®, ProTriTACTM, TriTAC-XRTM

WELL FUNDED

• Supported by top-tier investor syndicate with cash runway into 2026

Unaudited database cutoff as of 9/12/2023, subject to change

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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	~20,0004	14%5,6	77%7
Prostate Cancer (NEPC)
NET, High Grade	~11,500	mOS 10 months8	Highly expressed
		Stomach 9%9	Cervix 81%10
		Rectum 11%9	Gastroentero-pancreatic
Extrapulmonary NEC,	~2,600	Colon 15%9	77%11
except NEPC	Pancreas 20%9	Pancreas 19-50%12
		Small Intestine 43%9	Bladder 68%13
		Appendix 65%9
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)

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HPN328 Phase 1 Interim Update

Unaudited database as of 9/12/2023

Data subject to change

HPN328: A DLL3-TARGETED T CELL ENGAGER

• 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

Figure 1. HPN328 Mechanism of Action

HPN328 Mechanism of Action

T cell

T cell receptor complex

Anti CD3 domain

Anti albumin	HPN328
domain

Anti DLL3 domain

DLL3

Tumor Cell

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HPN328 Phase 1 Trial

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)

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Dose Escalation and Optimization Enrollment Nearing Completion

Monotherapy Cohorts - Q4'23; Combination Cohorts - 1H'24

Dose Escalation 3+3 Design Including Fixed & Step Dose Cohorts and Dose Optimization (N=71)

Ongoing 1 mg priming Step-dose Escalation

and Optimization Cohorts

Early Fixed Dose & Step dose Escalation Cohorts

2 24 mg

N = 4

2 12 mg

N = 5

3.6 7.2 mg

N = 4

0.015-3.6 mg

N = 11

Q1W

Q2W

HPN328: Q2W + Atezo Q4W

1 12 24 mg*

1 12 24 mg*

1 12 24 mg*

N = 8‡

N = 9‡

1 12 mg

1



12 mg

†

N = 8‡

1 12 mg

N = 6‡

1

 6 mg

* 1 mg to 24 mg cohorts use a 12 mg intermediate step up prior to moving to 24 mg target

N = 16

† 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

De-escalation to 1 mg prime

	Current 1mg Priming Cohorts
	Planned Cohorts
Early Step-dose Escalation Cohorts	Early Dose Escalation Cohorts

Fixed-dose Escalation

Unaudited database cutoff as of 9/12/2023, subject to change

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Phase 1 Population Includes Heavily Pre-treated Refractory Patients

Baseline Characteristics (N=71)

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%)

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%)

# Prior Therapies	n (%)
Median	2.5
Range	1-8
PD(L)-1 Inhibitors	56 (78.9%)

Unaudited database cutoff as of 9/12/2023, subject to change

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Adverse Events Manageable with No DLTs at Target Doses

No Grade 3 CRS with 1 mg Priming Regimens

Treatment-Related Adverse Events (TRAEs) Incidence ≥10% Patients by

Grade a (N=71)

Adverse Events	All Grades,	Grade ≥3,
	n (%)		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

Note: Post 9/12/2023 data cut-off, 1 Gr5 SAE (pneumonitis)

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

No DLTs Observed at Target Doses;

Target dose MTD Not Reached

ICANS=Immune effector cell-associated neurotoxicity syndrome

1. Grading per CTCAE v5.0, except cytokine release syndrome (grading per ASTCT 2019)
2. Includes both neutropenia and neutrophil count decreased
3. Two Grade 3 CRS events were DLTs at 2 mg priming dose (above current priming dose)
4. 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

Unaudited database cutoff as of 9/12/2023, subject to change

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