Spearheading Immunotherapies
Investor Presentation
March 2020
Forward-looking Statements
This presentation contains forward-looking statements about Harpoon Therapeutics, Inc.. All statements other than statements of historical facts contained in this presentation are forward-looking statements, including statements about our financial position, strategy, expectations regarding the timing and achievement of our product candidate development activities and ongoing and planned clinical trials, and plans and expectations for future operations. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to: our limited operating history; net losses; our expectation that we will incur net losses for the foreseeable future, and that we may never be profitable; our need for additional funding and related risks for our business, product development programs and future commercialization activities; the timing and success of preclinical and clinical trials we conduct; the ability to obtain and maintain regulatory approval of our product candidates; the ability to commercialize our product candidates; our ability to compete in the marketplace; risks regarding our license agreements; our ability to obtain and maintain intellectual property protection for our product candidates; and our ability to manage our growth. We operate in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. For a discussion of many of these and other risks and uncertainties, see our filings with the Securities and Exchange Commission, including the "Risk Factors" section in our Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, which are available on the SEC's website at www.sec.gov. Except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements. We undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in our expectations.
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 our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, we have not independently verified, and make 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 our 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 - Investment Overview
Therapeutic FocusClinical-stage immunotherapy company
Platform Technology
Tri-specific T cell Activating Construct (TriTAC®) platform
T cell engager technology, allows for "off-the-shelf" therapies
Multiple Product
Candidates
HPN424 (PSMA TriTAC) Phase 1 in prostate cancer initiated August 2018
HPN536 (mesothelin TriTAC) Phase 1/2a in ovarian cancer and other solid tumors initiated April 2019
Two additional TriTACs expected to enter clinic in 2020
Multiple Anticipated
Clinical Catalysts in
2020
HPN424 - Present Interim data in H1 2020; expansion study initiation in 2020
HPN536 - present interim data in 2020
Strong Financial
Position
Adjusted cash balance of $171.21million expected to fund operations into 2022
Successful IPO in February 2019 raised $70.7 million net cash
Nov 2019 - AbbVie HPN217 license and expanded discovery agreements
1- $121.2M at September 30, 2019 plus $50M upfront payments from AbbVie agreements in Nov. 2019
PSMA - prostate specific membrane antigen | 3 |
Broad Pipeline of Immuno-Oncology Programs
Four clinical stage TriTAC programs in 2020
Product | Target / Indication | Stage of Development | Anticipated | |
Candidate | Milestones | |||
Preclinical | Phase 1 | Phase 2 | Phase 3 | |
TriTAC
HPN424
HPN536
HPN217
HPN328
PSMA / Prostate cancer
MSLN / Ovarian, pancreatic and other solid tumors
BCMA / Multiple myeloma
DLL3 / Small cell lung cancer
H1 2020: Interim data
April 2019: Initiated Phase 1/2a clinical trial;
2020: Interim data
H1 2020: Initiate Phase 1/2 AbbVie licensing and option agreement
2020: Submit IND and initiate Phase 1
MSLN - mesothelin, BCMA - B-cell maturation antigen, DLL3 - delta-like 3
4
Deals with AbbVie - HPN217 & Broad Discovery Collaboration
Nov 2019 - Up to $100M in upfront / near-term milestones and $2.3B in future payments
HPN217 global licensing and option deal
- Option to license worldwide rights to HPN217
- Harpoon responsible for clinical development of HPN217 through Phase 1/2
- Upon exercise of option, AbbVie responsible for future development and commercialization
- Potential transaction value: $510M
- $80Mupfront/near-term
- $200M option fee
- $230M in future milestones, plus royalties
Expanded TriTAC® discovery collaboration
- Grants AbbVie worldwide exclusive rights to up to six new targets
- Harpoon responsible for initial R&D activities. AbbVie responsible for further development and commercialization efforts
- Expanded Deal Transaction Value: $1.86B
- $20M upfront for two new targets
- $40M: $10M each for up to four additional targets
- $300M in future milestones, plus royalties per target (6 potential)
Oct 2017 - Up to $617M in upfront and future milestones plus royalties on sales
- $17M upfront for TriTAC discovery collaboration for two initial targets
- $300M in future development milestones per target (two)
5
TriTAC - Next Generation T Cell Engagers Address Limitations of Existing IO Therapies
Checkpoint Inhibitors |
COMPANY |
CAR-T Cells | Bispecific T-Cell Engagers |
STRUCTURE |
ζ ζ
CD28 or CD137 Domain
• | Requires tumor-specific T cells and MHC-I | |
LIMITATIONS | expression | |
• | "Cold tumors" are unresponsive to | |
checkpoint inhibitors | ||
• | Single-agent response rate limited | |
compared to combination therapies | ||
- Limited activity or efficacy in solid tumors
- On-targettoxicities (cytokine release syndrome, neurotox)
- Inability todose-limit side effects
- Requires personalized manufacturing and treatment process
- Chemopre-conditioning and hospitalization after infusion (often not reimbursed)
- 1stgeneration BiTEs require continuous IV administration
- Other T cell bispecifics use antibody (Fc) to extendhalf-life which may compromise tumor penetration and safety
APPROVED | DRUGSIO | •Yervoy (2011) | •Tecentriq (2016) |
•Opdivo (2014) | •Bavencio (2017) | ||
•Keytruda (2014) | •Imfinzi (2017) |
•Yescarta (2017) | •Blincyto (2014) |
•Kymriah (2018) |
MHC - major histocompatibility complex, CAR - chimeric antigen receptor
6
TriTAC: Small Size and Flexibility, Albumin Domain Confers Extended Half Life
Molecular Molecular
Weight Structure
BiTE
~50kD
TriTAC ~50kD
Bispecific
Antibody
~150kD
HSA - human serum albumin, BiTE - bispecific T cell engager
7
Intellectual Property Strategy: Multiple Layers of Protection
TriTAC®
IP wholly owned by Harpoon
- Issued patentscovering each binding domain
- Issued platform patentscovering TriTAC domain orientation, with albumin binding in the middle of the construct
- Pending patentson each product sequence
- HPN424, HPN536, HPN217, HPN328
TargetHSACD3
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TriTACs Overcome Immune Escape Mechanisms and Induce Killing Independent of MHC Expression
MHC downregulation and
mutations are a major tumor
evasion mechanism
T Cell
TCR | ||
• | Does not require a T cell clone with | Complex |
specific T cell receptor | XTriTAC™ | |
•Any T cell can recognize a surface antigen | ||
•Does not require MHC expression | MHC | X |
for recognition by T cell | ||
Target Cell
MHC - major histocompatibility complex, TCR - T cell receptor | 9 |
Preclinical Validation of TriTAC Platform
Data Supports Once Weekly Treatment in Humans
TriTAC Potency | Extended Half Life | ||||
Comparison of TriTAC and BiTE | Serum Levels of PSMA TriTAC | ||||
Mediated Cell Killing |
- TriTACs observed to be more potent that the comparative BiTE molecule, and can induce T cells to kill tumor cells in bothcell-based and animal models
- TriTACs observed to have a terminalhalf-life of 80+ hours vs < 2 hours reported in Blincyto literature
10
Benefits of TriTACs - the Next Generation of T Cell Engagers
Extended Half-
Life and
Stability
Active at Low Antigen Level
MHC
Independence
Small Size and
Tissue
Penetration
Modularity
Safety Design
Elements
Conventional
Manufacturing
- Stable in bloodstream andlong-serumhalf-life allow for treatment without continuous IV administration
- Once-weeklydosing
- Active at low levels of antigen expression where other treatment modalities lose efficacy
- Does not require high levels of target antigen expression to engage T cells to kill disease cells (based on preclinical studies)
- Direct T cells to kill target cells independent of MHC expression
- Expected to be able to generate greater and more durable therapeutic responses than MHC dependent approaches
- Small size expected to allow for faster diffusion into human tumor tissue
- Designed for greater potential in solid tumors
- Structure is modular and antigen binding domain designed to be easily switched out
- Allows for potential rapid discovery and development of new product candidates
- No potential for Fc receptor binding
- Single-armedCD3 binding reduces likelihood of non-specific T cell activation
- Less complex manufacturing than personalized orcell-based therapies
- Off-the-shelftherapies
11
HPN424 TriTAC (PSMA)
12
Metastatic Prostate Cancer: >$5B Global Market Opportunity*
- 174K new cases of prostate cancer annually in the U.S.
- >31K U.S. deaths per year (2ndleading cause of cancer death in men)
- Mean survival time for mCRPC = 13 months
- 5-yearsurvival rate is ~30% in more aggressive forms
- ~ 23% initially diagnosed with advanced disease
Significant unmet need for patients with incurable mCRPC
- Continued high mortality rates of advanced disease
- Potential "fast to market" strategy forhigh-risk patient subgroups
U.S. Incidence and Mortality of
Cancer in Men
200,000
150,000
100,000
50,000
0
New Cases Deaths
Source: SEER, ACS, 2019 estimates
- Based on combined sales in 2017 oflater-generationanti-androgen drugs such as Zytiga and Xtandi.
mCRPC - metastatic castration resistant prostate cancer
13
HPN424 Targets PSMA - A Highly Expressed and Validated Target for Prostate Cancer
- Designed to bind to human PSMA, CD3, and albumin
- Redirects T cells to killPSMA-expressing target cells
- Target overexpressed in malignant cells, with limited expression in normal tissue
- Clinically validated by encouraging response data from Amgen's BiTE targeting PSMA in mCRPC patients
- Phase 1 trial initiated in patients with mCRPC cancer in August 2018
Prostate | ||||||
cancer cell | ||||||
PSMA | ||||||
anti-PSMA | ||||||
Cancer | Cytolytic | anti-albumin | ||||
cell | ||||||
synapse | ||||||
killing | anti-CD3ε | |||||
CD3 | ||||||
T cell
HPN424 is a tri-specific single
chain molecule of ~50 kDa
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HPN424 - Design of Open-label Ongoing Phase 1 Trial
Part 1 - Dose escalation
Dose escalation: single patient
- Gr 2 study drug related toxicity
Dose escalation: 3 + 3
(3 - 6 pts per dose level)
MTD or recommended
Phase 2 dose
Part 2 - Expansion
~20 pts treated at recommended Phase 2 dose determined in Part 1
- Target population
- Patients with mCRPC
- Disease progression on the prior systemic regimen
- At least two prior systemic therapies approved for mCRPC
- Trial objectives
- Assess safety and tolerability at increasing dose levels
- AEs
- Time on trial
- Pharmacokinetic and pharmacodynamic data
- Single-doseand multi-dose pK
- T-cellactivation: cytokines and chemokines
- Circulating tumor cells (CTC)
- Evaluate preliminaryanti-tumor activity
- PSA levels
- CT and bone scans
- Dosing & administration
- Weekly IV infusion of HPN424
- Initiation of expansion cohort expected in 2020
- Increase enrollment and continue dose escalation
- Planning for medical conference presentation of interim data H1 2020
15
HPN536 TriTAC (MSLN)
16
MSLN - Associated with Tumors with High Unmet Need and Low Survival Rates
New
MSLN
Ovarian Cancer
Patients
Cancer TypeExpression
Diagnosed
•5thmost common cause of cancer |
death among women in the U.S. |
in the U.S.
Non-Small Cell
Level (%)
• | ~22,000 new cases per year |
• | More than 70% diagnosed with |
Lung Cancer
199,000 60-65*
advanced disease | |
• | 5-year survival rate is 47%; ~14,000 |
die annually | |
• | Current treatment is rarely curative |
but provides moderate symptom relief | |
and limited increase in survival |
Ovarian
22,000 60-65
Carcinoma
Pancreatic
55,000 80-85
Carcinoma
Mesothelioma | 2,600 | 85-90 |
Triple-
Negative 40,000** 34-42
Breast Cancer
- Represents MSLN expression levels across all lung cancer types.
- Calculated as 15% ofSEER-estimated breast cancer incidence
17
HPN536 - Targets MSLN for the Treatment of Ovarian Cancer and Other MSLN-Expressing Tumors
- Designed to bind to human mesothelin, CD3, and albumin
- Redirects T cells to killMSLN-expressing target cells
- Target overexpressed in malignant cells, with limited expression in normal tissue
- Clinically validated and is overexpressed on a wide array of cancer types: ovarian, pancreatic, mesothelioma, NSCLC, TNBC
- Phase 1/2a trial initiated in patients with ovarian cancer in April 2019
Mesothelin | |||||
Expressing Target | |||||
MSLN | |||||
Target antigen | anti-MSLN | ||||
anti-albumin | |||||
anti-CD3ε | |||||
CD3 | |||||
T cell
HPN536 is a tri-specific single
chain molecule of ~50 kDa
18
HPN536 - Design of Open-label Ongoing Phase 1/2a Trial
Part 1 - Dose Escalation
Dose escalation: single patient
- Gr 2 study drug related toxicity
Dose escalation: 3 + 3
(3 - 6 pts per dose level)
MTD or recommended
Phase 2 dose
Part 2 - Expansion
3 parallel cohorts, ~20 patients each:
Ovarian, Pancreatic and Mesothelioma cancers
Treated at recommended Phase 2
dose determined in Part 1
- Target population
- Patients with advanced cancers associated with mesothelin expression who have failed standard available therapy
- Initial focus on ovarian cancer, expansion planned to pancreatic and mesothelioma cancers
- Trial objectives
- Assess safety and tolerability at increasing dose levels
- Pharmacokinetic and pharmacodynamic data
- Evaluate preliminaryanti-tumor activity
- Dosing & administration
- Weekly IV infusion of HPN536
- Successfully dosed through two cohorts(as of July 2019)
- Expect interim data in 2020
19
HPN217 TriTAC (BCMA) and HPN328 TriTAC (DLL3)
20
HPN217 - Targets BCMA for the Treatment of Multiple Myeloma and Other BCMA-Expressing Tumors
- Covered by global licensing and option agreement with AbbVie
- Designed to bind to human BCMA, CD3, and albumin
- Redirects T cells to killBCMA-expressing target cells
- Validated target: Amgen presented promising clinical responses on continuous IV BiTE candidate (AMG420)
- IND submitted in late 2019 and expect to initiate Phase 1/2 in H1 2020
BCMA
Expressing Target
BCMA
Target antigen
anti-BCMA
anti-albumin
anti-CD3ε
CD3
T cell
HPN217 is a tri-specific single
chain molecule of ~50 kDa
21
HPN328 - Targets DLL3 for the Treatment of Small Cell Lung Cancer
- Designed to bind to human DLL3, CD3, and albumin
- Redirects T cells to killDLL3-expressing target cells
- Preclinical data presentation at AACR-NCI-EORTC (Oct 2019), shows strong tumor cell killing incell-basedand animal SCLC models and stability data supporting at least once weekly dosing
- Phase 1 clinical trial is planned for 2020
DLL3
Expressing Target
DLL3
Target antigen
anti-DLL3
anti-albumin
anti-CD3ε
CD3
T cell
HPN328 is a tri-specific single
chain molecule of ~50 kDa
DLL3 - Delta-like 3 | 22 |
Seasoned Management Team with Deep Expertise in Oncology
STRONG HISTORY OF R&D INNOVATION, IMPACT ON PATIENTS AND VALUE TO STOCKHOLDERS
Jerry McMahon, Ph.D. | Georgia Erbez | Natalie Sacks, M.D. | Holger Wesche, Ph.D. |
President and CEO | Chief Financial Officer | Chief Medical Officer | Chief Scientific Officer |
Che Law, Ph.D. | Susan Dana Jones | Rachael Lester | Christopher Whitmore, |
VP, Translational | SVP, Product | VP, Corporate | CPA |
Medicine | Development | Development | VP, Finance |
CONTRIBUTED TO MANY DRUG APPROVALS AND COMMERCIALIZATION AT OTHER COMPANIES INCLUDING
23
Financial Snapshot - Strong Cash Position
Notes | |||
•$121.2M as of September 30, 2019 | |||
Cash1 | •Including $100mm upfront/milestone payments, adj. cash | ||
$171.2M | • | is $221.2 and expected to fund the company into 2H 2022 | |
No debt | |||
Shares Outstanding | 24.6M | • | As of September 30, 2019 |
Market Capitalization | $377M | • | As of February 28, 2020 |
Non-affiliated Institutional | 52.9% | • | As of December 30, 2019 |
Ownership | |||
1Cash adjusted to include $50M upfront payments from AbbVie agreements signed November 2019
24
Potential Clinical Milestones
Milestone | Timing | |
HPN424:Preliminary Phase 1 data | January 2019 | ✔ |
HPN536:Initiate Phase 1/2a clinical trial | April 2019 | ✔ |
HPN217:Submit IND | H2 2019 | ✔ |
HPN217: Initiate Phase 1/2 clinical trial | H1 2020 | |
HPN424:Presentation of interim Phase 1 data at medical | H1 2020 | |
conference | ||
HPN536:Present interim data | 2020 | |
HPN424:Initiate expansion cohort | 2020 | |
HPN328:Submit IND and initiate Phase 1 clinical trial | 2020 | |
Anticipate four TriTAC product candidates in the clinic in 2020
25
Harpoon Therapeutics - Investment Overview
Therapeutic FocusClinical-stage immunotherapy company
Platform Technology
Tri-specific T cell Activating Construct (TriTAC®) platform
T cell engager technology, allows for "off-the-shelf" therapies
Multiple Product
Candidates
HPN424 (PSMA TriTAC) Phase 1 in prostate cancer initiated August 2018
HPN536 (mesothelin TriTAC) Phase 1/2a in ovarian cancer and other solid tumors initiated April 2019
Two additional TriTACs expected to enter clinic in 2020
Multiple Anticipated
Clinical Catalysts in
2020
HPN424 - Present Interim data in H1 2020; expansion study initiation in 2020
HPN536 - present interim data in 2020
Strong Financial
Position
Adjusted cash balance of $171.21million expected to fund operations into 2022
Successful IPO in February 2019 raised $70.7 million net cash
Nov 2019 - AbbVie HPN217 license and expanded discovery agreements
1- $121.2M at September 30, 2019 plus $50M upfront payments from AbbVie agreements in Nov. 2019
PSMA - prostate specific membrane antigen | 26 |
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Harpoon Therapeutics Inc. published this content on 02 March 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 03 March 2020 09:05:15 UTC