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FORM
CURRENT REPORT
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| Item 8.01 | Other Events. |
On December 11, 2022, Harpoon Therapeutics, Inc. (the “Company”) issued a press release regarding the announcement of updated interim data from its Phase 1 clinical trial evaluating single-agent HPN217 in relapsed/refractory multiple myeloma in a poster presentation at the 64th American Society for Hematology Annual Meeting and Exposition. On December 12, 2022, the Company posted a presentation (the “Presentation”) regarding these updates across the Company’s pipeline of clinical development programs. A copy of the press release is attached hereto as Exhibit 99.1 and a copy of the Presentation is attached hereto as Exhibit 99.2. The exhibits are incorporated herein by reference.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits.
| Exhibit No. |
Description | |
| 99.1 | Press Release, dated December 11, 2022. | |
| 99.2 | Clinical Pipeline Update Presentation, dated December 12, 2022. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Harpoon Therapeutics, Inc. | ||||||
| Date: December 12, 2022 | By: | /s/ Julie Eastland | ||||
| Julie Eastland | ||||||
| President and Chief Executive Officer | ||||||
Exhibit 99.1
Harpoon Therapeutics Presents Updated Interim Results at ASH 2022 for Novel T Cell Engager HPN217 in Relapsed/Refractory Multiple Myeloma
| • | Clinically active across a wide dose range (2.15 to 24 mg) in a Phase 1 trial of heavily pretreated patients with relapsed/refractory multiple myeloma |
| • | 77% (10/13) objective response rate (ORR) observed across highest doses (12 and 24 mg) |
| • | Responses were durable, with many patients on treatment longer than a year |
| • | Generally well-tolerated with a low incidence of cytokine release syndrome (CRS): Low-grade CRS in 29% of patients across highest step dose regimens; 95% of events occurred following first or second dose; no Grade 3 or higher CRS |
| • | Dose and schedule optimization is ongoing; maximum tolerated dose not yet reached in step dose regimen |
| • | Management to host webcast and conference call to review the HPN217 data presented at ASH and provide a pipeline update on Monday, December 12, 2022, at 4:30 Eastern Time/3:30 Central Time |
SOUTH SAN FRANCISCO, Calif., December 11, 2022 – Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, today presented updated interim data from its Phase 1 clinical trial evaluating single-agent HPN217 in relapsed/refractory multiple myeloma (RRMM) in a poster presentation at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition being held in person and virtually in New Orleans. HPN217 targets B-cell maturation antigen (BCMA) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC®) platform designed to recruit a patient’s own immune cells to kill tumor cells.
The interim results, as of the data cut-off date of October 17, 2022, showed that HPN217 demonstrated continued evidence of clinical activity and a tolerable safety profile in heavily pre-treated patients with RRMM (62 patients treated across fixed dose and step dose regimens). HPN217 was active across a wide dose range (2.15 to 24 mg), with 77% (10/13) ORR observed across the highest step doses (12 and 24 mg). A majority of responders had decreases in the serum BCMA biomarker (sBCMA, a marker correlated with disease prognosis) by week two of treatment. Additionally, 86% (18/21) of responders remain on study treatment with sustained response, with many responders on treatment for over a year. Three patients in the study were evaluated for minimal residual disease (MRD), and all three were MRD negative (<10-5). sBCMA remained undetectable at 9 months in many responders who achieved very good partial response (VGPR) or better.
Low-grade CRS occurred in 29% of patients across the highest step dose regimens (12% Grade 1 and 18% Grade 2) and was seen primarily in the earliest doses. No Grade 3 or higher CRS or any immune effector cell associated neurotoxicity syndrome (ICANS) events have been observed.
“The encouraging initial clinical activity with deepening and durable responses observed in patients who have received multiple prior lines of therapy, combined with a generally well-tolerated safety profile, suggest the investigational T cell engager HPN217 may offer meaningful clinical benefits for patients with relapsed/refractory multiple myeloma,” said Al-Ola A. Abdallah, M.D., of University of Kansas Medical Center, a Principal Investigator in this study. “I look forward to continuing to study this promising drug candidate in these patients with advanced disease for whom there remains a significant unmet need for new treatment options.”
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“These data provide further validation of our proprietary TriTAC T cell engager platform, demonstrating robust clinical activity for HPN217 at higher doses, while maintaining tolerability in this heavily refractory patient population,” said Luke Walker, M.D., Chief Medical Officer of Harpoon Therapeutics. “These data support our continued clinical development efforts, and we look forward to continuing dose optimization with ongoing patient enrollment in the Phase 1 trial expected to reach completion in the first half of 2023.”
For more details about the ASH Annual Meeting, please visit: https://www.hematology.org/meetings/annual-meeting
The poster (publication #3240) will be available on Harpoon’s website following today’s presentation.
Conference Call and Webcast Details
Harpoon’s management will host a live call/webcast on Monday, December 12, 2022, at 4:30 ET/3:30 CT/1:30 PT, to review the interim results of its Phase 1 HPN217 clinical program and provide an update on other pipeline programs. The live call may be accessed by dialing 1-877-407-9039 for domestic callers and 1-201-689-8470 for international callers with conference ID code number 13734677. A live webcast of the call will be available from the Events and Presentations section of Harpoon’s website here and will be archived there shortly after the live event.
About HPN217
HPN217 targets B-cell maturation antigen (BCMA) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC®) platform designed to recruit a patient’s own immune cells to kill tumor cells.
In November 2019, Harpoon Therapeutics and AbbVie announced a licensing agreement and option to advance HPN217 and expand an existing discovery collaboration. Under the terms of the agreement, AbbVie may exercise its option to license HPN217 after completion of the Phase 1 clinical trial.
In March 2022, the FDA granted Fast Track designation to HPN217, underscoring its potential to address a serious unmet medical need for patients with relapsed, refractory multiple myeloma.
About the HPN217 Clinical Trial
HPN217 is being evaluated in an ongoing Phase 1, multicenter, open-label dose escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK) and clinical activity in patients with relapsed/refractory multiple myeloma who have had at least three prior systemic treatments, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody, including patients with prior exposure to BCMA therapy. Primary objectives are characterization of safety, tolerability, PK and determination of the recommended Phase 2 dose.
As of the cutoff date on October 17, 2022, maximum tolerated dose has not yet been reached in the step-dose regimen. Assessment of the Q2 cohort dosing schedule is ongoing.
For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT04184050.
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About Harpoon Therapeutics
Harpoon Therapeutics is a clinical-stage immuno-oncology company developing a novel class of T cell engagers that harness the power of the body’s immune system to treat patients suffering from cancer and other diseases. T cell engagers are engineered proteins that direct a patient’s own T cells to kill target cells that express specific proteins, or antigens, carried by the target cells. Using its proprietary Tri-specific T cell Activating Construct (TriTAC®) platform, Harpoon is developing a pipeline of novel TriTACs initially focused on the treatment of solid tumors and hematologic malignancies. Harpoon has also developed a proprietary ProTriTAC™ platform, which applies a prodrug concept to its TriTAC platform to create a therapeutic T cell engager that remains inactive until it reaches the tumor. Harpoon’s third proprietary technology platform, extended release TriTAC-XR, is designed to mitigate cytokine release syndrome. For additional information about Harpoon Therapeutics, please visit www.harpoontx.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “look forward,” “may,” “suggest,” “expect,” “potential,” “continued,” “will,” 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 Therapeutics’ expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause Harpoon Therapeutics’ 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 press release include, but are not limited to, statements about the expected timing, progress, and results of Harpoon Therapeutics’ clinical trials, including the anticipated timing of patient enrollment in the HPN217 Phase 1 trial; the association of interim clinical data and preclinical results with potential treatment outcomes; the possibility and timing of AbbVie’s option to license HPN217 and other statements that are not historical fact. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during clinical studies, preliminary data and trends may not be predictive of future data or results, may not demonstrate safety or efficacy or lead to regulatory approval by the FDA or other regulatory agencies, clinical trial site activation or enrollment rates that are lower than expected, unanticipated or greater than anticipated impacts or delays due to COVID-19, changes in expected or existing competition, changes in the regulatory environment, the uncertainties and timing of the regulatory approval process, the timing and results of unexpected litigation or other disputes, and the sufficiency of Harpoon Therapeutics’ cash resources. These and other factors that may cause Harpoon Therapeutics’ actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Harpoon Therapeutics’ filings with the U.S. Securities and Exchange Commission, including under “Risk Factors” in Harpoon Therapeutics’ quarterly report on Form 10-Q for the quarter ended September 30, 2022, and future filings by Harpoon Therapeutics. Except as required by law, Harpoon Therapeutics assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
Contacts:
Investors:
ICR Westwicke
Robert H. Uhl
Managing Director
858-356-5932
robert.uhl@westwicke.com
Media:
Uncapped Communications
512-825-2603 monique.greer@uncappedcommunications.com
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Spearheading Immunotherapies Ash 2022 review and business update December 12, 2022 Nasdaq: HARP Exhibit 99.2
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,” “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, and the timing of development milestones for platforms and product candidates, expectations of our cash runway and future business, strategy and financial performance. 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, unanticipated or greater than anticipated impacts or delays due to the COVID-19 pandemic, changes in expected or existing competition, 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, including the “Risk Factors” sections contained therein. 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. Forward-looking Statements
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