HPN424 / AbbVie, Merck (MSD) - LARVOL DELTA

HPN424-1001: Study of HPN424 in Patients With Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=104 | Terminated | Sponsor: Harpoon Therapeutics | Active, not recruiting ➔ Terminated; Decision not to continue to the expansion portion of the study

Metastases • Trial termination • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[VIRTUAL] Combinatorial antitumor effects of CD3-based trispecific T cell activating constructs (TriTACs) and checkpoint inhibitors in preclinical models (AACR 2021) - P1/2 | "TriTAC molecules are currently being investigated in multiple phase 1/2 clinical trials in solid tumors, including HPN424 targeting prostate-specific membrane antigen (PSMA) in prostate cancer (NCT03577028), HPN536 targeting mesothelin (MSLN) in multiple malignancies (NCT03872206) and HPN328 targeting Delta Like Canonical Notch Ligand 3 (DLL3) in small cell lung cancer (SCLC) (NCT04471727). In addition, in the MSLN-expressing NCI-H292 lung cancer model that co-expresses constitutive, high levels of PD-L1, both anti-PD1 and anti-PDL1 antibodies significantly enhanced the antitumor effects of the MSLN-targeting TriTAC HPN536 in vivo. Together these results demonstrate the potential utility of PD1/PDL1 blockade to enhance the potency of TriTAC-mediated tumor cell killing, supporting further investigation of these combinatorial approaches in patients."

Checkpoint inhibition • Preclinical • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3 • MSLN

HPN424-1001: Study of HPN424 in Patients With Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=110 | Active, not recruiting | Sponsor: Harpoon Therapeutics | Recruiting ➔ Active, not recruiting | N=40 ➔ 110 | Trial completion date: Dec 2020 ➔ Mar 2023 | Trial primary completion date: Dec 2020 ➔ Mar 2023

Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

HPN424, a Tri-specific T-cell Activating Construct, induces T cell-mediated cytotoxicity against human metastatic castration-resistant prostate cancers (mCRPC) (AACR 2022) - "HPN424, a PSMA-targeting TriTAC antibody construct, induced T cell activation and elicited T-cell mediated cytotoxicity against PSMA expressing mCRPC PDX-Os. Our data support further evaluation of this agent in advanced PC with membranous PSMA expression."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD69 • FOLH1 • IFNG • IL10 • IL1B • IL2 • IL2RA • IL4

Harpoon drug sunk by modest activity, challenging tolerability, forcing pivot from prostate cancer prospect (FierceBiotech) - "Harpoon Therapeutics has given up on its onetime lead prospect HPN424. A phase 1/2a prostate cancer clinical trial found the PSMA-targeting T-cell engager had 'modest activity with a tolerability profile that has been challenging,' driving Harpoon to discontinue development and focus on other assets....Harpoon CEO Julie Eastland said management decided to discontinue clinical development of HPN424 after reviewing data on the candidate."

Discontinued • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

Harpoon Therapeutics Provides Pipeline Development Milestones for 2022 (GlobeNewswire) - "Anticipated 2022 Milestones...HPN328 – Continue dose escalation to determine RP2D by year-end 2022; HPN217 – Select the RP2D and initiate dose expansion cohort during the first half of 2022; HPN536 – Complete dose escalation by year-end 2022; HPN424 – Complete dose escalation during the second half of 2022; HPN601 – IND submission by year-end 2022"

IND • Trial status • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

A phase I dose escalation and expansion study of HPN424, a PSMA-targeting T cell engager, in patients with advanced prostate cancer refractory to androgen therapy (SITC 2019) - "N/A"

Clinical • P1 data

[VIRTUAL] Results of an ongoing phase 1/2a dose escalation study of HPN424, a tri-specific half-life extended PSMA-targeting T-cell engager, in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2021) - P1/2 | "HPN424, a novel half-life extended PSMA-targeting T cell engager, was well tolerated when administered once weekly . AEs were transient, manageable and consistent with class of agent . Grade 3 CRS was observed in 4% of patients, occurring with first administration of target dose ."

Clinical • P1/2 data • Anemia • CNS Disorders • Epilepsy • Genito-urinary Cancer • Hematological Disorders • Oncology • Prostate Cancer • Solid Tumor • CTCs

[VIRTUAL] First-in-human phase I study of HPN424, a tri-specific half-life extended PSMA-targeting T-cell engager in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2020) - P1 | "HPN424 represents a novel half-life extended PSMA-targeting T-cell engager that can be safely administered once weekly. AEs have been transient and manageable. Cytokine increases indicate T-cell activation."

Clinical • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs

Harpoon Therapeutics Reports Second Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - “Research and development expense for the second quarter ended June 30, 2021, was $18.3 million compared to $11.9 million for the quarter ended June 30, 2020. For the six months ended June 30, 2021, R&D expense was $34.5 million compared to $24.4 million for the six months ended June 30, 2020. The increase for both periods, primarily arose from higher clinical development and personnel-related expense, which included conducting preclinical studies and the continuation and preparation of the clinical trials for HPN424, HPN536, HPN217 and HPN328…HPN424 – initiate a dose expansion cohort of the Phase 1/2a trial by year end 2021.”

Commercial • Trial status • Oncology

Sarah Cannon to present latest cancer research insights at ASCO20 Virtual Meeting (Businesswire) - "Sarah Cannon announced that it will present its latest cancer research insights at the American Society of Clinical Oncology’s (ASCO®) Annual Meeting being held virtually May 29 – 31, 2020. This year, Sarah Cannon’s drug development and research expertise is featured through more than 110 abstracts and presentations, including data from more than 50 phase 1 studies....Jesus Berdeja, MD...is the discussant on the plenary session focused on 'Carfilzomib, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide, and Dexamethasone for Initial Therapy of Newly Diagnosed Multiple Myeloma' on Sunday, May 31 from 12-2:30 PM CT. Dr. Berdeja will also highlight data in an oral presentation on 'Update of CARTITUDE-1: A Phase Ib/II Study of JNJ-4528, a B-Cell Maturation Antigen-Directed CAR-T-Cell Therapy, in Relapsed/Refractory Multiple Myeloma.' (Abstract 8505)."

Clinical data • Breast Cancer • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Gynecologic Cancers • Hematological Malignancies • Indolent Lymphoma • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Rectal Cancer • Small Cell Lung Cancer • Solid Tumor

HPN424: Initial data from dose expansion cohort of P1/2a trial (NCT03577028) for prostate cancer at the end of 2021 (Harpoon Therapeutics) - Corporate Presentation

P1/2 data • Oncology • Prostate Cancer

Updated Interim Efficacy and Safety Results from a Phase I/IIa Trial HPN424 in Metastatic Castration-Resistant Prostate Cancer (mCRPC) - Tomasz Beer (Urotoday) - "In this conversation with Charles Ryan, MD, Tomasz Beer, MD, medical oncologist highlight the updated interim results of the ongoing phase 1/2a HPN424-1001 trial assessing HPN424 in metastatic castration-resistant prostate cancer (mCRPC) that were presented at the ASCO 2021 annual meeting."

Video

Harpoon Therapeutics Provides Progress Update for TriTAC Clinical Programs and ProTriTAC Platform (GlobeNewswire) - P1/2, N=40; NCT03577028; Sponsor: Harpoon Therapeutics; "Harpoon Therapeutics...provided a pipeline update on its four clinical stage programs, including updating the interim data presented earlier today at ASCO from the ongoing dose escalation portion of the Phase 1/2a trial for HPN424 in patients with metastatic castration resistant prostate cancer (mCRPC)...The ASCO poster presentation, included the following observations: Antitumor activity includes a confirmed PR per RECIST, PSA declines and CTC reductions; Fifteen of 74 (20%) pts with >1 post-baseline value had PSA decreases from baseline ranging from -2% to -76%, including 4 pts with PSA50 response and 2 pts with PSA30 response; Treatment duration > 24 weeks observed in 15 of 74 (20%) pts, including 8 of 17 (47%) chemo-naïve patients."

P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer

Harpoon Therapeutics Presents Updated Interim Clinical Data for the PSMA-targeting TriTAC HPN424 at the 2021 ASCO Annual Meeting (GlobeNewswire) - P1/2, N=40; NCT03577028; Sponsor: Harpoon Therapeutics; "Harpoon Therapeutics...presented interim data from the ongoing dose-escalation portion of a Phase 1/2a trial for HPN424 in patients with metastatic castration-resistant prostate cancer (mCRPC) at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. HPN424 demonstrated dose proportional increase in Cmax and AUC. Reduction in CTCs was seen in 36 of 64 (56%) patients with available baseline and on-treatment CTC counts. Fifteen of 74 (20%) pts with >1 post-baseline value had PSA decreases from baseline ranging from -2% to -76%, including 4 pts with PSA50 response and 2 pts with PSA30 response."

P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer

HPN424: “HPN424 has antitumor activity including a confirmed PR per RECIST, PSA declines and CTC reductions"; Castration-resistant prostate cancer (Harpoon Therapeutics) - ASCO 2021: “Treatment duration > 24 weeks observed in 15 of 74 (20%) evaluable pts, including 8 of 16 (50%) chemo-naïve patients”

P1/2 data • Oncology • Prostate Cancer

Harpoon Therapeutics to Present Updated Interim Clinical Data for TriTAC HPN424 at the 2021 ASCO Annual Meeting (GlobeNewswire) - “Harpoon Therapeutics, Inc…announced today that updated interim Phase 1 data for HPN424 for prostate cancer will be presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting beginning on June 4,2021. The poster presentation will show interim data for HPN424 from its ongoing dose escalation Phase 1/2a clinical trial in patients with metastatic castration-resistant prostate cancer (mCRPC) and will be highlighted in a poster discussion session.”

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer

Harpoon Therapeutics Reports First Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Anticipated 2021 milestones: (i) HPN424 - present interim data from the dose escalation phase of the ongoing Phase 1/2a trial in the first half of 2021, and initiate the dose expansion cohort mid-year 2021; (ii) HPN536 - in the second half of 2021, initiate the dose expansion cohort of the ongoing Phase 1/2a trial and, by year end 2021, present interim Phase 1 data from the dose escalation phase of the trial."

P1 data • P1/2 data • Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer

Harpoon Therapeutics Reports Fourth Quarter and Full Year 2020 Financial Results and Provides Corporate Update (GlobeNewswire) - “Anticipated 2021 Milestones: HPN424 – in the first half of 2021, present interim data from the dose escalation phase of our Phase 1/2a trial and initiate the dose expansion cohort; HPN536 – in the second half of 2021, initiate the dose expansion cohort of our Phase 1/2a trial and, by year end 2021, present interim Phase 1 data from the dose escalation phase of the trial; HPN217 – in the second half of 2021, initiate the dose expansion cohort of our Phase 1/2 trial, and, in 2021, present interim data from the dose escalation phase of the trial; HPN328 – in the second half of 2021, present interim data from the dose escalation phase of our Phase 1/2 trial.”

Clinical data • Genito-urinary Cancer • Gynecologic Cancers • Hematological Malignancies • Multiple Myeloma • Oncology • Ovarian Cancer • Prostate Cancer

HPN424: Protection of patents related to composition-of-matter and methods of use for prostate cancer in US/ex-US until 2037 (Harpoon Therapeutics) - Annual Report 2020

Patent • Oncology

Harpoon Therapeutics Announces Pricing of Public Offering of Common Stock (GlobeNewswire) - "Harpoon Therapeutics, Inc...announced today the pricing of an underwritten public offering of 5,882,352 shares of its common stock at a price to the public of $17.00 per share...the net proceeds of the offering, together with other available funds, to fund the continued clinical development of HPN424 in metastatic castration-resistant prostate cancer, HPN536 in ovarian cancer and other solid tumors, HPN217 in multiple myeloma, and HPN328 for the treatment of small cell lung cancer and other neuroendocrine tumors expressing Delta-like canonical Notch ligand 3; to advance the development of....HPN601..."

Commercial • Genito-urinary Cancer • Gynecologic Cancers • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

Harpoon Therapeutics Reports Third Quarter 2020 Financial Results and Provides Corporate Update (GlobeNewswire) - "Additionally, we expect to advance our HPN424, HPN536, and HPN217 clinical programs in the fourth quarter and present preclinical data at SITC for our first ProTriTAC development program, HPN601, for the treatment of solid tumor malignancies.”"

Clinical • Preclinical • Oncology • Solid Tumor

HPN424: “1 patient had confirmed RECIST partial response”; Metastatic castration-resistant prostate cancer (Harpoon Therapeutics) - Clinical Pipeline Update: “Three of 7 (43%) had PSA reduction”

P1/2 data • Oncology • Prostate Cancer

HARPOON THERAPEUTICS TO HOST CLINICAL PIPELINE PROGRAMS UPDATE CALL AND WEBCAST ON DECEMBER 8, 2020 (GlobeNewswire) - “Harpoon Therapeutics, Inc…announced that it will host a conference call and webcast to review the status and provide a clinical update for its three most advanced TriTAC® programs. The discussion will be focused on HPN424 for the treatment of metastatic castration resistant prostate cancer, HPN536 initially in development for ovarian and pancreatic cancer and mesothelioma, and HPN217 for relapsed/refractory multiple myeloma.”

Clinical • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hematological Malignancies • Multiple Myeloma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer

Harpoon Therapeutics Reports Clinical Progress Across All Four TriTAC Pipeline Development Programs (GlobeNewswire) - P1/2, N=40; NCT03577028; Sponsor: Harpoon Therapeutics; "HPN424 was generally well tolerated and cytokine-related adverse events have been manageable. Reported Grade 3 or higher adverse events have included cytokine release syndrome (CRS) (10%), ALT increase (11%) and AST increase (11%)...Presentation of Phase 1 data and initiation of an expansion cohort is planned for the first half of 2021. Interim data from this expansion cohort is anticipated by the end of 2021."

P1 data • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer