podentamig (MK-4002) / Merck (MSD) - LARVOL DELTA

Study of HPN217 in Participants With Relapsed/Refractory Multiple Myeloma MK-4002 (HPN217) (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Study of HPN217 in Participants With Relapsed/Refractory Multiple Myeloma MK-4002 (HPN217) (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Trial completion date: May 2025 ➔ Nov 2025

Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

A Phase 1 Open-label, Multicenter, Dose Escalation Study of the Safety, Tolerability, and PK of HPN217 in Patients With R/R MM (clinicaltrials.gov) - P1 | N=97 | Active, not recruiting | Sponsor: Harpoon Therapeutics | Trial completion date: Jun 2024 ➔ May 2025 | Trial primary completion date: Jan 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Merck Completes Acquisition of Harpoon Therapeutics, Inc. (Merck (MSD) Press Release) - "Merck...announced the completion of the acquisition of Harpoon Therapeutics, Inc...Harpoon’s common stock will no longer be publicly traded or listed on the Nasdaq Stock Market...Harpoon’s lead candidate, MK-6070 (formerly known as HPN328), is a T-cell engager targeting delta-like ligand 3 (DLL3), an inhibitory canonical Notch ligand that is expressed at high levels in small cell lung cancer (SCLC) and neuroendocrine tumors...Additional pipeline candidates include HPN217, a T-cell engager targeting B-cell maturation antigen (BCMA), currently in Phase 1 clinical development for the treatment of patients with relapsed/refractory multiple myeloma, and several preclinical stage candidates, including HPN601...Merck is recording a non-tax deductible charge to R&D expense of approximately $650 million."

M&A • Multiple Myeloma • Neuroendocrine Tumor • Small Cell Lung Cancer • Solid Tumor

Merck to Acquire Harpoon Therapeutics, Further Diversifying Oncology Pipeline (Businesswire) - "Merck...and Harpoon Therapeutics, Inc...today announced that the companies have entered into a definitive agreement under which Merck, through a subsidiary, will acquire Harpoon for $23.00 per share in cash for an approximate total equity value of $680 million...'We look forward to further evaluating HPN328 in innovative combinations with other pipeline candidates.'...Additional pipeline candidates include HPN217 targeting B-cell maturation antigen (BCMA), currently in Phase 1 clinical development for the treatment of patients with relapsed/refractory multiple myeloma, and several preclinical stage candidates, including HPN601, a conditionally activated targeting epithelial cell adhesion molecule (EpCAM) for the treatment of certain patients with EpCAM expressing tumors....The transaction is expected to close in the first half of 2024 and will be accounted for as an asset acquisition."

M&A • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Small Cell Lung Cancer • Solid Tumor

HPN-217: “HPN217 was well tolerated and demonstrated clinical activity at doses of ≥ 2.15 mg in heavily pre-treated patients including patients with prior exposure to BCMA-targeted therapy”; Multiple myeloma (Harpoon Therapeutics) - ASH 2023: “Comparison between the highest dose levels administered indicates optimal activity and safety profile at the 12 mg dose”

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Results from the Completed Dose Escalation Portion of the Phase 1 Study of HPN217, a Half-Life Extended Tri-Specific T Cell Activating Construct (TriTAC®) Targeting B Cell Maturation Antigen (BCMA) for Relapsed/Refractory Multiple Myeloma (MM) (ASH 2023) - P1 | "Additional follow up of recently enrolled pts in 12 mg and 24 mg cohorts will inform the choice of the RP2D(s), and complete data on all pts enrolled will be presented. NCT04184050"

P1 data • Trispecific • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Transplantation

Harpoon Therapeutics Presents HPN217 Phase 1 Clinical Data in Relapsed/Refractory Multiple Myeloma (RRMM) at ASH 2023 and Announces Selection of Recommended Phase 2 Dose (RP2D) (GlobeNewswire) - P1 | N=97 | NCT04184050 | Sponsor: Harpoon Therapeutics | "Harpoon Therapeutics...reported data from the Phase 1 study of HPN217 in patients with RRMM in an oral presentation at...ASH Annual Meeting....Harpoon also announced the selection of 12 mg as the HPN217 RP2D. During the trial, 97 patients with RRMM who had received at least three prior therapies were enrolled across 15 dose escalation cohorts and three expansion regimens....The Overall Response Rate (ORR) across 12 mg cohorts was 63% (12/19, 95% CI: 38, 84). In addition, the depth of response was most significant at 12 mg, with 53% (10/19) of patients having a Very Good Partial Response (VGPR) or better. The median time to first response in the 12 mg and 24 mg cohort was 1.2 months, and the median duration of response for all responders was 20.5 months as of the data cutoff date. Out of all the responders, 58% (22/38) remain on treatment."

P1 data • Multiple Myeloma

Harpoon Therapeutics Abstract for HPN217 Accepted for Presentation at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition (GlobeNewswire) - "Harpoon Therapeutics, Inc...today announced abstract acceptance and upcoming oral presentation of the results from the completed dose escalation portion of the Phase 1 study of HPN217 in patients with relapsed/refractory multiple myeloma. The oral presentation will take place at the upcoming 65^th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 9-12, 2023, in San Diego."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Harpoon Therapeutics Presents HPN217 Interim Phase 1 Data at the IMS Annual Meeting (GlobeNewswire) - P1 | N=70 | NCT04184050 | Sponsor: Harpoon Therapeutics | "Harpoon Therapeutics...today announced the presentation of interim data for the 2.15 to 12 mg target dose cohorts from its Phase 1 clinical trial evaluating single-agent HPN217 in relapsed/refractory multiple myeloma (RRMM)...The data will be presented at the 20th International Myeloma Society (IMS) Annual Meeting in a poster presentation on September 28, 2023 in Athens, Greece...In patients at the 12 mg target dose (N=19), a manageable tolerability profile was observed with low rates of CRS (16%, all G1-2) and no ICANS. Additionally, robust, early clinical activity (63% ORR) was seen....Enrollment in dose escalation cohorts up to 24 mg is complete, and the maximum tolerated dose (MTD) has not been reached. Follow up is ongoing, and the evaluation of regimens will inform the choice of a recommended Phase 2 dose(s) at year end 2023."

P1 data • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

HPN-217: “Clinically active and differentiated tolerability profile at 12mg QW”; Multiple myeloma (Harpoon Therapeutics) - Corporate Presentation: “63% ORR, 53% with VGPR or better”

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

A Phase 1 Open-label, Multicenter, Dose Escalation Study of the Safety, Tolerability, and PK of HPN217 in Patients With R/R MM (clinicaltrials.gov) - P1 | N=97 | Active, not recruiting | Sponsor: Harpoon Therapeutics | Recruiting ➔ Active, not recruiting | N=70 ➔ 97

Enrollment change • Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

Harpoon Therapeutics Abstract for HPN217 Accepted for Poster Presentation at the 20th International Myeloma Society Annual Meeting (GlobeNewswire) - "Harpoon Therapeutics, Inc...announced abstract acceptance and a poster presentation of preliminary data (up to and including 12mg cohorts) from the dose escalation portion of the Phase 1 study of HPN217 in patients with relapsed/refractory multiple myeloma. The presentation will take place at the upcoming 20th International Myeloma Society (IMS) Annual Meeting being held September 27-30, 2023 in Athens, Greece."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Harpoon Therapeutics Provides an Update on the HPN217 Development and Option Agreement with AbbVie (GlobeNewswire) - "Harpoon Therapeutics...announced today that AbbVie has notified the company that it will not exercise the exclusive license option of the parties’ Development and Option Agreement in connection with Harpoon’s HPN217 program, which targets B cell maturation antigen, or BCMA. ​The Agreement, which will terminate effective October 12, 2023, granted AbbVie an option to a worldwide, exclusive license to the HPN217 program. The program has been and will remain exclusively owned by Harpoon, and the company plans to complete the ongoing Phase 1 clinical trial with data to support the next phase of development."

Licensing / partnership • Multiple Myeloma

Ongoing Phase 1 Study of HPN217, a Half-Life Extended Tri-Specific T Cell Activating Construct (TriTAC®) Targeting B Cell Maturation Antigen (BCMA) for Relapsed/Refractory Multiple Myeloma (MM) (IMW 2023) - P1 | "Dose escalation of HPN217, a novel half-life extended BCMA-targeting TCE, has been completed; target dose MTD was not reached. The 12 mg QW regimen is well tolerated with a manageable adverse event profile, low rates of CRS (16%) and robust early clinical activity (58% ORR). Evaluation of regimens using 24 mg QW and Q2W is ongoing to inform the choice of an RP2D(s)."

P1 data • Trispecific • Anemia • Cough • Fatigue • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Renal Disease • Respiratory Diseases • Transplantation

Harpoon Therapeutics Reports Second Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "HPN217 (BCMA) Phase 1 trial for relapsed, refractory multiple myeloma: Presentation of full Phase 1 data set, including 24mg cohorts, expected by the end of 2023; Harpoon expects to deliver the Phase 1 data package to AbbVie by the end of 2023."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Harpoon Therapeutics Announces Completion of Planned Patient Enrollment in Phase 1 Study of HPN217 in Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - "Harpoon Therapeutics...announced the completion of planned patient enrollment in the Phase 1 dose escalation study evaluating the safety, tolerability, and pharmacokinetics of HPN217 in patients with relapsed/refractory multiple myeloma. Additional patients currently in screening will also be allowed to enroll....'The identification of the recommended dose(s) for Phase 2 and the presentation of Phase 1 data is anticipated by the end of 2023'."

Enrollment status • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Updated Interim Results from a Phase 1 Study of HPN217, a Half-Life Extended Tri-Specific T Cell Activating Construct (TriTAC®) Targeting B Cell Maturation Antigen (BCMA) for Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2022) - P1 | "Changes in biomarkers associated with clinical responses were observed. NCT04184050"

IO biomarker • P1 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Hepatology • Immune Modulation • Inflammation • Liver Failure • Multiple Myeloma • Musculoskeletal Pain • Oncology • Transplantation • CD69 • CD8

Anti-tumor activity of HPN217, a BCMA-targeting tri-specific T cell engager, is enhanced by γ-secretase inhibitors in preclinical models (AACR 2023) - P1 | "To evaluate the effects of GSIs on BCMA expression, MM cell lines MOLP8, KMS-12-BM, and MM.1S were incubated with GSIs LY3039478, PF03084014, or RO4929097overnight. By contrast, the combination of HPN217 and LY3039478 led to a significant increase in survival compared to vehicle or either monotherapy, with a median survival of 43 days. Taken together these results demonstrate the potential utility of GSIs to enhance the anti-tumor activity of HPN217 and supports further investigation of this combinatorial approach in patients."

IO biomarker • Preclinical • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology

Harpoon Therapeutics Presents Preclinical Results for Novel T Cell Engagers HPN217 and HPN328 at AACR 2023 (GlobeNewswire) - "Harpoon Therapeutics,...presented preclinical data for two of its key clinical programs, HPN328 and HPN217, in three poster presentations at the American Association for Cancer Research (AACR) Annual Meeting being held in Orlando, Fla., April 14-19, 2023. 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."

Preclinical • Oncology • Solid Tumor

Harpoon Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "HPN217 (BCMA) Phase 1 trial for relapsed, refractory multiple myeloma: Phase 1 dose exploration is expected to complete in the first half of 2023, with up to 94 patients and identification of a recommended Phase 2 dose(s) by the end of 2023. Data presentation anticipated in the second half of 2023. HPN328 (DLL3) Phase 1/2 trial in small cell lung cancer (SCLC) and other neuroendocrine cancers: Enrollment in combination therapy of HPN328 with atezolizumab (Tecentriq) in patients with SCLC, as part of the Phase 1/2 dose escalation trial, is anticipated to begin in the second half of 2023. Phase 1 dose exploration is expected to complete in the second half of 2023, including the identifying of a recommended Phase 2 dose(s) in the monotherapy setting by the end of 2023. Data presentation anticipated in the second half of 2023."

Enrollment status • P1 data • P1/2 data • Trial status • Hematological Malignancies • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Harpoon Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "AACR 2023 – Five Preclinical Posters to be Presented: HPN217: Preclinical abstract to be presented at AACR on April 18, 2023. HPN328: Two preclinical abstracts to be presented at AACR on April 18, 2023. ProTriTAC: Two preclinical abstracts to be presented at AACR on April 17, 2023."

Preclinical • Hematological Malignancies • Oncology • Solid Tumor

Bispecific Antibodies in the Treatment of Multiple Myeloma: An Expert Case-Based Discussion : Episode 11: Bispecific Antibodies Promise to be ‘Transformative’ in Multiple Myeloma (Cancer Network) - "At a recent Around the Practice program, experts spoke about recent advances in multiple myeloma, including the approval of teclistamab-cqyv (Tecvayli), the utility of the FDA's accelerated approval process, and the promise of bispecific antibodies generally....Patel: Those [response rates] are phenomenal. We're all millennial doctors who [began working] in the last 10 years, [and], for us, this is going to be the new normal. [Even] if you see something lower than [those rates], it's still good."

Media quote

The Effects of BCMA Expression, Soluble BCMA, and Combination Therapeutics on the Anti-Tumor Activity of HPN217, a BCMA-Targeting Tri-Specific T Cell Engager Against Multiple Myeloma (ASH 2021) - P1/2 | "Herein, we describe translational studies to examine factors that may impact the therapeutic efficacy of HPN217, including the target BCMA, in membrane-bound or soluble form, and concomitant or combination therapeutics such as γ-secretase inhibitor (GSI) and dexamethasone...Interestingly, treatment of MM cell line RPMI8226 with the GSI LY-3039478 for 24 hours increased the cell surface expression of BCMA by 3.6 folds...On the other hand, Dex had limited negative effect. HPN217 in combination with approved and experimental MM therapeutics is being evaluated in the 3DTEBM and MM.1S-Luc models."

Combination therapy • IO biomarker • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

Harpoon Therapeutics Announces Acceptance of Five Abstracts for Presentation at AACR Annual Meeting 2023 (GlobeNewswire) - "Harpoon Therapeutics...announced that it will present data from five preclinical investigations in poster presentations at the American Association for Cancer Research (AACR) Annual Meeting being held in Orlando, Fla., April 14-19, 2023....'Additionally, the preclinical data investigating the activity of TriTAC in an immunocompetent mouse model provide further validation of our ongoing and planned clinical efforts with HPN328 and HPN217, leveraging our proprietary TriTAC T cell engager platform."'"

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor