noraramtide (BHV-1100) / PeptiDream, Biohaven - LARVOL DELTA

In depth characterization of autologous infused bhv-1100 armored memory-like NK cells in MRD+ multiple myeloma patients receiving autologous stem cell transplant (ASH 2025) - P1 | "2 pts received Daratumumab-Lenalidomide-Bortezomib-Dexamethasone (DaraRVD) and 5 pts RVD as induction therapy. This study provides detailed immune characterization of autologous, BHV-1100-coated CIMLNK cells in MM pts undergoing ASCT in first remission. Findings suggest robust NK cell expansion, BMinfiltration, and cytotoxic activity, with favorable cytokine profiles. These data support the potential ofARM-enhanced CIML NK therapy as an immunologic bridge in MM and warrant further investigation."

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • Septic Shock • Transplantation • CD8 • CST3 • CXCL11 • FLT3LG • GZMB • IFITM3 • IFNG • IL10 • IL12A • IL18 • IL6 • NCAM1 • PRF1 • TNFSF12 • XCL2

Expansion, Persistence, and Characteristics of Autologous, Bhv-1100 Armored Memory-like NK Cells Infused Prior to Autologous Stem Cell Transplant in MRD+ Multiple Myeloma Patients: A First-in-Human Trial (ASH 2023) - P1 | "CIML NK cells were manufactured with a 100% success rate and infused at a target dose of 5-10x106 cells/kg-body weight, 24 hours after 200 mg/m2 melphalan administration. Regulatory T cells increased by D+7 (3% vs 15% total PBMC) and returned to baseline after D+14 most likely reflecting the effect of IL-2 treatment. The functional capacity of the infused product was tested in vitro"

Clinical • First-in-human • IO biomarker • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • B3GAT1 • IL12A • IL15 • IL18 • KLRC1 • NCAM1

Autologous Memory-like NK Cell Therapy With BHV-1100 and Low Dose IL-2 in Multiple Myeloma Patients (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: Biohaven Pharmaceuticals, Inc. | Recruiting ➔ Completed | N=25 ➔ 7

Enrollment change • Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Autologous Memory-like NK Cell Therapy With BHV-1100 and Low Dose IL-2 in Multiple Myeloma Patients (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial completion date: Oct 2026 ➔ Dec 2024 | Trial primary completion date: Oct 2025 ➔ Dec 2024

Minimal residual disease • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Targeting Senescent Alveolar Epithelial Cells Using Engineered Mesenchymal Stem Cell-Derived Extracellular Vesicles To Treat Pulmonary Fibrosis. (PubMed, ACS Nano) - "CD38-ARM-MSC-EVs effectively restored the NAD+ levels, reversed the epithelial-mesenchymal transition phenotype, and rejuvenated senescent A549 cells in vitro, thereby mitigating multiple age-associated phenotypes and alleviating PF in aged mice. Thus, this study provides a technology to engineer MSC-EVs and support our CD38-ARM-MSC-EVs to be developed as promising agents with high clinical potential against PF."

IO biomarker • Journal • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CD38 • CD8

Expansion, persistence, and characteristics of autologous, BHV-1100 ARMored memory-like NK cells infused prior to autologous stem cell transplant in MRD+, newly diagnosed multiple myeloma patients (IMW 2023) - P1 | "The product was infused fresh on D0 after standard melphalan 200 mg/m2 myeloablative conditioning and followed by stem cells infusion. This is an ongoing trial (NCT04634435) with a median follow-up of 191 days. We are herein reporting data on in vivo expansion and functional characterization of ARMored CIML NK for the first 4 patients. CIML NK cells were manufactured with a 100% success rate and infused at a target dose of 5-10x106 cells."

Clinical • IO biomarker • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • B3GAT1 • IL12A • IL15 • IL18 • KLRC1

Autologous Memory-like NK Cell Therapy With BHV-1100 (Formerly KP1237), Low Dose IL-2 in Multiple Myeloma Patients (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial primary completion date: Oct 2023 ➔ Oct 2025

Minimal residual disease • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Autologous Memory-like NK Cell Therapy With BHV-1100 (Formerly KP1237), Low Dose IL-2 in Multiple Myeloma Patients (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial completion date: Jun 2026 ➔ Oct 2026 | Trial primary completion date: Jun 2023 ➔ Oct 2023

Minimal residual disease • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Autologous Memory-like NK Cell Therapy With BHV-1100 (Formerly KP1237), Low Dose IL-2 in Multiple Myeloma Patients (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Phase classification: P1/2 ➔ P1

Minimal residual disease • Phase classification • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Biohaven Enrolls Phase 1a/1b Clinical Trial of BHV-1100, Lead Asset from its ARM (Antibody Recruiting Molecule) Platform, in Combination with NK Cell Therapy for the Treatment of Multiple Myeloma (PRNewswire) - "Biohaven Pharmaceutical Holding Company Ltd...announced the enrollment of the first patient in a Phase 1a/1b trial in Multiple Myeloma using the ARM, BHV-1100, in combination with autologous cytokine induced memory-like (CIML) natural killer (NK) cells and immunoglobulin (Ig) to target and kill multiple myeloma cells expressing the cell surface protein CD38...Biohaven has initiated enrollment in the clinical trial and plans to enroll 25 patients for this single-center, open-label study...The study will enroll newly diagnosed multiple myeloma patients who have minimal residual disease (MRD+) in first remission prior to an autologous stem cell transplant (ASCT)."

Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Autologous Memory-like NK Cell Therapy With BHV-1100 (Formerly KP1237), Low Dose IL-2 in Multiple Myeloma Patients (clinicaltrials.gov) - P1/2; N=25; Recruiting; Sponsor: Biohaven Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Minimal residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Phase 1 Study of Autologous Memory-like NK Cell Therapy With KP1237, Low Dose IL-2 in Multiple Myeloma Patients (clinicaltrials.gov) - P1/2; N=25; Not yet recruiting; Sponsor: Biohaven Pharmaceuticals, Inc.; Trial completion date: Feb 2023 ➔ Jun 2026; Trial primary completion date: May 2022 ➔ Jun 2023

Clinical • Combination therapy • Minimal residual disease • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Phase 1 Study of Autologous Memory-like NK Cell Therapy With KP1237, Low Dose IL-2 in Multiple Myeloma Patients (clinicaltrials.gov) - P1/2; N=25; Not yet recruiting; Sponsor: Kleo Pharmaceuticals; Trial completion date: Feb 2022 ➔ Feb 2023; Initiation date: Nov 2020 ➔ Mar 2021; Trial primary completion date: Dec 2021 ➔ Mar 2022

Clinical • Combination therapy • Trial completion date • Trial initiation date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Phase 1 Study of Autologous Memory-like NK Cell Therapy With KP1237, Low Dose IL-2 in Multiple Myeloma Patients (clinicaltrials.gov) - P1/2; N=25; Not yet recruiting; Sponsor: Kleo Pharmaceuticals

Clinical • Combination therapy • New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

[VIRTUAL] A novel site-directed chemical conjugation technology confers antitumor activity via native Fc receptor to plasma immunoglobulin by attaching tumor binders (SITC 2020) - "Methods Design of synthetic chemical reagents included antibody binding group capable of covalent bond formation with specific lysine, CD38 binding moiety proven to work in our clinical candidate KP1237, and tunable non-cleavable linker...KPMW101 induces IvIg to adopt Fc effector mechanisms like ADCC and ADCP. Our in vitro data and in vivo studies confirm KPMW101 ability to kill tumor cells, making IvIg into an active antitumor therapeutic agent."

Oncology • FCGR3A

[VIRTUAL] A novel site-directed chemical conjugation technology confers antitumor activity via native Fc receptor to plasma immunoglobulin by attaching tumor binders (SITC 2020) - "Methods Design of synthetic chemical reagents included antibody binding group capable of covalent bond formation with specific lysine, CD38 binding moiety proven to work in our clinical candidate KP1237, and tunable non-cleavable linker...KPMW101 induces IvIg to adopt Fc effector mechanisms like ADCC and ADCP. Our in vitro data and in vivo studies confirm KPMW101 ability to kill tumor cells, making IvIg into an active antitumor therapeutic agent."

Oncology • FCGR3A

Kleo Pharmaceuticals Announces Orphan Drug Designation for KP1237 in Multiple Myeloma (GlobeNewswire) - "Kleo Pharmaceuticals..announced today that its lead compound, KP1237, has received Orphan Drug designation from the U.S. Food and Drug Administration (FDA) in multiple myeloma."

Orphan drug • Hematological Malignancies • Multiple Myeloma • Oncology

[VIRTUAL] A first-in-class ex vivo combination between cytokine-induced memory like (CIML) NK cells and a CD38 targeting antibody recruiting molecule (ARM) as a novel approach to target NK cells without cellular engineering for the treatment of multiple myeloma. (ASCO 2020) - "The activity of CIML NK cells towards CD38 expressing MM target cells is improved by the addition of KP1237 avoiding the need for cellular engineering with chimeric antigen receptors. This led to the development of the combination drug product consisting of patient autologous CIML NK cells, KP1237 and IVIG. Clinical development is under way for (MRD+) MM patients eligible for ASCT."

IO Biomarker • Preclinical • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • CD38 • CD57 • IL12A • IL15 • IL18 • NCAM1 • NKG2D

Kleo Pharmaceuticals to present preclinical data highlighting the synergistic potential of Kleo asset KP1237 and autologous NK Cells in the treatment of multiple myeloma at the 2020 American Society of Clinical Oncology Virtual Meeting (GlobeNewswire) - "Kleo Pharmaceuticals, Inc…announced preclinical data for the company’s lead program, KP1237 in combination with autologous, cytokine-induced, memory-like (CIML) natural killer (NK) cells with low dose IL-2 in multiple myeloma (MM). KP1237 is a CD38-targeting antibody recruiting molecule (ARMTM). These data, to be presented as a poster at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting being held May 29–31, will support the initiation of an upcoming Phase 1/2 clinical trial for MM patients receiving an autologous stem cell transplant (ASCT), who remain minimum residual disease positive (MRD+)."

New P1/2 trial • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology