CYNK-101 / Celularity - LARVOL DELTA

CYNK-101 in Combination with Trastuzumab and Pembrolizumab in Patients with Locally Advanced Unresectable or Metastatic HER2-Positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=1 | Terminated | Sponsor: Celularity Incorporated | N=52 ➔ 1 | Trial completion date: Feb 2025 ➔ Feb 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Feb 2023 ➔ Feb 2024; for business reasons

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

A phase I/IIa open label, nonrandomized, multicenter study of CYNK-101 in combination with trastuzumab and pembrolizumab in patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. (ASCO-GI 2023) - P1/2 | "Patients complete a disease assessment and then proceed to a lymphodepletion regimen of cyclophosphamide 900 mg/m2 and fludarabine 30 mg/m2 with MESNA for 3 days...Approximately 52 patients are planned for this Phase I/IIa study. Clinical trial information: NCT05207722."

Clinical • Combination therapy • Metastases • P1/2 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • HER-2

CYNK-101 in Combination With Trastuzumab and Pembrolizumab in Patients With Locally Advanced Unresectable or Metastatic HER2-Positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=52 | Active, not recruiting | Sponsor: Celularity Incorporated | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Celularity Presents Preclinical Data on CYNK-101, its Allogeneic Genetically-Modified Natural Killer Cell Therapy Candidate, at the Society for Immunotherapy of Cancer’s 37th Annual Meeting (GlobeNewswire) - "Celularity will report its findings in a poster presentation at the 37th Annual Meeting....The results demonstrate the synergistic effect of combining CYNK-101 with avelumab to drive antibody-dependent cellular cytotoxicity (ADCC) activity against PD-L1+ solid tumor cells in vitro, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and bladder cancer tumor cells. CYNK-101 cells provide a combination immunotherapy option by harnessing the anti-tumor activities of both targeted biologics and innate cytotoxicity of NK cells."

Preclinical • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • Triple Negative Breast Cancer • Urothelial Cancer

Developing placental CD34+-derived natural killer cells with high affinity and cleavage resistant CD16 (CYNK-101) in combination with Avelumab for enhanced therapy against PD-L1+ solid tumors (SITC 2022) - "Conclusions Our results demonstrate that CYNK-101 has enhanced Avelumab-mediated ADCC activity against PD-L1 + tumor cell lines, such as lung, breast, and bladder cancers. Further development of the combinational therapy for PD-L1 + solid tumor indications is warranted."

Combination therapy • IO biomarker • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD34 • CSF2 • IFNG

CYNK-101 in Combination With Trastuzumab and Pembrolizumab in Patients With Locally Advanced Unresectable or Metastatic HER2-Positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=52 | Recruiting | Sponsor: Celularity Incorporated | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Gastric/Gastroesophageal Junction Cell Therapy Trial Doses First Patient (CGTLive) - "'The dosing of the first patient in Celularity CYNK-101 gastric cancer program is an exciting milestone in the clinical development of cell therapies in solid tumors. Natural killer (NK) cells possess inherent direct anti-solid tumor activity, recruit non-cross resistant anti-tumor T cells, and may induce memory T cells for long-term anti-cancer immune surveillance,' Darren Sigal, MD...added to the statement....'We believe NK cells are poised to be the key components of multipronged therapeutic strategies for cancer. It is our understanding that we administered what is the highest dose of allogeneic NK cells so far over a 21-day period...We administered 36 X 106 transduced CYNK-101/kg weekly for four weeks in combination with pembrolizumab and trastuzumab to a patient with Her2 positive gastroesophageal carcinoma. All infusions occurred in the outpatient setting,' principal investigator Martin Gutierrez...added to the statement."

Media quote

Celularity Announces Treatment of First Patient in Phase 1/2a Clinical Trial for NK Cell Therapy CYNK-101, in Development for the First-Line Treatment of Advanced HER2 Positive Gastric and Gastroesophageal Junction (G/GEJ) Cancers (GlobeNewswire) - P1/2 | N=NA | NCT05207722| Sponsor: Celularity | "Dr. Darren Sigal...commented,'The dosing of the first patient in Celularity CYNK-101 gastric cancer program is an exciting milestone in the clinical development of cell therapies in solid tumors. NK cells possess inherent direct anti-solid tumor activity, recruit non-cross resistant anti-tumor T cells, and may induce memory T cells for long-term anti-cancer immune surveillance.'Dr. Martin Gutierrez...who treated the first patient said,'We believe NK cells are poised to be the key components of multipronged therapeutic strategies for cancer. It is our understanding that we administered what is the highest dose of allogeneic NK cells so far over a 21-day period...We administered 36 X 106 transduced CYNK-101/kg weekly for four weeks in combination with pembrolizumab and trastuzumab to a patient with Her2 positive gastroesophageal carcinoma. All infusions occurred in the outpatient setting.'"

Media quote • P1/2 data

Celularity Announces Treatment of First Patient in Phase 1/2a Clinical Trial for NK Cell Therapy CYNK-101, in Development for the First-Line Treatment of Advanced HER2 Positive Gastric and Gastroesophageal Junction (G/GEJ) Cancers (GlobeNewswire) - "Celularity...announced that the first patient has been treated with CYNK-101, a novel allogeneic off-the-shelf human placental CD34+ stem cell derived NK cell therapeutic candidate that is genetically modified to express high-affinity and cleavage-resistant CD16 (FCGRIIIA) variant to enhance antibody-dependent cell-mediated cytotoxicity (ADCC)....This study is utilizing a 3+3 open label design and will evaluate two escalating dosing cohort levels of CYNK-101 in combination with rhIL2 following an initial induction and lymphodepletion regimen. Once the maximum tolerated dose or recommended Phase 2 dose is determined in Phase 1, the Phase 2a portion of the study will commence..."

Trial status • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Celularity Receives Orphan Drug Designation from U.S. FDA for its NK Cell Therapy CYNK-101 in Development for the First-Line Treatment of Advanced HER2/neu Positive Gastric and Gastroesophageal Junction Cancers (GlobeNewswire) - "Celularity...announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for its investigational natural killer (NK) cell therapy, CYNK-101, for treatment of gastric/gastroesophageal junction cancer....'In our Phase 1/2a clinical trial of CYNK-101, we are excited to explore a multipronged strategy of our NK cells and activated T cells through check point inhibition to potentially enhance overall outcomes achieved with traditional chemotherapy and Traztuzumab in HER2/neu positive G/GEJ adenocarcinoma'."

Orphan drug • Trial status • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

A Phase I/IIa Open Label, Non-Randomized, Multicenter Study of CYNK-101 in Combination With Trastuzumab and Pembrolizumab in Patients With Locally Advanced Unresectable or Metastatic HER2-Positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=52 | Not yet recruiting | Sponsor: Celularity Incorporated

Combination therapy • New P1/2 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

CYNK-101 Gets FDA Fast Track Designation for HER2-Positive Gastric/GEJ Cancers (Cure Today) - "'(CYNK-101) is a potentially non-cross resistant therapy after initially cytoreducing the tumor mass and potentially diminishing resistance in the tumor microenvironment with combined chemotherapy, trastuzumab, and pembrolizumab induction followed by reinduction and maintenance with CYNK-101 cells in combination with trastuzumab and pembrolizumab,' Pecora noted."

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FDA Grants Fast Track Designation to CYNK-101 for HER2+ Gastric/GEJ Cancers (Cancer Network) - "'The addition of immune-based therapy of blocking PD-1 with a checkpoint inhibitor (pembrolizumab) to the prior standard of care (chemotherapy and trastuzumab) has recently been shown to be of benefit in patients with first-line HER2/neu positive unresectable G/GEJ cancer,' Andrew Pecora, MD...said in a statement. 'Our recently accepted IND enables the assessment to possibly further improve outcomes in gastric/GEJ treated with triple combination therapy by adding CYNK-101 cells.'"

Media quote • Regulatory

Celularity Receives Fast Track Designation from U.S. FDA for its NK Cell Therapy CYNK-101 in Development for the First-Line Treatment of Advanced HER2/neu Positive Gastric and Gastroesophageal Junction Cancers (GlobeNewswire) - "Celularity... announced the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for its genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy, CYNK-101, which is being developed in combination with standard chemotherapy, trastuzumab and pembrolizumab in patients in first-line locally advanced unresectable or metastatic HER2/neu positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. CYNK-101 is an investigational genetically modified NK cell therapy designed to synergize with approved antibody therapeutics through enhanced antibody-dependent cellular cytotoxicity (ADCC)."

Fast track designation • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Human Placental CD34+-Derived Natural Killer Cells with High Affinity and Cleavage Resistant CD16 (CYNK-101) in Combination with Daratumumab for Immunotherapy Against CD38 Expressing Hematological Malignancies (ASH 2021) - "Luciferase expressing Daudi cells (3×10 6 ) were intravenously (IV) injected on Day 0 three days after preconditioning with a myeloablative dose of busulfan to allow for better tumor cell engraftment...Furthermore, CYNK-101 in combination with daratumumab demonstrated an enhanced survival benefit with a median survival of 35 days versus a median survival of 28 days for the vehicle treated group (p<0.005). In summary, our results demonstrate enhanced in vitro and in vivo ADCC activities of CYNK-101 in combination with daratumumab against CD38 + hematological tumors and warrant further development of this combination therapy for these cancers."

Combination therapy • IO biomarker • Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD34 • CD38 • CSF2 • IFNG • IL15 • TNFA

Celularity Announces FDA Clearance of Investigational New Drug Application (IND) for Natural Killer Cell Therapy CYNK-101 in First-line Advanced Her2/neu Positive Gastric and Gastroesophageal Junction Cancer (GlobeNewswire) - "Celularity Inc....announced the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for the use of CYNK-101 in combination with standard chemotherapy, trastuzumab and pembrolizumab in patients with first-line locally advanced unresectable or metastatic HER2/neu positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma....The Phase 1/2a open-label, non-randomized clinical trial is designed to evaluate the safety and preliminary efficacy of the combination treatment strategy."

IND • New P1/2 trial • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Celularity Announces FDA Clearance of Investigational New Drug Application (IND) for Natural Killer Cell Therapy CYNK-101 in First-line Advanced Her2/neu Positive Gastric and Gastroesophageal Junction Cancer (GlobeNewswire) - "Andrew Pecora, M.D...said, 'Among patients with locally advanced unresectable or metastatic HER2/neu positive gastric or gastroesophageal junction adenocarcinoma, advances in patient outcomes have been achieved with the addition of trastuzumab, and more recently, pembrolizumab, to standard chemotherapy, leading to regulatory approval of this combination. We are now excited to begin assessing if our off-the-shelf allogeneic placental-derived NK cells that have been genetically modified to enhance ADCC and resist cleavage of CD16 can improve clinical outcomes when added to the current combination in this patient population.'"

Announcement

Celularity Presents Preclinical Data on Allogeneic Genetically Modified Natural Killer (NK) and Allogeneic CAR-NK Cell Therapy Programs at the 63rd American Society of Hematology Meeting and Exposition (GlobeNewswire) - "The results show the synergistic effect of combining CYNK-101 with daratumumab to drive antibody dependent cellular cytotoxicity activity against CD38+ hematological malignancies in vitro and in vivo. In these studies, CYNK-101 was not susceptible to daratumumab-directed fratricide and did not display on-target, off-tumor cytotoxicity, suggesting CYNK-101 may be a unique NK cell platform that preserves innate immune function in the presence of daratumumab."

Hematological Malignancies • Oncology

Developing placental CD34+-derived natural killer cells with high affinity cleavage resistant CD16 (CYNK-101) and Cetuximab for enhanced therapy of EGFR+ non-small cell lung and head and neck cancers (SITC 2021) - "Conclusions Our results demonstrate that CYNK-101 have enhanced Cetuximab-mediated ADCC activity against EGFR+ NSCLC and HNSCC tumor cell lines. Further development of the combinational therapy for these solid tumor indications is warranted."

Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD34 • CSF2 • EGFR • IFNG • TNFA

Celularity Presents Preclinical Data on Allogeneic Genetically-Modified Natural Killer Cells at the Society for Immunotherapy of Cancer 36th Annual Meeting (GlobeNewswire) - "The results demonstrate the synergistic effect of combining CYNK-101 with Cetuximab to drive antibody dependent cellular cytotoxicity activity against EGFR+ tumors. Further development of the combinational therapy against EGFR+ non-small cell lung cancer and head and neck squamous cell carcinomas is warranted."

Preclinical • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Celularity Reports Third Quarter 2021 Financial Results and Corporate Update (GlobeNewswire) - "Third Quarter Corporate Highlights:...Entered into a research collaboration with Oncternal Therapeutics...to evaluate placental derived-cellular therapies targeting receptor-tyrosine kinase-like Orphan Receptor 1 (ROR1) in preclinical studies. The collaboration will initially explore the use of Oncternal’s ROR1-targeted chimeric antigen receptor (CAR) gene modification as part of Celularity’s CYNK natural killer cell and CyCART platforms. The partnership will also explore the use of monoclonal antibody, cirmtuzumab, in combination with Celularity’s CYNK natural killer cells."

Licensing / partnership • Oncology

[VIRTUAL] Potent immunotherapy of human placental CD34+-derived natural killer cells with high affinity and cleavage resistant CD16 (CYNK-101) plus Trastuzumab for HER2+ gastric cancer (AACR 2021) - "CYNK-101 was generated from multiple placental CD34+ donors (n=7) with >90% CD56+CD3-and 74.1 ± 5.6% CD16 expression. While 4h PMAi treatment resulted in >89% CD16 cleavage on non-transduced NK cells, <11% cleavage from CYNK-101 demonstrated CD16 shedding resistance. At an effector to target (E:T) ratio of 1:1, CYNK-101 (n=7) showed enhanced lysis of NCI-N87 cells in the presence of Trastuzumab compared to IgG control, 59.6 ± 13.7% vs."

IO biomarker • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD34 • CSF2 • HER-2 • IFNG • NCAM1 • NKG2D • TNFA

Celularity Announces Multiple Presentations at the American Association for Cancer Research (AACR) Annual Meeting 2021 (GlobeNewswire) - "Celularity Inc....will display multiple presentations at the American Association for Cancer Research (AACR) Annual Meeting 2021. The presentations include one poster highlighting early clinical data of CYNK-001 (unmodified natural killer (NK) cell therapy) in COVID-19..."

P1/2 data • Infectious Disease • Novel Coronavirus Disease

Celularity Announces Multiple Presentations at the American Association for Cancer Research (AACR) Annual Meeting 2021 (GlobeNewswire) - “Celularity…will display multiple presentations at the American Association for Cancer Research (AACR) Annual Meeting 2021…Celularity will also deliver an oral presentation featuring preclinical studies of its genetically modified NK cell therapy, CYNK-101, under development for the treatment of HER2+ expressing gastric cancer. The AACR Annual Meeting will take place in a virtual format from April 10-15 and from May 17-21, 2021.”

Preclinical • Gastric Cancer • Oncology • Solid Tumor

Celularity and GX Acquisition Corp. Announce Merger Agreement to Create a Publicly Listed Leader in Allogeneic Cellular Therapy (PRNewswire) - "Celularity plans to submit its initial CYNK-101 investigational new drug ('IND') application in the first half of 2021...The Phase 1/2a clinical trial will commence in 2021...CyCART-19 is in development initially for the treatment of B-cell malignancies...Celularity plans to file its initial CyCART-19 IND application and to commence a Phase 1/2a clinical trial in the first half of 2021."

IND • New P1/2 trial • Diffuse Large B Cell Lymphoma • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Solid Tumor