CLD-101 / Calidi Biotherap, Northwestern University, City of Hope - LARVOL DELTA

Multiple Intracerebral Doses of Neural Stem Cell-Based Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: City of Hope Medical Center | Suspended ➔ Recruiting

Enrollment open • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oligodendroglioma • Oncology • Solid Tumor • BIRC5

Multiple Intracerebral Doses of Neural Stem Cell-Based Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas (clinicaltrials.gov) - P1 | N=36 | Suspended | Sponsor: City of Hope Medical Center | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oligodendroglioma • Oncology • Solid Tumor • BIRC5

Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma (clinicaltrials.gov) - P1 | N=20 | Suspended | Sponsor: Northwestern University | Recruiting ➔ Suspended

Trial suspension • Brain Cancer • Glioma • High Grade Glioma • Oncology • Solid Tumor

Neural stem cell delivery of oncolytic CRAd-S-pk7 immunotherapy for stage 3 ovarian cancer: Dose-regimen studies. (PubMed, Mol Ther Oncol) - "Repeated dosing further decreased tumor burden and increased median survival by 60% (from 57 to 91 days) in immunocompetent mice, suggesting a contribution from innate immune activation. These findings establish NSC.CRAd-S-pk7 as a promising oncolytic viro-immunotherapy treatment for advanced OVCA and support its advancement toward clinical translation."

Journal • Oncology • Ovarian Cancer • Solid Tumor

Multiple Intracerebral Doses of Neural Stem Cell-Based Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas (clinicaltrials.gov) - P1 | N=36 | Suspended | Sponsor: City of Hope Medical Center | Recruiting ➔ Suspended

Trial suspension • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oligodendroglioma • Oncology • Solid Tumor • BIRC5

Optimizing dose interval and formulation of neural stem cell-delivered Oncolytic adenovirus therapy for high-grade glioma (SNO 2025) - "A first-in-human trial combining single-dose NSC.CRAd-S-pk7 with standard chemoradiation for newly diagnosed glioma patients at Northwestern University and City of Hope showed safety and potential efficacy (2021 Lancet Oncology), prompting an ongoing phase lb multi-dose study...Our aim is to identify a regimen that maximizes therapeutic efficacy by balancing viral-induced immune activation while avoiding T-cell exhaustion. These studies inform next-phase clinical trial design and represent a key step toward optimizing this promising therapeutic platform."

Oncolytic virus • Brain Cancer • Glioma • High Grade Glioma • Solid Tumor • BIRC5 • CD21

Optimizing dose interval and formulation of neural stem cell-delivered Oncolytic adenovirus therapy for high-grade glioma (WFNOS 2025) - "A first-in-human trial combining single-dose NSC.CRAd-S-pk7 with standard chemoradiation for newly diagnosed glioma patients at Northwestern University and City of Hope showed safety and potential efficacy (2021 Lancet Oncology), prompting an ongoing phase lb multi-dose study...Our aim is to identify a regimen that maximizes therapeutic efficacy by balancing viral-induced immune activation while avoiding T-cell exhaustion. These studies inform next-phase clinical trial design and represent a key step toward optimizing this promising therapeutic platform."

Oncolytic virus • Brain Cancer • Glioma • Oncology • Solid Tumor • BIRC5 • CD21

Multiple Intracerebral Doses of Neural Stem Cell-Based Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2026 ➔ Aug 2026 | Trial primary completion date: Dec 2026 ➔ Aug 2026

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oligodendroglioma • Oncology • Solid Tumor • BIRC5

Multiple Doses of Neural Stem Cell Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Aug 2025 ➔ Dec 2026 | Trial primary completion date: Aug 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Anaplastic Oligoastrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • High Grade Glioma • Oligodendroglioma • Oncology • Sarcoma • Solid Tumor • BIRC5

Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Northwestern University | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Glioma • High Grade Glioma • Oncology • Solid Tumor

Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Northwestern University | Trial primary completion date: Apr 2027 ➔ Dec 2029

Trial primary completion date • Brain Cancer • Glioma • High Grade Glioma • Oncology • Solid Tumor

Stem Cell Delivered Viro-immunotherapy Advancements for Ovarian Cancer Treatment (ASGCT 2025) - P1 | "We have loaded these NSCs with a conditionally replication-competent adenovirus (CRAd-S-pk7) that has been genetically modified 1) with a pk7 poly-lysine fiber knob to increase tumor infectivity, and 2) the insertion of a survivin promoter to drive E1A transcription, making it selective to tumor cells with high survivin expression, including glioma and cisplatin resistant ovarian cancer. A phase I trial with a single dose intracerebral administration of NSC.CRAd-S-pk7 (CLD-101) as an adjuvant to temozolomide and radiation in newly diagnosed glioma patients yielded promising results (Lancet Oncol, 2021)...Translational biodistribution, efficacy, and safety/tox IND-enabling studies are ongoing with our goal of initiating a phase I clinical trial of NSC.CRAd-S-pk7 for patients with platinum resistant Stage III ovarian cancer in 2026. Disease Focus of Abstract:Cancer Solid Tumors"

IO biomarker • Oncolytic virus • Brain Cancer • CNS Tumor • Glioma • Infectious Disease • Oncology • Ovarian Cancer • Solid Tumor • BIRC5 • CD21

Calidi Biotherapeutics Reports Fourth Quarter and Full-Year 2024 Financial Results and Recent Operational Highlights (GlobeNewswire) - "Upcoming Anticipated Milestones: (i) Q2 2025: Payload and lead candidate information revealed on CLD-400 systemic platform; (ii) Q2 2025: First patient dosed in CLD-101 Phase 1 trial in collaboration with Northwestern University for newly diagnosed high-grade glioma patients."

Pipeline update • Trial status • Glioma

Calidi Biotherapeutics and City of Hope Provide Update on a Phase 1 Clinical Trial with CLD-101 Virotherapy in Patients with Recurrent High-Grade Glioma (GlobeNewswire) - "Calidi Biotherapeutics, Inc...and City of Hope...are pleased to jointly announce progress from a phase 1 clinical trial utilizing Calidi’s CLD-101 investigational agent (neural stem cell-based oncolytic virotherapy) that is administered intracerebrally. This trial is the first to evaluate the safety and therapeutic potential of a multiple-dose regimen of this novel virotherapy for recurrent high-grade glioma - among the most aggressive and deadly forms of brain cancer....To date, 14 participants have been treated and all treatment has been well tolerated. The study is currently enrolling participants to the highest treatment schedule."

Trial status • Glioma

Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Northwestern University | Trial primary completion date: Dec 2025 ➔ Apr 2027

Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Malignant Glioma • Oncology • Solid Tumor

Calidi Biotherapeutics Announces Commencement of Recruitment for Multiple Dose CLD-101 Trial in Patients with Newly Diagnosed High Grade Glioma at Northwestern University Hospital (GlobeNewswire) - "Calidi Biotherapeutics...announced that Northwestern University/Northwestern Memorial Hospital is starting recruitment for the CLD-101 clinical trial of its immunotherapy product. Calidi Biotherapeutics has completed the shipment of the first batch of CLD-101, which comprises allogeneic neural stem cells loaded with the oncolytic adenovirus CRAd-S-pk7. This batch will support a new clinical trial in patients with newly diagnosed high-grade glioma, an aggressive and often fatal form of brain cancer. This physician-led and NCI sponsored clinical trial, led by prominent experts Dr. Maciej Lesniak and Dr. Roger Stupp, represents a major step forward in cancer therapy."

Trial status • Glioma

Calidi Biotherapeutics Reports Third Quarter 2024 Operating and Financial Results (GlobeNewswire) - "CLD-101 is a novel stem-cell based platform designed to deliver oncolytic viruses to tumors, enhancing their antitumor effects. The Phase 1b/2 clinical trial in newly diagnosed high-grade glioma is expected to commence in early 2025 at Northwestern University."

New P1/2 trial • Glioma

Calidi Biotherapeutics Announces FDA Clearance of the Northwestern University IND Application for CLD-101 Clinical Trial in High-Grade Glioma (GlobeNewswire) - "Calidi Biotherapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has cleared Northwestern University’s Investigational New Drug (IND) application for Calidi’s CLD-101....The Phase 1b/2 clinical trial is expected to commence in late 2024 at Northwestern University....CLD-101 is also being evaluated in a Phase 1 trial in collaboration with City of Hope, a non-profit clinical research center, for recurrent high-grade glioma patients. Calidi expects to report interim clinical data from the trial in the first half of 2025."

IND • New P1/2 trial • Brain Cancer • CNS Tumor • Glioma • Oncology

Phase 1 study of multiple intracerebral doses of a neural stem cell-based oncolytic virotherapy for treatment of recurrent high-grade gliomas. (ASCO 2024) - P1 | "This NSC line was genetically modified to produce a tumor-selective, conditionally replicating adenovirus (CRAd; NSC-CRAd-S-pk7)...We are currently enrolling participants to Treatment Schedule 4. Multi-center sites for enrolling patients to the expansion cohort include City of Hope, Stanford University, Wake Forest University, and Northwestern University."

Oncolytic virus • P1 data • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Calidi Biotherapeutics Presents CLD-101 Phase 1 Trial Update and Preclinical Data Highlighting RTNova and CLD-201 at 2024 ASCO Annual Meeting (Businesswire) - "CLD-101 is a cutting-edge therapeutic candidate in Calidi’s NeuroNova program, comprising tumor-tropic neural stem cells (NSCs) that deliver an oncolytic adenovirus – CRAd-S-pk7 – selectively to tumor sites....All participants receive a uniform dose of 1.50 x 108 NSCs and 1.875 x 1011 viral particles, the maximum feasible dose from the initial human study. Secondary objectives for the study include assessing the biological activity, biodistribution, immunogenicity, safety, and preliminary clinical efficacy of CRAd-S-pk7. The initial patient began treatment in May 2023. Currently, three patients in Treatment Schedule 2 and three in Treatment Schedule 3 have been enrolled and treated safely."

Trial status • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Calidi Biotherapeutics Announces Upcoming Presentations at the 2024 ASCO Annual Meeting (Businesswire) - "Calidi Biotherapeutics...announced the acceptance of three abstracts that will be presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting....The posters will include an update from a City of Hope-led Phase 1 study of Calidi's CLD-101 program, focusing on the treatment of recurrent high-grade glioma, now advancing into its fourth cohort of participants....Calidi will also present preclinical data highlighting its RTNova delivery platform...and its CLD-201 program, which is expected to dose its first patient in a Phase 1 trial in the second half of 2024 subject to Calidi’s ability to raise additional capital."

New P1 trial • P1 data • Preclinical • Glioma

Calidi Biotherapeutics Presents New Data on the Mechanisms of Action for Virotherapy-Loaded Stem Cells Used in the Company’s Novel Immunotherapies at the AACR Annual Meeting 2024 (Businesswire) - "Calidi previously announced that its partner, City of Hope, dosed the first patient in a Phase 1 clinical trial evaluating CLD-101 in recurrent high-grade glioma patients. The company expects to report a clinical update in the second quarter of 2024....The company expects to start clinical trials with CLD-201 by the end of 2024, subject to the company’s continued ability to raise the capital necessary to fund its clinical development programs."

New trial • P1 data • Trial status • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Calidi Biotherapeutics Presents New Data on the Mechanisms of Action for Virotherapy-Loaded Stem Cells Used in the Company’s Novel Immunotherapies at the AACR Annual Meeting 2024 (Businesswire) - "In the studies presented at AACR, scientists at Calidi Biotherapeutics and City of Hope researched the stem cells secretome transcriptomic of CLD-101 and CLD-201. The transcriptomic analysis showed that immunomodulatory cytokines, and chemokines, are induced following oncolytic virus infection demonstrating a potential immunotherapeutic role of the cells, in addition to the delivery and protection of the oncolytic viruses. Together these findings suggest that the enhanced antitumor actions of Calidi’s therapies are partially due to the alterations in the stem cells’ secretome, reinforcing the potential of the company’s novel approach to treat solid tumors."

Preclinical • Oncology • Solid Tumor

Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Northwestern University | Initiation date: Jan 2024 ➔ Jun 2024

Combination therapy • Trial initiation date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Calidi Biotherapeutics Reports Fourth Quarter and Full-Year 2023 Operating and Financial Results (Businesswire) - "Upcoming Anticipated Milestones: (i) 1H 2024: Interim clinical update from CLD-101 Phase 1 trial in collaboration with City of Hope for recurrent high-grade glioma patients; (ii) 1H 2024: First patient dosed in CLD-101 Phase 1 trial in collaboration with Northwestern University for newly diagnosed high-grade glioma patients; (iii) 2H 2024: First patient dosed in CLD-201 Phase 1 trial."

P1 data • Trial status • Glioma