AV-GBM-1 / AiVita Biomedical - LARVOL DELTA

Final results of phase 2 trial of personal dendritic cell (DC) vaccines loaded with autologous tumor antigens (ATA) in newly diagnosed glioblastoma (GBM). (ASCO 2023) - P2 | "DC-ATA AV-GBM-1, a personal vaccine consisting of autologous DC pulsed with ATA, was investigated in a multicenter trial in patients with newly diagnosed GBM...Prior to initiating concurrent radiation therapy (RT) and temozolomide (TMZ), patients were enrolled with intent-to-treat (ITT) with DC-ATA after RT/TMZ...Longer OS was associated with 8 DC-ATA doses (p 6 cycles of adjuvant TMZ (p = 0.0054), & KPS 90 or 100 (p = 0.010) at enrollment... DC-ATA was reliably produced and injections well-tolerated in combination with various TMZ-based regimens, but the primary OS objective was not achieved. PFS was encouraging, but did not translate into improved OS, perhaps because DC-ATA was limited to 8 injections. Clinical trial information: NCT03400917."

Clinical • P2 data • Brain Cancer • CNS Disorders • CNS Tumor • Epilepsy • Glioblastoma • Oncology • Solid Tumor • CSF2 • IL4 • MGMT

AV-GBM-1 vs Control as Adjunctive Therapy Following Surgery and RT/TMZ in Newly Diagnosed GBM (clinicaltrials.gov) - P3 | N=672 | Not yet recruiting | Sponsor: Aivita Biomedical, Inc. | Trial completion date: Mar 2027 ➔ Mar 2029 | Trial primary completion date: Mar 2026 ➔ Mar 2028

Surgery • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

Phase II trial of AV-GBM-1: dendritic cell vaccine pulsed with lysate enriched for autologous tumor-initiating cell antigens in the treatment of patients with newly diagnosed glioblastoma (SITC 2021) - P2 | "Background Standard therapy of glioblastoma (GBM), which includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, is associated with poor overall survival (OS). PFS was very encouraging but did not translate into OS, perhaps because of discontinuation of treatment after 8 months. Trial Registration [Clinicaltrials.gov NCT03400917]"

Clinical • Late-breaking abstract • P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CSF2 • IL4

Tumor collection and establishment of tumor-initiating cell cultures as antigen source for AV-GBM-1 dendritic cell vaccines for a phase II trial in patients with newly diagnosed glioblastoma (SITC 2021) - P2 | "Background Despite standard aggressive therapy (maximum safe surgical resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ), then maintenance TMZ), 2-year survival is only about 25% for patients with newly diagnosed primary glioblastoma (GBM). Conclusions Self-renewing GBM TIC cultures can be reliably and rapidly established for use as the antigen source for personal DC-ATA vaccines. Clinicaltrials gov NCT03400917"

P2 data • Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Changes in proteomic markers after injections of personal AV-GBM-1 dendritic cell/tumor initiating cell vaccines in a phase II trial in patients with newly diagnosed glioblastoma (SITC 2021) - P2 | "Background Despite standard aggressive therapy, including maximum safe surgical resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, survival is still extremely poor for patients with newly diagnosed primary glioblastoma (GBM). More sophisticated analyses of this data set, such as principal component analysis, may be needed to understand the effects of AV-GBM-1. Clinicaltrials gov NCT03400917"

Clinical • P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • ANGPT1 • CSF2 • FGF • LCN2

Leukaphereses to obtain monocytes to produce dendritic cells in manufacturing of personal autologous AV-GBM-1 vaccines in a phase II trial in patients with newly diagnosed glioblastoma (SITC 2021) - P2 | "Background For patients with newly diagnosed primary glioblastoma (GBM), maximum safe surgical resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ results in a 2-year survival of only 25%. Success after a single leukapheresis was not related to the interval from surgery to pheresis procedure, or distance from the processing site. Clinicaltrials gov NCT03400917"

Clinical • P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IL4

Tumor markers associated with increased survival in a phase II trial of dendritic cell/tumor-initiating-cell vaccine AV-GBM-1 in patients with newly diagnosed glioblastoma (SITC 2021) - P2 | "Background Standard aggressive therapy of glioblastoma (GBM), which includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, is associated with a 25% 2-year overall survival (OS). Conclusions Both MGMT promotor methylation and IDH mutation were associated with a substantial and similar survival benefit in primary GBM patients treated with AV-GBM-1 in addition to standard aggressive therapy. Clinicaltrials gov NCT03400917"

Clinical • P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CSF2 • IL4 • MGMT

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment. (PubMed, J Exp Clin Cancer Res) - P2 | "AV-GBM-1 was reliably manufactured. Treatment was well-tolerated, but there were numerous treatment-emergent central nervous system AEs. mPFS was longer than historical benchmarks, though no mOS improvement was noted."

Journal • P2 data • P2 data • Brain Cancer • CNS Disorders • CNS Tumor • Epilepsy • Glioblastoma • Movement Disorders • Oncology • Pain • Solid Tumor • CSF2

Leukapheresis to obtain monocytes to produce dendritic cells for manufacturing AV-OVA-1 personal vaccines in a randomized phase II trial in patients with newly diagnosed advanced ovarian cancer (SITC 2022) - P2 | "Batches of patient-specific AV-GBM-1 were produced by incubating autologous DC with a lysate of irradiated TICs, then aliquoted into individual doses. Trial Registration Clinicaltrials. gov NCT00331526 Ethics Approval This study was approved by the Western IRB, approval number 20171661; all participants gave written informed consent before taking part"

Clinical • P2 data • Oncology • Ovarian Cancer • Solid Tumor • IL4

Adverse events in a phase II trial of AV-GBM-1: dendritic cell vaccine pulsed with lysate enriched for autologous tumor-initiating cell antigens for patients with newly diagnosed glioblastoma (SITC 2021) - P2 | "Background Standard glioblastoma (GBM) therapy includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ), and maintenance TMZ, but it is associated with a 2-year survival of only about 25%. The high frequency of focal neurologic events may be secondary to local inflammation induced by AV-GBM-1. Clinicaltrials gov NCT03400917"

Adverse events • Clinical • P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CSF2 • IL4

AIVITA Biomedical Announces Publication Detailing 50% Enhanced Survival in Phase 2 GBM Study (PRNewswire) - P2 | N=55 | NCT03400917 | Sponsor: Aivita Biomedical, Inc. | "AIVITA Biomedical, Inc...announced that the Journal of Oncology Research and Therapy has published data from its completed Phase 2 glioblastoma (GBM) study which demonstrates enhanced progression-free survival (PFS)....AIVITA completed a multi-center Phase 2 trial of its immunotherapy candidate, AV-GBM-1, which had demonstrated an encouraging 50% improvement in PFS over standard of care in patients with a recent diagnosis of GBM. This publication focuses on PFS resulting from AV-GBM-1 administration and compares the results to those reported in GBM trials of other therapies. The data suggest that continuous treatment could further improve progression-free survival and overall survival."

P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Seizures as treatment-emergent adverse events during glioblastoma clinical trials. (ASCO 2022) - "Such seizures typically can be controlled with anti-epileptics, and the risk of seizures seems to decrease after concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ). The frequency of seizures that occur in GBM patients receiving standard RT/TMZ is not well-documented in publications of large, randomized trials. AV-GBM-1 may be associated with a higher rate of seizures because of treatment-induced inflammation at the tumor site, but a randomized trial would be needed to determine this."

Adverse events • Clinical • Brain Cancer • CNS Disorders • Epilepsy • Ewing Sarcoma • Glioblastoma • Immunology • Inflammation • Oncology • Solid Tumor • EGFR • HAVCR2

Plasma proteomic markers prognostic or predictive for survival of patients with newly diagnosed glioblastoma who were treated in a phase II trial with standard care and the addition of the novel patient-specific dendritic cell vaccine AV-GBM-1 (AACR 2022) - "Standard aggressive therapy for primary newly diagnosed glioblastoma (GBM), which includes surgical resection followed by concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) and then maintenance TMZ, is associated with poor survival rates. The only markers that appeared predictive for survival (p<0.05) based on changes from baseline to week-2 were increased lipocalin-2, associated with longer survival (p=0.0369), and decreased brain-derived neurotrophic factor (BDNF) associated with shorter survival (p=0.0186). Because of the large number of analyses, these results are considered hypothesis generating and not definitive."

Clinical • P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • BDNF • CD14 • CSF2 • LCN2 • TIMP1

Autologous Dendritic Cells Loaded With Autologous Tumor Associated Antigens for Treatment of Newly Diagnosed Glioblastoma (clinicaltrials.gov) - P2; N=55; Active, not recruiting; Sponsor: Aivita Biomedical, Inc.; Trial primary completion date: Jun 2021 ➔ Dec 2021

Clinical • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

PHASE II TRIAL OF VACCINE IMMUNOTHERAPY IN PRIMARY GLIOBLASTOMA: ADJUNCTIVE AUTOLOGOUS DENDRITIC CELLS PULSED WITH LYSATE FROM IRRADIATED SELF-RENEWING AUTOLOGOUS TUMOR CELLS (AV-GBM-1) (SNO 2021) - P2 | "feasibility, safety, and PFS were encouraging. A phase III trial is in development. Clinicaltrials.gov NCT03400917."

IO biomarker • P2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • ANGPT1 • CSF2 • FGF • IL4 • LCN2 • MGMT

Randomized Trial of AV-GBM-1 vs Control as Adjunctive Therapy for Newly Diagnosed GBM (clinicaltrials.gov) - P3; N=726; Not yet recruiting; Sponsor: Aivita Biomedical, Inc.

Clinical • New P3 trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

AIVITA Biomedical's Phase 2 Glioblastoma Trial Shows Improved Progression Free Survival (Businesswire) - P2, N=55; NCT03400917; Sponsor: Aivita Biomedical, Inc; “The median length of PFS was 10.4 months (95% confidence interval; 8.6 to 11.7 months), an improvement of approximately 50% compared to a median PFS of 6.9 months (95% confidence interval; 5.8 to 8.2 months) in the landmark STUPP study1 that established the standard of care for patients with newly diagnosed GBM. This represents a 42% reduction in the risk of progression or death at 6.9 months. Median survival has not been reached and will be assessed after the final patient has a minimum follow up of 15 months. Overall, the treatment was well tolerated. There were 54 serious adverse events among 28 of 57 patients but none were attributed to the vaccine.”

P2 data • Glioblastoma • Oncology

AIVITA Biomedical Closes $25 Million Financing Round (PRNewswire) - "AIVITA Biomedical, Inc...has closed its Series B-2 financing round for up to $25 million. Financing was provided by several life sciences investment firms...Proceeds will support clinical development of AIVITA's personalized immunotherapy programs, including Phase 2 studies in glioblastoma and ovarian cancer, as well as AIVITA's application for commercial approval of its melanoma immunotherapy..."

Financing • Glioblastoma • Gynecologic Cancers • Melanoma • Oncology • Ovarian Cancer

AIVITA Biomedical's Phase 2 Glioblastoma Trial Shows Improved Progression Free Survival (PRNewswire) - P2, N=55; NCT03400917; Sponsor: Aivita Biomedical, Inc; “AIVITA Biomedical, Inc…announced data from its multi-center Phase 2 clinical trial of its personalized cancer vaccine, AV-GBM-1, in patients with newly diagnosed glioblastoma (GBM)…The median length of progression free survival was 10.0 months (95% CI 8.5 to 11.5 months), an improvement of approximately 45% compared to a median of 6.9 months (95% CI 5.8 to 8.2 months) progression free survival in the landmark study that established the standard of care for patients with newly diagnosed GBM. This represented a 38% reduction in risk of progression or death at 6.9 months of treatment.”

P2 data • Glioblastoma • Oncology

AIVITA Biomedical Completes Treatment of Patients in Phase 2 Clinical Trial of Glioblastoma Immunotherapy (PRNewswire) - P2, N=55; NCT03400917; Sponsor: Aivita Biomedical, Inc; "AIVITA Biomedical, Inc...announced...that treatment has been completed for all 57 patients in the Phase 2 clinical trial of AV-GBM-1 in patients with glioblastoma...AIVITA achieved a 97% success rate in both growing tumor-initiating cells from each patient and in collecting sufficient monocytes from the peripheral blood from which to derive dendritic cells, resulting in a 94% overall success rate for manufacturing a final treatment given to patients. AV-GBM-1 was well-tolerated, and no patients experienced severe adverse events...AIVITA expects new interim findings to be presented at future medical meetings in November."

P2 data • Glioblastoma • Oncology

AIVITA Biomedical presents updates from ongoing ovarian cancer and glioblastoma clinical studies at 2020 AACR Virtual Annual Meeting (Businesswire) - P2, N=55; NCT03400917; Sponsor: Aivita Biomedical, Inc; "AIVITA Biomedical, Inc...announced...that updates from ongoing clinical trials in ovarian cancer and glioblastoma were presented as part of the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting I....The presentation from Daniela Bota, MD, Ph.D., of the University of California, Irvine, and principal investigator of the Phase 2 clinical trial of AV-GBM-1 in newly diagnosed glioblastoma, included data obtained through March 2020. The study has completed enrollment, and the treatment has been well-tolerated to date with encouraging preliminary survival data."

Enrollment closed • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

"AV-GBM-1 Active in Frontline Glioblastoma https://t.co/xSdUqjqdLT" (@OncLive)

AIVITA Biomedical provides update of ongoing phase 2 glioblastoma trial from year-end survival analysis (Businesswire) - P2, N=55; NCT03400917; Sponsor: Aivita Biomedical, Inc; "AIVITA Biomedical, Inc...announced...updated survival data from a year-end analysis of its ongoing Phase 2 clinical trial of AV-GBM-1 in patients with newly diagnosed glioblastoma (GBM)...In the analysis, the overall survival rate at both 12 and 15 months is 76% in AV-GBM-1-treated patients (n=50), compared to overall survival of 61% at 12 months and 48% at 15 months in control patients (n=287) receiving standard of care. Patient recruitment is complete in the study....The clinical trial in advanced ovarian cancer is a Phase 2 randomized study currently enrolling patients at the time of initial diagnosis."

Enrollment closed • Enrollment open • P2 data

AIVITA Biomedical completes patient recruitment in phase 2 GBM trial (PRNewswire) - “AIVITA Biomedical, Inc., a biotech company specializing in innovative stem cell applications, announced today that it has reached its patient enrollment target in the Company's Phase 2 clinical trial for glioblastoma. The trial has achieved its enrollment target…”

Enrollment closed

Autologous Dendritic Cells Loaded With Autologous Tumor Associated Antigens for Treatment of Newly Diagnosed Glioblastoma (clinicaltrials.gov) - P2; N=55; Active, not recruiting; Sponsor: Aivita Biomedical, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Jun 2023 ➔ Feb 2023; Trial primary completion date: Oct 2020 ➔ Jun 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date