dexamethasone sodium phosphate (AVM0703) / AVM Biotechnology - LARVOL DELTA

AI Technology Group Signs Definitive Agreement to Acquire AVM Biotechnology (The Manila Times) - "Under the agreement, a newly formed subsidiary of Ai Technology Group will merge with AVM, and AVM will become a wholly owned subsidiary at closing, subject to customary closing conditions summarized in the filing....AVM Biotechnology is commercializing "AVM0703”, a fully developed small‑molecule drug, intended to fight all forms of cancer..."

M&A • Solid Tumor

Evaluating AVM0703 for Treatment of COVID-19 or Influenza-mediated ARDS (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: AVM Biotechnology Inc | Trial completion date: Mar 2025 ➔ Mar 2032 | Trial primary completion date: Dec 2024 ➔ Dec 2031

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Influenza • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

The OPAL Study: AVM0703 for Treatment of Lymphoid Malignancies (clinicaltrials.gov) - P1/2 | N=144 | Recruiting | Sponsor: AVM Biotechnology Inc | Trial completion date: Jun 2025 ➔ Dec 2026 | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Oncology • Primary Central Nervous System Lymphoma

Effect of AVM0703 treatment on the limitations of R-CHOP and survival in a model applicable to ABC subtype DLBCL. (ASCO 2024) - "Background: The current treatment regimen for DLBCL consisting of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (RCHOP), is challenged by molecular and prognostic characterization of DLBCL...2016), neoadjuvant AVM0703 was additive/synergistic, when cyclophosphamide/fludarabine (CyFlu) was dosed 3 and 24 hr later, with no additional toxicities... AVM+RCHOP demonstrated anti-tumor activity in A20 lymphoma mice, with reduced toxicity, compared to RCHOP. Larger preclinical studies are underway to confirm the activity of AVM0703+RCHOP against RCHOP resistant ABC DLBCL, and the potential to reduce total RCHOP exposure to only 3 cycles while maintaining or improving efficacy."

Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Oncology

Durable complete response and overall survival in patients with heavily pretreated, poor-prognosis non-Hodgkin lymphoma to immunoactivating AVM0703 with few and mild drug-related adverse effects. (ASCO 2024) - P1/2 | "RP2D AVM0703, with consolidation therapy at day 28 median (range 7 to 240 days) showed no concerning safety signals and promising long-term survival."

Adverse events • Clinical • CNS Disorders • Diabetes • Hematological Disorders • Hematological Malignancies • Insomnia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pruritus • Sleep Disorder

AVM Biotechnology Selected by the National Cancer Institute to Present at Bio Investor Forum 2023 (Businesswire) - "AVM Biotechnology...will present at the Bio Investor Forum, held in San Francisco, CA October 17-18, 2023. AVM Biotechnology’s pipeline includes the small molecule AVM0703 with applications to solid tumors as well as blood cancers, small molecule AVM0704 to induce blood cell formation to reduce need for transfusions and granulocyte-colony stimulating factor treatments, and an allogeneic ‘off-the shelf’ bispecific Natural Killer T-like cell that expresses both the gamma delta TCR and the invariant TCR."

Clinical data • Hematological Malignancies • Oncology • Solid Tumor

Expanded Access to Immunomodulatory AVM0703 for Solid Tumor and Blood Cancer Patients (clinicaltrials.gov) - P=N/A | N=N/A | Available | Sponsor: AVM Biotechnology Inc

Immunomodulating • New trial • Brain Cancer • Breast Cancer • CNS Tumor • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Hematological Malignancies • Hepatology • Immune Modulation • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Sarcoma • Solid Tumor • Spindle Cell Sarcoma • Squamous Cell Carcinoma

AVM Biotechnology Announces Twenty-Eight (28) Solid Tumor and Blood Cancer Patients have been Treated with Immunomodulatory AVM0703 through Expanded Access/Compassionate Use Programs (Businesswire) - "AVM Biotechnology...today announced that twenty-eight (28) solid tumor and blood cancer patients have been treated with its immunomodulatory drug AVM0703 through Expanded Access (EAP)/Compassionate Use (CUP) programs. Cancers that have been treated include highly relapsed/refractory, some imminently terminal, patients with glioblastoma, metastatic breast cancer (two with advanced bone metastases), metastatic ovarian cancer, metastatic gastric cancer, Hodgkin’s Lymphoma, mixed phenotype acute leukemia, B-ALL, metastatic colon cancer, malignant myxoid spindle cell neoplasm, non-small cell lung cancer, DLBCL with CNS involvement, desmoplastic small round cell tumor, metastatic esophageal adenocarcinoma, prostate cancer, anaplastic T-cell Non-Hodgkin’s Lymphoma and inoperable/chemotherapy ineligible CNS squamous cell carcinoma."

Clinical • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Induction and Mobilization of Endogenous Bispecific Gamma Delta TCR+ Invariant TCR+ Natural Killer T Cell-Like Cells in Non-Hodgkin's Lymphoma and Solid Tumor Patients (IO-SUMMIT EUROPE 2023) - "Preclinically, activity has been demonstrated against autoreactive T/B cells, immune-resistant lymphoma, xenografted human T-ALL, melanoma, and multiple myeloma. AVM0703 is also effective as neoadjuvant before chemoimmunotherapy or cell transplant."

Clinical • Brain Cancer • CNS Tumor • Hematological Malignancies • Lymphoma • Melanoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia • Transplantation

Immunomodulatory AVM0703 lacks the association between anti-cancer activity and immune-mediated side-effects of the checkpoint Inhibitors. (ASCO 2023) - "As monotherapy in the A20 lymphoma model, AVM0703 completely eradicates ~20% of flank tumors, and used as a neoadjuvant prior to cyclophosphamide/fludarabine (CyFlu) it provided additive/synergistic A20 killing...Based on its activity in combination with CyFlu, and since teplizumab anti-CD3 has been approved to prevent progression to grade 3 T1D in at risk people (4), we investigated the combination with AVM0703 to reverse recent onset T1D in the NOD mouse... We hypothesize that the combination of AVM0703 and anti-CD3 will be more effective when anti-CD3 is added 5 days after AVM0703. 1) Tocut, Autoimmun Rev 2018. 2) Sakowska, Front Immunol 2022."

Adverse events • Checkpoint inhibition • Immunomodulating • IO biomarker • Diabetes • Hematological Malignancies • Hodgkin Lymphoma • Immune Modulation • Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Obesity • Oncology • Solid Tumor • Type 1 Diabetes Mellitus

Immunomodulatory AVM0703 enhances R-CHOP anti-lymphoma effect with reduced toxicity: Immune-resistant, aggressive A20 lymphoma model. (ASCO 2023) - "Background: Rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (RCHOP) is the standard of care for most aggressive B-cell lymphomas...For example, addition of Lenalidomide with RCHOP improved outcomes in ABC-DLBCL patients (3), but leads to therapy related myeloid neoplasm in recent studies (4)...In the aggressive, immune resistant A20 mouse lymphoma model, neoadjuvant AVM0703 was additive/synergistic, when cyclophosphamide/fludarabine (CyFlu) was dosed 3 + 24 hours later, with no additional toxicities... Based on this study we plan to determine whether 3 cycles of AVM0703+RCHOP can induce long term CR and if AVM0703 could replace R and reduce long term side effects. 1) Poeschel Lancet 2019. 2) Spurgeon J Natl Canc Inst 2016."

Immunomodulating • Diffuse Large B Cell Lymphoma • Geriatric Disorders • Hematological Malignancies • Immune Modulation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The OPAL Study: AVM0703 for Treatment of Lymphoid Malignancies (clinicaltrials.gov) - P1/2 | N=144 | Recruiting | Sponsor: AVM Biotechnology Inc | Trial completion date: Jun 2023 ➔ Jun 2025 | Trial primary completion date: Apr 2023 ➔ Apr 2025

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Oncology

Very-High Dose Dexamethasone Mobilizes Endogenous Bi-Specific Gamma Delta+ NKT Cells (ASH 2021) - P1/2 | "Leukocytosis and lymphocytosis were reported 24 hours post infusion from the B-cell ALL patient but resolved by 7-days without reported intervention. Because a single AVM0703 dose triggers the rapid mobilization and activation of an endogenous bi-specific gamma-delta+ NKT cell with a favorable emerging safety profile, AVM0703 shows promise as a therapeutic agent in treating this serious disease."

Brain Cancer • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Glioblastoma • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Prostate Cancer • Solid Tumor • T Acute Lymphoblastic Leukemia

Adoptive cell therapy (ACT) with bispecific gamma delta TCR+ invariant TCR+ NKT-like cells for multiple myeloma (MM): Comparison of preconditioning (PC) on outcome (ESMO 2022) - "When tumor volume reached ∼400mm 3 well-established tumors, mice were PC'd with human equivalent dose (HED) cyclophosphamide-fludarabine (CyFlu HED 500/30 mg/mm 2 ), with Placebo (PL) or with AVM0703 HED 18 mg/kg. Table: 18P Conclusions AVM0703 could be a less-toxic PC agent before CarT or other ACT. 1 Blood 2021:138(S1) 4557"

Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

NIH Awards AVM Biotechnology SBIR Grant to Study AVM0703 Combined with Standard of Care in Non-Hodgkin’s Lymphoma (NHL) to Improve Complete Response Rates Without Additional Toxicities (Businesswire) - "AVM Biotechnology today announced the award of a third Phase I Small Business Innovation Research (SBIR) grant from the National Cancer Institute (NCI). This grant will evaluate the ability of the company’s small molecule, AVM0703, in combination with the standard chemotherapy regimen, R-CHOP, to reduce R-CHOP cycles in an aggressive, immune-resistant murine B cell Non-Hodgkin’s Lymphoma (NHL) model."

Financing • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The mobilization of endogenous bi-specific natural killer T-like cells and independent of glucocorticoid receptor activation related to acute supra-pharmacologic weight-based dexamethasone (AVM0703) and 18 mgs/kg body weight. (ASCO 2022) - "Prophylactic use of physiologic hydrocortisone reduces the risk of GC neuropsychiatric side-effects (Warris, L. T. et al...Endocrine (1999) 10: 271) and the non-GCR mineralocorticoid receptor has high affinity for prednisone but not Dex... a) Apoptosis via the tmGCR was observed at expected concentrations between 10nM and 100uM and was blocked by the GCR antagonist RU486... CBC’s and clinical chemistries from enrolling clinical trial confirmed the in vitro non-GCR findings."

Hematological Malignancies • Hepatology • Lymphoma • Oncology • Pancreatitis • Psychiatry • IL12A • IL2 • NCAM1

AVM Biotechnology Awarded $2 Million National Cancer Institute SBIR Phase II Grant from the National Institutes of Health to Advance AVM0703 in Cancer (Businesswire) - "VM Biotechnology...announced that it has been awarded a Phase II Small Business Innovative Research (SBIR) grant. This $2 million National Cancer Institute (NCI) grant will assist in the continuation of the company’s existing clinical trial (AVM0703 for Treatment of Leukemia or Lymphoma, NCT04329728). This Phase II grant has been awarded for continued support of the adaptive-design, expansion cohort clinical trial of AVM0703 for 'no-option,' Relapsed/Refractory (R/R) NHL/Leukemia patients. The study is currently enrolling at City of Hope, UCLA, Norton Cancer Institute, and the University of Texas Southwestern....The company has requested breakthrough therapy designation and plans for accelerated approval for commercial launch in mid 2024."

Breakthrough therapy designation • Grant • Launch • Trial status • Hematological Malignancies • Leukemia • Lymphoma • Oncology

The effects of AVM0703 mobilization of endogenous gamma delta/invariant TCR+ bispecific natural killer T-like cells against solid tumors and blood cancers. (ASCO 2022) - "Prophylactic use of circadian physiologic hydrocortisone reduces the risk of GC neuropsychiatric side-effects (Warris LT, et al. AVM0703 led to: i) complete response (CR) in 27% of immune-resistant mouse A20 tumors as monotherapy and CR in 60% when combined with 2 doses of cyclophosphamide/fludarabine (CyFlu); ii) tumor eradication and long-term memory against xenografted human T-ALL; iii) enhancement of ACT equivalent to CyFlu preconditioning in mouse melanoma; and iv) preliminary 95% CR against mouse multiple myeloma."

Hematological Malignancies • Hepatology • Lymphoma • Melanoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Pancreatitis • Psychiatry • Solid Tumor • T Acute Lymphoblastic Leukemia

AVM Biotechnology to Present Poster Highlighting the Effects of AVM0703 Against Solid Tumors and Blood Cancers at the 2022 ASCO Annual Meeting (Businesswire) - P1/2 | N=144 | WWRD Study (NCT04329728) | Sponsor: AVM Biotechnology LLC | "...AVM0703...is the subject of an ongoing adaptive design expansion cohort clinical trial treating relapsed refractory 'no-option' Non-Hodgkin’s Lymphoma/Leukemia. The company is finalizing the dose escalation portion of the trial with positive results including 80% of dosed patients experiencing clinical benefit/immune status improvement and 60% of patients achieving a durable response. Notably, a Peripheral T-cell Lymphoma (PTCL) patient has experienced a durable response with stable disease for 9 months, demonstrating enormous potential for peripheral T-cell lymphoma. The efficacy portion of the trial is anticipated to begin next month."

P1/2 data • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

AVM Biotechnology to Present Poster Highlighting the Effects of AVM0703 Against Solid Tumors and Blood Cancers at the 2022 ASCO Annual Meeting (Businesswire) - "AVM Biotechnology...announced that its abstract, 'The effects of AVM0703 mobilization of endogenous gamma delta invariant TCR+ bi-specific Natural Killer T-like cells against solid tumors and blood cancers' has been accepted for a poster presentation at the 2022 ASCO (American Society of Clinical Oncology) Annual Meeting...complete response in 27% of immune-resistant mouse A20 tumors as monotherapy and complete response in 60% when combined with 2 doses of cyclophosphamide/fludarabine (CyFlu)....A second abstract, 'Acute supra-pharmacologic weight-based dexamethasone (AVM0703), 18 mgs/kg body weight, mobilizes endogenous bi-specific Natural Killer T-like cells independent of glucocorticoid receptor activation', was chosen for print and online publication."

Preclinical • Hematological Malignancies • Melanoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia

The WWRD Study: AVM0703 for Treatment of Leukemia or Lymphoma (clinicaltrials.gov) - P1/2 | N=144 | Recruiting | Sponsor: AVM Biotechnology LLC | Trial primary completion date: Jun 2022 ➔ Apr 2023

Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Evaluating AVM0703 for Treatment of COVID-19 or Influenza-mediated ARDS (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: AVM Biotechnology LLC | Trial completion date: Jun 2023 ➔ Mar 2025 | Trial primary completion date: Jun 2022 ➔ Dec 2024

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

AVM0703 Tumor Debulking Enhances Cy/Flu Efficacy (ASH 2021) - "AVM0703 has been tested in an aggressive mouse B-cell lymphoma model (A20) alone and in combination with cyclophosphamide/fludarabine (CyFlu). AVM0703 has the potential to be one solution when used in combination with chemotherapy. Future clinical trials will determine if debulking with AVM0703 results in a reduction of the number of necessary R-CHOP cycles while maintaining or enhancing the efficacy rate."

Clinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

FDA Approves Accelerated Dosing in Non-Hodgkin’s Lymphoma/Leukemia Clinical Trial (Businesswire) - "AVM Biotechnology...announced...FDA permission to modify its ongoing clinical study, AVM0703-001, entitled 'The WWRD Study: AVM0703 for Treatment of Leukemia or Lymphoma'. The initial protocol, a 3 x 3-based design, called for dose escalation of 3 mg/kg for each of the six cohorts, ranging from 6 mg/kg to 21 mg/kg, with a minimum of three patients per cohort as part of an adaptive-design/expansion cohort trial...The approved protocol modification involves the elimination of three of the cohorts and reduction of the interval between cohorts. Eliminating the 9, 12 and 15 mg/kg dose requirements and moving directly to the anticipated effective clinical dose of 18 mg/kg is important for this study...A single dose of AVM0703 triggers the rapid activation and mobilization of novel gamma delta positive Natural Killer T (NKT) cells. NKT cells exhibit properties of both innate and adaptive immunity."

Clinical protocol • Preclinical • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

AVM Biotechnology Announces Full Enrollment of First Cohort of Relapsed/Refractory Non-Hodgkin's Lymphoma Patients Dosed with AVM0703 at major Cancer Centers in USA (PRNewswire) - “AVM Biotechnology announced today that the first cohort has been fully enrolled in their clinical study…All three patients had failed multiple prior therapies, and one had failed two transplants…The study is an adaptive design/expansion cohort trial such that cohort enrollment of relapsed/refractory Non-Hodgkin's Lymphoma patients for the pivotal trial can immediately follow the dose-escalation phase.”

Trial status • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology