ALA-101 / Arovella Therap, Imperial College London - LARVOL DELTA

AROVELLA FULLY FUNDED TO COMPLETE PHASE 1 WITH $20M PLACEMENT (Arovella Therap Press Release) - "Arovella Therapeutics...pleased to announce that it has received firm commitments from institutional and sophisticated investors, to raise approximately $20 million (before costs) under a placement of 117.6 million new fully paid....Funds raised under the Placement will be used to complete and report data from the planned phase 1, first-in-human clinical trial for Arovella’s lead product, ALA-101. The phase 1 clinical trial is for patients with CD19- positive non-Hodgkin’s lymphoma and leukemia. Funds raised under the placement will also be used to strengthen Arovella’s iNKT cell therapy pipeline and advance Arovella’s solid tumour products, and for general working capital purposes."

Financing • Gastric Cancer • Leukemia • Non-Hodgkin’s Lymphoma • Pancreatic Cancer

AROVELLA FULLY FUNDED TO COMPLETE PHASE 1 WITH $20M PLACEMENT (Arovella Therap Press Release) - "Over the remainder of CY2025, Arovella expects to achieve several critical milestones, including: Securing IND approval through the US FDA to conduct a phase 1 clinical trial in CD19-positive non-Hodgkin’s lymphoma and leukemia; Commencing a phase 1 clinical trial; Obtaining clinical data from initial patients dosed with ALA-101; and Securing proof-of-concept data for its solid tumour programs directed toward gastric and/or pancreatic cancer."

IND • New P1 trial • Preclinical • Gastric Cancer • Leukemia • Non-Hodgkin’s Lymphoma • Pancreatic Cancer

AROVELLA RECEIVES R&D TAX REBATE OF $3.0 MILLION WITH A FURTHER $0.3 MILLION EXPECTED (Arovella Therap Press Release) - "Arovella Therapeutics Ltd...is pleased to announce that it has received part of its FY2024 R&D Tax Incentive refund of $3.0 million. The company is also expecting to receive a further $0.3 million in the coming months in relation to eligible expenditure covered by an advanced overseas finding that was successfully obtained post lodgment of its income tax return that resulted in the $3.0 million refund. These funds further strengthen Arovella’s cash position as it progresses development if its lead asset, ALA-101, towards first-in-human clinical trials."

Financing • Hematological Malignancies • Oncology

UPDATED DETAILS ‐ INVESTOR WEBINAR (Arovella Therap Press Release) - "Arovella Therapeutics Ltd...released an announcement earlier today that incorrectly listed the date of the webinar as Thursday, 18 September 2024. The correct date is Wednesday, 18 September 2024...Following completion of process development and scale-up for the CAR-iNKT manufacturing process and a positive pre-IND meeting with the FDA for a first-in-human study of ALA-101 in CD19-positive blood cancers, the webinar will discuss the nextsteps for Arovella and its opportunities in developing the iNKT cell platform...Presenting on the webinar will be CEO and MD, Dr Michael Baker...Time: 11:00 AM (AEST)."

Commercial • FDA event • Hematological Malignancies • Leukemia • Lymphoma • Oncology

POSITIVE PRE-IND FEEDBACK FROM FDA FOR ALA-101 (Arovella Therap Press Release) - "Arovella Therapeutics...is pleased to announce that it has received positive feedback from the FDA during a pre-IND meeting in the lead up to its phase 1 study of ALA-101 as a treatment for CD19+ blood cancers...The meeting provided a clear path forward to submitting an IND for ALA-101, with no major changes proposed for the development program...The FDA guidance included a review of Arovella’s CMC program, a plan for nonclinical safety and efficacy studies, and the proposed phase 1 clinical trial design....Based on the precise information provided by the FDA, Arovella expects to file its IND for ALA-101 in early Q1 CY2025."

Clinical protocol • FDA event • IND • New P1 trial • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Arovella unveils new cancer therapy insights and strengthens leadership team (Proactiveinvestors) - "It was a busy quarter for Arovella Therapeutics Ltd...in its aim to develop an invariant Natural Killer T (iNKT) cell therapy platform for cancer treatment...Arovella has started preparing for its phase 1 first-in-human clinical trial to treat patients with CD19-positive blood cancers. During FY25, Arovella will focus on bringing ALA-101 into the clinic."

New P1 trial • Hematological Malignancies • Oncology

Arovella Therapeutics' cell therapies potential highlighted in Spark Plus note (Proactiveinvestors) - "A new desk note from Spark Plus analyst Cyprus Sia has provided a comprehensive look at Arovella Therapeutics Ltd (ASX:ALA) and the work the biotech company is doing towards developing invariant natural killer T (iNKT) cell therapies, including its pioneering ‘armoured’ CAR-iNKT product...The company intends to commence a Phase 1 clinical trial for CD19+ lymphoma and leukaemia patients in late 2024....By the end of 2024, ALA will attempt to produce CLDN18.2- iNKT cells, integrate IL-12-TM into its solid tumour programs, and validate their activities in preclinical studies."

New P1 trial • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pancreatic Cancer • Solid Tumor

AROVELLA ACHIEVES IMPORTANT MILESTONE BY COMPLETING PROCESS DEVELOPMENT AND SCALE-UP FOR MANUFACTURE OF ALA-101 (Arovella Therap Press Release) - "Arovella Therapeutics...is pleased to announce that it has achieved a significant milestone by completing process development for its patent protected manufacturing process required for large-scale Good Manufacturing Practice (GMP) manufacturing of its lead product, ALA-101...The modular, semi-automated process, developed at Cell Therapies Pty Ltd, is suitable for large-scale manufacturing and produces a high yield of Chimeric Antigen Receptor (CAR)-positive iNKT cells with very high purity. A well-controlled and reproducible GMP manufacturing process is essential for regulatory approval for first-in-human clinical trials. Arovella can now proceed with engineering and GMP batches to produce material for phase 1 clinical trials. The manufacturing process uses well-known automated cell therapy equipment....The final product characteristics are consistent with the expectations of global regulators such as the US FDA for product quality and safety."

Commercial • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Solid Tumor

Allogeneic CD19-directed CAR-iNKT cells and their phenotypic subsets for the treatment of CD19+ hematological malignancies (AACR 2024) - "In summary, inclusion of both CD4+ and CD4- iNKT cells is critical for the functionality of allogeneic CAR-iNKT cell therapy. Extensive characterization is crucial for clinical translation, but additional research, including preclinical and clinical trials, is essential to determine the safety and effectiveness of CAR19-iNKT cell therapy in real-world applications."

IO biomarker • Hematological Malignancies • Oncology • CD27 • CD4 • CD8 • IL15 • PD-1

AROVELLA PRESENTS ALA-101 DATA AT AACR (Arovella Therap Press Release) - "Arovella Therapeutics Ltd...today presented data characterising its CD19-targeting allogeneic cell therapy, ALA-101, at the American Association for Cancer Research (AACR) Annual Meeting in San Diego...The data summarises two distinct phenotypes of cells within the drug product, each of which plays a different role in responding to tumour cells. In particular, ALA-101 CAR-iNKT cells were separated based on whether or not they produced CD4 on their surface (CD4+ vs CD4-). Cells negative for CD4 (CD4-) were better able to kill target tumour cells via the CD19 Chimeric Antigen Receptor (CAR). In contrast, CD4+ cells proliferated faster in response to CD19+ tumour cells. The two groups of cells also produced a different cytokine response following CAR activation....'We look forward to progressing ALA-101 towards Phase 1 clinical trials in humans.'"

Preclinical • Hematological Malignancies • Oncology

AROVELLA FUNDED TO PHASE 1 DATA: COMPLETES $12.5M PLACEMENT (Arovella Therap Press Release) - "Arovella Therapeutics Limited...is pleased to announce that it has received firm commitments from institutional and sophisticated investors, to raise approximately $12.5 million (before costs) under a placement of 125 million...Funds raised under the Placement will be used to progress Arovella’s lead product, ALA-101, into a Phase 1 clinical trial and generate preliminary data from patients dosed with ALA-101...Funds raised under the Placement will also be used to strengthen Arovella’s iNKT cell therapy pipeline and advance Arovella’s solid tumour products, and for general working capital purposes...Over the coming 12 months, Arovella expects to achieve several critical milestones, including: Completing scale-up of its CAR-iNKT manufacturing process for ALA-101....Securing regulatory approval to conduct a Phase 1 clinical trial in non-Hodgkin’s lymphoma; Commencing a Phase 1 clinical trial in Non-Hodgkin’s lymphoma..."

Commercial • Financing • P1 data • Regulatory • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

AROVELLA TO PRESENT AT AACR ANNUAL MEETING (Arovella Therap Press Release) - "Arovella Therapeutics Ltd...is pleased to announce that it will present data summarising characterisation of its ALA-101 CAR-iNKT cell therapy at the upcoming American Association for Cancer Research (AACR) Annual Meeting in San Diego on 8 April 2024...The data summarises two distinct phenotypes of cells within the drug product, each of which plays a different role in responding to tumour cells. In particular, ALA-101 CAR-iNKT cells were separated based on whether or not they produced CD4 on their surface (CD4+ vs CD4-). Cells negative for CD4 (CD4-) were better able to kill target tumour cells via the CD19 Chimeric Antigen Receptor (CAR). In contrast, CD4+ cells proliferated faster in response to CD19+ tumour cells. The two groups of cells also produced a different cytokine response in response to CAR activation."

Preclinical • Hematological Malignancies • Oncology

ALA‐101 + ONCARLYTICS COLLABORATION UPDATE (Arovella Therap Press Release) - "Arovella Therapeutics Ltd...announces that the partnership to combine ALA-101 and onCARlytics has ended...On 26 September 2022, Arovella announced that it had entered into a research collaboration with Imugene to combine Arovella’s ALA-101 with Imugene’s onCARlytics platform. Imugene has advised Arovella that it no longer wishes to continue the collaboration, which will be terminated with immediate effect. As such, in vivo data for the combination of ALA-101 and onCARlytics will no longer be generated....The termination of the collaboration will not impact Arovella’s development of ALA-101 for CD19-positive blood cancers. Since initiating the Imugene collaboration 18 months ago, Arovella has also secured a globally leading target for gastric and pancreatic cancers (claudin 18.2) and its IL-12-TM armouring technology, which it will continue to develop for a range of solid tumours. There is no financial impact from the cessation of the collaboration for Arovella."

Licensing / partnership • Hematological Malignancies • Oncology • Solid Tumor

Arovella Therapeutics well-placed to advance iNKT cell therapy cancer treatment towards first-in-human clinical trials (Proactiveinvestors) - "Arovella Therapeutics Ltd...capped off the December quarter in a 'solid financial position' with pro-forma cash and cash equivalents of $4.76 million to continue advancing its iNKT cell therapy platform for cancer treatment...On the manufacturing front, Arovella completed the GMP manufacturing and release of the ALA-101 lentiviral vector, a key component required for GMP manufacturing of its lead CD-19-targeting iNKT cell product...the company also continued its manufacturing process development and scale-up activities, with process optimisation remaining on track to support the clinical manufacture of ALA-101 for phase I clinical trials in the first half of 2024...SPX-101, has completed all preclinical proof-of-concept, safety and specificity studies and toxicology studies required to commence a phase 1 trial to treat gastric cancers....Initial proof-of-concept data to demonstrate the potential of this approach is expected to be available in the first half of 2024."

Commercial • New P1 trial • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Solid Tumor

CAR-iNKT CELL PLATFORM DATA PRESENTED AT ASH - "Arovella Therapeutics Ltd..is pleased to announce its research collaborators from Imperial College London presented data using Arovella’s CAR-iNKT cell therapy platform. Team members from Professor Karadimitris’ lab have presented new data using the CAR-iNKT cell platform in a poster presented at the 65th Annual American Society for Hematology (ASH) conference in San Diego, California...The poster, presented by Dr Kanagaraju Ponnusamy, describes the use of the platform to produce CAR-iNKT cells targeting B-cell maturation antigen (BCMA) to eliminate Multiple Myeloma and describes the optimisation of the CAR construct. The work identified that the CD28 co-stimulatory domain (shown by the green line in the Kaplan Meier Survival Curve) was more effective than other co-stimulatory domains and led to substantially improved anti-tumour activity in mice. This CD28 co-stimulatory domain is also incorporated into Arovella’s ALA-101 product."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

Arovella Therapeutics to fully focus on lead cancer programs on terminating DKK1 licence (Investing.com) - "Following a strategic review of its pipeline, Arovella Therapeutics Ltd...has terminated its licence agreement with MD Anderson Cancer Centre for the DKK1-targeting technology as it concentrates on its invariant Natural Killer T (iNKT) cell therapy platform. This decision enables the company to focus resources on its lead program, ALA-101 for CD19+ blood cancers, and the newly licensed ALA-105 for Claudin 18.2+ solid tumours, as well as its ongoing collaboration with Imugene Ltd, combining ALA-101 with Imugene’s onCARlytics platform, and the potential acquisition of a cytokine technology from the Lineberger Comprehensive Cancer Center."

Licensing / partnership • Hematological Malignancies • Oncology • Solid Tumor

Oncology stocks advance at pace despite lukewarm market (Proactiveinvestors) - "...Arovella intends to achieve several critical milestones, including:...Reporting initial animal data on ALA-101 in combination with Imugene’s onCARlytics (H2 CY23); Optimising and scaling up its CAR-iNKT manufacturing process suitable for phase I clinical trials, including completing cGMP manufacture of its lentiviral vector (H2 CY23); Completing Investigational New Drug (IND)-enabling non-clinical safety and efficacy studies (H1 CY24); Manufacturing clinical batches for phase I clinical trials (H1 CY24); Securing an Investigational New Drug (IND) application with the FDA and/or regulatory filing with TGA to conduct a phase I clinical trial in Non-Hodgkin’s lymphoma (H2 CY24)..."

Commercial • IND • New P1 trial • Non-US regulatory • Preclinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Arovella Therapeutics’ milestones to positively reflect on valuation: Diamond Equity Research (Proactiveinvestors) - "Arovella has successfully secured the announced A$4.1 million placement from institutional and sophisticated investors, and A$2.2 million Share Purchase Plan (SPP) for eligible shareholders. The funds procured will be directed towards pushing Arovella’s primary product, ALA-101, towards Phase 1 clinical trials for patients with CD19-positive non-Hodgkin’s lymphoma. Additionally, these funds will fortify Arovella's iNKT cell therapy pipeline and offer general working capital....The company anticipates the commencement of Phase I clinical trial in non-Hodgkin’s lymphoma in H2 CY24."

Financing • New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Arovella Therapeutics’ milestones to positively reflect on valuation: Diamond Equity Research (Proactiveinvestors) - "In a study of 16 mice with solid tumor xenografts, CAR-iNKT cells engineered to express a cytokine significantly extended the animals' lifespan and led to an approximately tenfold increase in circulating iNKT cells four weeks post-treatment. Specifically, the study shows 75% of mice treated with CAR-iNKT cells incorporating a cytokine survived until the end of the 61-day study, with none dying before 40 days....The positive data has triggered an Option fee of US$15k payable to UNC Lineberger, leading to ongoing discussions about a potential definitive license agreement, expected to be signed before the expiry of the Option term in March 2024."

Licensing / partnership • Preclinical • Oncology • Solid Tumor

Binding Mechanism of CD47 with SIRPα Variants and Its Antibody: Elucidated by Molecular Dynamics Simulations. (PubMed, Molecules) - "Significant effects were observed in the energy and structural analyses of the residues (Glu35, Tyr37, Leu101, Thr102, Arg103) in the C strand and FG region of CD47 when it binds to the SIRPα variants. For B6H12.2, the residues Tyr32, His92, Arg96, Tyr32, Thr52, Ser53, Ala101, and Gly102 in its initial half of the light and heavy chains exhibit obvious energetic and structural impacts upon binding with CD47. The elucidation of the binding mechanism of SIRPαv1, SIRPαv2, and B6H12.2 with CD47 could provide novel perspectives for the development of inhibitors targeting CD47-SIRPα."

Journal • Oncology • SIRPA

Engineering allogeneic off-the-shelf CD19-directed CAR-iNKT cells without additional genetic manipulations for the treatment of hematological malignancies (AACR 2023) - "These data demonstrate a unique, off the shelf CAR19-iNKT cell platform for targeting hematological malignancies that combines the specificity of CD19 targeting CAR with the innate features of iNKT cells. The data indicates that iNKT cells are a potent cell type for generating allogeneic off the shelf products for treating a broad spectrum of hematological malignancies and solid tumors by targeting different receptors on the respective tumors."

IO biomarker • B Acute Lymphoblastic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Oncology • Solid Tumor • CD19

Arovella Therapeutics to present new CAR19-iNKT cell data at prestigious cancer research conference (Proactiveinvestors) - "Arovella Therapeutics Ltd (ASX:ALA) will present its iNKT cell platform and lead product ALA-101 at the prestigious annual American Association for Cancer Research (AACR) conference in April 2023....The company, which is developing the invariant Natural Killer T (iNKT) cell platform to treat cancer, will present new in vitro (test tube) and in vivo (mouse) data demonstrating how its lead candidate ALA-101 acts against patient-derived tumour cells and in aggressive leukemia models."

Preclinical • Hematological Malignancies • Leukemia • Oncology