Traumakine (IFN beta-1a) / Faron Pharma, Maruishi Pharma - LARVOL DELTA

Phase I/II Study to Evaluate the Safety, Feasibility, and Efficacy of FP-1201 (Intravenous Interferon-Beta-1a) to Prevent Toxicities after CD19-Directed CAR T-Cell Therapy: Trial in Progress (ASH 2023) - P1/2 | "STUDY DESIGN AND METHODS Objectives and endpoints: Primary objective: To evaluate the safety and feasibility of FP-1201 in patients undergoing treatment with axi-cel or brexu-cel with two co-primary endpoints: i) to estimate the incidence of dose-limiting toxicity rates within the first 14 days following the last administration of FP-1201; ii) to study the type, frequency, and severity of adverse events according to the NCI CTCAE v5.0 from the first administration of FP-1201 and until day +28 after CAR T-cell infusion Secondary objectives: i) To decrease the incidence and severity of ICANS; ii) to decrease the incidence and severity of CRS; iii) to decrease corticosteroid usage; iv) to evaluate the effect of FP-1201 on anti-tumor efficacy Exploratory objectives: To characterize the in vivo effects of FP-1201 on endothelial function, the systemic cytokine milieu, and CAR T-cell function Key inclusion criteria: Adults ≥18 years of age with Karnofsky performance..."

CAR T-Cell Therapy • Clinical • P1/2 data • Acute Respiratory Distress Syndrome • B Cell Non-Hodgkin Lymphoma • CNS Disorders • Hematological Malignancies • Immunology • Lymphoma • Multiple Sclerosis • Non-Hodgkin’s Lymphoma • Oncology • CD73 • IFNA1 • IL6 • NT5E

CD73: agent development potential and its application in diabetes and atherosclerosis. (PubMed, Front Immunol) - "The upregulation of CD73 with agents, including AGT-5, Aire-overexpressing DCs, Aspirin, BAFFR-Fc, CD4+ peptide, ICAs, IL-2 therapies, SAgAs, sCD73, stem cells, RAD51 inhibitor, TLR9 inhibitor, and VD, decreased diabetes and atherosclerosis development...Only FP-1201, a CD73 agonist, was investigated in clinical trials but its further development was discontinued...circNT5E may be a promising target for agent development. This mini-review focuses on the current state of knowledge of CD73 in diabetes, atherosclerosis, and its potential role in agent development."

Journal • Review • Atherosclerosis • Cardiovascular • Developmental Disorders • Diabetes • Metabolic Disorders • CD4 • CD73 • IL2 • NT5E • RAD51 • TLR9

Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Fred Hutchinson Cancer Center | N=24 ➔ 0 | Not yet recruiting ➔ Withdrawn

CAR T-Cell Therapy • Enrollment change • Trial withdrawal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Nov 2026 ➔ Oct 2027 | Initiation date: May 2024 ➔ Apr 2025 | Trial primary completion date: Nov 2026 ➔ Oct 2027

CAR T-Cell Therapy • Trial completion date • Trial initiation date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center | Initiation date: Dec 2023 ➔ Mar 2024

Trial initiation date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center

CAR T-Cell Therapy • New P1/2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Immune Modulation • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"Traumakine Data Presented at MHSR Symposium https://t.co/BswsgzoCUk" (@CisionNews)

HIBISCUS: Human Intravenous Interferon Beta-Ia Safety and Preliminary Efficacy in Hospitalized Subjects With COVID-19 (clinicaltrials.gov) - P2 | N=7 | Terminated | Sponsor: Faron Pharmaceuticals Ltd | N=140 ➔ 7 | Trial completion date: Apr 2023 ➔ Apr 2022 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2022 ➔ Apr 2022; The decision is based on changes in the pandemic and further weakening of the recruitment that will not enable a completion of the study in any reasonable time

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease

Induction of CD73 prevents death after emergency open aortic surgery for a ruptured abdominal aortic aneurysm: a randomized, double-blind, placebo-controlled study. (PubMed, Sci Rep) - P2 | "Trial registration: ClinicalTrials.gov NCT03119701. Registered 19/04/2017 (retrospectively registered)."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Gastroenterology • Heart Failure • Hematological Disorders • Hepatology • Immunology • Liver Cirrhosis

HIBISCUS: Human Intravenous Interferon Beta-Ia Safety and Preliminary Efficacy in Hospitalized Subjects With CoronavirUS (clinicaltrials.gov) - P2; N=140; Recruiting; Sponsor: Faron Pharmaceuticals Ltd; Trial completion date: Apr 2022 ➔ Apr 2023; Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • PCR

HIBISCUS: Human Intravenous Interferon Beta-Ia Safety and Preliminary Efficacy in Hospitalized Subjects With CoronavirUS (clinicaltrials.gov) - P2; N=140; Recruiting; Sponsor: Faron Pharmaceuticals Ltd; Not yet recruiting ➔ Recruiting; Initiation date: May 2021 ➔ Aug 2021

Clinical • Enrollment open • Trial initiation date • Infectious Disease • Novel Coronavirus Disease • PCR

"US rights to patent related to Traumakine https://t.co/mCqTJY1ig9" (@CisionNews)

HIBISCUS: Human Intravenous Interferon Beta-Ia Safety and Preliminary Efficacy in Hospitalized Subjects With CoronavirUS (clinicaltrials.gov) - P2; N=140; Not yet recruiting; Sponsor: Faron Pharmaceuticals Ltd

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease

Financial statement release January 1 to December 31, 2020 (PharmiWeb) - "On track to initiate a Faron-sponsored trial investigating the potential of Traumakine to treat COVID-19. The Phase II/III HIBISCUS...study will be conducted in approximately 5-10 study sites across the US...In April 2020, the Company successfully raised a total of €14.0 million gross (€13.0 million net) from new and existing shareholders, through issuance of total of 3,500,000 new ordinary shares. The majority of these proceeds are being used to expand Clevegen in additional targets in the MATINS trial, support Traumakine in the ongoing REMAP-CAP trial and to strengthen the Company’s balance sheet."

Financing • Infectious Disease • Novel Coronavirus Disease

FDA approves next two phases of Faron's Traumakine trial (Sharecast) - "...United States Food and Drug Administration (FDA) has approved the phase 2 and 3 ‘HIBISCUS’ trial assessing its intravenous IFN beta-1a ‘Traumakine’ for the treatment of hospitalised patients with Covid-19....Study’s sponsorship had now been changed to Faron...The ‘Human intravenous Interferon Beta-Ia Safety and preliminary efficacy in hospitalised subjects with CoronavirUS’, or ‘HIBISCUS’, phase 2 and 3 study would be conducted at between five and 10 study sites across the US in hospitalised patients with Covid-19, who did not yet require mechanical ventilation, but maximally low flow oxygen support....The study would recruit 140 hospitalised Covid-19 patients with 1:1 randomisation, assessing Traumakine against placebo with a primary endpoint of clinical status at day 14."

New P2/3 trial • Infectious Disease • Novel Coronavirus Disease

"Update on TRAUMAKINE development https://t.co/PPQLYA0g3Y" (@CisionNews)

"US Department of Defense (DoD) to support TRAUMAKINE development https://t.co/Z3X6xrhKGX" (@CisionNews)

Big global study finds remdesivir doesn’t help Covid-19 patients (CNN) - P3, N=11,266; "...World Health Organization said the antiviral drug remdesivir has 'little or no effect on mortality' for patients hospitalized with coronavirus and it doesn't seem to help patients recover any faster, either....The WHO study reviewed remdesivir and three other repurposed drugs: hydroxychloroquine, the HIV combination of lopinavir and ritonavir and interferon. None of them helped patients live any longer or get out of the hospital any sooner, WHO said. The trial was able to generate conclusive evidence on the impact the drugs had on mortality, the need for ventilation, and duration of hospital stay....'Newer antiviral drugs, immunomodulators and anti-SARS COV-2 monoclonal antibodies are now being considered for evaluation via the Solidarity Therapeutics trial,' WHO said."

P3 data: top line • Infectious Disease • Novel Coronavirus Disease

Faron Pharmaceuticals Oy : First Results from WHO Solidarity Trial (Market Screener) - P3, N=11,266; "The results show that subcutaneous interferon (IFN) beta-1a was found to be safe, but ineffective to reduce overall mortality in hospitalized patients with COVID-19....The WHO's intent-to-treat analysis compared 1412 patients who received IFN beta-1a and 2050 control subjects not receiving IFN beta-1a. The use of corticosteroids was 50% across the study....The WHO reports that patients mainly received subcutaneous IFN beta-1a (Rebif, Merck KGaA)....The WHO has not been able to verify how many patients received Traumakine at the time of this analysis."

P3 data: top line • Infectious Disease • Novel Coronavirus Disease

"Traumakine might be the solution..?" (@PiviSaarela)

Traumakine update (Faron Press Release) - "Faron also announces today that AGC Biologics...has been selected as the new manufacturing house for the commercial scale production of the Company's IV IFN beta-1a....Traumakine continues to be investigated as a potential COVID-19 treatment in global trials, including the World Health Organization's (WHO) Solidarity trial....Faron continues to investigate Traumakine in two other clinical trials, the ongoing global REMAP-CAP...and the US HIBISCUS....HIBISCUS will be an investigator-initiated study at Harvard Medical School's Beth Israel Deaconess Medical Center."

Commercial • New P2/3 trial • Trial status • Novel Coronavirus Disease

Faron hosts virtual R&D Day today (Cision) - "Faron Pharmaceuticals...will today host a virtual R&D Day via webcast to present its R&D strategy and provide insight into Faron’s two clinical stage programmes, Clevegen and Traumakine. The event will take place today at 3.00 p.m. EEST, 1.00 p.m. BST, 8.00 a.m. EDT. Further to the announcement earlier today, no new price sensitive information will be disclosed.In addition, the following external experts will provide additional perspectives on both Clevegen and Traumakine...Dr. Petri Bono...MATINS study Part I safety and clinical efficacy."

Announcement

[VIRTUAL] Femto Pulse Analysis of Exosome RNA from Plasma of Renal Transplant Patients Confirmed the Unique Benefits of Plasma Exosome for Messenger RNA (mRNA) Transcript Analysis (ATC 2020) - "6 RNA samples were analyzed on the Agilent Femto Pulse system with the FP-1201 Ultra Sensitivity RNA kit and ProSize data analysis software... RNA analysis on the Femto Pulse system suggested that full-length mRNA exist and are well protected in exosomes from peripheral plasma of renal transplant patients. This analysis and our previous RT-qPCR study confirmed that plasma exosome is ideal for mRNA transcript analysis. The Femto Pulse system exhibited superior capacity to quantify and characterize RNA including longer RNA (500-6000 nt) in ultra-low quantity."

Clinical • Antibody-mediated Rejection