trans sodium crocetinate (TSC) / CervoMed, University of Virginia - LARVOL DELTA

DFFN: Strategic Review Underway; Planning to Initiate Phase 2 GBM Trial in 1Q23… (Yahoo Finance) - "Phase 2 GBM Trial to Initiate in 2H22: While the strategic review process continues, Diffusion continues to focus on the initiation of an open label, dose escalation, Phase 2 safety and efficacy study (Study 200-208) of TSC in patients with newly diagnosed glioblastoma multiforme (GBM)....In the meantime, the company is preparing for the Phase 2 trial in GBM, which we currently anticipate initiating in the first quarter of 2023."

New P2 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology

ILD-DLCO: Study of Trans Sodium Crocetinate in Patients With Interstitial Lung Disease (clinicaltrials.gov) - P2 | N=18 | Terminated | Sponsor: Diffusion Pharmaceuticals Inc | N=27 ➔ 18 | Recruiting ➔ Terminated; Due to, among other things, positive results from the 200-302 trial, the trial has been terminated early. Resources shifted to new 200-208 GBM trial using information gained from 200-302.

Enrollment change • Trial termination • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Diffusion Pharmaceuticals to Initiate Phase 2 Trial in Patients with Glioblastoma Multiforme Incorporating Innovative Imaging Methodology to Evaluate Tumor Oxygenation (GlobeNewswire) - "Diffusion Pharmaceuticals Inc...announced that after collaboration with the United States Food and Drug Administration ('FDA') on the design of their Phase 2 clinical trial entitled 'Open-Label, Dose-Escalation, Phase 2 Safety and Efficacy Study of TSC in Newly Diagnosed Glioblastoma ('GBM') Patients when Administered with Standard of Care ('SOC')'. The trial will be designated Study 200-208. The Company expects to initiate the trial by the end of 2022 and anticipates dosing the first patient in the trial in the first quarter of 2023....The study trial will incorporate PET scans to directly evaluate the oxygen enhancing effects of TSC on tumor hypoxia using one of two radiotracers, 18F-FMISO or 18F-FAZA, with initial data readouts expected to be available within one year of the study’s initiation."

Clinical protocol • New P2 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology

Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Trans Sodium Crocetinate in Healthy Volunteers Exercising at Altitude (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Diffusion Pharmaceuticals Inc | Recruiting ➔ Completed | Trial completion date: Jan 2022 ➔ Apr 2022 | Trial primary completion date: Dec 2021 ➔ Apr 2022

Trial completion • Trial completion date • Trial primary completion date

Diffusion Pharmaceuticals Announces Issuance of U.S. Patent 11,185,523 (GlobeNewswire) - "Diffusion Pharmaceuticals Inc...announced that it has been granted United States Patent No. 11,185,523, 'Use of Bipolar Trans Carotenoids With Chemotherapy and Radiotherapy for Treatment of Cancer,' by the United States Patent and Trademark Office. This patent includes new claims related to methods of treating cancerous tumors by administering the Company’s lead product candidate, trans sodium crocetinate ('TSC'), in combination with radiation therapy and chemotherapy."

Patent • Gastrointestinal Cancer • Glioblastoma • Glioma • Oncology • Pancreatic Cancer • Solid Tumor

ILD-DLCO: Study of Trans Sodium Crocetinate in Patients With Interstitial Lung Disease (clinicaltrials.gov) - P2; N=27; Recruiting; Sponsor: Diffusion Pharmaceuticals Inc; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Diffusion Pharmaceuticals Doses First Patients in ILD-DLCO Trial (GlobeNewswire) - "While the Company intends to continue developing data to support TSC’s potential uses across a broad spectrum of indications complicated by hypoxia, it recently announced that its near-term focus will be the design and execution of a clinical program to support the use of intravenously administered TSC as an adjunctive treatment for hypoxic solid tumors, and that it intends to obtain input from the U.S. Food and Drug Administration on the program’s design in early 2022."

Clinical • Gastrointestinal Cancer • Glioblastoma • Glioma • Oncology • Pancreatic Cancer • Solid Tumor

Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Trans Sodium Crocetinate in Healthy Volunteers Exercising at Altitude (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Diffusion Pharmaceuticals Inc; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Safety and Efficacy of Trans Sodium Crocetinate (TSC) in SARS-CoV-2 (COVID-19) Infected Subjects (clinicaltrials.gov) - P1/2; N=25; Completed; Sponsor: Diffusion Pharmaceuticals Inc; Recruiting ➔ Completed; N=224 ➔ 25; Trial completion date: Dec 2021 ➔ Apr 2021; Trial primary completion date: Nov 2021 ➔ Mar 2021

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

ILD-DLCO: Double-Blind, Placebo-Controlled Study of Trans Sodium Crocetinate in Patients With Interstitial Lung Disease (clinicaltrials.gov) - P2; N=27; Not yet recruiting; Sponsor: Diffusion Pharmaceuticals Inc

Clinical • New P2 trial • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Trans Sodium Crocetinate in Healthy Volunteers Exercising at Altitude (clinicaltrials.gov) - P1; N=30; Not yet recruiting; Sponsor: Diffusion Pharmaceuticals Inc

Clinical • New P1 trial

Safety and Efficacy of Trans Sodium Crocetinate (TSC) in Enhancing Tissue Oxygen Levels in Healthy Volunteers (clinicaltrials.gov) - P1; N=30; Completed; Sponsor: Diffusion Pharmaceuticals Inc; Recruiting ➔ Completed

Clinical • Trial completion

Safety and Efficacy of Trans Sodium Crocetinate (TSC) in Enhancing Tissue Oxygen Levels in Healthy Volunteers (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Diffusion Pharmaceuticals Inc

Clinical • New P1 trial

Diffusion Pharmaceuticals Reports 2020 Financial Results and Provides Business Update (GlobeNewswire) - "Research and development expenses were $9.4 million for 2020, compared to $6.6 million for 2019. The increase was primarily attributable to the company’s clinical trial evaluating TSC in hospitalized COVID-19 patients, which resulted in a $1.1 million uptick in manufacturing costs and a $2.2 million increase in clinical trial and other R&D related expenses."

Commercial • Infectious Disease • Novel Coronavirus Disease

Diffusion Pharmaceuticals Completes Phase 1b Study of TSC in Hospitalized COVID-19 Patients (GlobeNewswire) - P1/2, N=224; NCT04573322; Sponsor: Diffusion Pharmaceuticals Inc.; "Diffusion Pharmaceuticals Inc....announced completion and topline data from the open-label, Phase 1b clinical trial...External safety monitoring committee, established as part of the trial protocol, met to review safety data from the final, 1.5 mg/kg dose, cohort and determined that no dose-limiting toxicities or serious adverse events were observed. This result is consistent with the committee’s determinations following their analyses of the safety data from each of the other dose cohorts in the trial. Evaluation of secondary endpoint data is ongoing and will be available early in the second quarter of 2021."

DSMB • P1 data • Infectious Disease • Novel Coronavirus Disease

INTACT: Safety and Efficacy Study of Trans Sodium Crocetinate (TSC) in Newly Diagnosed Glioblastoma (GBM) Biopsy-Only Subjects (clinicaltrials.gov) - P3; N=22; Completed; Sponsor: Diffusion Pharmaceuticals Inc; Active, not recruiting ➔ Completed; Trial completion date: Jun 2022 ➔ Nov 2020; Trial primary completion date: Jun 2021 ➔ Nov 2020

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

PHAST-TSC: Efficacy and Safety of Trans Sodium Crocetinate (TSC) for Treatment of Suspected Stroke (clinicaltrials.gov) - P2; N=6; Terminated; Sponsor: Diffusion Pharmaceuticals Inc; N=160 ➔ 6; Trial completion date: Jan 2022 ➔ Oct 2020; Recruiting ➔ Terminated; Trial primary completion date: Jan 2022 ➔ Oct 2020; The study was stopped due to lack of meaningful enrollment due to the COVID-19 pandemic.

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cardiovascular

Diffusion Pharmaceuticals Reports Third Quarter 2020 Financial Results and Provides Business Updates (GlobeNewswire) - "As of November 11, 2020, patient enrollment continues, and no dose-limiting toxicities have been observed....Designing and initiating additional studies in effort to accomplish strategic objectives: Evaluating possibility of expanding 100-303 COVID Trial to include additional doses...; Designing additional clinical studies intended to evaluate (i) the effects of TSC using short-term experimental models...and (ii) depending on whether or not the Company decides to implement the expansion of the 100-303 COVID Trial, additional doses of TSC on a more frequent dosing regimen....Diffusion intends to provide certain additional details regarding the design of these new studies in January 2021 and to initiate the studies during the first quarter of 2021. The Company also now expects the 100-303 COVID Trial...to be completed with topline data available by the end of first quarter of 2021....Research and development ('R&D') expenses were $3.1 million during the third quarter of 2020..."

Commercial • Enrollment status • New trial • P1/2 data • Trial status • Infectious Disease • Novel Coronavirus Disease

Safety and Efficacy of Trans Sodium Crocetinate (TSC) in SARS-CoV-2 (COVID-19) Infected Subjects (clinicaltrials.gov) - P1/2; N=224; Recruiting; Sponsor: Diffusion Pharmaceuticals Inc

Clinical • New P1/2 trial • Infectious Disease • Novel Coronavirus Disease

Diffusion Pharmaceuticals Doses First Two Patients with TSC in COVID-19 Clinical Trial (GlobeNewswire) - "Diffusion Pharmaceuticals Inc....today announced dosing of the first two patients in the Company’s open-label Phase 1b lead-in trial of its novel, oxygen-enhancing therapeutic, trans sodium crocetinate ('TSC')....In addition to evaluating the safety and tolerability of TSC, this trial will collect preliminary data on TSC’s effects on arterial blood oxygenation....The planned follow-on efficacy trial...will be conducted in the United States and Europe after consultation with, and approval from, local regulatory authorities."

Trial status • Infectious Disease • Novel Coronavirus Disease

Diffusion Pharmaceuticals Receives FDA Guidance for International Phase 1b/2b COVID-19 Clinical Program with TSC (GlobeNewswire) - "Diffusion Pharmaceuticals Inc....today announced receipt of guidance from the U.S. Food and Drug Administration (FDA) on the Company’s recently-filed Investigational New Drug (IND) application for trans sodium crocetinate....This guidance suggests certain study design changes with regard to endpoints and statistical considerations....They are being submitted for clearance by the Romanian National Agency for Medicines and Medical Devices (NAMMD)....Company now expects the first patient will be enrolled by the end of August, with first data available early in the fourth quarter of 2020."

Enrollment status • FDA event • Non-US regulatory • P1 data • Trial initiation date • Infectious Disease • Novel Coronavirus Disease

Diffusion Pharmaceuticals Files IND for International Phase 1b/2b COVID-19 Clinical Program With TSC (GlobeNewswire) - "Diffusion Pharmaceuticals Inc....today announced the filing of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for trans sodium crocetinate (TSC)....Newly titled as Phase 1b/2b, testing the Company’s lead drug TSC in a total of approximately 424 COVID-19 patients....The new IND details three studies, comprised of an open-label Phase 1b lead-in trial which, if successful, will be followed by two randomized double-blinded Phase 2b trials....Diffusion expects to begin dosing in this trial later this month....The Company expects this trial to read-out by the end of Q3 2020....Diffusion plans to begin two Phase 2b trials – one in the U.S. and one at the NIID....Data from the Romanian and U.S. Phase 2b trials are targeted for Q1 and Q2 2021, respectively."

IND • New P1/2 trial • P1/2 data • Infectious Disease • Novel Coronavirus Disease

Diffusion Pharmaceuticals files Clinical Trial Application for European phase 1a/1b study of TSC in Covid-19 Patients (GlobeNewswire) - "Diffusion Pharmaceuticals Inc....announces the submission of a Clinical Trial Application (CTA) to the Romanian National Agency for Medicines and Medical Devices (NAMMD) to initiate a Phase 1a/1b clinical trial of...trans sodium crocetinate....Diffusion plans to begin the 24 patient Phase 1a portion of the clinical trial by the end of Q2 2020. The entire Phase 1a/1b trial will enroll approximately 224 patients and is expected to last approximately 12 months. First data readout on the initial 24 patients is expected in Q3 2020, followed by an interim readout on 50 patients in Q4 2020 and final data in Q2 2021."

New P1 trial • P1 data • Infectious Disease • Novel Coronavirus Disease

Diffusion Pharmaceuticals Receives Accelerated FDA Response to Proposed TSC COVID-19 Clinical Trial Program (GlobeNewswire, Diffusion Pharmaceuticals Inc.) - "Diffusion Pharmaceuticals Inc....announces it has received an accelerated response from the U.S. Food and Drug Administration (FDA) to the Company’s Pre-Investigational New Drug (PIND) meeting request....PIND meeting request recommended that the first U.S. TSC COVID-19 study employ a double-blinded, controlled, randomized clinical trial....The FDA also recommended incorporating, where available, the drug remdesivir, which has been newly approved for emergency use, into TSC clinical trials....The FDA agreed with the safety and oxygenation marker endpoints proposed by the Company for early trials of TSC in COVID-19 patients..."

Clinical • FDA event • Infectious Disease • Novel Coronavirus Disease

Diffusion Pharmaceuticals Expands Clinical Trial Program of TSC for the Treatment of COVID-19 Patients to Include the Romanian National Institute of Infectious Diseases (GlobeNewswire, Diffusion Pharmaceuticals Inc.) - "Diffusion Pharmaceuticals Inc....today announced that it has entered into an agreement with the Romanian National Institute of Infectious Diseases (NIID) to begin a clinical trial....The NIID trial is planned to be conducted in two phases, with a possible third to follow. The first trial, which is fully funded by existing Diffusion resources, is a Phase 1 open-label, pharmacokinetic/pharmacodynamic, ascending-dose safety lead-in trial....This trial is expected to be completed in the third quarter of 2020....Assuming positive results, Diffusion intends to promptly commence a follow-on trial....Diffusion also is preparing for U.S-based clinical trials of TSC..... A pre-IND submission is currently under review by the U.S. Food and Drug Administration (FDA) with a response expected before the end of this month."

IND • Licensing / partnership • New P1 trial • New trial • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases