Protollin

Scientists from Brigham and Women’s Hospital are ready to start a clinical trial that will evaluate the use of an intranasal vaccine to prevent Alzheimer’s disease. Following years of preparation, scientists from Brigham and Women’s Hospital are ready to start a clinical trial that will evaluate the use of an intranasal vaccine to prevent Alzheimer’s disease (AD). The candidate vaccine uses the immune modulator Protollin and works by activating monocytes in the cervical lymph nodes, which then travel to the brain and initiate the clearance of beta amyloid plaques, one of the hallmarks of AD, without creating antibodies. Protollin is developed, produced, and commercialized by I-Mab Biopharma and Jiangsu Nhwa Pharmaceutical . It has been over 25 years in the making for study lead Howard L. Weiner, M.D., the co-director of the Ann Romney Center for Neurologic Diseases at the hospital. This first human trial is inspired by the success of animal models. Its immunological approach presents a significant milestone in the treatment of Alzheimer’s disease, which to date has yet to see preventive therapies. “Where others have triggered antibody creation by amyloid vaccination or artificially put anti-amyloid antibodies into the patient intravenously, what we’re doing is stimulating the immune system in a natural way not only to clear the beta-amyloid, but also to address other abnormalities in the brain,” said Dr. Weiner, in an earlier statement . The initial trial will involve 16 participants who are already part of the Ann Romney Center and diagnosed with early, symptomatic Alzheimer’s disease. They will receive two doses (single ascending) of the vaccine, to be administered nasally, one week apart. Though having a small sample size, the goal of this study is to determine the drug’s tolerability and safety. It will also measure Protollin’s effect on the immune response. This is not the first time that Protollin is being used for human treatment. In fact, it is used as a popular adjuvant for other types of vaccines. “Over the last two decades, we’ve amassed preclinical evidence suggesting the potential of this nasal vaccine for AD. If clinical trials in humans show that the vaccine is safe and effective, this could represent a nontoxic treatment for people with Alzheimer’s, and it could also be given early to help prevent Alzheimer’s in people at risk,” noted Dr. Weiner. Dr. Weiner published three key papers on the vaccine’s potential to prevent Alzheimer’s Disease over the last 20 years, with the latest being a mouse study in 2012 . His work on developing a human vaccine is conducted alongside his long-time research partner Dennis J. Selkoe, M.D., the co-director of the Ann Romney Center and a known expert in the study of amyloid proteins and Alzheimer’s disease.

I-Mab announced positive interim data from its U.S. Phase II/III clinical trial of plonmarlimab for treatment of cytokine release syndrome in severe COVID-19. I-Mab announced positive interim data from its U.S. Phase II/III clinical trial of plonmarlimab for treatment of cytokine release syndrome (CRS) in severe COVID-19. CRS, or cytokine storm, is one of the potentially deadly components of COVID-19, where the immune system overreacts, releasing huge amounts of inflammatory cytokines. “We are very excited about the data and plonmarlimab could be a very promising treatment for hospitalized patients with COVID-19,” said Deepa Gotur, associate professor of clinical medicine at Houston Methodist. The antibody was discovered and developed by I-Mab, which has offices in Shanghai, Beijing, Hangzhou, Hong Kong and Gaithersburg, Maryland. The antibody targets human granulocyte-macrophage colony-stimulating factor (GM-CSF), which is a cytokine associated with acute and chronic inflammation. The Phase II/III trial is still ongoing. The trial is focused on determining the safety, efficacy and effects on cytokine levels in patients with severe COVID-19 after receiving a single 6 mg/kg dose of plonmarlimab compared to placebo. The recent interim analysis demonstrated positive early results in patients who were mechanical ventilation free (MVF) at baseline. Patients in this category who received plonmarlimab had a higher MVF rate, 83.6% compared to 76.7% by day 30. They also had a lower mortality rate of 4.9% compared to 13.3% in the same time frame, and greater recovery rates, 68.9% compared to 56.7% at day 14 and 80.3% compared to 70.0% at day 30. There was also a decreased time to recovery and shorter hospital stays compared to placebo. The company indicates the level of clinical improvements are comparable to those seen with Humanigen’s monoclonal antibody, lenzilumab, in a similar patient population, although the clinical trial is not a head-to-head study. It is difficult to compare two products on the basis of different studies and different endpoints. Humanigen’s product was accepted for review in the U..K on July 9 and the company submitted an application to the U.S. Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) on May 28. Humanigen’s data suggests lenzilumab was responsible for 37% more recoveries than standard of care (SOC) in patients hospitalized for COVID-19. I-Mab also reported that biomarker data were consistent with the clinical outcomes, suggesting that patients receiving plonmarlimab had decreased levels of pro-inflammatory cytokines and chemokines associated with CRS in their blood plasma. The antibody also appeared to be well tolerated in all patients. “Plonmarlimab has shown very promising results from the interim data analysis in our Phase II/III trial, and we intend to continue advancing the study in the U.S. at this critical juncture of the COVID-19 pandemic and continue exploring other clinical opportunities associated with CRS,” said Joan Shen, chief executive officer of I-Mab. At this time, patients with severe COVID-19 are typically treated with steroids such as dexamethasone and Gilead Sciences’ antiviral remdesivir. I-Mab focus is on monoclonal antibodies for a wide range of diseases, including cancer, autoimmune disorders, and COVID-19. On July 30, the company reported the FDA had cleared its Investigational New Drug (IND) submission for a Phase I trial of Protollin, an investigational drug for Alzheimer’s disease. The drug is an immunotherapy designed to stimulate the innate immune system to create a response against beta-amyloid protein plaques and tau tangles associated with memory loss and cognition problems with the disease.