Powerful Alliance: Yale University School of Medicine and AI Therapeutics Company yesterday presented results of this Phase II in vitro clinical trial of candidate drug LAM-002A (apilimod dimesylate) to treat newly diagnosed patients with COVID-19. . Among the findings revealed that LAM-002A hinders the entry and trafficking of the SARS-CoV-2 virus into cells. (Shutterstock)

Among the few things that, until today, this time of global pandemic due to the SARS-COV-2 coronavirus left in print for the scientific world it is that it is better to walk on a field of research already known and to promote proactive and complementary partnerships.

Even more so when what governs the career of science that tirelessly pursues the cure for COVID-19 is the so-called fast track scientific, a still winding and gravel road, but nevertheless it is projected clear and with several hands round trip, as in the best highways. And whose ultimate purpose is not to skip the steps of the rigor that inhabits the scientific nature, but to speed up the times to stop the damage caused by the plague.

In that sense the Yale School of Medicine and AI Therapeutics Biopharmaceutical Company they formed an almost perfect alliance, according to the times. And to account for its stimulating “scientific pairing” yesterday they published the successful results of a in vitro clinical study Phase II – doors inside the laboratory – with the use of the candidate drug LAM-002A (apilimod dimesylate, according to its chemical name) to treat newly diagnosed patients with COVID-19.

The Phase II randomized, double-blind, placebo-controlled trial will evaluate the safety, tolerability, and efficacy of LAM-002A at decreasing viral load. Known as LAM-002A (apilimod), the drug has a proven safety record. Preliminary in vitro research has shown that it can block cellular entry and trafficking of the SARS-CoV-2 virus, the cause of COVID-19.

The study will also investigate measures of clinical efficacy, such as mortality, hospitalization, and oxygen saturation. And now that the study must be verified in humans, up to 142 people with ambulatory COVID-19 will be part of the test.

The candidate drug – selected from many – LAM-002A is a highly selective PIKfyve kinase inhibitor. The active component of the drug candidate is expected to allow its combination with other therapies, particularly with drugs targeting protein or viral functions.

With the encouraging results of the preliminary stage, the best contribution of Yale are their brilliant minds, and in this specific study the leadership was assumed by the renowned doctor Murat Gunel, president of neurosurgery at Yale University. AND on the side of the biopharma laboratory AI Therapeutics its best contribution is its innovative view on medicines, almost of an ecological matrix: the reuse of what is already known and proven.

Gunel de Yale, professor of genetics and neuroscience, is in turn the main scientific advisor to AI Therapeutics, and who promoted a scientific logic in which the company identifies new therapies using an artificial intelligence algorithm designed to match drugs with new indications.

This is how the idea that the reuse of known drugs could significantly accelerate the deployment of new therapies for COVID-19 comes into force.

The characteristics of the preclinical trial were randomized, double blind, placebo controlled Phase II. It will evaluate the safety, tolerability and efficacy of LAM-002A at a decreasing viral load. It created a lot of expectation with an innovative strategy. (Shutterstock)

Behind in vitro success

Again: So far, auspicious laboratory results have revealed that LAM-002A makes it difficult for the SARS-CoV-2 virus to enter and traffic in cells. Murat Gunel himself, president of neurosurgery at Yale University, spoke about the Phase II results that were released yesterday. : « The safety of LAM-002A has been demonstrated in more than 700 healthy subjects and patients with inflammatory and malignant conditions. It is one of the most powerful drugs in preclinical tests against SARS-CoV-2. Its safety and effectiveness profile provides a strong reason to urgently evaluate this drug in patients with COVID-19, who have few options to delay disease progression. « 

Yale scientist Gunel specified in the official statement, before starting tests on humans: « LAM-002A promises to be a powerful new therapy for COVID-19 patients to prevent disease progression, hopefully avoiding the need for hospitalization. »

AI Therapeutics’ innovative strategy is to use artificial intelligence, an algorithm, to discover new uses for drugs that have already been studied, and then they must prove their effectiveness. AI Therapeutics aims to accelerate drug development and increase clinical success by matching drugs to the right patients.

The drug candidate is intended to provide an outpatient treatment option to prevent disease progression and hospitalization of symptomatic patients with COVID -19.

Testing will now begin on 142 humans to achieve the promising conclusions of the Phase II preclinical trial. The candidate drug in question LAM-002A is a highly selective PIKfyve kinase inhibitor. (Shutterstock)

A recent independent study found that LAM-002A is the most effective of the 13,000 compounds evaluated to inhibit SARS-CoV-2, AI Therapeutics noted.

Yale’s Gunel noted in that same statement that if LAM-002A shows effectiveness at this stage, the trial could be expanded to assess whether it would help prevent the development of the disease after exposure, particularly in high-risk populations, such as the elderly in nursing homes, healthcare and frontline workers, or people in underserved communities. The company AI Therapeutics already has 70,000 ready doses of LAM-002, another 70,000 in preparation and the compound in preparation for almost five million additional doses.

Consulted by Infobae, the infectious medicine doctor Gustavo Lopardo, member of SADI and prominent member of the expert advisory panel of President Alberto Fernández explained, « This well-known Phase II work promoted by the Yale School of Medicine is clearly a new and innovative study. The most serious international database is already registered at Clinicaltrials.org, where scientific studies in general, whether COVID and Non-COVID, are registered. Any scientific team that is seriously developing a research study and wants to announce it must register it on that global platform. Until today there are 2800 studies registered in that database, when the word COVID is typed! Most are for treatment and some are for prevention. Looking for COVID-19 and LAM002 (the drug apilimov) the only one that appears is the Yale study ”.

The mechanism of action of the drug candidate is expected to allow its combination with other therapies, particularly with drugs targeting proteins or viral functions. In vitro, the drug candidate showed potent antiviral activity against various isolates of SARS-CoV-2, the virus that causes COVID-19 disease. (Shutterstock)

Lopardo added to Infobae, “This is an innovative strategy, a Phase II study, for patients with mild disease. In relation to this study, the aim is to prevent the progression of the disease. In other words, the bad evolution. Very different from what is done with other drugs like interferon or tocilizumab which is for when the patient is already advanced, and already has the cytokine storm. A limited number of patients will be recruited and good antiviral activity was demonstrated in vitro (within the laboratory). Now we will have to demonstrate in humans if this is true  »

Context, background and innovation

It is likely that the development of a vaccine requires at least 12-18 months, according to the most recent publication in Nature, a medium specialized in medical topics, specialists Laura Riva and Shuofeng Yuan. That “typical time frame for approval of a new antiviral treatment can exceed 10 years. Therefore, the reuse of known drugs could significantly accelerate the deployment of new therapies for COVID-19 ″.

Previous trials with more than 700 patients have shown that LAM-002A is safe for the treatment of autoimmune diseases and follicular lymphoma. The drug has received fast track status from the Food and Drug Administration for the treatment of lymphoma.

The aforementioned multi-agency study published in Nature, which analyzed more than 13,000 existing drugs against two live SARS-CoV-2 virus strains, found that LAM-002A is the most effective in fighting the virus, even in lung cells.

In another study in the journal Cell, another group of researchers independently demonstrated that LAM-002A could fight SARS-CoV-2 infections in human lung cells.

Unpublished data from AI Therapeutics along with data recently released by the Scripps Research Institute suggest that LAM-002A, already approved to treat COVID-19, may increase the effectiveness of the antiviral agent.

Charles S. De la Cruz, associate professor of medicine and microbial pathogenesis and director of the Yale University Lung Infection Research Center, will lead this study. « We are delighted to partner with AI Therapeutics to see if LAM-002A can help improve the devastating impact of this coronavirus pandemic on our society, » Dela Cruz said in the statement released by Yale.

The Yale Clinical Research Center is now enrolling patients in a Phase II trial for the use of the drug as a COVID-19 treatment. The study is expected to enroll 142 newly diagnosed patients to evaluate the drug’s safety and efficacy in reducing virus levels in infected individuals.

AI Therapeutics, a biopharmaceutical company based in Guilford, Connecticut, United States, is created by Yale alumnus Jonathan Rothberg, owns the intellectual property rights to the drug.

In this biotechnology laboratory, model systems, patient samples derived from our clinical trials, next-generation sequencing, genome editing, chemical genomics, expression profiling, and combinatorial drug detection are used to continuously teach the Guardian Angel ™ algorithm how to combine drugs with patients. AI Therapeutics has advanced four drugs in clinical trials: LAM-001 for lymphangioleiomyomatosis, LAM-002 for B-cell and ALS non-Hodgkin lymphoma, LAM-003 for acute myeloid leukemia, and LAM-004 for facial angiofibroma.

« We all want to do our part so that the people we love can go back to work, school and play. At AI Therapeutics, we believe that we must do everything possible to ensure that our medication, LAM-002, has the best opportunity to help. Working with Yale is the perfect place to start, ”said Jonathan Rothberg, co-founder of AI Therapeutics, in an official company statement. and winner of the National Medal of Technology and Innovation for inventing high-speed “Next-Gen” DNA sequencing.

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