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NanoViricides, based in Shelton, Connecticut, outlined its approach to developing therapies against COVID-19 at the LD 500 investor conference yesterday. Anil R. Diwan, company president and executive chairman, indicated that since January 2020, they have been working with very limited resources and boot-strapping on the company’s past work against coronaviruses, but is close to announcing a clinical candidate.

On July 8, the company announced it had tested three different drug candidates at three different dosage levels in mice and they were safe and well tolerated. The nanoviricides, as they are called, act by a novel mechanism of action, trapping viral particles like, the company said, the “’Venus-fly-trap’ flower does for insects.” They compare this to antibodies, which “only label the virus for other components of the immune system to take over.”

The nanoviricide approach would be broad-spectrum, and would likely work even if the SARS-CoV-2 virus mutates. The early work on the development candidates have demonstrated effectiveness against multiple coronaviruses in the company’s BSL2 Virology Lab, as well as effective in an animal study against a related coronavirus that uses the same ACE2 receptor as SARS-CoV-2.

As a result, NanoViricides completed Chemistry, Manufacture, and Controls (CMC) studies that would be needed for an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA). It is working on the IND for the COVID-19 drug candidate now and running more studies to finalize the clinical candidate.

Diwan also discussed the company’s plans on an “integrated approach” to fighting COVID-19 based on the two parts of the virus lifecycle: first, re-infection of a host cell by external virus after primary infection from outside the body, and second, replication of new virus particles in infected cells, which leads into a re-infection cycle. Diwan says that if both parts of the viral lifecycle can be blocked, a virus infection could be cured except in cases of latent viruses.

A nanoviricide is able to attack both parts of the viral lifecycle. The nanoviricide is designed to block the re-infection cycle and can also carry a payload to block the replication cycle. In the case of their candidates, they have successfully loaded Gilead’s remdesivir inside the nanoviricides, which they believe will be superior to remdesivir alone. They are currently testing them in preclinical studies.

Remdesivir inhibits the replication cycle by blocking the RNA polymerase activity. The company notes that also it was very effective in cell cultures against a broad range of viruses, it has been more limited in human clinical studies, likely because of how fast it is metabolized inside the bloodstream. Encapsulation in a nanoviricide should protect the drug from the metabolism, which would improve its clinical effect.

The company’s nanoviricides are biomimetics, meaning they are designed to resemble the cell surface of the virus. This allows direct attacks at multiple locations on a virus particle. This is believed to making the virus ineffective at infecting cells.

After it files the IND for a COVID-19 drug candidate, NanoViricides plans to re-engage its NV-HHV-101 shingles drug candidate clinical trials program toward an IND. This program was put on hold due to the COVID-19 pandemic.

On June 23, the company announced it had filed a quarterly report for the period ending March 31, and it had about $6.44 million in cash. It had raised in May about $10.22 million in a registered direct offering of 1.4 million shares of common stock. It believes it has sufficient funding for planned expenditures for the “ensuing year.”

Vir Biotechnology and GlaxoSmithKline dosed the first patient last week in a Phase II/III clinical trial of VIR-7831, a fully human monoclonal antibody against COVID-19. The trial is evaluating the therapy as early treatment for COVID-19 patients at high risk of hospitalization.

They now join a number of other companies, including Regeneron Pharmaceuticals, in testing monoclonal antibodies against COVID-19. Regeneron, with the U.S. National Institute of Allergy and Infectious Diseases (NIAID), launched their Phase III trial of REGN-COV2, a two-antibody cocktail against SARS-CoV-2, in late July.

This is different than the convalescent plasma treatment that recently receivedEmergency Use Authorization (EUA) from the U.S. Food and Drug Administration. Convalescent plasma antibody therapy takes blood plasma collected from patients who have recovered from COVID-19, using their antibodies against the virus as treatment.

In monoclonal antibody therapy, companies isolate antibodies from immune cells and screen them for their affinity for the SARS-CoV-2 virus and concentrate them into a therapeutic. Although not a vaccine, they are believed to offer a potential resistance and effectiveness against infections for a limited period of time, perhaps up to three months.

The Vir-GSK COMET-ICE study plans to enroll about 1,300 patients globally who have early symptoms of infection. The goal is to evaluate VIR-7831, a single-dose monoclonal antibody, to see if it can prevent hospitalization from the disease. They expect results before the end of the year with complete data in the first quarter of 2021, and possibly early access to treatment in the first half of 2021.

“Treating those with early COVID-19 disease so that it doesn’t become worse is critical both for the patients and for society,” said George Scangos, chief executive officer of Vir. “Hospital systems are overwhelmed worldwide, with new infections continuing to strain already limited resources. This study is designed to demonstrate whether VIR-7831 can significantly reduce the need for hospitalization in high-risk individuals, such as the elderly or those with pre-existing conditions such as lung or heart disease.”

Preclinical studies with VIR-7831 show affinity for the SARS-CoV-2 spike (S) protein and demonstrated high potency in neutralizing the virus. This at least suggests a high barrier to resistance and an ability the recruit immune cells to kill already infected cells. The antibody has also been designed to improve the antibody’s availability to the lungs.

COMET-ICE has two parts. The first will act as the first-in-human evaluation for safety and dosing. It will test the safety and tolerability of a single 500mg intravenous (IV) infusion of VIR-7831 compared to placebo over a 14-day period in non-hospitalized patients. It hopes to recruit 20 patients across the U.S.

After the first part is completed, the Expansion phase will determine whether it reduces the need for hospitalization. It will test the safety and efficacy of a single IV infusion of VIR-7831 or placebo in about 1,300 non-hospitalized patients around the world. The primary efficacy endpoint is percentage of patients with mild or moderate COVID-19 who worsen, as defined as the need for hospitalization or death, within 29 days of randomization.

The COMET clinical development program has two more planned trials, one for severely ill hospitalized patients and another for prophylaxis of symptomatic infection.

The companies also have another potential antibody, VIR-7832, which is similar to VIR-7831, but might act as a therapeutic or potentially prophylactic T-cell vaccine.

“Monoclonal antibodies directed against the SARS-CoV-2 virus could provide an effective and immediate immune response to COVID-19, bypassing the need for our body to produce its own antibodies, which is particularly important in the absence of an effective vaccine,” said Hal Barron, chief scientific officer and president R&D, for GSK. “This study will assess the ability of VIR-7831 to prevent high-risk individuals from progressing to severe disease, and in future studies we will also test the antibody’s ability to prevent infection in high-risk patients and to reduce disease severity in patients who are already hospitalized.”

Another Kevzara study in hospitalized COVID-19 patients failed to meet primary and secondary endpoints. This marks the second such failed study for Kevzara and at least the third with IL-6 inhibitors as a potential treatment for these patients.

This morning, Sanofi announced the disappointing results from the Phase III study of intravenously-dosed Kevzara (sarilumab). Sanofi and its developmental partner Regeneron launched the study in April outside the United States. The study, which was conducted in Italy, Spain, Germany, France, Japan, Canada and Russia, assessed Kevzara doses of 200mg and 400 mg in severely or critically ill patients hospitalized with COVID-19. The hope was for Kevzara, and Interleukin-6 inhibitor, to calm an overactive immune response in these patients. Following some anecdotal success with Roche’s Actemra in China in the early days of the COVID-19 outbreak, it had been thought that IL-6 may play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19 infection.

John Reed, Sanofi’s Global Head of Research and Development, expressed his disappointment in the outcomes of this study.

“In times like these, commitment to properly designed, controlled clinical trials, provides the information and understanding the scientific community needs for fact-based decision making.  At Sanofi, we are committed to help combat the global COVID-19 pandemic, including developing vaccine candidates that can be manufactured at large-scale,” Reed said in a statement.

While the trial failed to hit its primary and secondary endpoints, Sanofi said it noticed some positive numerical trends, although they were not statistically significant. Those trends were a decrease in duration of hospital stay as well as an acceleration in time to improve clinical outcomes, the company said. A trend was also observed towards reduced mortality in the critical patient group which was not seen in the severe patient group and the time to discharge was shortened by 2-3 days in patients who were treated with Kevzara. Again though, these were not considered statistically significant, the company added.

There were some serious adverse events in the study. Sanofi said 26-29% of Kevzara patients and 24% of placebo patients experienced some negative issues. Serious infections (including COVID-19 pneumonia) were observed in 11-13% of Kevzara patients and 12% of placebo patients.  Detailed results of the study will be submitted to a peer-reviewed publication later this year.

The latest Kevzara let down in COVID-19 follows data from a Phase III study of Kevzara in COVID-19 patients requiring mechanical ventilation released in July that showed the study did not meet its primary and key secondary endpoints. The trial was stopped following those results, although the companies said they did observe some “minor positive trends” in the primary pre-specified analysis group.

That same month, Genentech, a Roche company, reported that Actemra, another IL-6 inhibitor, failed to meet primary and secondary endpoints in a COVID-19 related study. Like Kevzara though, Genentech said it saw some positive trends with Actemra, but they were not statistically significant.

With the disappointing results in hand, Sanofi and Regeneron said they do not anticipate conducting further clinical studies for Kevzara in COVID-19.

The modern life sciences environment is increasingly focused around cloud-based work and collaboration. This requires secure, reliable and GxP-compliant data transfer software, such as that offered by Egnyte.

Therapeutics, medical devices and diagnostics require effective collaboration to successfully progress from early-stage development through to clinical testing. This inevitably involves the transfer of very large datasets between teams at different stages, which need to be strictly monitored and regulated for maximised reliability, traceability and security. Since the 1990s, biotech and pharmaceutical companies have implemented systems designed to store, exchange and analyse data that fully comply with GxP standards, which certify that pharmaceutical products are safe, fulfil their intended use and adhere to quality processes across the supply chain.

But the technological landscape in 2020 is very different from that of the 1990s. Modern software must be prepared for this constantly evolving technological environment and capable of meeting the needs of a clinical trials industry that is increasingly going global. Today, many companies are looking to reduce IT costs and leverage new technologies, such as cloud-based software, artificial intelligence and machine learning. While this switch may appear daunting and complex, especially with uncertainly surrounding digital transformation and compliance with FDA regulations, new data infrastructure that utilises user and file-based audit trails allow administrators to track the behaviour of specific files and individuals. This helps achieve complete transparency and compliance with GxP standards. Furthermore, regional data-related governance requirements are developing to account for modern security risks to ensure that data platforms can securely track sensitive data.

Egnyte for Life Sciences streamlines compliance with these ever-increasing and more strictly enforced regulations by enabling biotech companies to manage data, documents and governance in one platform. Its cloud-based data management solutions allow companies to collaborate efficiently and securely with external partners, such as CRO or CMO, consultants and sponsors, even with very large datasets. Checksum values are assigned to every file for absolute data integrity and leveraging automation using cloud-based solutions also means that deviations can be flagged, assessed and triaged accordingly.

Clinical study reports and batch records can be shared with granular permissions to ensure that data is firewalled and secure, and only accessible to the intended reader. For large data sets, Egnyte can centralise and cache data files for use both inside and outside of the network without the latency limitations associated with older systems, as well as enabling secure remote access.

With outsourcing and global collaboration leading to data being shared across more locations than ever before, and more people working remotely, this secure and reliable transfer of data is essential. Life sciences depends on collaboration, collaboration depends on trust, and that trust depends on secure, easy-to-use data transfer systems that comply with regulations. Software is now rarely built by in-house development teams, instead, it is provided by cloud vendors, such as Egnyte. With collaboration and partnership as a core ethos of modern science, Egnyte provides ongoing support along with its software to ensure that it is effectively implemented and meets requirements in FDA 21 CFR Part 11 for data integrity. In addition, the software is rigorously scrutinised to produce a validation package that shows that the software functions correctly.

Egnyte for Life Sciences enables companies to efficiently and rapidly create a compliant repository, validate it and use it for their regulated data, all while putting less strain on IT departments and increasing security. With clinical trials going global and work being carried out remotely, cloud-based file-sharing services and automation are transforming the way clinical trials are managed.

There are more than 1,300 clinical trials in hepatology, either ongoing or planned, in Asia-Pacific. This represents about 60% of all ongoing and planned hepatology trials globally.

Liver diseases are highly prevalent in the Asia-Pacific region. The region hosts some of the most active key opinion leaders and investigators with strong experience working with biotechnology companies on hepatology trials.

The leading Asia-Pacific biotech specialist CRO Novotech has released a new webinar about the advantages of conducting hepatology clinical trials in the Asia-Pacific.

The panel included leading key opinion leaders from Hong Kong, Australia and New Zealand, as well as a US-based biotech sponsor.

Given the high incidence of liver-related diseases in Asia Pacific, it really has become a core area of focus for Asia-Pacific biotech CRO Novotech.

Biotech sponsors are experiencing very high patient enrolment rate for clinical studies in the Asia-Pacific region across a broad range of liver and metabolic conditions.

According to biotech sponsors, the clinical trial application process is very straight forward in the region with a low risk for regulatory drama. Furthermore, biotech sponsors may end up amending protocols several times to expand studies, and that amendment process is extremely rapid across Asia-Pacific particularly in Australia and New Zealand.

Pieces of advice to biotechs looking to expand trials in Asia-Pacific.

The key advice for biotech companies aiming at Asia-Pacific for their next trials is to work with the experts in the region, with a broad reach, who know that through the ins and outs of how the CTA process works there and what is typical for regulatory processes in each of the various countries.

This webinar also covered:

• The latest research and trends in hepatology clinical trials globally and in Asia-Pacific
• The benefit for biotechnology companies to involve sites in Asia-Pacific for hepatology trials
• Feedback from sponsors and investigators

Watch the full webinar here

The trial is designed towards addressing the need for an investigation on this new formulation based on encouraging preclinical evidence for the treatment of Covid-19, Mankind Pharma said in a statement.

Mankind Pharma on Tuesday said it has collaborated with South Korean firm Daewoong Pharmaceutical Co for conducting phase-I clinical trial of a novel formulation of Niclosamide for the treatment of Covid-19 patients in India. The trial is designed towards addressing the need for an investigation on this new formulation based on encouraging preclinical evidence for the treatment of Covid-19, Mankind Pharma said in a statement.

“We are excited to collaborate with Daewoong Pharmaceutical Co Ltd to bring novel formulation of Niclosamide (DWRX2003) for the treatment of Covid-19 patients in India.

“We believe that the product would provide for a safe and effective alternative to patients suffering from this disease,” Mankind Pharma COO Arjun Juneja said.

Both the companies have received approval from the Drugs Controller General of India (DCGI) to conduct phase-1 clinical trials.

Daewoong Pharmaceutical CEO Sengho Jeon said, “Through development of candidates for Covid-19 treatments such as Nicosamide, which Daewoong Pharmaceutical is currently developing, we expect to provide innovative treatment option for patients suffering from Covid-19.”

Mankind Pharma is one of the best partners to accelerate the clinical development and supply of DWRX2003 for India, he added.

Two Phase 3, randomized, placebo-controlled, double-blind clinical trials testing whether experimental monoclonal antibodies (mAbs) can prevent infection by SARS-CoV-2 coronavirus are now enrolling healthy adults at clinical trial sites in the United States. Many of the trial sites and study investigators are part of the COVID-19 Prevention Network(link is external) (CoVPN), recently established by the National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health. SARS-CoV-2 is the virus that causes coronavirus disease 2019 (COVID-19). The trials are enrolling adults who are at risk of infection due to close contact at work or home to persons with SARS-CoV-2 infection.

“The COVID-19 Prevention Network is designed to conduct large-scale trials rapidly and efficiently,” said NIAID Director Anthony S. Fauci, M.D. “This network will allow us to test the safety and efficacy of monoclonal antibodies and other preventive measures to help identify how best to reduce the level of SARS-CoV-2 infection and ultimately end the COVID-19 pandemic.”   

Monoclonal antibodies(link is external) are laboratory-made versions of proteins naturally produced by the immune system in response to invading viruses or other pathogens. Neutralizing antibodies, whether natural or monoclonal, can bind directly to portions of viruses that they use to attach to and enter cells, preventing them from initiating the infection cycle. Monoclonal antibodies may provide short-term protection from SARS-CoV-2 and could serve as important components of the COVID-19 pandemic response until vaccines become available.

One trial is being conducted jointly by NIAID and trial sponsor Regeneron Pharmaceuticals of Tarrytown, New York. It will evaluate Regeneron’s investigational double mAb combination, REGN-COV-2, which is designed to bind to two points on the SARS-CoV-2 spike protein and prevent it from entering healthy cells. The trial will enroll approximately 2,000 asymptomatic adults who are household contacts of persons with SARS-CoV-2 infection. Participants must have been in close contact (typically due to residing at the same address) with the infected person in a 96-hour window preceding administration of either REGN-CoV-2 or placebo. In addition to assessing safety, the trial will seek to define whether REGN-COV-2 can prevent infection or disease symptoms in those already infected. The efficacy assessment will be a one-month period following administration of REGN-COV-2 or placebo. All trial participants will be followed for safety for seven months after efficacy assessment period ends.

Additional details about this trial are available at clinicaltrials.gov using the identifier NCT04452318. Interested participants can also visit the CoVPN website(link is external) for details. Doctors or potential participants may also contact the sponsor’s Clinical Trials Administrator at 844-734-6643 or clinicaltrials@regneneron.com(link sends e-mail) for information on enrolling. 

A second trial, sponsored by Eli Lilly and Company of Indianapolis, Indiana, and implemented in collaboration with NIAID, will evaluate LY-CoV555, a mAb isolated from a recovered COVID-19 patient by scientists at AbCellera (Vancouver, British Columbia, Canada) and the NIAID Vaccine Research Center, and developed by Eli Lilly and Company. This trial will assess whether LY-CoV555 can prevent SARS-CoV-2 infection among people at high risk of exposure due to residing or working in skilled nursing or assisted living facilities. Within one week of identification of a case of SARS-CoV-2 infection at a facility, study investigators will enroll trial volunteers and evaluate the prevention efficacy and safety of LY-CoV555, compared to placebo, over an 8-week period. The trial will also evaluate efficacy in preventing symptoms of a given severity in those already infected. Participants will continue to be followed for safety for an additional 16 weeks. Up to 2,400 participants will be randomized to receive intravenous infusion of either LY-CoV555 or placebo.

Additional information about this trial is available at clinicaltrials.gov using the identifier NCT04497987. Clinical investigators, hospitals or clinical sites interested in participating in one of Lilly’s clinical trials for a potential COVID-19 treatment, should call 1-877-CT-LILLY (1-877-285-4559) or email covid19potentialsite@lilly.com(link sends e-mail).

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Celularity has received funding to support a phase I/II clinical trial of human placental hematopoietic stem cell-derived natural killer cells (CYNK-001) for the treatment of COVID-19.

The company was awarded $750,000 by the California Institute for Regenerative Medicine. The funds will be used to evaluate antiviral activities of the cryopreserved product in underserved and disproportionately affected populations with COVID-19.

During the phase I portion, CYNK-001 will be administered intravenously in up to 14 patients in three doses over the course of seven days. Clearance of SARS-CoV-2 and clinical improvement will be evaluated with chest x-ray during the study. The phase II portion will be a randomized, multisite study that will measure multiple doses to determine efficacy and symptom progression.

Celularity received clearance from the U.S. Food and Drug Administration in April to move forward with the study. The University of California, Irvine is the first site to open for patient enrollment.

Biopharmaceutical company Romark has commenced a Phase III trial of its new investigational drug candidate NT-300 (nitazoxanide) for the treatment of mild or moderate Covid-19.

The multicentre, randomised, double-blind trial of the NT-300 drug containing nitazoxanide extended-release tablets will involve the participation of nearly 800 people aged 12 and older with coronavirus-related fever and respiratory symptoms.

These participants will be randomised with either NT-300 or placebo twice a day for five days.

According to the company, efficacy analysis will examine those subjects who have laboratory-confirmed SARS-CoV-2 infection, a virus that causes Covid-19.

The primary endpoint will be achieved if there is a reduction in the recovery time compared with placebo, while the secondary endpoint is a reduction in the rate of progression to severe Covid-19 illness when compared to placebo.

Romark chief medical and scientific officer Jean-François Rossignol said: “As the Covid-19 pandemic continues to take a toll on our collective health, economy and well-being, we are pleased to broaden our NT-300 Covid-19 clinical programme through the initiation of a third trial evaluating NT-300 as a treatment in addition to our two ongoing prophylactic trials.

“Along with vaccines and treatments for severe illness, oral treatments that can be given outside of a hospital setting to prevent infection or used as soon as symptoms appear to reduce the duration of illness and prevent hospitalisations are desperately needed.”

Nitazoxanide, which is an active ingredient in NT-300, prevents the duplication of a wide range of respiratory viruses, including SARS-CoV-2.

Earlier this year, Romark began two Phase III clinical trials for the prevention of coronavirus, as well as other viral respiratory illnesses.

Romark anticipates sharing the results of these trials by the end of this year.

The UK government has signed its fourth coronavirus vaccine deal, snapping up 60 million doses of an experimental shot being developed by Sanofi and GlaxoSmithKline.

The order has come in even before the vaccine has started clinical development, with a phase 1/2 trial not due to get underway until September. Sanofi is providing the vaccine candidates itself while GSK is contributing the adjuvant used to boost immune responses to it.

The UK has already claimed 100 million doses of the ChAdOx1 vaccine in development at the University of Oxford and AstraZeneca, as well as 30 million doses of a candidate from BioNTech/Pfizer and 60 million doses of another shot created by Valneva.

There has been speculation that the government was gearing up to place an order for the Sanofi/GSK vaccine over the last few weeks, and it is the first official order to come in since the two companies started collaborating on the programme in April.

The value of the order has not been publicly disclosed but has previously been estimated at up to £500 million.

Orders for the vaccine candidates in development for COVID-19 are coming in thick and fast from western governments, leading to concerns of “vaccine nationalism”, with affluent countries buying up the first available stocks and leaving poorer nations at the back of the queue.

The US and the UK – both among the countries worst affected by the pandemic – have been particularly active in signing coronavirus vaccine access deals.

GSK and Sanofi maintain they are committed to making their vaccine available around the world, and plan to provide a significant portion of total worldwide available supply capacity in 2021/22 to ACT Accelerator, an organisation set up to secure access to COVID-19 tests, treatments and vaccines in lower-income countries.