Coronavirus Stimulates Biopharma and Academia Research Activities and Collaborations

To date, the coronavirus that causes COVID-19 has infected more than 93,000 people worldwide resulting in more than 3,200 deaths. Although the outbreak appears to be slowing in China, where it originated, it seems to be speeding up in South Korea, Italy, Iran and the United States. As of March 4, 2020, there were about 130 cases in the U.S. in 16 states with 11 fatalities.

One of the heartening aspects of the crisis is the way in which biopharma companies, government regulatory and health agencies, and academic centers are stepping forward and working to test or develop vaccines and therapeutics for the disease.

On March 4, Japanese drugmaker Takeda Pharmaceutical indicated it was attempting to develop a drug based on the blood of patients who recovered from COVID-19. The thinking is that antibodies culled from the patients could boost the immune systems of new patients, attacking the disease. In concept, it’s similar to immunotherapies used to treat certain types of cancers, as well as some treatments in other severe viral respiratory infections.

“While we don’t know for sure that it will work, we think it’s definitely a relevant asset that could be of help here,” said Rajeev Venkayya, president of Takeda’s vaccines business.

According to a Wall Street Journal report, Takeda has assigned about 40 staffers to work on the project, which was only conceptual a few weeks ago until they triggered the program. If Takeda’s team is successful, they believe a therapy could be made available to patients in nine to 18 months.

Vir Biotechnology and Alnylam Pharmaceuticals also announced on March 4 they were expanding their existing collaboration to include RNAi therapeutics targeting SARS-CoV-2, the virus that causes COVID-19. They plan to leverage Anlylam’s advances in lung delivery of novel siRNA conjugates with Vir’s infectious disease expertise. Alnylam recently identified siRNA targets in highly conserved regions of the coronavirus RNAs.

Also on March 4, the Bioscience Institute announced news from chinaXiv.org, a Chinese open repository for scientific researchers maintained and operated by the Chinese Academy of Science. A group of researchers from Baoshan People’s Hospital led by Bing Liang reported on a critically ill 65-year-old Chinese woman who improved after an infusion of mesenchymal stem cells. They also reported results of the approach on seven COVID-19 pneumonia patients, one critically severe, four severe and two common, that were treated with MSCs at Beijing YouAn Hospital, with improved function.

In late February, Gilead Sciences announced it was launching two Phase III clinical trials of its investigational antiviral drug remdesivir in adults diagnosed with COVID-19.

Gilead’s trials will evaluate two dosing durations of the drug, which is given intravenously. The randomized, open-label, multicenter studies will enroll about 1,000 patients mostly in Asia, as well as in countries that have had high numbers of diagnosed cases. The trials are planned to start in March.

These trials are on top of two clinical trials in China’s Hubei province led by the China-Japan Friendship Hospital and a recently launched trial in the U.S. led by the National Institute of Allergy and Infectious Diseases (NIAID). Gilead donated the drug and provided scientific expertise for those trials. The China trial data is expected in April.

“Gilead’s primary focus is on rapidly determining the safety and efficacy of remdesivir as a potential treatment for COVID-19, and this complementary array of studies helps to give us a more expansive breadth of data globally on the drug’s profile in a short amount of time,” said Merdad Parsey, Gilead’s chief medical officer. “The speed with which remdesivir has moved into clinical development for this coronavirus reflects the pressing need for treatment options and the shared commitment of industry, governments, global health organizations and healthcare providers to respond to this public health threat with the highest urgency.”

On February 25, Moderna shipped its first batch of mRNA-1273, a vaccine against the virus, for a planned Phase I clinical trial in the U.S. The experimental vaccine was sent to the NIAID. mRNA-1273 is a mRNA vaccine that encodes for a prefusion stabilized form of the Spike (S) protein. It was chosen by Moderna researchers in collaboration with scientists at the NIAID Vaccine Research Center (VRC). Funding for the manufacture of the batch came from the Coalition for Epidemic Preparedness Innovations (CEPI).

On the biopharma and response side, the University of Nebraska Medical Center in Omaha and NIAID have initiated a clinical trial of Gilead’s remdesivir in COVID-19. It was originally developed to treat Ebola and in animal studies showed promise in treating SARS and MERS, which are caused by coronaviruses.

The first patient being treated is an American who was brought back to the U.S. after being quarantined on the Diamond Princess cruise ship docked in Yokohama, Japan. He volunteered to participate. Clinical trials of the drug are also ongoing in China.

UK-based GlaxoSmithKline stated Monday that it was working with China-based Clover Biopharmaceuticals to develop a vaccine candidate.

“We are proud to contribute to cutting edge research from scientists at Clover Biopharmaceuticals in China as part of our strategy to make our adjuvant technology available to selected partners,” said Thomas Breuer, GSK Vaccines’ chief medical officer.

State-owned pharmaceutical companies China Resources Pharmaceutical Group and China Medicine Health Industry Co. are speeding production of chloroquine. This drug appears to be effective in treating the coronavirus with no severe side effects. It has been in clinical use for more than 70 years.

Another study is ongoing of favipiravir compared to AbbVie’s Kaletra, an antiretroviral for HIV. China health officials have recommended broader clinical use of the drug based on 80 coronavirus patients. Zhejiang Hisun Pharmaceutical Co. manufactures favipiravir.

Paris-based Sanofi’s Sanofi Pasteur, its global vaccines business, is collaborating on a vaccine with the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response, part of the U.S. Department of Health and Human Services (HHS).

Sanofi plans to continue investigating an advanced preclinical SARS vaccine candidate that it had worked on during the 2002-2003 SARS outbreak.

“Addressing a global health threat such as this newest coronavirus is going to take a collaborative effort, which is why we are working with BARDA to quickly advance a potential vaccine candidate,” said David Loew, Global Head of Vaccines at Sanofi. “While we are lending our expertise where possible, we believe the collaboration with BARDA may provide the most meaningful results in protecting the public from this latest outbreak.”

Johnson & Johnson is also working on drugs for the disease with BARDA.

Innovation Pharmaceuticals is evaluating Brilacidin, what is called a defensin mimetic drug candidate, as a potential treatment for coronavirus. The drug has demonstrated antibacterial, anti-inflammatory and immunomodulatory activity in several clinical trials.

Inovio Pharmaceuticals is collaborating with Beijing Advaccine Biotechnology on Inovio’s vaccine, INO-4800, against the coronavirus. It has launched preclinical testing for clinical product manufacturing. It is supported by a $9 million grant from the Coalition for Epidemic Preparedness Innovations (CEPI). Inovio’s INO-4700, an investigational DNA immunotherapy, is also being developed in partnership with GeneOne Life Science. It was originally developed for MERS.

Vaxart is working on an oral recombinant vaccine using its proprietary oral vaccine platform, VAAST.

CytoDyn is studying leronlimab (PRO 140), a CCR5 antagonist, as a possible treatment. It is being studied in Phase II clinical trials for HIV and the U.S. Food and Drug Administration (FDA) has granted it Fast Track status.

LineaRx, a subsidiary of Applied DNA Sciences, created a joint venture with Takis Biotech on February 7 to develop a linear DNA vaccine for the virus. The joint venture will leverage PCR-based DNA manufacturing technology for the vaccine.

Bioxytran is looking for partners to develop its lead drug candidate, BX-25, as a treatment for Acute Respiratory Distress Syndrome (ARDS) in patients in the later stages of COVID-19. The drug is designed to be 5,000 times smaller than blood cells and helps transport oxygen through the body for about nine hours before being filtered by the liver.

Novavax had developed a vaccine for MERS in 2013. The COVID-19 causing virus has similarities to MERS and SARS.

BioCryst Pharma’s Galidesivir is a broad-spectrum antiviral. It has shown survival benefits in Ebola, Zika, Marburg and Yellow fever.

Regeneron Pharmaceuticals' combination of REGN3048 and REGN3051 is being evaluated in a first-in-human clinical trial sponsored by NIAID. Both antibodies bind to the S-protein of MERS coronavirus.