Coronavirus Vaccine & Treatment
The drug companies are racing to repurpose or develop treatments against the potential pandemic COVID-19. The death toll has crossed 3,000. On February 29, Washington state reported the first death associated with SARS-CoV-2 in the US. As of March 5, the novel coronavirus has killed 3,285 and infected 95,416 around the globe. Apart from China, COVID-19 has seriously struck countries like South Korea, Italy, and Iran.
The coronavirus vaccine & treatment consists of 35 active drug development programs in China, Europe, and North America and it has been revealed by a new survey by Genetic Engineering & Biotechnology News (GEN). The 35 treatments include those developed by pharma companies like Sanofi, GlaxoSmithKline, Gilead Sciences and Moderna which received the greatest public attention in recent days.
Gilead’s antiviral drug, remdesivir had shown positive results in cases involving an American patient and Chinese in vitro tests
According to a report published by the state-run Xinhua News Agency on February 28, the statistics strengthen China’s position as the center of the SARS-CoV-2 outbreak: Of the 234 clinical trials registered in the Chinese Clinical Trial Registry, almost half (105) focus on treatments for the new coronavirus.
The ClinicalTrials.gov has already
listed 67 studies related to COVID-19 and SARS-CoV-2. 331,715 trials from 209 countries are listed on the US website.The guidelines for clinical studies of vaccines and drugs against the novel coronavirus has published, announced Wu Yuanbin, director-general of Science and Technology for social development with China’s Ministry of Science and Technology (MOST). Priority is given to the already marketed drugs, whose efficacy has been proven in vitro studies and animals.
As seen in GEN’s A-List of the top 35 treatments under development and/or clinical study for COVID-19, as disclosed by drug developers and/or authorities in recent weeks, repurposing existing drugs is just one proverbial arrow in the quiver of drug developers and health agencies worldwide. Each experimental treatment is listed by its developer, followed by the treatment name or description, the mechanism and type of treatment, and a brief update about recent developments including the links to clinical trial pages and recent news reports in GEN. And some of them have yet to be named or identified.
Chinese companies, hospitals, and authorities are studying potential treatments outside the auspices of their original developers, in some cases. The Xiangya Hospital of Central South University and the Hospital of Changsha are partnering with Hu’nan Haiyao hongxingtang Pharmaceutical Co. on a clinical trial for studying the combination of AbbVie’s Kaletra® and Beijing Genova Biotech’s Novaferon, a recombinant interferon-alpha (IFN-α) like viral protein for hepatitis B in treating patients with COVID-19.
An idiopathic pulmonary fibrosis drug, Pirfenidone by Roche and Esbriet will be studied in COVID-19 patients under a planned and randomized clinical trial in Tongji Hospital of Tongji Medical College, part of Huazhong Science and Technology University.
The potential of Dyadic International’s C1 gene expression platform to express gene sequences and targets developed into monoclonal antibodies and rVaccine will be explored by the Israeli Institute for Biological Research. A day earlier, Cocrystal Pharma agreed to license norovirus from Kansas State University Research Foundation and proprietary broad-spectrum antiviral compounds for COVID-19.
On January 28, AbCellera and its partners, including researchers at the National Institute of Allergy and Infectious Diseases (NIAID) announced that they will use its pandemic response platform to develop field-ready medical countermeasures within 60 days of isolation of an unknown viral pathogen.
This list will keep growing in the coming weeks as governments, global health agencies, and drug developers are stubborn to find a solution against the SARS-CoV-2 virus.
AbbVie
AbbVie’s Kaletra® which is also marketed as Aluvia is an HIV-1 protease inhibitor in combination with other antiretroviral agents used in the treatment of HIV-1 infection. AbbVie announced on January 27 that China’s National Health Commission has authorized Kaletra for the treatment of pneumonia caused by SARS-CoV-2. As an experimental option to contain the outbreak, AbbVie donated RMB 10 million ($1.4 million) of Kaletra to Chinese authorities. Three confirmed cases of COVID-19 were recovered after taking Kaletra, as per the announcement made by the Health Commission of Henan Province on January 31. Until now, 20 confirmed cases of COVID-19 tested negative after taking Kaletra, according to Ascletis Pharma.
AIM ImmunoTech
The Ampligen® (rintatolimod), an immune modulator for severe chronic fatigue syndrome is developed by AIM Immunotech. On February 27, AIM Immunotech announced that it is collaborating with ChinaGoAbroad, an advisory group for cross border dealings with China to negotiate with China’s government to market Ampligen in China as a prophylactic/early-onset therapeutic against COVID-19. In 2019, AIM had attained FDA authorization to market Ampligen in Argentina to treat severe chronic fatigue syndrome.
Altimmune
Altimmune designed a single-dose, intranasal vaccine to provide systemic immunity, based on Altimmune’s proprietary platform vaccine technology. It’s the technology used in developing NasoVAX, the company’s perspective influenza vaccine currently under clinical trials. On February 28, the company announced that they have completed the design and synthesis of the vaccine. The clinical trials of the vaccine will begin by August.
APEIRON Biologics
The APEIRON’s APN01 is a recombinant human angiotensin-converting enzyme 2 (rhACE2) invented for the treatment of acute respiratory distress syndrome, pulmonary arterial hypertension, and acute lung injury. A pilot investigator-initiated clinical trial of APN01 was launched in China on February 26 to assess its potential in treating the COVID-19 patients. The clinical trial will be carried out in 24 patients for seven days to obtain preliminary data on safety and on the impact of rhACE2 on physiologic, biological, and clinical outcomes.
Ascletis Pharma
Asclitis has introduced HIV protease inhibitors like ASC09 and ritonavir; Ganovo® (danoprevir) plus ritonavir; ritonavir and oseltamivir; ASC09 and oseltamivir for the treatment of patients diagnosed with COVID-19. On February 26, they claimed that patients with COVID-19 were discharged from the Ninth Hospital of Nanchang following the treatment with its combination therapy Ganovo® (danoprevir) plus ritonavir. Ascletis is actively assisting medical researchers and medical institutions for the clinical trial of a combination of Ascletis’ ritonavir and ASC09 for COVID-19. The company is hoping to include ASC09 and ritonavir combination into the national emergency channel.
Bayer and several Chinese manufacturers
Bayer’s Resochin is a chloroquine phosphate, a quinoline compound with anti-inflammatory and antimalarial properties. In 1947, Resochin was discovered by Bayer to treat malaria. The drug showed fairly good efficacy in clinical trials over 10 hospitals in China’s Hunan Province, south China’s Guangdong Province, and Beijing. On February 4, a team of scientists reported in Cell Research that “ Chloroquine and remdesivir were “highly effective in the control of 2019-nCoV infection in vitro”. Eight Chinese companies accelerated the manufacturing and supply of the drug after it was included in the latest treatment guidelines for COVID-19 pneumonia by China’s National Health Commission.
Beijing Staidson Biopharma and InflaRx
Chinese authorities approved clinical trials of their IFX-1, an Anti-C5a monoclonal antibody as a COVID-19 treatment in February.
Biocryst
Galidesivir (BCX4430) is a nucleoside RNA polymerase inhibitor developed by Biocryst to prevent the replication process of the virus inside cells. The drug exhibited broad-spectrum activity in vitro against more than 20 RNA viruses in viral disease and coronavirus families that include togaviruses, bunyaviruses, filoviruses, paramyxoviruses, arenaviruses, and flaviviruses.
BioXyTran
BioXyTran’s BXT-25 is an anti-necrosis drug whose glycopolymers structure consists of hybrid molecules integrating a proprietary polymer chemical structure and a Hemoglobin molecule. When the blood flow is blocked, BXT-25 is designed to carry oxygen to tissues. BioXyTran is partnering with several other international companies to develop BXT-25 for treating Acute Respiratory Distress Syndrome (ARDS) prominent in end-stage COVID-19 patients. The company will use MDX Life Sciences’ MDX Viewer to assess the safety and efficacy of the drug, as the drug molecule is 5,000 times smaller than red blood cells.
Celularity and Sorrento Therapeutics
To expand the therapeutic usage of Allogeneic, off-the-shelf, placental-derived Natural Killer (NK) cell therapy CYNK-001 to COVID-19, Celularity and Sorrento launched their collaboration on January 30. They agreed to assess the efficiency of CYNK-001 as a potential therapy for COVID-19. Sorrento Therapeutics granted its cGMP cell therapy manufacturing facilities in San Diego to supplement Celularity’s new cGMP facility in Sorrento. The companies are in contact with local Chinese experts and leading scientists to discuss logistics requirements and clinical validation to fast-track CYNK-001 in China.
Chugai Pharmaceutical and Zhejiang Hisun Pharmaceutical
Tocilizumab by Chugai Pharmaceutical and Zhejiang Hisun Pharmaceutical is a humanized mAb targeting interleukin-6. The First Affiliated Hospital of the University of Science and Technology of China has registered a clinical trial of Tocilizumab in 94 patients.
The University of Queensland And CSL
University of Queensland and CSL have developed an unspecified vaccine based on MF59, a subsidiary Seqirus’ proprietary adjuvant technology. CSL will donate its MF59 and technical expertise to the University of Queensland to develop the vaccine. The viral protein they are developing using the molecular clamp technology will be tested using the adjuvant. CSL will also donate RMB 1 million ($143,000) to the Red Cross in China as support to contain the epidemic.
CureVac
CureVac developed an mRNA-based vaccine using the mRNA development platform. The public-private Coalition for Epidemic Preparedness Innovations (CEPI) partnered with CureVac to develop a coronavirus vaccine. CEPI will provide $8.3 million as additional funding to expedite clinical tests, manufacturing, and development. CEPI CEO Richard Hatchett said that they expect the vaccine to be ready for clinical testing in a few months.
CytoDyn
CytoDyn’s humanized IgG4 monoclonal antibody called Leronlimab (PRO 140) is a potential candidate for the treatment of COVID-19. The drug is a CCR5 antagonist with many therapeutic implications. On March 5, CytoDyn will provide an update about its plans to file an IND and Phase II clinical trials in FDA as they are planning to evaluate leronlimab as a coronavirus treatment. Longen China Group and CytoDyn will begin evaluating the potential of leronlimab in the treatment of cancer as well as COVID-19. The drug has completed its nine clinical trials in 800 people successfully. As a highly active antiretroviral combination therapy (HAART) for metastatic triple-negative breast cancer patients and HIV-infected patients, Leronlimumab has the FDA’s fast-track status.
Fujifilm Holdings and Zhejiang Hisun Pharmaceutical
Favipiravir is marketed by Fujifilm as Avigan and by Hisun in China as Favilavir. It is a broad-spectrum antiviral agent designed to potently and selectively inhibit RNA viruses’ RNA-dependent RNA polymerase (RdRp). The drug was previously used to treat Ebola patients in Guinea and Japan had approved Avigan for novel or re-emergent influenza. Avigan, developed by Fujifilm-owned Toyama Chemical was recommended by Japan’s Health Minister Katsunobu Kato for the treatment of COVID-19 after the dosages appeared effective in mild and asymptomatic patients. Hisun’s version of the drug was approved for an investigational treatment for SARS-CoV-2 in an upcoming clinical trial in China
Generex Biotechnology
Generex Biotechnology’s Ii-Key peptide vaccine is based on Generex’s Ii-Key immune system activation technology platform. Generex has received a contract from Biology Institute of Shandong Academy of Sciences, Beijing Zhonghua Investment Fund Management Co. Ltd., Sinotek-Advocates International Industry Development (Shenzhen) Co. Ltd., and the China Technology Exchange to develop the Ii-key vaccine. Generex will receive $1 million upfront to initiate project work in the U.S, payment by the Chinese consortium for all costs and expenses related to the development of a COVID-19 vaccine, a 20% royalty on each dose of vaccine produced and a $5 million licensing fee for the Ii-Key technology.
Gilead Sciences
The clinical trial of Gilead Sciences’ nucleotide prodrug Remdesivir (GS-5734) will be done on COVID-19 patients at the University of Nebraska Medical Center in Omaha. Members of the Washington State 2019-nCoV Case Investigation Team reported in a case study published in The New England Journal of Medicine that the drug showed no adverse events in the first American confirmed to be infected with SARS-CoV-2. Following the National Medical Products Administration, China’s approval of applications by the China-Japan Friendship Hospital and the Chinese Academy of Medical Sciences to conduct the studies, China began the clinical studies for Gilead Sciences’ remdesivir. A team of researchers reported in the journal of Cell Research that Remdesivir and chloroquine phosphate were “highly effective in the control of 2019-nCoV infection in vitro”.
GlaxoSmithKline and Clover Biopharmaceuticals
GSK’s COVID-19 S-Trimer is a protein-based coronavirus vaccine. GSK will provide its pandemic adjuvant system to Clover to further evaluate S-Trimer in preclinical studies. The companies have a partnership whose value is not revealed. As Clover has one of the largest in-house, commercial-scale cGMP biomanufacturing capabilities in China, Clover would be able to scale up and manufacture large quantities of coronavirus vaccine.
iBio and Beijing CC-Pharming
iBio and Beijing CC-Pharming developed a plant-derived Vaccine that is to be manufactured using iBio’s FastPharming System™. The companies revealed their plans to develop and test a COVID-19 vaccine, combining the vaccine R&D experience, including work on the MERS-coronavirus in the rapid design of manufacturing processes for biopharmaceutical production in plant-based expression systems. Product candidates for production at iBio’s FastPharming Manufacturing Facility could be generated through the research.
ImmunoPrecise Antibodies
ImmunoPrecise Antibodies plans to develop Vaccines and coronavirus-neutralizing antibodies using ImmunoPrecise’s proprietary discovery platforms and ImmunoPrecise subsidiary Talem Therapeutics’ access to the transgenic animal platform OmniAb® for direct generation of human antibodies. ImmunoPrecise announced on February 20, its commitment to developing treatments for COVID-19 and designation of Ilse Roodink, Ph.D., chairwoman of Talem’s scientific committee, as its Coronavirus Global Project Leader.
Incyte and Shanghai Hengrui Pharmaceuticals
Thymosin and Camrelizumab are Humanized monoclonal antibodies targeting a 5-Da polypeptide hormone secreted by the thymus gland called PD-1 (Camrelizumab). Wuhan Jinyintan Hospital and Southeast University registered the combination treatment for clinical trials.
Innovation Pharmaceuticals
For the coronavirus vaccine & treatment, Brilacidin developed by Innovation Pharmaceuticals is a defensin mimetic in Phase II development in oral muscositis in Head and Neck Cancer patients. To study Brilacidin as a potential novel treatment for COVID-19, Innovation submitted a Material Transfer Agreement with an unidentified “leading U.S.-based virology laboratory”. Innovation will accelerate the research and development of Brilacidin through government grants, pharmaceutical partnerships, and academic collaborations once the test results are positive. The company also submitted a preliminary summary to the Biomedical Advanced Research and Development Authority (BARDA) about Brilacidin’s potential to treat COVID-19.
Inovio Pharmaceuticals and Beijing Advaccine Biotechnology
The development of INO-4800 as a coronavirus vaccine & treatment by Inovio Pharmaceuticals will be assisted by Beijing Advaccine Biotechnology’s expertise to run a Phase 1 trial in China. The company has launched preclinical testing for clinical product manufacturing and will develop INO-4800 through Phase I testing in the U.S. The Coalition for Epidemic Preparedness Innovations (CEPI) will fund the development of INO-4800 with $9 million grant.
Janssen Pharmaceutical Cos. (Johnson & Johnson)
The coronavirus vaccine & treatment by Janssen includes Prezcobix™ (darunavir and cobicistat) and a vaccine to be developed with BARDA. Prezcobix is an HIV protease inhibitor. To support efforts in finding a solution against COVID-19, around 300 boxes of Prezcobix was donated to the Shanghai Public Health Clinical Center and Zhongnan Hospital of Wuhan University on January 29. For laboratory-based investigations, 50 more boxes are given to the Chinese Center for Disease Control and Prevention. Shanghai Public Health Clinical Center has Prezcobix understudy in a trial (NCT04252274), another Chinese trial (ChiCTR2000029541) is assessing Precobix or the lopinavir-ritonavir combination combined with thymosin a1.
On February 11, to develop a vaccine candidate for SARS-CoV-2, an existing collaboration with the Biomedical Advanced Research and Development Authority (BARDA) was expanded by Janssen separately. They agreed to share the costs of R and D and are working towards speeding up the investigational vaccine into clinical trials. to accelerate the discovery of potential COVID-19 treatments and to screen its library of antiviral molecules, Janssen said it is also working closely with global partners.
LineaRx (Applied DNA Sciences) and Takis Biotech
The treatment involves a Linear DNA vaccine, which is designed to induce antibodies that can neutralize COVID-19 and it is to be based on PCR-produced linear DNA. On February 7, LineaRx, a majority-owned subsidiary of Applied DNA Sciences of Stony Brook, NY, and Rome-based Takis Biotech said that to develop the preclinical vaccine using PCR-based DNA manufacturing technology, they have formed a joint venture. The companies said that there has been no commercial partner identified to take the coronavirus vaccine to the market. In this technology, the absence of any bacterial contaminants and the effectiveness of the vaccine gene without insertion into the patient’s genome, the powerful immunogenicity proved in a prior linear DNA vaccine, the simplicity of design, the purity of the DNA, the absence of antibiotics and their resistance genes, and the speed of production serves as the advantages of their technology.
Moderna
The treatment mRNA-1273, a novel lipid nanoparticle (LNP)-encapsulated mRNA vaccine is against a prefusion stabilized form of the Spike (S) protein present in the coronavirus. For using it in a planned Phase I study in the U.S., the first batch of mRNA-1273 to the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) was shipped by Moderna on February 24. Evaluating the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults is the primary aim of the Phase I open-label, dose-ranging trial study (NCT04283461), which had yet to recruit patients at the deadline. Investigators at the NIAID Vaccine Research Center (VRC) and Moderna collaborated to design the vaccine.
NanoViricides
NanoViricides developed an antiviral therapy based on the company’s novel nanomedicines platform which acts as a broad-spectrum virus-binding ligand to trap the viruses. On January 30, NanoViricides announced that they have found some lead candidates in its chemical library while developing COVID-19 treatment. The company claimed that the ligand can bind to the spike protein of SARS-CoV like the way it binds to cognate receptor ACE2. The technology is based on copying the human cell receptor to make ligands that can bind to nanomicelle, forming a nanoviricide. When a virus encounters a nanoviricide, the nanomicelle polymer will fuse with the virus’s lipid envelope.
At the company’s BSL-2 virology laboratory in Shelton, CT, campus, they have started to test the potential ligand candidates in cell cultures against low threat coronaviruses. To identify an effective drug candidate and advance its COVID-19 program, NanoViricides is working on developing collaborations.
Novavax
The Vaccine candidate is yet to be selected. To generate antigens derived from the coronavirus spike (S) protein, the vaccines designed to apply the company’s proprietary recombinant protein nanoparticle technology platform. To improve immune responses, Novavax is hoping to use its proprietary saponin-based Matrix-M™ adjuvant with coronavirus vaccine candidates. On February 26, Stanley C. Erck, the President, and the CEO said, “The COVID-19 vaccine candidate is now well-positioned to advance the to Phase I clinical testing in May or June.”
Pharmstandard
The treatment involves the drug known as Arbidol (umifenovir), a membrane fusion inhibitor that was originally developed for the treatment of influenza. Arbidol is being assessed by Pharmstandard in clinical trials as a monotherapy and also in combinations which include Bromhexine Hydrochloride, carrimycin, ritonavir, lopinavir, Ascletis Pharma’s ASC09, and AbbVie’s Kaletra. ClinicalTrials.gov listed five trials including Arbidol. Various Chinese hospitals are investigating the combination therapies and China’s Ruijin Hospital is conducting the monotherapy trial.
Q Biomed and Mannin Research
They are developing drugs to treat vascular diseases in people infected with SARS-CoV. In COVID-19 and other infectious diseases, endothelial dysfunction and vascular leakage are seen. An adjunct treatment for this, which is designed to target the activation of the Angiopoietin-Tie2 signaling pathway is to be developed based on the lead platform of research partner Mannin Research. Mannin Research and Biomed announced their partnership on February 4th. For the advancement of Mannin’s novel therapeutics, including drugs and biologics that reduce endothelial dysfunction and loss of endothelial barrier integrity, the German state of Saxony awarded the company approximately a US $7.7 million grant in September 2019.
Regeneron Pharmaceuticals
The treatment involves a combination of neutralizing monoclonal antibodies, REGN3048 and REGN 3051. Part of the company’s VelociSuite™ technologies, a monoclonal antibody discovery platform called VelocImmune® was leveraged. To develop multiple monoclonal antibodies that, individually or in combination could be used to treat new treatments, the Biomedical Advanced Research and Development Authority (BARDA) said it was expanding upon an earlier partnership agreement with Regeneron on February 4. Last year, the combination completed a Phase I trial (NCT03301090) in MERS-CoV.
Sanofi
The treatment involves a vaccine that is still unnamed. Sanofi’s recombinant DNA platform enabled the development of the vaccine. The platform is designed to generate an exact genetic match to the viral surface proteins. The vaccine that contains a large amount of the coronavirus antigen can stimulate the immune system to combat the virus. This will be done by combining the DNA sequence encoding the antigen into the DNA of the baculovirus expression platform. Through a collaboration with the Biomedical Advanced Research and Development Authority (BARDA), Sanofi aims to accelerate the development of a COVID-19 vaccine. On February 18, the company said that to this vaccine, its previous development work for a SARS vaccine will be applied by its Sanofi Pasteur vaccines global business unit. Sanofi said that the SARS vaccine candidate afforded partial protection and was immunogenic as assessed in animal challenged models. Sanofi stated that the earlier work by Protein Sciences, acquired by Sanofi in 2017 is providing a head start in expediting a COVID-19 vaccine.
Tonix Pharmaceuticals Holding
Their coronavirus vaccine & treatment involves a live modified horsepox virus vaccine percutaneous administration, TNX-1800. As a vaccine treatment for COVID-19, on February 26, Tonix said it has partnered with Southern Research to develop TNX-1800 as the treatment. TNX-1800 is under development as monkeypox preventing vaccine and as potential smallpox preventing vaccine for the U.S. strategic national stockpile.
Vaxart
Their treatment involves a vaccine based on proprietary VAAST™ Platform and it is an oral recombinant vaccine administered by tablet. Based on the published genome of the 2019 COVID-19 (SARS-nCoV-2), Vaxart plans to generate the vaccine candidates. Then, based on their ability to generate both systemic and mucosal immune responses, they will be evaluated in preclinical models.
Vir Biotechnology and WuXi Biologics
Their coronavirus vaccine & treatment include human monoclonal antibodies, which are not yet made known publicly. From patients who had survived SARS (Severe Acute Respiratory Syndrome) infection, human antibodies that are shown to bind to SARS-Cov-2 are isolated. To advance and produce human monoclonal antibodies as potentials treatments for Covid-19, a development and manufacturing collaboration with WuXi Biologics was announced by Vir Biotechnology on February 25. The company’s antibody platform has been previously used to identify and develop antibodies for pathogens including malaria, influenza A, hepatitis B virus, Ebola (mAb114, currently in use in the Democratic Republic of Congo) and others. The same platform was used to discover the antibodies. Vir will have the right to commercialize therapies in all markets worldwide and WuXi Biologics will have the right to commercialize therapies in Greater China if the antibodies receive regulatory approvals.
Author: Namitha Thampi & Prathibha HC
Editor’s Note: Coronavirus Vaccine & Treatment, Coronavirus Vaccine & Treatment, Coronavirus Vaccine & Treatment, Coronavirus Vaccine & Treatment, coronavirus vaccine & treatment
