Candidate: LAM-002 (apilimod)
Type: Selective first-in-class, oral PIKfyve kinase inhibitor being developed in B-cell non-Hodgkin lymphoma and amyotrophic lateral sclerosis/frontotemporal dementia
Status: AI Therapeutics co-founder Jonathan Rothberg, PhD, told GEN the company is preparing INDs for submission to the FDA, with the goal of launching clinical trials of LAM-002 in COVID-19 in the second quarter. He citing new data that he said showed the drug was effective in cell assays in inhibiting the entry of SARS-CoV-2 through its first-in-class molecular mechanism. SAM-002 can also be combined with other antiviral drugs, which typically target other molecular mechanisms, like viral replication. AI is looking to combine SAM-002 with Gilead Sciences’ Remdesivir, said Rothberg, recipient of the 2013 National Medal of Technology and Innovation in Engineering for pioneering inventions and commercialization of next generation DNA sequencing technologies.
AI is collaborating with Yale University Medical School (clinical studies), and Zhejiang University (nonclinical). AI Therapeutics and collaborators have shown that in cell cultures, LAM-002 was effective alone and lowered the level of SARS-CoV-2 virus even more when combined with Gilead Sciences’ Remdesivir. “We have 50,000 pills ready to go, we have a drug that has been shown to be safe in 800 patients, and we just made a commitment for 110,000 more pills and material for 5 Million more,” Rothberg added.
Candidate: Ampligen® (rintatolimod)
Type: Immune modulator indicated for severe chronic fatigue syndrome
Status: AIM ImmunoTech said April 6 it entered into a Material Transfer and Research Agreement (MTA) with Shenzhen Smoore Technology to research in China the efficacy of Smoore’s vaping device using Ampligen, to enable inhalation of the drug deep into the lungs at the first signs of COVID-19.
In March, the company said it was in talks with regulators in the Netherlands, where Ampligen was recently used to treat pancreatic cancer patients, to explore expedited preclinical and clinical trials of Ampligen. Protocols for those trials are in final stages of development. AIM ImmunoTech also said it was actively seeking investigators and sites for clinical trials—and disclosed talks with a potential partner in Argentina, GP-Pharm, to advance Ampligen in COVID-19. The drug is approved in Argentina to treat myalgic encephalomyelitis/chronic fatigue syndrome.
AIM ImmunoTech has stated in a prospectus that it partnered with ChinaGoAbroad, a matchmaking and advisory service for cross-border deals involving China, to facilitate the entry of Ampligen into China for use as a prophylactic/early-onset therapeutic against COVID-19. AIM ImmunoTech also said Japan’s National Institute of Infectious Diseases (NIID) will study Ampligen as a potential treatment for COVID-1, through a study to be conducted at NIID and the University of Tokyo.
The company filed three provisional patent applications with the U.S. Patent and Trademark Office in January.
AlloVir and Baylor College of Medicine
Candidates: T-cell immunotherapies
Type: Allogeneic, off-the-shelf, virus specific T-cell therapy designed to restore natural T-cell immunity to fight off viral infections and diseases in immunocompromised patients, including recipients of stem cell and solid organ transplants
Status: Allovir said March 23 it is expanding its R&D collaboration with Baylor College of Medicine to include the discovery and development of allogeneic, off-the-shelf, virus specific T-cell therapies to combat SARS-CoV-2. The company aims to develop a therapy for multiple coronaviruses—including SARS-CoV and MERS-CoV—that can be used as a standalone treatment or incorporated into its multi-respiratory virus therapy candidate, ALVR106. The allogenic, off-the-shelf multi-specific T cell (VST) is being developed as a treatment for respiratory syncytial virus (RSV), influenza, parainfluenza virus (PIV), and human metapneumovirus (HMPV).
Altimmune and University of Alabama at Birmingham (UAB)
Candidate: AdCOVID ●
Type: Single-dose, intranasal vaccine designed to provide systemic immunity. Altimmune based the vaccine on proprietary platform technology that was applied in developing NasoVAX™, the company’s influenza vaccine candidate that showed positive Phase IIa results.
Status: Altimmune said March 30 it will partner with UAB to develop AdCOVID. The company said it is preparing for immunogenicity studies and manufacture of Phase I clinical trial material. Initially, Altimmune will work with UAB investigators on preclinical animal studies and characterization of the vaccine immunogenicity with the goal of enabling a Phase I trial in the third quarter.
On February 28, Altimmune said it completed the design and synthesis of the vaccine, and was “actively engaged in discussions with a number of potential partners.” Six UAB labs will work with Altimmune on the urgent collaboration, the University said.
Candidate: DAS181 ●
Type: Recombinant sialidase with broad antiviral properties for the treatment of severe COVID-19
Status: Ansun on April 2 reported positive preliminary data from an investigator-initiated trial of DAS181 (NCT04324489), conducted in collaboration with the Renmin Hospital of Wuhan University. The study evaluated a 10-day treatment regimen of nebulized DAS181 administered to four patients with severe bilateral viral pneumonia and hypoxemia.
In the study’s first 14 days, the first two patients no longer required supplemental oxygen, and showed stabilized vital signs, increased oxygen saturation, and resolution of infiltrates on chest CT scans, according to Zuojiong Gong, MD, PhD, and Ke Hu, MD, the study’s principal investigators at Renmin Hospital. They added: “The third patient, who had been a persistent SARS-CoV-2 carrier for more than 33 days, was completely virus-free before the end of the 10-day DAS181 regimen and met all discharge criteria, and the fourth is currently undergoing treatment and showing positive trends.”
Baylor College of Medicine
Candidate: Vaccines against COVID-19 ●
Types: Recombinant protein-based vaccine consisting of the receptor binding domain (RBD) of the spike protein of the coronavirus, designed to bind to receptors found deep in the host lung tissue.
Status: Peter J. Hoetz, MD, PhD, professor and dean of the National School of Tropical Medicine at Baylor College of Medicine (BCM), told China’s state news agency Xinhua on March 17 that his group at BCM’s Texas Children’s Hospital Center for Vaccine Development was working to develop a vaccine in collaboration with U.S. institutions that included the University of Texas Medical Branch, and the New York Blood Center, as well as the Virology Center at Fudan University in Shanghai.
The RBD for SARS has already been manufactured for clinical use, BCM said, and additional preclinical tests are being conducted to advance it into clinical trials to determine if it is safe, sufficiently protective, or cross-reactive against COVID-19. The Baylor College of Medicine teams are also developing the RBD from COVID-19.
Brii Biosciences, Tsinghua University, and Third People’s Hospital of Shenzhen
Candidates: “Multiple” monoclonal antibodies to prevent and treat COVID-19 ●
Type: Fully human neutralizing monoclonal antibodies from patients in China who have recovered from COVID-19
Status: Brii Bio joined Tsinghua University and Third People’s Hospital of Shenzhen on March 31 to announce a partnership and license agreement to discover, develop, manufacture and commercialize fully human neutralizing monoclonal antibodies against COVID-19. The collaboration aims to achieve an accelerated six-month timeline from the selection of a lead development candidate to first-in-human clinical trials, with potential for additional timeline acceleration, the partners said.
The partners also cited research by Linqi Zhang at Tsinghua University and Professor Zheng Zhang at Third People’s Hospital of Shenzhen, in a preprint published March 26 in bioRxiv. The researchers characterized antibody responses in eight COVID-19 patients and isolated 206 monoclonal antibodies specific to the SARS-CoV-2 receptor-binding domain. Of the antibodies with potential therapeutic potential against SARS-CoV-2, the most potent were P2C-1F11 and P2B-2F6.
British American Tobacco (Kentucky BioProcessing)
Candidate: Vaccine ●
Type: Vaccine based on BAT’s proprietary, fast-growing tobacco plant technology
Status: British American Tobacco’s Kentucky biotech subsidiary, Kentucky BioProcessing (KBP), said April 1 it has developed a potential COVID-19 vaccine that is in preclinical testing. Subject to finding partners and gaining government support, KBP said, it could manufacture between 1 and 3 million doses of the vaccine per week, starting in June. Work on the COVID-19 vaccine project will be carried out on a not-for-profit basis, according to KBP, which is a commercial entity.
KBP said it recently cloned a portion of COVID-19’s genetic sequence which led to the development of a potential antigen. The antigen was inserted into tobacco plants for reproduction and, once the plants were harvested, the antigen was then purified, and is now undergoing preclinical testing.
Type: Potent and selective small molecule CRAC channel inhibitor designed to prevent CRAC channel overactivation,
Status: CalciMedica on April 9 said it received a “Study May Proceed” letter from the FDA allowing it to study CM4620-IE in patients with severe COVID-19 pneumonia who are at risk for progression to acute respiratory distress syndrome (ARDS).
The company said it plans to enroll 60 patients with severe COVID-19 pneumonia in an open-label Phase II clinical study comparing 40 patients dosed with CM4620-IE plus standard of care to 20 patients assigned to standard of care alone. The first patients are being enrolled at Regions Hospital in St. Paul, MN, with additional patients are expected to be enrolled within the next week at Henry Ford Hospital in Detroit. Additional study sites are being evaluated.
Candidate: CAP-1002 ●
Type: Cardiac cell therapy consisting of allogeneic cardiosphere-derived cells. The cells are designed to function by releasing exosomes that are taken up largely by macrophages and T-cells and begin a cycle of repair.
Status: Capricor on April 3 said it has begun providing CAP-1002 to patients with advanced COVID-19 under the compassionate use pathway. Two patients were treated last week at “a leading healthcare center” in Los Angeles, with additional patients planned in coming weeks. Capricor cited previously published preclinical data showing that CAP-1002 mitigated the release of anti-inflammatory cytokines as well as macrophage activation in a number of models of inflammation including sepsis and autoimmune diseases.
Capricor added that it has submitted an expanded-access IND application to the FDA, seeking to investigate using CAP-1002 in certain COVID-19 patients. The application is under review.
Candidate: Ligand Antigen Epitope Presentation System (LEAPS) peptides
Type: Immunotherapy based on CEL-SCI’s patented LEAPS peptide platform technology, directed towards antigens within the NP protein of COVID-19 that elicit cytolytic T cell responses. Such responses attack the virus infected cellular “factories” within the infected host in order to eliminate the source of virus and help subdue the infection, CEL-SCI reasons. LEAPS peptides use conserved regions of coronavirus proteins to stimulate protective cell mediated T cell responses and reduce viral load.
Status: CEL-SCI on March 23 said it signed a collaboration agreement with the University of Georgia’s Center for Vaccines and Immunology to develop a LEAPS COVID-19 immunotherapy designed to treat patients at highest risk of dying from COVID-19. The collaboration will commence with pre-clinical studies based on the experiments previously conducted with LEAPS immunotherapy in collaboration with the National Institutes for Allergies and Infectious Diseases (NIAID) against another respiratory virus, H1N1, involved in the 2009 H1N1 flu pandemic.
The proposed LEAPS peptides for the COVID-19 study are directed towards antigens within the NP protein of SARS-Cov-2 virus that elicit cytolytic T cell responses. Unlike the viral glycoprotein “spike” antigens which are important for antibody-based vaccines, these NP-antigens are less variable between viral strains and less likely to change in response to antibodies elicited by prior infection or other vaccines, according to CEL-SCI. Cytolytic T cell responses attack the virus infected cellular “factories” within the infected host in order to eliminate the source of virus and help subdue the infection.
Also in March, CEL-SCI said it will develop an immunotherapy to treat COVID-19 and other diseases for which disease associated antigenic peptide(s) sequences have already been identified—including several other infectious diseases, some types of cancer, allergic asthma and allergy, select CNS diseases such as Alzheimer’s, and autoimmune diseases such as rheumatoid arthritis.
According to CEL-SCI, LEAPS has shown in several animal models the ability to design antigen-specific immunotherapeutic peptides that preferentially direct the immune response to a cellular, humoral (antibody) or mixed response and are also capable of enhancing important T-regulatory (Treg) responses. CEL-SCI has been awarded a $1.5 million grant by the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases toward IND-enabling studies of a LEAPS-based treatment in arthritis.
Candidate: Antiviral treatment targeting COVID-19 ●
Type: Monoclonal antibody to be selected
Status: Celltrion Group said April 3 it had begun the second phase of development for an antiviral treatment, in which it will partner with the Korea Centers for Disease Control and Prevention (KCDC) to screen antibodies to find the ones most effective in neutralizing SARS-CoV-2. The company last month secured 300 different types of antibodies that bind to the antigen last month during the first phase, creating a library of antibodies using the blood of recovered patients in South Korea.
Celltrion said it anticipates the candidate screening for the therapeutic monoclonal antibody will be complete by mid-April, sooner than originally expected. Upon candidate selection, “We will roll out mass production of the therapeutic antibody treatment, with a view to starting human trials this July,” Ki-Sung Kwon, Head of Celltrion’s R&D Unit, said in a statement.
In addition, Celltrion aims to launch a rapid self-testing diagnostic kit that could provide results within 15-20 minutes. The South Korean biologics developer has been selected as a preferred developer for a monoclonal antibody project to treat and prevent COVID-19 by KCDC. Celltrion also plans to develop a ‘super antibody’ candidate that can attach and neutralize multiple coronavirus related strains, including those causing COVID-19 and SARS.
Clover Biopharmaceuticals and Dynavax Technologies
Candidate: Vaccine to prevent COVID-19 ●
Type: Combination of Clover’s protein-based coronavirus vaccine candidate (COVID-19 S-Trimer), plus Dynavax’s proprietary toll-like receptor 9 (TLR9) agonist adjuvant CpG 1018
Status: Dynavax and Clover on March 24 said they launched a research collaboration to develop a vaccine candidate to prevent COVID-19. Clover agreed to advance the evaluation of COVID-19 S-Trimer in preclinical studies. The companies said Clover could rapidly scale-up and produce large-quantities of a new coronavirus vaccine since it has one of the largest in-house, commercial-scale cGMP biomanufacturing capabilities in China.
Clover said it applied its patented Trimer-Tag© technology to design the viral spike (S)-protein construct and complete its gene synthesis once the genomic DNA sequence of SARS-CoV-2 became public in late January.
Cocrystal and Kansas State University Research Foundation
Candidates: Broad-spectrum antiviral compounds ●
Type: Protease inhibitors
Status: Cocrystal on March 6 said it was “aggressively” pursuing the development of novel antiviral compounds to treat Coronavirus infections using its established proprietary drug discovery platform. The company is leveraging patent rights and antiviral compounds it has licensed from Kansas State University Research Foundation (“KSURF”) to treat Coronavirus as well as Norovirus, an agreement announced in February. Cocrystal said its primary goal was to advance its program into preclinical development, and pursue collaborations as the program progressed through clinical phases.
CSL Behring and SAB Biotherapeutics
Type: High-potency immunotherapy delivering human polyclonal antibodies targeted to SARS-CoV-2, generated from SAB’s proprietary DiversitAb™ platform
Status: CSL Behring and SAB Biotherapeutics said April 8 they will partner to develop SAB-185, which they said is expected to be ready for clinical evaluation as early as summer 2020.
CSL Behring has provided seed funding to offset some of SAB’s initial development costs, while SAB earlier this year secured approximately $7.2 million in funding from the Biomedical Advanced Research and Development Authority (BARDA) through an interagency agreement with the Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO – CBRND). That funding will support SAB efforts to complete manufacturing and preclinical studies. CSL Behring has agreed to commit clinical, regulatory, manufacturing and supply chain expertise and resources to deliver the therapeutic to the market as soon as possible, on terms to be agreed with SAB.
Earlier this year, the companies agreed to apply DiversitAB technology as a new source for human immunoglobulin G (IgG), and the potential for new therapies to treat challenging autoimmune, infectious and idiopathic diseases.
Candidate: Cell therapy targeting COVID-19
Type: Mesenchymal stem cell (MSC) based treatments
Status: Cynata and CEO Ross Macdonald have discussed the company’s therapeutic approach in a March 11 statement and recent interviews. That approach uses MSC to treat complications of COVID-19 such as sepsis, pneumonia and acute respiratory distress syndrome (ARDS). The company said it has achieved positive preclinical data for MSC therapies in sepsis and lung disease, and is collaborating with the Critical Care Research Group at Prince Charles Hospital in Brisbane, Australia, to investigate in an animal model the utility of Cymerus MSCs as a treatment for ARDS.
Cynata says the potential of MSCs in treating the consequences of COVID-19 is underpinned by a study published March 13 in Aging and Disease, concluding that the intravenous transplantation of MSCs was “safe and effective for treatment” in seven enrolled patients with COVID-19 pneumonia in Beijing. Pulmonary function and symptoms of all seven patients significantly improved in two days after MSC transplantation, while two patients with common pneumonia and one severe pneumonia patient recovered and were discharged 10 days after treatment.
Candidates: COVID-HIG and COVID-EIG ●
Types: Human polyclonal hyperimmune with antibodies to SARS-CoV-2 (COVID-HIG) for severe hospitalized patients and protection for at-risk individuals; Equine-derived polyclonal hyperimmune with antibodies to SARS-CoV-2 (COVID-EIG) for severe hospitalized patients
Status: Emergent Biosolutions said March 11 it began development of COVID-HIG and COVID-EIG using its hyperimmune platforms. Hyperimmunes are polyclonal antibody therapeutics derived from plasma that leverage the immune response in humans or animals and can provide immediate protection from infection. Emergent said it has initiated plasma collection efforts for both human and equine platforms, with a goal of manufacturing clinical material within the next four to five months in anticipation of beginning a clinical study as early as the third quarter.
Candidate: ENU200 ●
Type: Repurposed, patent-pending, oral antiviral drug previously approved by FDA
Status: Ennaid said April 2 it is advancing development of ENU200 to treat the up to 80% of asymptomatic, mild to moderate cases of COVID-19 viral infections. Ennaid said in-silico modeling conducted by the company has shown that ENU200 delivers specific antiviral activity against two SARS-CoV-2 proteins, S glycoprotein and Mpro. Ennaid reasons that the simultaneous blockage may result in enhanced antiviral activity that could successfully and broadly treat COVID-19 and other coronaviruses.
Ennaid said it is in talks with the FDA and other regulatory agencies worldwide on its planned Phase III in-home, self-dosing clinical trial, which would assess ENU200 in patients with asymptomatic, mild to moderate coronavirus infections. The trials would be monitored through the iClickCare® secure clinical reporting software service.
eTheRNA, EpiVax, Nexelis, REPROCELL, and CEV
Candidate: mRNA vaccine against SARS-CoV-2 ●●
Type: Intranasal vaccine integrating eTheRNA’s Trimix technology, an mRNA-based vaccine adjuvant that stimulates dendritic cells into activating a strong CD4 and CD8 T cell response; a combination of T cell epitopes from the virus on a single mRNA construct, using an in-silico epitope prediction and design approach from EpiVax to identify the target; and an intranasal vaccine delivery platform using a nasal atomizer and a proprietary formulation that delivers the mRNA to the nasal mucosa and optimizes expression.
eTheRNA said a formulation candidate is being repurposed for clinical use in collaboration with REPROCELL.
Status: eTheRNA said March 24 that it has started preclinical development of an mRNA vaccine against SARS-CoV-2 that is intended primarily for high-risk populations such as healthcare workers and families of confirmed cases. It is also designed to be protective against future variations of the virus by targeting conserved epitopes from the whole CoV-2 genome.
eTheRNA said it has formed a consortium with EpiVax, Nexelis, REPROCELL and CEV to develop the vaccine and help accelerate progress towards clinical trials; patient enrolment is expected in early 2021. Chinese partners may join the consortium “in due course,” the company added.
The consortium’s approach selects conserved epitopes from the whole viral genome to create a vaccine that mounts a strong T cell-based response against these epitopes, which the partners reason offers a better chance to overcome viral variability.
ExpreS2ion Biotechnologies, AdaptVac, and partners
Candidate: Vaccine against COVID-19 ●
Type: Vaccine applying ExpreS2ion’s Drosophila S2 insect cell expression system, and AdaptVac’s capsid virus-like particle (cVLP) technology.
Status: ExpreS2ion said March 6 it is part of a consortium of vaccine developers and institutions that have been awarded an E2.7 million ($2.9 million) grant through the European Union’s Horizon 2020 funding program to support development of a COVID-19 vaccine candidate, including conducting a Phase I/IIa clinical trial. Joining ExpreS2ion as members of the consortium are AdaptVac, Leiden University Medical Center, Institute for Tropical Medicine (ITM) at University of Tübingen, University of Copenhagen, and Wageningen University.
The consortium aims to launch clinical investigations within 12 months, according to ExpreS2ion. The Danish developer of vaccines and diagnostics first announced its plan to develop a COVID-19 vaccine in February, saying it use Drosophila S2 to produce 2019-nCoV viral antigens in the company’s clinically validated cell lines, as well as in its HighMan-S2™ immunogenicity-enhancing cell line. The company said its goal was to produce the vaccine antigens and test these in mice to demonstrate immunogenicity, and through collaborations demonstrate efficacy in in vitro or animal models as they become available.
Fudan University, Shanghai JiaoTong University, and RNACure Biopharma
Candidate: Vaccine against COVID-19 ●
Type: mRNA vaccine employing two strategies: researchers have placed the most emphasis on formulating mRNAs that can instruct the host to produce virus-like particles (VLPs) with morphological and structural features similar to those of native COVID-19 viruses and activate immune responses. The other approach uses mRNA to express the receptor-binding domain of the spike protein of COVID-19 to induce neutralizing-antibodies in the human body.
Status: Fudan University on March 7 announced the partnership, led by Fudan’s Prof. Lin Jinzhong, PhD. Researchers have formulated an mRNA cocktail containing three genes of COVID-19, which produce VLPs when used to co-transfect human cells— “the first time the world has witnessed modified mRNAs that can synthesize VLPs,” according to Fudan.
Generex Biotechnology (NuGenerex Immuno-Oncology) and EpiVax
Candidate: Ii-Key peptide vaccine ●
Type: Vaccine based on Generex’s Ii-Key immune system modulation technology platform
Status: Generex on March 19 said it has been in talks with the Biomedical Advanced Research and Development Authority (BARDA) and the U.S. Departments of Veterans Affairs and Health and Human Services, as well as with authorities in Canada, Greece, Iceland, Indonesia, Italy, Philippines, Romania, Saudi Arabia, and the U.K. for licensing Ii-Key-SARS-2 peptide vaccines as well as new, patented immunotherapy technology allowing those countries co-ownership of the Intellectual Property in their territories.
A week earlier, Generex said it would spin out its NuGenerex Immuno-Oncology (NGIO) subsidiary into a separate public company focused on advancing Ii-Key peptide vaccines into development to treat and prevent COVID-19 and other infectious diseases, as well as cancer, with partners in the U.S. and China. Generex filed a Form 10 Registration Statement for NGIO, to be effective in 60 days.
Earlier, Generex said it will use EpiVax’s computational tools to predict epitopes that can be used to generate peptide vaccines against SARS-CoV-2 using li-Key technology. The companies reached agreement after EpiVax identified a number of hotspots in the amino acid sequences of SARS-CoV-2 proteins.
Using epitopes predicted by EpiVax, Generex agreed to manufacture a series of synthetic amino acid peptides that mimic the epitopes of the virus and send them to Chinse researchers for testing in blood samples from patients who have recovered from COVID-19. The research team plans to select the best Ii-Key hybrid peptides to create a commercially viable vaccine that can proceed to human testing, Generex said.
According to the company, NGIO’s Ii-Key antigenic peptides have been shown to supercharge the immune system up to 100 times more than peptides alone.
Generex said in February it received a contract from the China Technology Exchange, Beijing Zhonghua Investment Fund Management Co. Ltd., Biology Institute of Shandong Academy of Sciences, and Sinotek-Advocates International Industry Development (Shenzhen) Co. Ltd. to develop a Ii-key vaccine. Generex said it would receive $1 million upfront to initiate project work in the U.S., a $5 million licensing fee for the Ii-Key technology, payment by the Chinese consortium for all costs and expenses related to the development of a COVID-19 vaccine, and a 20% royalty on each dose of vaccine produced.
GeoVax Labs and BravoVax
Candidates: Vaccine for prevention/control of COVID-19 ●
Type: Vaccine based on GeoVax’s GV-MVA-VLPTM vaccine platform
Status: GeoVax said March 18 that the companies completed three vaccine candidates after making rapid progress with design, construction and in vitro characterizations. The companies will narrow down the candidates to the one that shows the best safety, immunogenicity and protective efficacy in upcoming animal studies. GeoVax and BravoVax aim to advance a vaccine candidate to human clinical trials before year’s end, GeoVax President and CEO David Dodd stated.
GeoVax said it was in talks with, and submitted applications to, the Biomedical Advanced Research and Development Authority (BARDA) and other U.S. and international funding agencies. The company noted that BARDA has $3.5 billion available toward supporting the manufacturing, production and purchase of vaccines, therapeutics, and diagnostics under the $2 trillion Coronavirus Aid, Relief, and Economic Security Act (CARES ACT), signed into law by President Donald Trump on March 27.
GeoVax disclosed its intent to collaborate with BravoVax, a vaccine developer in Wuhan, China, to develop a COVID-19 vaccine in January.
German Primate Center-Leibniz Institute for Primate Research, University of Aarhus, and partner institutions
Candidate: Camostat mesylate
Type: Inhibitor of the serine protease TMPRSS2. The drug is approved in Japan and South Korea for use in pancreatic inflammation.
Status: University of Aarhus on March 25 disclosed via ClinicalTrials.gov plans for the Phase I/II CamoCO-19 trial (NCT04321096). The estimated 180-patient, placebo-controlled randomized clinical trial is designed to assess camostat mesilate as a potential treatment for COVID-19. The study’s estimated primary completion date is December 31, 2020.
The trial was launched less than a month after a research team led by investigators at the German Primate Center reported in the journal Cell that they tested SARS-CoV-2 isolated from a patient, and found that camostat mesilate blocked entry of the virus into lung cells. “Our results suggest that camostat mesilate might also protect against COVID-19,” stated lead author Markus Hoffmann, PhD, of the Primate Center.
GlaxoSmithKline (GSK), CEPI, and University of Queensland
Candidate: Vaccine to prevent SARS-CoV-2 ●
Type: Vaccine based on UQ “molecular clamp” technology, using GSK’s vaccine adjuvant platform
Status: GSK and the Coalition for Epidemic Preparedness Innovations (CEPI) said February 3 they would partner to develop a vaccine for SARS-CoV-2. CEPI agreed to coordinate engagements between GSK and CEPI-funded entities interested in combining their vaccine platforms with GSK’s adjuvant technology against SARS-CoV-2—starting with the University of Queensland, which is partnering with CEPI to develop its “molecular clamp” vaccine platform, in which a recombinant subunit vaccine of SARS-CoV-2 S protein is locked in prefusion conformation by polypeptide moiety.
Last month, GSK identified University of Queensland as one of five partner companies and research groups worldwide with which GSK is collaborating on COVID-19 vaccines using GSK’s vaccine adjuvant technology. GSK said it expected data to be reported from the collaborations over the next three months.
Candidate: Vaccine to protect against COVID-19 ●
Type: Fully-deleted, helper virus-independent adenovirus-based vector vaccine based on the company’s GreVac™ Plug-And-Play Technology
Status: Greffex on March 11 said it was prepared to advance its vaccine candidate into animal testing, with a commitment to distributing its vaccine for free to other countries upon approval. Two days earlier, Greffex CEO John Price told Fox News Channel’s “America’s Newsroom” broadcast that his company aimed to get its vaccine approved and available to patients by year’s end.
Last year, Greffex was awarded an $18.9 million contract from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), toward developing its GreVac™ Plug-And-Play Technology to expedite the production of vaccine candidates for biodefense and emerging infectious diseases.
Greffex says it has developed the world’s first universal vaccine platform that delivers unprecedented time-to-market, cost efficiency, efficacy, and safety by using proprietary clean viral vectors. The company has a pipeline of 12 vaccines that includes candidates for influenza, MERS-CoV, anthrax, Ebola, tetravalent Dengue, and Zika.
Grifols, BARDA, and FDA
Candidate: Anti-SARS-CoV-2 hyperimmune globulin therapy
Type: Plasma from convalescent COVID-19 patients, processed into a hyperimmune globulin
Status: Grifols on March 25 said it entered into a formal collaboration with the Biomedical Advanced Research Development Authority (BARDA), the FDA and other federal public health agencies to support preclinical and clinical studies to determine if anti-SARS-CoV-2 hyperimmune globulin therapy can successfully be used to treat COVID-19 disease.
Grifols said it will volunteer its expertise and resources by using its network of FDA-approved plasma donor centers; testing and qualifying donors in conjunction with other health agencies; processing plasma into hyperimmune globulin at a Clayton, NC, facility; and support studies to determine whether the treatment can be a viable treatment for COVID-19 and future emerging infectious diseases.
Hoth Therapeutics and Voltron Therapeutics (HaloVax)
Candidate: Vaccines to prevent, intercept or treat COVID-19 ●
Type: Vaccines to be based upon VaxCelerate, a self-assembling vaccine platform exclusively licensed by Voltron from the Vaccine and Immunotherapy Center at Massachusetts General Hospital (MGH).
Status: Hoth and Voltron subsidiary HaloVax said April 2 they entered into a Sponsored Research Agreement with the Vaccine and Immunotherapy Center (VIC) of Massachusetts General Hospital to co-develop a new vaccine designed to protect patients at risk of COVID-19 infection, applying the Self-Assembling Vaccine (SAV) platform developed by the VIC and licensed exclusively to Voltron. The vaccine is expected to enter animal testing within the next 30 days, the companies said.
On March 27, Hoth and HaloVax said they agreed to jointly develop a salf-assembling vaccine to develop a vaccine designed to protect patients at risk COVID-19. The companies said the technology initially showed proof of concept in Lassa Fever, with support from the U.S. Department of Defense (DoD).
Four days earlier, Hoth and Voltron said they formed HaloVax, a joint venture, to begin preclinical studies for COVID-19 vaccine candidates with support from MGH. VaxCelerate—which consists of a fixed immune adjuvant and a variable immune target and offers several potential advantages over other compounds in combination therapy. In infectious applications, it allows rapid development against viruses and other pathogens. The vaccine focuses on both DNA and internal/external mutated proteins providing the immune system with more potential targets to attack.
iBio, TAMUS, and Beijing CC-Pharming
Candidate: IBIO-200, vaccine for preventing SARS-CoV-2 infection ●
Type: Plant-derived vaccine SARS-CoV-2 Virus-Like Particle (VLP)-based constructs manufactured using iBio’s FastPharming System™, designed to produce the nanoparticles in, and purify them from, plants.
Status: iBio said April 9 the Infectious Disease Research Institute (IDRI) will support preclinical development and provide clinical trial oversight for iBio’s IBIO-200 vaccine development program for COVID-19. iBio and IDRI also agreed to establish a separate, additional agreement within the next 60 days if the company opts to include one of IDRI’s novel adjuvants in the program.
In March, iBio said it advanced iBIO-200 to immunization studies at Texas A&M University System (TAMUS) laboratories, under a Master Joint Development Agreement established between iBio and TAMUS in 2016. The partners seek to optimize a combination of VLP and adjuvant to advance to human clinical trials. iBio has developed two types of VLPs, glycosylated and non-glycosylated, as options for development.
iBio said it created its proprietary VLP candidates in just a few weeks using FastPharming, then deployed the VLP platform to deliver VLPs for further development just weeks after designing the biologics. On March 18, iBio announced creation of the constructs and the filing seven days earlier of four provisional U.S. patent applications supporting the platform and other technologies for treating or preventing SARS-CoV-2 infections.
In February, iBio and Beijing CC-Pharming disclosed plans to develop and test a COVID-19 vaccine, combining the vaccine R&D experience—including work on the MERS-coronavirus—by CC-Pharming Chairman and CSO Kevin Wang, PhD, and iBio VP Upstream Bioprocessing Sylvain Marcel, PhD, in rapid design of manufacturing processes for biopharmaceutical production in plant-based expression systems. If successful, the research will deliver product candidates for production at iBio’s FastPharming Manufacturing Facility, built in 2010 with funding from the Defense Advanced Research Projects Agency (DARPA). The facility is equipped with automated hydroponics and vertical farming systems designed to produce biologics, using a relative of the tobacco plant.
ImmunoPrecise Antibodies (IPA) and EVQLV
Candidates: Coronavirus-neutralizing antibodies ●
Type: PolyTope mAb Therapy™, a defined antibody combination designed to target multiple epitopes and mechanisms of viral evasion, and enabled by IPA’s discovery platforms (including B Cell Select™ and DeepDisplay™) and ImmunoPrecise subsidiary Talem Therapeutics’ access to the transgenic animal platform OmniAb® for direct generation of human antibodies.
Status: IPA said March 30 that its collaboration partner EVQLV submitted its first panel of candidate therapeutic antibody sequences, comprised of DNA sequences encoding for potentially therapeutic antibodies against SARS-CoV-2. The sequences were generated in less than one week using computational antibody design, which combines mathematics, statistics, and computer science to identify high-affinity antibodies.
IPA said it will review the antibody candidates, then select approximately 1,200 ideal candidates characterized and screened by EVQLV’s artificial intelligence, and validate the antibody candidates in vitro at IPA’s lab facilities. The companies said they will continue to work on additional panels of computationally generated sequence candidates against SARS-CoV-2.
Earlier last month, IPA announced its PolyTope mAb Therapy approach to developing a COVID-19 treatment. The company also spoke of potentially developing a vaccine for COVID-19, but has not announced any such effort since then.
On February 20, IPA said it designated Ilse Roodink, PhD, chairwoman of Talem’s scientific committee, as its Coronavirus Global Project Leader.
Imperial College London
Candidate: Vaccine to protect against COVID-19 ●
Type: Self-amplifying RNA vaccine, designed to inject new genetic code into a muscle, and instructing that muscle it to make a protein found on the surface of coronavirus, triggering a protective immune response.
Status: Imperial said March 20 that Prof. Robin Shattock, PhD, and colleagues developed a vaccine candidate within 14 days of getting the sequence from China. The researchers have been testing the vaccine on animals since February 10, and plan to move to clinical trials in the summer, Imperial said. “If all goes well it could be available sometime next year,” Shattock told the U.K.’s Channel 4 News.
InflaRx and Beijing Defengrei Biotechnology (BDB)
Candidate: IFX-1 ●
Type: Potentially first-in-class monoclonal anti-human complement factor C5a antibody in development for COVID-19 as well as inflammatory indications that include hidradenitis suppurativa, ANCA-associated vasculitis and Pyoderma Gangraenosum.
Status: InflaRx on March 31 said it had enrolled the first patient into a randomized clinical trial in the Netherlands that is investigating the safety and efficacy of IFX-1 in patients with severe COVID-19-induced pneumonia. The patient is being treated at Amsterdam University Medical Centers, with additional centers in Germany and potentially other European countries planned.
InflaRx said it had received from its Chinese licensee BDB initial positive human data from the first two patients treated in a Chinese clinical trial with BDB-001, an anti-C5a antibody produced in China by BDB from the IFX-1 cell line. That data is part of a larger study on the role of complement activation in COVID-19, made public through a preprint and not yet independently verified by InflaRx.
Candidate: Brilacidin ●●
Types: Vaccine and antiviral small molecule drug formulations against COVID-19 containing Defensin mimetic. The drug is in Phase II development in oral muscositis in head and neck cancer
Status: Innovation on April 1 announced a study published in the International Journal of Infectious Diseases that supported small molecule Brilacidin’s direct inhibition of SARS-CoV-2, based on testing on Vero cells at an undisclosed U.S. Regional Biocontainment Laboratory (RBL). At 16 hours post-infection, researchers observed a dose-dependent reduction in the SARS-CoV-2 infectious viral titers from Brilacidin treated cells as compared to the vehicle-alone control (Dimethyl sulfoxide or DMSO).
According to Innovation, the antiviral activity showed Brilacidin’s 3-in-1 therapeutic potential—antiviral, anti-inflammatory, antimicrobial—against COVID-19 and associated complications. In other indications, the company said, Brilacidin has shown the ability to inhibit interleukin-6 (IL-6) and other pro-inflammatory cytokines and chemokines identified as key drivers in worsening prognoses of COVID-19 patients.
Innovation said in March it was studying Brilacidin as a vaccine independent of the small molecule drug studies involving the RBL.In February, Innovation stated that it submitted a Material Transfer Agreement with a “leading U.S.-based virology laboratory” to study Brilacidin for SARS-CoV-2. If lab tests prove successful, Innovation said, it will expedite research and clinical development of Brilacidin “via pharmaceutical partnerships, academic collaborations and government grants.” Innovation has also submitted a preliminary summary of Brilacidin’s potential for treating coronavirus to the Biomedical Advanced Research and Development Authority (BARDA).
Institut Pasteur, Themis, and University of Pittsburgh
Candidate: Vaccine to treat COVID-19 ●
Type: Measles vector vaccine engineered to express SARS-CoV-2 proteins on its surface
Status: The Institut Pasteur leads a consortium that includes Themis and the University of Pittsburgh’s Center for Vaccine Research (CVR). The consortium has been awarded an initial $4.9 million by CEPI, the Coalition for Epidemic Preparedness Innovations. As a first step, CEPI funding will support the preclinical testing, initial manufacture of vaccine materials, and preparatory work for Phase I studies, CEPI said on March 19.
Pitt said CVR researchers expect to have a vaccine candidate ready for animal testing in Paris and Pittsburgh in April, to be complemented by development of an aerosol model of COVID-19 at CVR. By the end of the year, Pitt added, a total of 60 to 80 human volunteers in two sites in Europe will have been dosed with the vaccine. At the same time, Themis plans to generate a stockpile of the vaccine candidate in anticipation of a Phase II trial set to start early next year.
Candidate: Namilumab (IZN-101) ●
Type: Fully human monoclonal antibody therapy targeting granulocyte-macrophage colony stimulating factor (GM-CSF), in development for rheumatoid arthritis and ankylosing spondylitis
Status: Izana said April 6 it initiated a two-center compassionate use study of namilumab to treat patients with rapidly worsening COVID-19 before ICU admission and prior to ventilation. The study is being conducted in cooperation with the Humanitas research group, led by Prof. Carlo Selmi, MD, PhD, head of the Rheumatology and Clinical Immunology Unit at Humanitas Research Hospital and Associate Professor of Internal Medicine at Humanitas University.
Separately, Ergomed said it is providing support for namilumab’s clinical development program. The study will take place in Bergamo and Milan, Italy.
According to Izana, namilumab is a Phase III-ready treatment being studied under emergency access. Discussions focused on COVID-19 are in progress with global regulatory authorities, including in the U.K.
Janssen Pharmaceutical Cos. (J&J) and BARDA
Candidate: Antiviral treatment for COVID-19 ●
Type: To be determined
Status: J&J said March 30 that the company and the Biomedical Advanced Research and Development Authority (BARDA) will both provide unspecified additional funding intended to enable expansion of ongoing work to identify potential antiviral treatments against COVID-19.
Janssen plans to accelerate its ongoing work in screening compound libraries, including compounds from other pharmaceutical companies, with the goal of identifying potential treatments against the novel coronavirus. These antiviral screening efforts are being conducted in partnership with the Rega Institute for Medical Research (KU Leuven/University of Leuven), in Belgium.
Janssen and BARDA said in February that they have been working closely with global partners to screen Janssen’s library of antiviral molecules to accelerate the discovery of potential COVID-19 treatments.
Candidates: Antibodies targeting SARS-CoV-2 ●
Types: Antibodies from the blood plasma or serum of people who have recovered from COVID-19 infection.
Status: Johns Hopkins researchers Arturo Casadevall, MD, PhD, and Liise-anne Pirofski, MD, published a paper March 13 in The Journal of Clinical Investigation detailing their treatment approach to COVID-19: “Human convalescent serum is an option for prevention and treatment of COVID-19 disease that could be rapidly available when there are sufficient numbers of people who have recovered and can donate immunoglobulin-containing serum.” The Johns Hopkins Research Team has put initial funding toward Casadevall’s project, to purchase equipment and set up an operation in Baltimore. Casadevall and his team are working now with state and federal officials to try to secure more resources, according to Johns Hopkins.
Kleo Pharmaceuticals and Green Cross LabCell (GCLC)–65
Candidate: COVID-19-targeting allogeneic Natural Killer (NK) cell combination therapy
Type: Combination of Kleo’s first non-oncology application of its Antibody Recruiting Molecule (ARM™) and GCLC’s NK cells
Status: Kleo on March 31 said it had entered a research collaboration with GCLC to rapidly develop a COVID-19-targeting allogeneic NK cell combination therapy, combining Kleo’s next-gen fully synthetic bispecific compounds designed to emulate or enhance the activity of biologics with GCLC’s allogeneic, or “off-the-shelf” NK cell therapies.
Earlier this year, Kleo received approval from the FDA to proceed with an ARM/NK clinical trial assessing the combination cell therapy in newly diagnosed, multiple myeloma patients. The ARM in that trial targets the cell surface protein CD38 and uses autologous cytokine induced memory like (CIML) NK cells to kill tumor cells.
In the context of COVID-19, the partners said, ARM acts as a neutralizing antibody to block direct binding on the virus to human cells, then enlists immune effector cells to eliminate viral particles and/or infected cells. The ARM can produce a long-term vaccination effect by activating and expanding immune memory cells.
La Jolla Pharmaceutical
Candidate: GIAPREZA™ (angiotensin II)
Type: Vasoconstrictor approved by the FDA in 2017 and indicated to increase blood pressure in adults with septic or other distributive shock. The drug was approved by the European Commission in August 2019 for refractory hypotension in adults with septic or other distributive shock, but is not yet commercially available in Europe.
GIAPREZA is designed to mimic the body’s endogenous angiotensin II peptide, which is central to the renin-angiotensin-aldosterone system, which in turn regulates blood pressure.
Status: La Jolla has disclosed five instances where it agreed to providing GIAPREZA for emergency use in patients with septic shock due to COVID-19: University Hospital Münster in Germany (April 7), Royal Surrey County Hospital in Guildford, Surrey, UK (April 6), University Hospital Frankfurt in Germany (announced April 3), Guy’s and St Thomas’ NHS Foundation Trust in London (April 2), and Italy (March 13).
Candidate: Vaccine ●
Type: Vaccine providing a fully synthetic scaffold for mimicking T-cell receptor and antibody binding epitopes, which can be rapidly custom-tailored to new mutant forms of a virus
Status: Ligandal presented its approach for rapid vaccine prototyping on its website, stating that its synthetic scaffold can additionally serve as a targeting ligand mimicking viral entry to target diseased cells and tissues with therapeutic agents. These “mini viral scaffolds can be synthesized in hours, and rapidly scaled to 100kg+ scale to meet global needs, Ligandal stated.
“Our next steps will relate to synthesis and characterization of these scaffolds, as well as additional techniques for mapping known and predicted immune-epitopes onto variable domains of the scaffolds,” the company added.
Unlike recombinant and other approaches, Ligandal said, its vaccine approach needs to use fewer than 70 amino acids out of an approximately 1,200 amino acid spike protein in order to generate a predicted trifunctional scaffold for ACE2 binding and TCR/antibody recognition.
Candidates: Vaccine and antibody candidates ●●
Types: Virus-Like Particle (VLP) vaccine and antibodies against SARS-CoV-2 developed through the company’s plant-based technology platform in collaboration with Laval University’s Infectious Disease Research Centre headed by Gary Kobinger, PhD, whose lab developed a successful Ebola vaccine. That research is being funded in part by the Canadian Institutes for Health Research.
Status: The Government of Canada announced March 23 that Medicago was among companies set to receive an unspecified amount of funding from the $192 million available for new, large-scale projects under the new Strategic Innovation Fund COVID-19 funding stream—part of the government’s $1 billion COVID-19 Response Fund. Two days earlier, the Government of Quebec awarded C$7 million (about $5 million) toward the company’s vaccine development effort.
Medicago said March 12 it successfully produced a coronavirus VLP 20 days after obtaining the SARS-CoV-2 gene—the first step in developing a vaccine for COVID-19. The vaccine will undergo preclinical testing for safety and efficacy, followed by human trials anticipated to start by summer (July/August) 2020.
Candidate: MN-166 (ibudilast)
Type: First-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor (MIF) inhibitor and phosphodiesterase (PDE) -4 and -10 inhibitor
Status: MediciNova said April 8 it will initiate a clinical trial of MN-166 for acute respiratory distress syndrome (ARDS) caused by COVID-19. The study will be conducted by Yale’s Advanced Therapies Group. The lead principal investigator for the trial is Geoffrey Chupp, MD, professor of medicine (Pulmonology), director of the Yale Center for Asthma and Airway Disease and director of the Pulmonary Function Laboratory at Yale-New Haven Hospital.
Earlier human studies have shown significant reductions of serum MIF level after treatment with MN-166. It also attenuates activated glial cells, which play a major role in certain neurological conditions, MediciNova said. The company reasons that MN-166 could reduce the mortality of COVID-19 by limiting the hyperinflammation and ARDS associated with severe cases.
Candidate: Rebif® (interferon beta-1a)
Type: Interferon beta approved by the FDA for the treatment of relapsing forms of multiple sclerosis.
Status: Merck KGaA said March 19 it donated Rebif to the French Institut National de la Santé et de la Recherche Médicale (INSERM) following a request for use in a clinical trial. The trial (DisCoVeRy; 2020-000936-23 and NCT04315948)—sponsored by INSERM and launched March 11—is comparing Rebif to AbbVie’s Kaletra, Gilead Sciences’ Remdesivir, and Sanofi’s Plaquenil (hydroxychloroquine) in 3,100 patients.
Monash Biomedicine Discovery Institute (BDI) and Peter Doherty Institute of Infection and Immunity
Candidate: Ivermectin (marketed by Merck & Co. under the names Stromectol® and Mectizan®, but also available as a generic drug) ●
Type: Anti-parasitic drug approved by the FDA for Strongyloidiasis of the intestinal tract, and onchocerciasis (river blindness). Since 1987, Merck has committed to donating Mectizan—as much as needed, for as long as needed—with the goal of eliminating river blindness through the public-private partnership Mectizan Donation Program. The program was extended in 1998 to include lymphatic filariasis (LF).
Status: BDI and the Doherty Institute on April 3 published a preprint study in Antiviral Research showing that Ivermectin essentially stopped the SARS-CoV-2 virus growing in cell culture within 48 hours, and reduced viral RNA significantly at 24 hours. The in vitro study will be followed up with human clinical trials, the institutions said.
Candidate: Antiviral therapy based on company’s novel nanomedicines platform. ●
Type: Broad-spectrum virus-binding ligand: “It is like a ‘Venus-Fly-Trap’ for the virus,” says Anil R. Diwan, PhD, president and executive chairman.
Status: NanoVirocides on March 16 said it completed the synthesis of “a number of” nanoviricide drug candidates for cell culture testing a few weeks after identification of virus-binding ligands, a result of the company tapping into its inventory of novel custom chemicals, including a polymer backbone that was previously manufactured in multi-kilogram quantities.
NanoVirocides confirmed in January that it was developing a COVID-19 treatment, stating that it “already found some lead candidate ligands in its chemical library” that can bind to the SARS-CoV spike protein just as it binds to cognate receptor angiotensin converting enzyme type 2 (ACE2).
The company’s technology relies on copying the human cell-surface receptor to which the virus binds, and making ligands that chemically attach to a nanomicelle, to create a nanoviricide®. When a virus comes in contact with the nanoviricide, the nanomicelle polymer is designed to fuse with the virus lipid envelope. The company said it has started preparing for testing of potential candidates in cell cultures against “low-threat” coronaviruses, including ones that use the ACE2 receptor, in its own BSL-2 virology laboratory at its Shelton, CT, campus.
NanoViricides added that it is working on developing collaborations to advance its COVID-19 program should an effective drug candidate be identified. If initial work suggests a potential for developing a successful antiviral, NanoVirocides said in a Form 10-Q quarterly report filed February 24, it will pursue a license allowing use for coronaviruses from the license-holder of its technology TheraCour, whose 90% owner is NanoViroCides president and chairman Anil Diwan, PhD.
NanoVirocides also said it acquired and expanded two low-threat circulating coronaviruses in its BSL-certified virology lab, and has already expanded them to enable testing of drug candidates. One coronavirus, NL63, uses the same ACE2 receptor on human cells as SARS-CoV-2, although it does not cause a similarly severe disease in humans. If the test candidates show effectiveness in the cell culture studies against coronaviruses, the company reasons, that would provide a strong rationale for expecting they would be effective against SARS-CoV-2.
NanoVirocides added that it also successfully developed antiviral drug testing assays based on cell culture infection of low-threat coronaviruses in the BSL2 lab—a feat accomplished in a few weeks due to the expertise of senior virologist Brian Friedrich, PhD.
Neurimmune and Ethris
Candidate: Immunotherapy designed to produce inhaled mRNA-based antibodies directly in the lungs of COVID-19 patients ●●
Type: mRNA-encoded, neutralizing anti-SARS-CoV-2 antibodies administered by inhalation
Status: The companies on March 31 announced their COVID-19 collaboration, designed to combine Neurimmune’s expertise in developing human antibodies via its RTM™ Technology platform, based on high-throughput immunoglobulin sequence analyses from COVID-19 patients who have recovered from the disease with Ethris’ pulmonary SNIM®RNA therapeutics platform.
The first product candidate is expected to begin clinical testing in the fourth quarter, pending regulatory approval, Neurimmune and Ethris said. The companies have agreed to jointly conduct R&D activities while sharing costs and revenues resulting from the collaboration—and intend to begin manufacturing of the drug product for clinical trials this summer.
Novavax and Emergent Biosolutions
Candidate: NVX-CoV2373 ●
Type: Stable, prefusion protein made using Novavax’ proprietary nanoparticle technology, and incorporating its proprietary saponin-based Matrix-M™ adjuvant.
Status: Novavax on April 8 said it identified a COVID-19 vaccine candidate, and will initiate a first-in-human clinical trial in mid-May. The Phase I trial is a placebo-controlled observer blinded study of ~130 healthy adults and includes assessment of dosage amount and number of vaccinations. The trial is expected to begin in mid-May with preliminary immunogenicity and safety results in July.
The company said NVX-CoV2373 was shown to be highly immunogenic in animal models measuring spike protein-specific antibodies, antibodies that block the binding of the spike protein to the receptor, and wild-type virus neutralizing antibodies. High levels of spike protein-specific antibodies with ACE-2 human receptor binding domain blocking activity and SARS-CoV-2 wild-type virus neutralizing antibodies were also seen after a single immunization.
In March, Emergent disclosed it retained an option to allocate manufacturing capacity for an expanded COVID-19 program under an agreement with Novavax to provide “molecule-to-market” contract development and manufacturing (CDMO) services to produce Novavax’s NanoFlu™, its recombinant quadrivalent seasonal influenza vaccine candidate.
Earlier in March, Emergent announced similar services to support clinical development of Novavax’s COVID-19 vaccine candidate, saying March 10 it agreed to produce the vaccine candidate and had initiated work, anticipating the vaccine candidate will be used in a Phase I study within the next four months. In February, Novavax said it had produced and was assessing multiple nanoparticle vaccine candidates in animal models prior to identifying an optimal candidate for human testing.
Novoteris and Mallinckrodt
Candidate: Thiolanox®, a high-dose inhaled nitric oxide therapy for the treatment of patients infected with SARS-CoV-2
Type: Pharmaceutical nitric oxide gaseous formulation supplied via Mallinckrodt’s high-pressure cylinders at 5,000 ppm (0.5% v/v) nitric oxide gas for inhalation canisters.
Status: Novoteris and Mallinckrodt said April 1 that the Therapeutic Products Directorate of Health Canada cleared the companies’ joint pilot clinical trial to investigate Thiolanox in patients infected with SARS-CoV-2 at Vancouver Coastal Health Authority facilities. The study is designed to assess the safety and effectiveness of Thiolanox in treating COVID-19 and its associated lung complications. The companies said they expected to begin recruiting patients “in the coming days.”
Candidate: CORVax12 ●
Type: Prophylactic vaccine against COVID-19, consisting of OncoSec’s TAVO™ (interleukin-12 or “IL-12” plasmid), in combination with a DNA-encodable version of the SARS-CoV-2 spike or “S” glycoprotein
Status: OncoSec said April 6 that Providence Cancer Institute, part of Providence St. Joseph Health, submitted to the FDA an IND application and have designed a protocol for a Phase I clinical trial evaluating CORVax12 in healthy adult volunteers, using OncoSec’s next-generation, investigational APOLLO generator technology for the first time clinically.
CORVax12 combines OncoSec’s IL-12 plasmid TAVO with an immunogenic component of the SARS-CoV-2 virus recently developed by researchers at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and licensed non-exclusively to OncoSec.
Candidate: Immune-boosting microbiome therapeutic to help prevent and fight SARS-CoV-2
Type: Treatment designed to be taken at the onset of symptoms or with a vaccine or antiviral drug to mount an effective immune response with long-lasting immunity and boost the immune system of those exposed to the virus. The treatment is being developed as a general enhancer of the immune system “may be effective against mutations, seasonal flu and future pandemics,” Persephone says.
Status: Persephone on April 2 announced the development of the immune-boosting microbiome therapeutic, and a stool-based diagnostic, and is seeking partners for preclinical development or clinical trials. The company’s proprietary Decode.Design.Cure® technology platform is designed to collect and analyze gut microbiome samples from thousands of patients through its nationwide Poop For The Cure® campaign, using artificial intelligence and next-generation genome sequencing technologies.
Candidate: Aplidin® (plitidepsin)
Type: Anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. It specifically binds to the eEF1A2 and targets the non-canonical role of this protein, resulting in tumor cell death via apoptosis (programmed death).
Status: PharmaMar on April 2 said it it submitted its protocol for the Phase II APLICOV clinical trial of Aplidin to the Spanish Medicines and Healthcare Products Agency (AEMPS). The planned 160-patient trial would be a multicenter, randomized study in which two different doses of plitidepsin will be evaluated in hospitalized patients with COVID-19 pneumonia, to assess whether plitidepsin, administered intravenously for 5 days, reduces the proportion of patients who progress to Acute Respiratory Distress Syndrome (ARDS).
In March, PharmaMar announced the results of in vitro studies of plitidepsin in human coronavirus HCoV-229E, with a mechanism of multiplication and propagation that is very similar to that of SARS-CoV-2. The studies were carried out at the National Biotechnology Centre of the Spanish National Research Council (CSIC; Centro Nacional de Biotecnología). The studies confirmed that the therapeutic target of Aplidin, EF1A, is key to the multiplication and spread of the virus.
Candidate: PLX Cells for COVID-19
Type: “Off the shelf,” placenta-based allogeneic mesenchymal-like cells with immunomodulatory properties that induce the immune system’s natural regulatory T cells and M2 macrophages. Pluristem reasons PLX cells may prevent or reverse dangerous overactivation of the immune system by reducing the incidence and\or severity of COVID-19 pneumonia and pneumonitis.
Status: Pluristem on April 7 announced positive preliminary data from its compassionate use program treating seven patients suffering from acute respiratory failure and inflammatory complications associated with COVID-19 with PLX cells at three medical centers in Israel. Four of six patients who completed a one-week follow up showed improvement in respiratory parameters, of which three are in advanced stages of weaning from ventilators. One such patient showed no change, and one showed deterioration.
The company plans to apply to initiate a multinational regulated clinical trial program for the potential use of PLX cells in the treatment of patients suffering from complications associated with COVID-19.
In March, Pluristem said it had dosed three patients in two different Israeli hospitals under a compassionate use program for the treatment of COVID-19, as approved by the Israeli Ministry of Health. The company expects to enroll additional patients in Israel in coming days. Pluristem is studying the therapeutic effects of PLX cells through a collaboration with the BIH Center for Regenerative Therapy (BCRT) and the Berlin Center for Advanced Therapies (BeCAT) at Charite’ University of Medicine Berlin.
The company added that it is in talks with U.S. and European regulators to define its clinical strategy for COVID-19.
Candidates: Opaganib (Yeliva®, ABC294640) and RHB-107, in combination and individually
Types: Opaganib is a first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anticancer and anti-inflammatory activities, targeting multiple oncology, inflammatory and gastrointestinal indications. RHB-107 is a first-in-class, orally-administered inhibitor of S1 family of trypsin-like serine proteases with potential for use in multiple oncology, gastrointestinal and inflammatory indications.
Status: RedHill said April 13 the first two patients were treated with opaganib at “a leading hospital in Israel” under the company’s compassionate use program according to Israeli Ministry of Health guidelines, in addition to standard-of-care, which included hydroxychloroquine (HCQ) as background therapy. Preliminary findings from both patients, who suffered from moderate to severe acute respiratory symptoms related to SARS-CoV-2 infection, showed clinical improvement within days following the start of treatment with opaganib, RedHill said.
To date, both patients showed decreased supplemental oxygen requirements and decreased C-reactive protein (CRP) levels, and an increase in lymphocyte levels. One of the patients was released from the ICU within days of treatment initiation with opaganib.
RedHill said April 6 the first patient with a confirmed COVID-19 diagnosis had been dosed with opaganib at “a leading hospital in Israel.” Opaganib was administered under a compassionate use program in accordance with the Israeli Ministry of Health guidelines, with additional patients expected to be treated in the coming days.
Approximately 160 patients at three Italian hospitals will be treated with opaganib under an expanded access program (EAP) allowing immediate compassionate use of the drug, RedHill also said April 6.
RedHill said March 11 it was exploring opaganib and RHB-107 individually and in combination with hydroxychloroquine and other compounds as a COVID-19 treatment, based on preclinical data and literature indicating potential anti-viral activity. Opaganib was originally developed by Apogee Biotechnology, which received U.S. federal and state grants and contracts toward development. RedHill has licensed rights to RHB-107 from Heidelberg Pharma (formerly Wilex) worldwide except China, Taiwan, Macao, and Hong Kong.
Ridgeback Biotherapeutics and Drug Innovations at Emory (DRIVE)
Type: Oral broad-spectrum NHC-prodrug (Beta-D-N4 hydroxycytidine-5’-isopropyl ester), a highly potent ribonucleoside analog designed to inhibit replication of multiple RNA viruses including SARS-CoV2.
Status: Ridgeback and DRIVE, a not-for-profit biotechnology company wholly owned by Emory University, said April 7 the FDA approved DRIVE’s IND application to begin human clinical trials of EIDD-2801
Ridgeback and DRIVE announced their collaboration to rapidly advance EIDD-2801 into human trials in March. Ridgeback agreed to advance EIDD-2801 through clinical development and ensure that it is available during the current pandemic.
Under the collaboration, Ridgeback has exclusively licensed EIDD-2801, which has shown broad spectrum activity against influenza, SARS, MERS, chikungunya, and equine encephalitis. On March 20, Ralph Baric, PhD, at The University of North Carolina at Chapel Hill, and colleagues from there, Emery, Vanderbilt University Medical Center, and the U.S. Centers for Disease Control and Prevention posted a preprint of a study reporting that both prophylactic and therapeutic administration of EIDD-2801 in mice infected with SARS-CoV or MERS-CoV improved pulmonary function, and reduced virus titer and body weight loss.
“The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses,” Baric and colleagues concluded.
In addition to COVID-19, EIDD-2801 is being developed to treat seasonal and pandemic influenza under a contract awarded to Emory Institute for Drug Development by the National Institute of Allergy and Infectious Diseases (NIAID) and for Venezuelan and Eastern equine encephalitis virus (VEEV and EEEV) by the Defense Threat Reduction Agency (DTRA).
Candidate: Gimsilumab ●
Type: Fully human monoclonal antibody targeting granulocyte-macrophage colony stimulating factor (GM-CSF).
Status: On March 27, Roivant’s contract research organization Altasciences said it completed a Phase I trial (NCT04205851) of gimsilumab in patients with or at risk of developing acute respiratory distress syndrome (ARDS). Nine days earlier on March 18, Roivant said it had engaged with regulators in the U.S., Europe, and Asia to rapidly advance clinical development of gimsilumab to treat ARDS associated with SARS-CoV-2. Roivant cited research from Chinese patients showing that GM-CSF is a pro-inflammatory cytokine found to be up-regulated in the serum of COVID-19 patients.
According to Roivant, GM-CSF boosts the expression of pro-inflammatory cytokines such as TNF, IL-6, and IL-23, in addition to promoting the differentiation of Th1/17 cells and the polarization of macrophages to a M1-like phenotype. Gimsilumab has been tested in several non-clinical studies and two clinical studies, including the four-week, 36-patient Phase I study, which evaluated a subcutaneous formulation in healthy volunteers.
Roivant said it will prioritize trials of gimsilumab in patients with COVID-19 instead of a Phase II trial in a separate disease area which had been previously planned.
Candidate: STI-4398 (COVIDTRAP™), a vaccine to protect against SARS-CoV-2 infection ●
Type: ACE2 (angiotensin-converting enzyme 2)-Fc fusion protein (COVIDTRAP) designed to bind to the S1 domain of the spike protein of SARS-CoV-2. COVIDTRAP is a soluble recombinant fusion protein trap designed to block the SARS-CoV-2 virus from binding and infecting respiratory epithelial cells, which is expected to effectively interrupt the viral life cycle.
Status: Sorrento said March 20 it produced a preclinical batch of the STI-4398 (COVIDTRAP) protein, and anticipates completing enabling studies for an expedited IND filing “in the next few months.”
In vitro cell studies for SARS-CoV-2 virus infection and neutralization are expected to be conducted in the next few weeks in collaboration with “world-leading” coronavirus experts, Sorrento said. Sorrento scientists are in parallel working speedily to generate a stable CHO (Chinese Hamster Ovary) manufacturing cell line that would enable high-yield cGMP production of the COVIDTRAP fusion protein.
Late last month, Sorrento said it entered into a research testing agreement with The University of Texas Medical Branch at Galveston for preclinical testing of Sorrento’s COVID-19 therapeutic product candidates.
Candidate: STI-6991 to prevent SARS-CoV-2 infection ●
Type: I-CellTM COVID-19 “decoy” cellular vaccine made of replication-deficient human erythroleukemia K562 immune-training cells expressing membrane-bound S1 protein of the SARS-CoV-2 virus.
Status: Sorrento said March 25 it was developing STI-6991, and was in active discussions with the FDA’s Center for Biologics Evaluation and Research under IND#019724 concerning IND-enabling studies, CMC (chemistry, manufacturing and controls), clinical protocol and end-points for potential accelerated approval. Sorrento said intends to submit a full package for an IND filing that would enable human clinical trials to start “as soon as possible.”
Sorrento expects to use a replicating cell line (human erythroleukemia, K562) to incorporate SARS-CoV-2’s spike protein or its S1 domain onto the cellular membrane so that the viral antigen is presented on a decoy cell surface to elicit both T cell and B cell immunities.
Late last month, Sorrento said it entered into a research testing agreement with The University of Texas Medical Branch at Galveston for preclinical testing of Sorrento’s COVID-19 therapeutic product candidates.
Candidate: TAK-888 ●
Type: Anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG) a plasma derived-therapy designed to treat high-risk individuals with COVID-19.
Status: Takeda said March 4 it began development of TAK-888, part of the H-IG class of treatments that have previously shown effectiveness in treating severe acute viral respiratory infections. Such therapies are designed to concentrate pathogen-specific antibodies from plasma collected from recovered patients or vaccinated donors in the future.
Takeda said it had begun talks with health and regulatory agencies and healthcare partners in the U.S., Asia, and Europe to quickly advance its research into TAK-888. Those talks will include how to access plasma from people who have successfully recovered from COVID-19, or who have been vaccinated once a vaccine is developed, since these donors would have developed antibodies to the virus that could potentially prevent illness in COVID-19 patients, or at least mitigate its severity.
Takeda said it will initially produce the therapy in a segregated area within its manufacturing facility in Georgia, since the plasma needed for TAK-888 is unlikely to come from current plasma donors.
Ufovax (Scripps Research)
Candidate: Vaccine targeting SARS-CoV-2 ●●
Type: Nanoparticle vaccine based on one component self-assembling protein nanoparticle (1c-SApNP) platform technology invented by Jiang Zhu, PhD. The vaccine consists of self-assembling virus-like particles made from identical proteins that are synthesized through the insertion of a single plasmid encoding the relevant gene into a CHO or C1 (DYAI) host cell, followed by one-step expression and two subsequent purifications.
The vaccine prototype features SARS-CoV-2 protein spikes protruding from a protein nanoparticle scaffold.
Status: Ufovax, a Scripps Research spinout company, said March 23 it successfully extended its vaccine platform technology to a vaccine against SARS-CoV-2. The platform previously delivered promising vaccine candidates to address global health challenges such as HIV, hepatitis C vaccine, Ebola, and respiratory syncytial virus (RSV).
“We hope to soon begin initial tests to see whether our vaccine can induce an immune response against SARS-CoV-2 in animal models and eventually in clinical trials,” Zhu stated.
University Hospitals (UH), ARMS Pharmaceutical, and Case Western Reserve University
Candidate: ARMS-1 ●
Type: Oral spray antiviral applied before or during exposure to airborne pathogens.
Status: UH said April 2 it will lead the ARMS-I COVID Study, a clinical trial of ARMS Pharmaceutical’s ARMS-1. The trial will study ARMS-1 in UH caregivers, to assess whether the drug helps prevent airborne transmission of coronavirus and reduces the symptoms of healthcare providers who have tested positive for SARS-CoV-2. The randomized placebo-controlled crossover study is expected to begin within two weeks, according to Daniel I. Simon, MD, Chief Clinical & Scientific Officer and President, UH Cleveland Medical Center.
ARMS Pharmaceutical has articulated ARMS-1’s potential mechanism of action: A microbe-impermeable barrier is applied at the oropharynx, a gateway to the pathogenesis of viral upper respiratory infections, potentially blocking the ability for pathogens to reach mucosal tissue and begin the infection cycle. The barrier is infused with an antiviral which is believed to be resistant to antigenic drift and viral mutation which has the potential to kill pathogens that come into contact with the barrier, thus intensifying the effect of the barrier action
The Cleveland Foundation has authorized $1 million in emergency funding to support a significant portion of the clinical trial, using previously-restricted health-related research grant dollars.
University of Oxford and partners
Candidate: ChAdOx1 nCoV-19 ●
Type: Vaccine based on an adenovirus vaccine vector and the COVID-19 spike protein. After vaccination, the surface spike protein of the coronavirus is produced, which primes the immune system to attack the coronavirus if it later infects the body.
Status: University of Oxford’s Oxford Vaccine Group said March 27 it has started screening healthy volunteers (aged 18-55) for the upcoming COV001 trial (NCT04324606) assessing ChAdOx1 nCoV-19. The trial, a collaboration between the Group and the University’s Jenner Institute, is set to recruit up to 510 volunteers who will receive either the ChAdOx1 nCoV-19 vaccine or a control injection.
Oxford’s team is led by Professors Sarah Gilbert, PhD; Andrew Pollard, MBBS, PhD; Teresa Lambe, PhD; Sandy Douglas, DPhil; and Adrian Hill, DPhil, started work designing a vaccine on January 10. On March 23, Gilbert was awarded £2.2 million ($2.7 million) by the U.K. government toward the research, one of six COVID-19 research projects to receive a combined £20 million ($24.5 million).
Cobra Biologics said March 31 it was part of an Oxford-led consortium to rapidly develop, scale-up and produce ChAdOx1. Joining Cobra and the Jenner Institute are cGMP contract manufacturing organizations ADVENT and Halix, Pall Life Sciences, University of Oxford Clinical Biomanufacturing Facility, and the Vaccines Manufacturing and Innovation Centre.
Cobra said it is actively planning for a fast set-up phase to facilitate efficient production of a GMP working cell bank, then 200L GMP viral vaccine. Consortium partners expect to develop and manufacture the vaccine candidate in multiple batches, to support a 1 million dose scale batch size, by summer 2020.
University of Queensland (UQ), CEPI, CSL Behring and Dynavax
Candidate: Vaccine ●
Type: “Molecular clamp” vaccine; UQ has isclosed work toward a version using CSL subsidiary Seqirus’ proprietary adjuvant technology, MF59®, as well as a version using Dynavax’s toll-like receptor 9 (TLR9) agonist adjuvant, CpG 1018™
Status: UQ on March 22 announced pledges of A$10 million ($6 million) from the government of Queensland, and A$3 million ($1.8 million) from Australia’s national government, toward accelerating development of its preclinical “molecular clamp” vaccine against COVID-19 by six months.
The University said in February it achieved proof of concept showing the feasibility of using molecular clamp technology to engineer a vaccine candidate that could be more readily recognized by the immune system, triggering a protective immune response. Keith Chappell, PhD, told The Australian his team experimented with 250 different formulations before settling on a candidate vaccine virus. UQ plans to produce greater quantities of the vaccine to enable additional testing, then advance to investigational clinical testing after the middle of the year.
Dynavax in March disclosed plans to partner with UQ on a COVID-19 prevention vaccine applying CpG 1018, building on a partnership launched by UQ and the Coalition for Epidemic Preparedness Innovations (CEPI) in January 2019 to develop a “molecular clamp” vaccine platform against multiple viral pathogens. Earlier this year, CEPI requested UQ use its rapid response technology, which allows for rapid generation of new vaccines from a virus’s genetic sequence information, to develop a vaccine against COVID-19.
On March 26, Dynavax added that it would make CpG 1018 available to other vaccine developers through CEPI, with both partners agreeing to identify vaccine programs that could benefit from the adjuvant, then coordinate engagements with those programs. CpG 1018 is the adjuvant used in HEPLISAV-B® [Hepatitis B Vaccine (Recombinant), Adjuvanted], an adult hepatitis B vaccine marketed by Dynavax following FDA approval in 2017.
CSL said in February it will provide technical expertise and a donation of MF59 to the University of Queensland’s preclinical development program. The University will use the adjuvant to test the viral protein it is developing with its molecular clamp technology, CSL said. The company also committed a donation of RMB 1 million ($143,000) to the China Red Cross toward efforts to combat the epidemic.
University of Saskatchewan (USask), Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac)
Candidate: Vaccine to protect against SARS-CoV-2 ●
Type: Not specified
Status: USask on March 13 said VIDO-InterVac researchers had successfully grown SARS-Cov-2 in a cell culture, and were testing the vaccine candidate in animals. VIDO-InterVac said it was collaborating with several labs in and outside Canada, including the National Microbiology Laboratory in Winnipeg.
Volker Gerdts, DVM, director and CEO of VIDO-InterVac, said in a statement that resarchers hoped to have an indication by early April whether the vaccine generated at VIDO-InterVac can successfully protecting against SARS-coV-2. He anticipated another six months of testing, development and manufacturing would be needed before the vaccine would be ready for clinical testing.
VIDO-InterVac said it is working to build a pilot-scale manufacturing facility within its Level 3 containment facility. VIDO-InterVac received funding to start Phase 1 of the facility, but will need another C$10 million ($7 million) to fully establish the manufacturing facility to industry standards, Gerdts said.
University of Wisconsin-Madison, FluGen, and Bharat Biotech
Candidate: CoroFlu ●
Type: Intranasal vaccine for COVID-19 based on FluGen vaccine candidate M2SR, with production scale-up by Bharat
Status: UWMadison, FLuGen and Bharat said April 2 they had begun development and testing of CoroFlu, based on FluGen’s M2SR, a self-limiting version of the influenza virus that induces an immune response against the flu. M2SR was based on an invention by UWMadison virologists and FluGen co-founders Yoshihiro Kawaoka, PhD, and Gabriele Neumann, PhD, with Kawaoka’s lab planning to insert gene sequences from SARS-CoV-2 into M2SR so that the new vaccine will also induce immunity against the coronavirus.
The partners said they expect to refine the CoroFlu vaccine concept and carry out tests in animal models at UW–Madison over the next three to six months. Bharat Biotech of Hyderabad, India, will then begin production scale-up for safety and efficacy testing in humans. CoroFlu could be in human clinical trials by the fall of 2020, the partners added.
Vanderbilt University Medical Center (VUMC)
Candidates: Antibody-based treatments to protect people exposed to COVID-19. ●
Types: To be identified. Researchers plan to rapidly isolate B cells producing antibodies targeting specific viral proteins. The monoclonal antibodies will be studied to find those capable of neutralizing SARS-CoV-2.
Status: VUMC said March 23 its Vanderbilt Vaccine Center (VVC) is building a comprehensive “toolkit” designed to identify and analyze antibodies isolated from the blood of survivors for their ability to neutralize SARS-CoV-2. With corporate, academic, and government partners, VVC is analyzing the antibodies based on their ability to inhibit the virus, with plans to develop and manufacture the most promising lead antibodies and advance them into clinical study. “Our goal is to prepare antibodies for human clinical trials by this summer,” VVC director James Crowe, MD, stated.
VUMC said it working with numerous providers of tools, technology, and services, including Berkeley Lights (“Beacon” cell selection platform), STEMCELL Technologies (custom cell-type specific isolation reagents), Twist Biosciences (rapid silicon-based DNA synthesis of antibody gene sequences), and 10x Genomics (Chromium Single Cell Immune Profiling Solution).
Vaxart and Emergent BioSolutions
Candidates: Five vaccines based on proprietary VAAST™ Platform ●
Type: Oral recombinant vaccines administered by room temperature-stable tablet
Status: Vaxart on March 31 disclosed that it had produced five COVID-19 vaccine candidates for testing in its preclinical models. Each vaccine construct is based on a different coronavirus antigen combination, Vaxart said, adding that it expects to advance the best performing vaccine to manufacturing for clinical trials.
Earlier in March, Vaxart agreed to use the “molecule-to-market” contract development and manufacturing (CDMO) services of Emergent BioSolutions in preparation for cGMP production of a vaccine. Those development services have since started, with Emergent expected to produce bulk cGMP vaccine for use in a Phase I study that Vaxart said it expects to initiate early in the second half of 2020. Vaxart also said it was prioritizing development of the COVID-19 vaccine by putting several vaccine programs on hold, including its therapeutic HPV vaccine program and a norovirus vaccine program for which the company completed a successful Phase I study, and was actively seeking a development partner.
Emergent has said it will provide development services out of its Gaithersburg, MD location and manufacture drug substance at its Bayview facility in Baltimore, designated a Center for Innovation in Advanced Development and Manufacturing (CIADM) by the U.S. Department of Health and Human Services.
Vaxart disclosed plans in January to generate vaccine candidates based on the published genome of SARS-CoV-2, and evaluate them in preclinical models based on their ability to generate both mucosal and systemic immune responses. The company cited a study published in The Lancet Infectious Diseases, showing that the Vaxart oral H1 influenza tablet vaccine primarily protected against infection based on mucosal immunity, compared with the injectable flu vaccine that protected primarily through systemic immunity.
VBI Vaccines and National Research Council of Canada (NRC)
Candidate: Pan-coronavirus vaccine targeting COVID-19, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). ●
Type: Multivalent vaccine candidate based on VBI’s virus-like particle (eVLP) platform technology, and designed to co-express SARS-CoV-2, SARS-CoV, and MERS-CoV spike proteins on the same particle
Status: Cambridge, MA-based VBI Vaccines on March 31 announced its vaccine development collaboration with NRC, Canada’s largest federal research and development organization. The collaboration will combine VBI’s viral vaccine expertise, eVLP technology platform, and coronavirus antigens with the NRC’s COVID-19 antigens and assay development capabilities.
The NRC and VBI agreed to evaluate and select the optimal vaccine candidate. Following IND-enabling preclinical studies conducted at both the NRC’s core facilities and VBI’s research facility in Ottawa, ON, VBI said it believes clinical study materials could be available in the fourth quarter.
“We believe the trivalent construct could allow for the production of broadly reactive antibodies, which offer potential for protection from mutated strains of COVID-19 that may emerge over time,” stated Francisco Diaz-Mitoma, MD, PhD, VBI’s chief medical officer.
Candidate: GENOSYL® (nitric oxide) gas with GENOSYL DS delivery system
Type: Inhaled nitric oxide plus tankless delivery system
Status: VERO Biotech said March 24 that the first patient with COVID-19 infection complicating pulmonary hypertension has been treated with GENOSYL via the GENOSYL DS at home, under an emergency IND approved by the FDA. The patient was also treated with oxygen via nasal canula, and monitored remotely by clinicians. Two days later, VERO said the FDA granted the company “expanded access emergency use” allowing GENOSYL DS, to immediately be used for the treatment of cardiopulmonary symptoms associated with COVID-19.
Walter Reed Army Institute of Research and U.S. Army Medical Research Institute of Infectious Diseases
Candidates: Five vaccines to protect from COVID-19 ●
Types: Not specified
Status: Secretary of the Army Ryan D. McCarthy said March 19 that the U.S. Army Medical Research and Development Command and U.S. Army Medical Research Institute of Infectious Diseases were working to develop five separate COVID-19 vaccines. McCarthy said the Army had received an additional $900 million toward efforts to prevent, detect, and treat the disease.
Among the vaccine candidates is one that was already in preclinical development in animal models, Col. Wendy Sammons-Jackson, director of the Military Infectious Diseases Research Program under USAMRDC, told Stars and Stripes.
Xijing Hospital and Massachusetts General Hospital
Candidate: Inhaled nitric oxide (iNO) for treatment of mild/moderate COVID-19
Type: Inhaled nitric oxide as a supportive measure for COVID-19 patients with associated pulmonary complications based on formulations shown to have successfully treated patients with SARS-CoV, due to its genomic similarity to SARS-CoV-2
Status: Xijing and MGH have launched two Phase II trials assessing inhaled nitric oxide in patients with mild/moderate COVID-19 (NCT04290871, withdrawn March 24; and NCT04305457, recruiting patients). A day later, the nitric oxide delivery device developer Nu-Med Plus said it was closely monitoring the trials, and had talks with the FDA about bringing its products to market more quickly. Nu-Med has also had talks with the U.S. Department of Veterans Affairs about research opportunities related to iNO technology and COVID-19.