Candidate: Vaccine to prevent COVID-19 ●
Type: Not specified
Status: AJ Vaccines said March 6 it would develop a COVID-19 vaccine designed to use “the best possibly designed” antigens to mimic closely the authentic native structures of the virus. “The use of such technology is expected to induce the relevant immune responses and therefore protect against disease with a lower risk for side effects,” COO Jerome Cabannes stated.
Applied DNA Sciences and Takis Biotech
Candidate: Linear DNA vaccine ●
Type: To be based on PCR-produced linear DNA designed to induce antibodies that can neutralize SARS-CoV-2. Four preclinical vaccines have been designed based on the structure of the “Spike” protein, which enables uptake of the coronavirus by binding to specific receptors on the host cells.
Status: Applied DNA said March 24 that it filed a provisional patent application with the U.S. Patent and Trademark Office (USPTO) for its diagnostic assay under development for SARS-CoV-2—five days after announcing it had completed the design of the assay. The assay uses PCR-based detection of viral sequences that code for the Spike protein that is also the target of Applied DNA’s vaccine candidate partnered with Takis Biotech.
Rome-based Takis has won approval from the Italy’s Ministry of Health to begin a preclinical trial of Applied DNA’s COVID-19 vaccine candidate, with the first results expected to be available in April.
Applied DNA began large-scale production of the four vaccine candidates in March via the company’s proprietary PCR-based DNA (“LinearDNA”) manufacturing systems. “Within weeks of arrival we expect to immediately scale up PCR-based production of each vaccine candidate and ship them back to Takis who will determine each vaccine’s relative abilities to provoke an immune response in vaccinated mice” stated James A. Hayward, President and CEO of Applied DNA.
Applied’s majority-owned subsidiary LineaRx and Takis said in February they had formed a joint venture to develop the preclinical vaccine using PCR-based DNA manufacturing technology. The companies said advantages of their technology include the speed of production, the absence of antibiotics and their resistance genes, the purity of the DNA, the simplicity of design, the powerful immunogenicity proved in a prior linear DNA vaccine, the absence of any bacterial contaminants and the effectiveness of the vaccine gene without insertion into the patient’s genome.
Arcturus Therapeutics and Duke-NUS
Candidate: LUNAR-COV19 ●●
Type: Very low dose, potential single-shot, self-replicating mRNA vaccine devoid of viral material or co-adjuvants. The vaccine is based on its STARR™ (Self-Transcribing And Replicating RNA), which combines self-replicating RNA with LUNAR® (Lipid-enabled and Unlocked Nucleomonomer Agent modified RNA) lipid-mediated delivery system into a single solution to produce proteins inside the human body.
Status: Arcturus on April 9 announced plans to initiate a human clinical trial this summer for LUNAR-COV19. Under the guidance of the Singapore Health Sciences Authority (HSA), the trial plans to enroll up to 76 healthy volunteer adults including elderly individuals, with follow-up over several months to evaluate extent and duration of immune response. The initial GMP batch is to be delivered in June.
In March, Arcturus said its vaccine will incorporate the genetic correlation system developed by Duke-NUS Medical School in Singapore, designed to augment testing of vaccines by tracking genetic changes and their correlations. These gene expression changes can be measured within the first five days following vaccination and the data may also guide dose selection, Arcturus said.
Arcturus and Duke-NUS disclosed their partnership to produce a COVID-19 vaccine on March 4.
Candidate: Monoclonal antibodies to prevent COVID-19 disease. ●
Type: Coronavirus-neutralizing antibodies developed through the company’s program to use the Defense Advances Research Project Agency’s Pandemic Prevention Platform (P3).
Status: AstraZeneca said April 8 it is exploring three potential sources for antibodies against SARS CoV-2: Patients who have recovered from COVID-19, immunized humanized mice, and lab techniques such as phage display: “AstraZeneca is aiming for clinical evaluation in the next 3 to 5 months.”
AstraZeneca also disclosed collaborations with external partners: The Chinese Academy of Sciences, and Vanderbilt University Medical Center have provided genetic sequences for antibodies they have discovered against SARS2-CoV-2 for further in silico and in vitro assessment, while the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the University of Maryland School of Medicine are conducting preclinical safety and efficacy assessments of antibody candidates discovered through internal research.
The company said March 24 it will donate 9 million face masks for healthcare workers worldwide, with Italy receiving the first shipments.
Type: Portable inhaled nitric oxide system (iNO) for the treatment of COVID-19. INOpulse has generated positive top-line Phase II results in pulmonary hypertension associated with pulmonary fibrosis (PH-PF), with a pivotal Phase III trial planned.
Status: Bellerophon on April 8 said it submitted an IND to the FDA for clinical trials of INOpulse, with plans for an up-to-500 patient randomized, open-label study (PULSE-CVD19-001) for which the company has applied for funding to the NIH and the Biomedical Advanced Research and Development Authority (BARDA). Three COVID-19 patients have completed treatment with INOpulse under an emergency expanded access program while several other patients are now on the therapy.
On March 31, the company said it treated its first COVID-19-diagnosed patient diagnosed with INOpulse at the University of Miami School of Medicine, after the FDA granted the company emergency expanded access allowing immediate use of the inhaled nitric oxide system to treat COVID19 patients under the care and supervision of their physician.
Bellerophon noted that SARS-CoV-2 is approximately 82% identical to severe acute respiratory syndrome related coronavirus (SARS-CoV), the virus behind the 2003-04 global SARS outbreak. The company cited past studies showing that nitric oxide could benefit SARS-CoV patients by preventing viral replication, improving arterial oxygenation, reducing the need for ventilation support, and preventing the proliferation of lung infiltrates.
Candidate: Nanobody-based treatment
Type: Modified nanobody
Status: Beroni Group on April 3 said that its SARS-CoV-2 IgG/IgM Antibody Detection Kit received CE certification in Europe. The test, based on colloidal gold, is a rapid single-use immunochromatographic test intended for the qualitative detection of IgG and IgM protein from the SARS-CoV-2 virus in capillary “fingerstick” whole blood, plasma, and serum samples. The kit is designed to yield results in 10 minutes, and according to the company has a 97% accuracy rate.
Beroni said March 9 it was partnering with Tianjin University in China on cytological experiments set to begin for a nanobody-based COVID-19 treatment—to be followed by animal experiments, then clinical trials which are expected to occur in April. Beroni said it was in talks with “an international CRO/CDMO company with operations in the USA, Europe, and China” to use their research and manufacturing facilities to accelerate clinical trials for both the medical treatment and diagnostic kit.
Type: Novel oral small molecule T-cell co-stimulator
Status: BeyondSpring said March 11 it submitted a provisional U.S. patent application designed to protect BPI-002 for methods of treating viral infections, including COVID-19, when administered alone or in combination with a vaccine.
According to the company, BPI-002 can potentially activate the adaptive immune system (including CD4+ helper T cells and CD8+ cytotoxic T cells) to directly attack and kill virally infected cells, including RNA virus, such as those causing COVID-19. If combined with a vaccine including COVID-19 vaccine, BeyondSpring reasons, BPI-002 could function as an adjuvant to provide improved long-term humoral (B-cell dependent) protection against future viral infection.
Type: Recombinant human plasma gelsolin therapy based on intellectual property licensed from Harvard Medical School
Status: BioAegis on April 2 said it is submitting requests to the FDA and other regulators seeking to accelerate clinical trials of its lead product rhu-pGSN in severe infection, specifically severe community-acquired pneumonia (sCAP), including COVID-19, and has engaged “leading” infectious disease experts to advise the proof of concept clinical trial strategy. The company reasons that administering rhu-pGSN as an adjunct to standard-of-care measures could prevent or limit organ injury and death in patients with severe coronavirus infections.
BioAegis said plasma gelsolin has been tested in over 20 animal studies, as well as a recent phase Ib/IIa study in hospitalized community-acquired pneumonia patients with no adverse safety signals.
Candidates: Vaccine to emerge from three options in development ●
Type: mRNA vaccine based on previous pipelines for creation of mRNA-oncovaccines, an area where the company has specialized.
Status: Biocad said March 19 it was working to develop a COVID-19 vaccine, with the first animal studies scheduled for the end of April. Biocad disclosed that researchers from the Dongfang Hospital at Shanghai Tongji University and Chinese biotechnology company Stemirna have been working on the vaccine since the end of January, synthesizing matrix ribonucleic acid (mRNA) with several sequences of different antigens. The company said its vaccine can be manufactured in “less than five to six months” since it uses mRNA as opposed to recombinant proteins.
Candidate: Galidesivir (BCX4430) ●
Type: Nucleoside RNA polymerase inhibitor designed to disrupt the viral replication process
Status: BioCryst said April 9 it has begun enrolling patients into a randomized, double-blind, placebo-controlled clinical trial to assess the safety, clinical impact and antiviral effects of galidesivir in patients with COVID-19. The trial, which will study 24 hospitalized adults diagnosed with moderate to severe COVID-19, is being funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
On March 5, the company said it was in active dialogue with U.S. public health authorities about whether galidesivir could be useful among potential approaches to treat and prevent COVID-19. Galidesivir has shown broad-spectrum activity in vitro against more than 20 RNA viruses in nine different families, including coronaviruses and viral disease families that include filoviruses, togaviruses, bunyaviruses, arenaviruses, paramyxoviruses, and flaviviruses.
“The virus causing COVID-19 is a coronavirus, but we do not yet know if galidesivir has activity against this specific virus,” BioCryst CEO, President, and Director Jon P. Stonehouse told analysts on the company’s quarterly conference call.
Since 2013, BioCryst has partnered with NIAID and BARDA to develop galidesivir under contracts totaling $82 million: “We have been working with them to figure out how we might help in this global health emergency,” Stonehouse said, adding that talks have focused on testing galidesivir on SARS-CoV-2, learning how to participate in clinical trials, and increasing drug supply.
Galidesivir is also being assessed for yellow fever in a Phase II trial (NCT03891420) under contracts with the National Institute of Allergy and Infectious Diseases (NIAID) and U.S. Department of Health and Human Services (HHS). Last year, galidesivir completed a 32-patient Phase I study in Marburg Virus Disease (NCT03800173).
Type: Polysaccharide galectin inhibitor designed to restore the adaptive immune system to normal function by binding to and neutralizing Galectin-3 and Galectin-1. Binding activity is localized to the galactose containing side branches, preventing the virus from entering the host cell, and thus modulating any existing cytokine storm. The company cites preclinical evidence that a galectin inhibitor can bind to the protein spikes of the coronavirus.
Status: Bioxytran on March 31 disclosed BXT-10’s expected mechanism of action against COVID-19 in a presentation that cited several studies published over the past five years indicating that Galectin-1 is implicated in viral pathogenesis. Studies in mice showed that mice share the same N-terminal domain as humans—and that both SARS and COVID-19 share the similar N-terminal domain. Bioxytran reasons that a galectin-1 inhibitor could bind to coronavirus spikes and reduce viral load.
“The journal articles provide a strong foundation that galectin-1 is implicated in COVID-19,” CEO David Platt stated.
A day earlier, BioXyTran said it intended to internally develop a novel carbohydrate Galectin inhibitor—and terminated an agreement announced March 24 to license a galectin inhibitor from its CEO and Chairman David Platt, PhD, saying the novel candidate “can be more responsive to the immediate needs posed by COVID-19.” Bioxytrain added that it planned to obtain additional funding for the internal development effort, and file for expedited trials under new FDA guidelines.
Chongqing Sidemu Biotechnology Technology
Candidate: Natural killer (NK) cell therapy
Type: Universal off-the-shelf NKG2D-ACE2 CAR-NK cells
Status: Chongqing Sidemu Biotechnology Technology and sponsor Chongqing Public Health Medical Center disclosed March 27 they are recruiting patients for an up to 90-patient Phase I/II clinical trial (NCT04324996) assessing the company’s universal off-the-shelf NKG2D-ACE2 CAR-NK cells secreting IL15 superagonist and granulocyte-macrophage colony-stimulating factor (GM-CSF)-neutralizing single-chain variable fragment (scFv).
Codagenix and Serum Institute of India
Candidate: Vaccine against CoVID-19 ●
Type: Live-attenuated vaccine
Status: Codagenix said February 13 it will collaborate with the Serum Institute of India to rapidly co-develop a COVID-19 vaccine, adding that it has already designed “multiple” novel coronavirus vaccine candidate genomes using its proprietary deoptimization technology, which can digitally generate a full-length, deoptimized genome based on the outbreak sequence 3–5 days after acquiring the sequence.
Vaccine viruses will be grown and tested in vivo by contracted laboratories suitable for containment, before testing in clinical trials. The Serum Institute of India, a vaccine manufacturer and distributor with a global presence, will scale-up the manufacture of the vaccine to ensure its availability. Codagenix and Serum Institute said they are pursuing an accelerated development pathway and were eager to manufacture and test their vaccine candidates “as quickly as possible.”
Cytovia Therapeutics and Macromoltek
Candidate: Natural Killer (NK) immunotherapy targeting SARS-CoV-2
Type: NK cells leveraging Cytovia’s proprietary bi-functional technology, developed by co-founder Jean Kadouche, PhD. and novel antibodies neutralizing or blocking SARS CoV2, designed by Macromoltek, a computational antibody discovery company. The selected bi-functional antibodies
Status: Cytovia and Macromoltek said April 7 it will expand its NK immunotherapy programs beyond cancer and infectious diseases to include COVID-19, with plans to select an NKI immunotherapy candidate to begin clinical trials by year’s end, and make it available to patients in 2021. The companies will use a bi-functional approach they said holds potential to minimize virus escape from the immune response, thereby inhibiting the intensification of the inflammation leading to Acute Respiratory Syndrome (ARS). The activation of NK cells through the NKp46 receptor aims to destroy the virus-infected cells while the other arm can either block the entry of the virus into epithelial cells or neutralize circulating viruses.
NK activating antibodies were licensed last month from Yissum, the technology-transfer company of the Hebrew University of Jerusalem.
Emmaus Life Sciences
Candidate: Endari® (L-glutamine oral powder)
Type: Amino acid indicated to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients 5 years of age and older.
Status: Emmaus said March 24 it is exploring whether Endari may be potentially beneficial to patients with COVID-19 as part of their oral rehydration therapy (ORT). According to the company, a study regarding ORT has suggested that an oral hydration solution containing glutamine and glucose might be superior to conventional glucose ORT in viral enteritis, but added that further research was warranted to confirm that hypothesis.
Candidate: To be determined ●
Type: Existing antiviral and respiratory candidates, plus drugs to be discovered
Status: Enanta on March 13 said it had begun a program to discover direct-acting antiviral drug candidates to treat COVID-19, using a two-pronged approach: Testing compounds from its antiviral compound library for potential activity against the virus, and discovering new candidates by using its expertise in direct-acting antiviral mechanisms. Four days later, Baird Equity Research cited that strategy, and the company’s antiviral experience, in upgrading Enanta to “Outperform”: “In our view, Enanta’s core competencies are a perfect fit for tackling the COVID-19 pandemic, head on.”
Enanta also said it will launch a Phase II dose ranging study in pediatric respiratory syncytial virus (RSV) patients and a Phase II study in adult transplant patients with RSV, in addition to its ongoing Phase IIb RSVP study in adult outpatients with community-acquired RSV, noting that patients at higher risk for RSV such as older adults and people with weakened immune systems show a similar patient profile as patients with COVID-19.
EUSA Pharma/The Papa Giovanni XXIII Hospital
Candidate: Sylvant (siltuximab) ●
Type: Monoclonal antibody targeting Interleukin-6 (IL-6), approved in the U.S., Europe, and other countries for the treatment of patients with multicentric Castleman disease (MCD).
Status: EUSA Pharma on April 1 announced initial preliminary results from the Papa Giovanni XXIII Hospital-sponsored SISCO (Siltuximab In Serious COVID-19) Study (NCT04322188). Interim data from the first 21 patients treated with Sylvant and followed for up to seven days showed that seven patients experienced a clinical improvement with a reduced need for oxygen support, while another nine patients saw their condition stabilize, indicated by no clinically relevant changes. C-Reactive Protein levels, a marker of systemic inflammation, declined from baseline through to Day 5 following treatment in all 16 patients who showed sufficient recorded values.
The next phase of data will compare outcomes in matched case-control patients not treated with Sylvant, and is expected in coming weeks. Twenty-one patients were enrolled in the study, which evaluated Sylvant in COVID-19 patients who had developed serious respiratory complications.
Candidate: FlowVax™ COVID-19 ●
Type: Rapid synthetic peptide vaccine designed to protect against SARS-CoV-2 infection by targeting antigens at the center of the virus, which are least likely to mutate. FlowVax COVID-19 is an adjuvanted, room temperature stable, biodegradable microsphere peptide vaccine targeting nucleocapsid, loaded with a suite of 16 peptides with > 95% predicted world-wide population coverage. The vaccine can be given by injection or nasal spray.
Status: Flow Pharma said April 8 researchers at The University of Texas Medical Branch at Galveston (UTMB) at Galveston will begin testing FlowVax COVID-19 by challenging nonhuman primates with SARS-CoV-2 after the animals are vaccinated this month with FlowVax COVID-19.
The company has posted a presentation on its website noting that its COVID-19 vaccine uses the same platform as its FlowVax Ebola targeting nucleocapsid that had been shown effective in a mouse model at UTMB.
“Nucleocapsid proteins within COVID-19 contain multiple class I epitopes with predicted HLA [human leukocyte antigen] restrictions consistent with broad population coverage. A similar approach to a CTL [cytotoxic T-lymphocytes] vaccine design may be possible for that virus,” Flo Pharma Founder, CEO, and Director Reid Rubsamen MD, and colleagues concluded in a preprint paper posted March 9 on bioRxiv.
Flow Pharma’s vaccines use patented Size Exclusion Antigen Presentation Control (SEAPAC™) technology based on making vaccine microspheres the same size as human white blood cells.
Candidate: rCIG (recombinant anti-coronavirus 19 hyperimmune gammaglobulin) ●
Type: Recombinant polyclonal antibody therapy for the treatment of COVID-19.
Status: GigaGen on March 30 disclosed its effort to deveop rCIG, an intravenous therapy designed to reproduce whole antibody repertoires of recovered COVID-19 patients, including high concentrations of antibodies that target and prevent further replication of the COVID-19 virus. GigaGen uses its single-cell technology to capture and recreate complete libraries of antibodies from COVID-19 convalescent patients that can directly translate into antibody therapies—a method the company says is much more scalable than plasma from recovered COVID-19 patient donors since one person’s B cell repertoire can be used to generate a drug that treats millions of patients.
Other advantages cited by GigaGen include a decreased risk of contamination, greater batch to batch consistency, and “hundreds-fold” higher potency than plasma-derived equivalents, which may yield better clinical outcomes.
GigaGen is recruiting patients who have recovered from COVID-19 to donate blood for the development of rCIG. The company has signed a collaboration agreement with plasma collector/manufacturer Access Biologicals to expedite patient identification and assist with sample collection. GigaGen added that it will continue talks with the FDA toward expediting development.
GlaxoSmithKline (GSK) and Clover Biopharmaceuticals
Candidate: COVID-19 S-Trimer ●
Type: Protein-based coronavirus vaccine
Status: GSK agreed to provide Clover with its pandemic adjuvant system for further evaluation of S-Trimer in preclinical studies, the companies said in February, under a research collaboration whose value was not disclosed. GSK reasons that 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.
On March 25, GSK said that Clover was 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.
GSK also said it was donating $10 million to The COVID-19 Solidarity Response Fund, created by the UN Foundation and WHO, to support WHO and partners to prevent, detect, and manage the pandemic.
“GSK is the world leader in vaccines, and partnering with them significantly boosts our hopes of both the timely development of a vaccine, and the capability to produce it in large enough quantities necessary to curb the coronavirus outbreak,” said Michael Breen, director, Infectious Diseases, Pharma at GlobalData.
Heat Biologics and University of Miami
Candidate: Vaccine to protect against SARS-CoV-2 and other coronaviruses ●
Type: Vaccine based on Heat’s gp96 platform, designed to generate open docking sites for insertion of multiple SARS-CoV-2 antigens.
Status: Heat said March 23 that it will collaborate with University of Miami Miller School of Medicine to develop a proprietary UM COVID-19 point-of-care diagnostic test—more than two weeks after the partners agreed to develop a vaccine targeting SARS-CoV-2.
“The vaccine is designed to induce a multi-epitope specific memory CD8 T-cell response that protects against multiple, distinct coronavirus strains, and against potential future mutations of SARS-CoV-2 and other coronaviruses,” Heat said. The approach is designed to activate a potent immune response, without the potential for genomic integration of foreign DNA or viral vector instability possible with attenuated viral vaccines.
Candidate: Vaccine ●
Type: Peresonalized vaccines using technology originally developed against cancer
Status: Helix will use the personalized vaccine technology it created over two years against cancer to fight COVID-19, co-founder and CEO Hannu Rajaniemi told The Wall Street Journal in a report updated March 15. Also last month, the company received an investment of undisclosed size from Sam Altman, advisor to Y Combinator and president of the Silicon Valley accelerator from 2014–2019.
Immune System Regulation (ISR) Holding and TCER
Candidate: Immunolid ISR50 ●
Type: Vaccine based on TCER AB’s platform technology for the production of proteins and ISR’s drug pipeline with immunostimulating immunolides.
Status: ISR said March 19 that it is partnering with TCER to develop a COVID-19 vaccine. Data from animal studies are expected to be ready during the second quarter of 2020, with the goal of starting testing in humans during the last quarter of this year. TCER conducts its research in close collaboration with Hans Grönlund, PhD’s research group Therapeutic Immune Design at the Center for Molecular Medicine at Karolinska Institutet.
ISR said in February it was exploring the potential of developing its Immunolid ISR50 vaccine as a treatment for COVID-19. Immunolid50 is in the final phase of toxicological studies, carried out in collaboration with Innostars in Shanghai, in anticipation of a future IND application allowing for human clinical trials.
Candidates: Multiple COVID-19 vaccines
Type: Vaccines based on company’s ADDomer® platform, a synthetic, self-assembling, nature-inspired virus-like particle (VLP)
Status: Imophoron statesd on its website that preclinical trials of its vaccine candidates will begin “within weeks.” The U.K. startup, based at the Unit DX Incubator in Bristol, said it is looking for partners to further the development of the COVID-19 candidates and the ADDomer rapid-response platform for vaccines to combat present and future infectious diseases. Imophoron cites as advantages of its approach the avoidance of induction of disease-enhancing antibody responses, ready manufacture and thermostability, avoiding the need for cold chain storage.
Candidates: Linebacker and Equivir
Type: Unspecified compounds with the potential to bind Angiotensin converting enzyme 2 (ACE2) and block SARS-CoV-2 entry into cells
Status: Impact’s parent company Singapore eDevelopment said March 17 that Impact and scientific research partner GRDG Sciences conducted molecular docking studies using advanced computational models showing that its Linebacker and Equivir compounds successfully inhibited infection by SARS-CoV-2. The compounds will undergo testing after they were shown to block 3 integral viral mechanisms for SARS-CoV-2 replication and infection: the viral spike interaction point, helicase, and protease.
Israel Institute for Biological Research (IIBR)
Candidate: Vaccine to prevent COVID-19 ●
Type: Not specified
Status: IIBR’s vaccine prototype has begun to be tested on rodents at its biochemical defense lab, Reuters reported March 31, after Israeli Prime Minister Benjamin Netanyahu issued a statement saying he was informed of “significant progress” in designing the prototype by IIBR’s director Shmuel Shapira, MD.
At a March 24 virtual conference hosted by Jerusalem Venture Partners, IIBR chief innovation officer Eran Zahavy, PhD, said the institute had shifted its entire focus to COVID-19, with three groups trying to develop a vaccine against the novel coronavirus, and other groups researching potential treatments.
Netanyahu directed IIBR, an Israeli government defense research institute, to develop a COVID-19 candidate in February. Netanyahu and the chief of Israel’s military, Lieutenant-General Aviv Kohavi, went into self-isolation at the end of March following exposure to coronavirus carriers. Both men have tested negative for the virus.
Jagiellonian University (Malopolska Centre of Biotechnology) and Nanjing University
Candidate: HTCC (N-(2-hydroxypropyl)-3-trimethylammonium 47 chitosan chloride) ●
Type: Antiviral compound designed to potentially inhibit 48 currently circulating coronaviruses
Status: Professor Krzysztof Pyrć, PhD, and colleagues at the Virogenetics Laboratory of Virology at Jagiellonian University’s Malopolska Centre of Biotechnology joined researchers from Nanjing University in publishing a March 31 preprint study in bioRxiv describing the antiviral activity of HTCC, which the researchers concluded may be used as a potential inhibitor of 48 highly pathogenic coronaviruses based on its inhibition of viral replication in Vero cells: “We believe that HTCC is a promising drug candidate that should be further studied, as it provides a ready-to-use solution for SARS-CoV-2 and future emerging coronaviruses.
Janssen Pharmaceutical Cos. (Johnson & Johnson)
Candidates: Prezista® (darunavir); Prezcobix™ (darunavir and cobicistat)
Types: HIV-1 protease inhibitor (darunavir); CYP3A inhibitor (cobicistat). Prezista and Prezcobix are approved treatments for HIV-1 infection.
Status: Johnson & Johnson confirmed March 16 that it was screening its marketed HIV treatment Prezista and other antiviral compounds to determine potential in vitro effect against SARS-CoV-2—and decried “anecdotal, unsubstantiated reports” that Prezista has antiviral effect against COVID-19. J&J emphasized that the drug “should not be administered without a boosting agent (ritonavir or cobicistat).”
The company cited preliminary, unpublished results from a previously reported in-vitro experiment in asserting: “it is not likely [Prezista] will have significant activity against SARS-CoV-2 when administered at the approved safe and efficacious dose for the treatment of HIV-1 infection.” The company also cited results from a single center, open label, randomized, and controlled trial conducted at Shanghai Public Health Clinical Center of Prezista and cobicistat in treating laboratory-confirmed 30 COVID-19 patients, which it said showed that the combination was not effective.
Janssen said in January it donated 300 boxes of Prezcobix to the Shanghai Public Health Clinical Center and Zhongnan Hospital of Wuhan University for use in research to support efforts in finding a solution against SARS-CoV-2. Another 50 boxes were provided to the Chinese Center for Disease Control and Prevention for laboratory-based investigations. Prezcobix is under study alone in one Chinese trial (NCT04252274), while another Chinese study is assessing Prezcobix compared with Kaletra (lopinavir/ritonavir) combined with thymosin a1 (ChiCTR2000029541). A Spanish trial is evaluating Prezcobix and chloroquine (NCT04304053), while a trial in Bangkok is assessing Prezcobix among numerous HIV protease inhibitors (THDMS-COVID19; NCT04303299).
Junshi Biosciences and Institute of Microbiology of the Chinese Academy of Sciences (IMCAS)
Candidate: Neutralizing antibodies
Type: Multiple strains of neutralizing antibodies (Nab) capable of keeping an infectious agent, usually a virus, from infecting a cell by neutralizing or inhibiting its biological effect. It could potentially facilitate virus clearance, altering the course of infection, Junshi reasons.
Status: Junshi Biosciences said March 20 that it signed a collaboration agreement with IMCAS to jointly develop neutralizing antibodies against COVID-19. The partners said they obtained multiple strains of neutralizing antibodies capable of effectively blocking viral invasion in laboratory assays and have conducted animal experiments. Preliminary in vitro and in vivo studies have verified the blocking activity of the NAb strains, Junshi said.
The company added that it was verifying the preclinical toxicology and in vivo activity of the antibodies in order to file IND applications with regulatory agencies in and outside China.
Candidate: Anti-Corona Immunoglobulin (IgG)
Type: Polyclonal immunoglobulin based on company’s proprietary plasma-derived IgG platform technology as a potential treatment for severely ill coronavirus patients. The treatment is expected to be produced from plasma derived from donors recovered from the virus, which is anticipated to include antibodies to COVID-19.
Status: Kamada on March 11 announced plans to initiate development of an Anti-Corona IgG, emphasizing that its development and manufacturing plans were “highly” dependent on the availability of hyper-immune plasma and on the treatment’s to-be-determined regulatory path. “We are working with the Israeli regulatory authorities and local medical institutions to advance our program,” Kamada CEO Amir London stated.
Candidate: INOmax® (nitric oxide)
Type: Inhaled nitric oxide (iNO) indicated in the U.S. for term and near-term neonates with hypoxic respiratory failure associated with pulmonary hypertension.
Status: Mallinckrodt said April 1 it was working with the FDA to make INOmax available to U.S. patients with pulmonary complications of COVID-19 “as quickly as possible through the appropriate regulatory mechanism.”
On March 12, Mallinckrodt said it was assessing “limited published evidence” of a potential role for its marketed INOmax as a supportive measure in treating patients with SARS-CoV-2 and associated pulmonary complications. The company cited a 2005 in vitro study showing iNO’s inhibitory effect on the replication cycle of severe acute respiratory syndrome-related coronavirus (SARS-CoV), and a 2004 study showing improved blood oxygenation, reduced supplemental oxygen, and reduced ventilator support in six SARS-CoV patients treated with iNO.
Mallinckrodt said it had submitted information to the NIH about evaluating iNO in acute respiratory distress syndrome (ARDS), informed the Biomedical Advanced Research and Development Authority (BARDA) of its ongoing study, and begun early talks with the FDA on submitting a pre-IND package in support of the potential use of iNO in coronavirus-associated ARDS.
Migal Galilee Research Institute
Candidate: Vaccine against COVID-19 ●
Type: Oral vaccine for adults and children based on existing vaccine against avian coronavirus Infectious Bronchitis Virus (IBV)
Status: Chen Katz, PhD, research team leader with the Institute, told The Times of Israel on March 10 that the vaccine is on track to start months of clinical testing in “a few weeks.” Migal generated headlines February 27 by announcing “a scientific breakthrough” and expressing as its goal: “achieve safety approval in 90 days.” The Institute later clarified the breakthrough as its adapting for COVID-19 a convertible vaccine it spent four years researching with support from Israel’s Ministry of Science and Technology and Ministry of Agriculture.
Type: Prodrug of 2-DG (2-deoxy-D-glucose)
Status: Moleculin said March 17 it has partnered with the University of Texas Medical Branch at Galveston (UTMB) to conduct research on its lead candidate WP1122 and the rest of Moleculin’s patented portfolio of molecular inhibitors, for antiviral properties against COVID-19 and other viruses. The company cited a 2014 study showing 2-DG to be effective in treating porcine epidemic diarrhea virus (PEDV) infection. Three days later, Moleculin filed a new patent application covering the use of WP1122 and its analogs as therapies to limit the ability of coronavirus and other viruses to replicate.
Moleculin agreed to supply WP1122 and related inhibitors, as well as technical support, while UTMB agreed to begin testing the candidates against various viral disease models, including COVID-19, in connection with the UTMB Center for Biodefense and Emerging Infectious Diseases.
Mount Sinai Health System and Harbour BioMed (HBM)
Candidates: Monoclonal antibodies against the coronavirus SARS CoV 2 ●
Type: Fully human monoclonal antibodies using HBM’s H2L2 Harbour Mice® platform.
Status: Mount Sinai and Harbour BioMed said March 6 they entered into a multi-year, multifaceted collaboration to generate monoclonal antibodies against SARS CoV 2 as well as develop novel, fully human antibodies to prevent and treat diseases in areas that include oncology and immunology.
Candidate: Topical oral or nasal treatment for COVID-19
Type: Nitric oxide treatment designed to target the reduction of viral shedding and transmission.
Status: Novan on March 23 said it will explore the use of its NITRICIL™ technology toward a COVID-19 treatment. NITRICIL is designed to facilitate use of nitric oxide by controlling its level of storage, rate of release, and molecule size for targeted delivery. Through NITRICIL, nitric oxide is stored on large polymers that allow the gas to be applied as timed-release chemical entities.
Candidate: OYA1 ●
Type: Broad-spectrum antiviral showing activity in lab-based assays against SARS-CoV-2 and MERS-CoV, as well as dual target-specific antiviral activity against filoviruses such as Ebola. OYA1 won IND approval in the 1960s as a candidate to treat cancer, but showed a lack of efficacy.
Status: OyaGen on March 11 announced it will further study OYA1 for COVID-19 following unpublished positive results from collaborative research with the National Institute of Allergy and Infectious Diseases’ (NIAID) Integrated Research Facility at Fort Detrick, MD. The research, OyaGen said, suggested strong dose-dependent antiviral activity of its lead compound OYA1 against live SARS-CoV-2, based on in cell culture infectivity studies, the company said, adding that it will conduct further studies.
“The company anticipates that inhibition of SARS-CoV-2 using OYA1 will serve as a stop-gap treatment until appropriate vaccines are developed,” OyaGen added.
Candidate: Arbidol (umifenovir) ●
Type: Membrane fusion inhibitor developed as a treatment for influenza
Status: Pharmstandard is assessing Arbidol in clinical trials as monotherapy and in combinations that include AbbVie’s Kaletra (See above), Ascletis Pharma’s ASC09 (See above), lopinavir, ritonavir, carrimycin, and Bromhexine Hydrochloride (enrolling by invitation). A 240-patient study compared Arbidol to favipiravir, and concluded that “favipiravir can be considered as a preferred treatment approach to ordinary COVID-19 pneumonia,” according to a preprint posted March 27 on medRxiv: “Favipiravir has higher 7 day’s clinical recovery rate (71.43%) than arbidol (55.86%), and the time of cough relief and fever reduction of fabiravir was significantly shorter than that of arbidol.”
A 44-patient trial (NCT04252885) also generated disappointing results, researchers reported in a preprint posted March 23 on medRxiv. They found that both Arbidol and Kaletra “seems little benefit for improving the clinical outcome of mild/moderate COVID-19,” that Kaletra might lead to more adverse events—and that further verification was needed because of the small sample size.
Those trials were two of six that included Arbidol to be listed on ClinicalTrials.gov. China’s Ruijin Hospital is conducting the monotherapy trial (NCT04260594), while Jiangsu Famous Medical Technology Co. is including Arbidol among Western medicine options in a trial comparing it to traditional Chinese medicine in treating COVID-19 (NCT04306497) and various Chinese hospitals are investigating the other combination therapies (NCT04273763, NCT04261907, NCT04286503)
Type: Advanced Therapy Medicinal Product (ATMP) for human use, based on umenchenal cord-derived mesenchymal stromal cells (hUCT MSCs – Human Umbilical Cord Tissue Mesenchymal Stromal Cells)
Status: PrimeCell said March 27 that it finished research and submitted pharmaceutical documentation to the Czech national regulator of the pharma market, the State institute for drug control or SUKL, seeking to authorize compassionate use of Remescor.
Remescor was developed as part of a joint project by PrimeCell in the labs of the National Center of Tissues and Cells (NATIC) with St. George’s University Hospital, and St. Anne’s University Hospital Brno, International Clinical Research Center (FNUSA-ICRC)
Q Biomed and Mannin Research
Type: Potential first-in-class drug for Intraocular Eye Pressure in Primary Open Angle Glaucoma, is also being developed as an adjunct treatment for vascular leakage and endothelial dysfunction seen in COVID-19 and other infectious diseases, based on the lead platform of research partner Mannin Research, which is designed to target the activation of the Angiopoietin-Tie2 signaling pathway.
Status: In its Form 10-K annual report filed February 28, Q Biomed said MAN-01’s mechanism of action may ameliorate vessel damage in diseases that include “infectious diseases, such as influenza and the current coronavirus outbreak.” Q Biomed and Mannin Research announced their collaboration on February 4.
In September 2019, the German state of Saxony awarded Mannin approximately a US $7.7 million grant to advance its novel therapeutics, including drugs and biologics that reduce endothelial dysfunction and loss of endothelial barrier integrity. Mannin recently submitted a funding application to the NIH’s Small Business Technology Transfer Grant to investigate specific applications of Mannin’s therapeutic platform.
Shanghai Hengrui Pharmaceutical
Candidate: Combination of anti-PD-1 antibody and thymosin ●
Type: Humanized monoclonal antibody targeting PD-1; 5-Da polypeptide hormone secreted by the thymus gland (thymosin)
Status: Chinese clinical trials assessing the combination treatment have been registered by Wuhan Jinyintan Hospital (Wuhan Infectious Diseases Hospital), which identified the anti-PD-1 antibody it is assessing as camrelizumab (120 patients; ChiCTR2000029806); West China Hospital, Sichuan University (ChiCTR2000030028); and Southeast University (120 patients; NCT04268537).
Candidate: Vaccine targeting SARS-CoV-2 ●
Type: Formaldehyde inactivated vaccine with alum adjuvant
Status: Sinovac’s website discloses that the company is developing a vaccine against SARS-CoV-2, but offers little additional information beyond that offered by the World Health Organization. The vaccine type is similar to a Phase I vaccine candidate developed by Sinovac against SARS in the early 2000s, VP Meng Weining told Science.
Soligenix and University of Hawaiʻi (UH) at Mānoa
Candidate: Vaccine to prevent COVID-19 ●
Type: Vaccine based on heat stable subunit filovirus platform, with enhanced stability at elevated temperatures.
Status: Soligenix said March 23 its ongoing collaboration with UH Mānoa was expanding to include vaccines against COVID-19. The partners will use a vaccine platform that includes a viral surface glycoprotein designed to mediate entry and fusion of the virus with host cells and is manufactured with a proprietary insect cell expression system coupled with protein-specific affinity purification. The protein antigen is one of three essential components of the platform; the other two are an adjuvant shown to enhance both cell mediated and humoral immunity, and a formulation which enables thermostabilization of the resulting mixture, avoiding the need for cold chain storage and shipping.
Soligenix’s Public Health Solutions business segment is partnering with Axel Lehrer, PhD, of the Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine (JABSOM).
Sorrento Therapeutics and Mabpharm
Candidate: STI-4920 (CMAB020) to treat COVID-19
Type: ACE-MABTM bi-specific fusion protein designed to bind to the spike protein of coronaviruses—including SARS-CoV-2 and SARS-CoV—which is expected to block SARS-CoV-2 from binding and infecting respiratory epithelial cells or ACE2-expressing cells to interrupt the viral life cycle.
Status: Sorrento said March 24 it will partner with Mabpharm to develop STI-4920, through a collaboration whose value was not disclosed. ACE-MABs have two functional arms: A fully human antibody that targets the spike protein of SARS-CoV-2 with high affinity, and a truncated ACE2 protein that binds to a different epitope of the spike protein. The fusion protein could also block the receptor binding domain with CD147 to mitigate lung inflammation and cytokine storm, according to Sorrento.
Sorrento has agreed to develop and commercialize ACE-MAB in North America and Europe, while Mabpharm retains rights in the rest of the world, including China and Japan. Sorrento has entered into a research testing agreement with The University of Texas Medical Branch at Galveston for preclinical testing of the company’s COVID-19 therapeutic product candidates.
Sorrento Therapeutics and SmartPharm Therapeutics
Candidate: Vaccine to protect against SARS-CoV-2 infection ●●
Type: Next-generation, gene-encoded antibody vaccine
Status: Sorrento and SmartPharm said March 23 they will partner to develop a vaccine against COVID-19 by using monoclonal antibodies against SARS-CoV-2 discovered and/or generated by Sorrento that will be encoded into a gene for delivery using SmartPharm’s non-viral nanoparticle platform.
Plans for the collaboration may include candidate development as well as filing of an IND application in the next few months, the companies added. Sorrento has entered into a research testing agreement with The University of Texas Medical Branch at Galveston for preclinical testing of the company’s COVID-19 therapeutic product candidates.
Stermirna Therapeutics and Shanghai East Hospital of Tongji University
Candidate: Vaccine targeting COVID-19 ●●
Type: mRNA vaccine targeting SARS-CoV-2
Status: Chinese news website Yicai.com reported February 10 that the mRNA vaccine being developed by Stermirna Therapeutics and Shanghai East Hospital of Tongji University had begun testing on animals, following approval on an urgent basis in January. Li Hangwen, CEO of Stermirna Therapeutics, told Xinhua in January that no more than 40 days will be needed to manufacture a vaccine sample.
Candidate: bacTRL-Spike ●
Type: Bifidobacteria monovalent SARS-CoV-2 DNA oral vaccine for prevention of COVID-19
Status: Symvivo disclosed April 6 on ClinicalTrials.gov that it was recruiting up to 84 participants for an observer-blinded Phase I trial (NCT04334980) evaluating the safety, tolerability, and immunogenicity of bacTRL-Spike in healthy adults.
The vaccine is produced using Symvivo’s platform, in which orally administered, genetically modified probiotic bacteria colonize the gut, bind directly to intestinal epithelial cells and constitutively replicate, secrete and deliver plasmid DNA molecules encoding antigenic transgenes and neutralizing nanobodies.
Tiziana Life Sciences
Candidate: TZLS-501 ●
Type: Fully-human anti-interleukin-6 receptor (anti-IL6R) monoclonal antibody (mAb) for treatment of patients infected with SARS-CoV-2, delivered directly into the lungs using a handheld inhaler or nebulizer.
Status: Tiziana said Aprl 9 it has submitted a provisional patent application for the delivery technology. The application covers treatment with the monoclonal antibody, as well as prophylactic intervention with a vaccine candidate, designed from Spike (S) protein of COVID-19. Tiziana acquired TZLS-501, formerly called NI-1201, from Novimmune in 2017 for undisclosed upfront, milestone, and future royalty payments: “We view NI-1201 as a potential game-changer for addressing the high unmet need of autoimmune and inflammatory diseases,” Tiziana Executive Chairman Gabriele Cerrone stated at the time.
Tianjin Sinobloway Biology
Type: A form of interferon alpha that has been used to treat some patients with AIDS-related Kaposi sarcoma, hairy cell leukemia, and melanoma that has been removed by surgery, and some infections caused by viruses, such as hepatitis C virus.
Status: A team of Chinese, Cnadian, and Australian researchers on April 10 published a preprint study in medRxiv showing that among 77 COVID-19 patients admitted to Union Hospital, Tongii Medical College in Wuhan, China, treatment with IFN-alpha2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. “These findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases,” the researchers concluded.
Tonix Pharmaceuticals Holding and Southern Research Institute
Candidate: TNX-1800 (live recombinant horsepox virus [rHPXV/SARS-CoV2-S3] vaccine from cell culture) ●
Type: Live modified horsepox virus vaccine for percutaneous administration to protect against COVID-19
Status: Tonix said March 24 that it will partner with Southern Research to develop and test TNX-1800, which is designed to express the Spike protein from the SARS-CoV-2 virus. Tonix plans to test whether vaccination of animals with TNX-1800 will elicit an immune response to the SARS-CoV-2 Spike protein and if so, whether such an immune response will protect animals against COVID-19-like disease. The company expects preliminary animal data in the third quarter of 2020, “but the COVID-19 pandemic may lead to a delay in this timeline,” Tonix acknowledged.
Candidates: Treatments, vaccines, and nanotechnology-based diagnostics ●
Types: To be determined
Status: The Tulane National Primate Research Center (TNPRC) said March 25 it was working on COVID-19 drugs, vaccines, and nanotechnology-based diagnostics, after becoming one of the first research facilities in the country to obtain approval from the U.S. Centers for Disease Control and Prevention (CDC) to receive live samples of COVID-19. TNPRC researchers are creating a nonhuman primate model to study COVID-19’s clinical progression, how it is transmitted through the air and how it specifically affects aging populations.
TNPRC Director Jay Rappaport, PhD, will lead researchers—who include Tony Hu, PhD, Weatherhead Presidential Chair in Biotechnology Innovation is working to develop a rapid test for COVID-19 using highly sensitive blood or saliva tests. Tulane announced the launch of its COVID-19 research program in February.
Type: Novel “optimized salt” formulation of antihelminthic drug approved as a treatment for parasitic infections
Status: Union Therapeutics said April 12 it launched a program in partnership with Institut Pasteur Korea to test niclosamide, asserting that the drug showed potency more than 25 times higher than chloroquine and more than 40 times higher than Gilead Sciences’ remdesivir. A development program for niclosamide in COVID-19 being prepared for submission to Danish medical authorities, Union said. The drug is now the subject of a Phase IIb study in atopic dermatitis patients.
Vanda Pharma and University of Illinois at Chicago (UIC)
Candidate: Small molecules with the potential to treat COVID-19
Type: Small molecules that may prevent cathepsin-L cleavage of SARS-CoV-2 (COVID-19) glycoproteins that are required for viral processing in the host cell.
Status: Vanda on April 8 said it has launched a research partnership with UIC focused on the investigation of small molecules with the potential to treat COVID-19. In addition to studying cathepsin-L enzyme inhibition, Vanda said, the partners will also explore drugs that may block SARS-CoV-2 virus entry at the angiotensin converting enzyme 2 receptor, and the transmembrane protease serine 2 precursor.
The partners plan to launch in New York a clinical trial called ODYSSEY, a study of tradipitant in hospitalized patients with severe COVID-19 pneumonia that was announced on April 2.
Candidate: Vaccine to protect against COVID-19 ●
Type: Vaccine based on signal peptide technology identified by Vaxil’s proprietary VaxHit™ bioinformatics platform, as well as in vivo experiments testing a tuberculosis signal peptide vaccine.
Status: Vaxil on March 10 said it submitted a new patent application for its anti-infective vaccines platform following the discovery of its COVID-19 vaccine candidate discovery. The application (U.S 62/987,310) covers claims for a coronavirus vaccine that is intended to provide broad patent protection for novel vaccines, pharmaceutical compositions and methods of treating and preventing an infectious disease as well as methods for producing a peptide vaccine against coronaviruses, Vaxil said.
Vaxil disclosed its COVID-19 vaccine candidate in February, saying that it planned to initiate non-GMP manufacturing followed by testing as the company explores partnerships and other possibilities.
Type: Proprietary synthetic, peptide-containing surfactant similar to human surfactant, approved by the FDA in a previous liquid dose formulation for respiratory distress syndrome in premature infants.
Status: Windtree said March 24 it will pursue the clinical study of its KL4 surfactant to potentially mitigate the pulmonary effects of severe COVID-19 infection. The company said it is actively pursuing several non-dilutive opportunities to fund this project, including government agencies and private foundations.
WPD Pharmaceuticals and CNS Pharma
Type: Prodrug of 2-deoxy-D-glucose (2-DG) whereby chemical elements are added to 2-DG to improve its delivery in vivo, then removed by normal metabolic processes.
Status: WPD on April 9 said independent research on WP1122 found 2-DG to reduce replication of SARS-CoV-2 by 100% in in vitro testing. WPD and CNS intend to move into clinical trials of WP1122 and other preclinical drugs on SARS-CoV-2 and other viruses. WPD has licensed a portfolio of drug candidates from Moleculin Biotech.
Candidates: Vaccines targeting SARS-CoV-2 ●
Types: Two approaches in development. In one approach, plasmid DNA is introduced into the host cells for translation into the viral protein, designed to elicit a strong immune response mediated by the cellular and humoral arms of the human immune system.
The other approach is a live attenuated recombinant measles virus vectored vaccine: The recombinant measles virus (rMV) produced by reverse genetics is expressed codon-optimized proteins of COVID-19 and induces long-term specific neutralizing antibodies, designed to provide protection from the infection.
Status: Zydus Cadila said February 15 it launched an accelerated research program. The company’s Vaccine Technology Centre in India is working on the plasmid DNA vaccine, while the company’s research arm in Europe, Etna Biotech is working on measles reverse genetics technology that had been successfully used in developing a SARS vaccine.