Anthony Fauci, MD, Director of the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), offered hope to the thousands of people with confirmed cases of COVID-19, and the millions around the world whose lives have been disrupted by the pandemic caused by SARS-CoV-2, when he expressed to a congressional panel last week his hope that the first patients would be dosed with vaccines in development for the novel coronavirus “in a few weeks.”
Fauci’s hope was realized less than a week later—on Monday, to be precise, when Moderna and the NIAID, which Fauci has headed since 1984, dosed the first patient in a clinical trial of the company’s vaccine candidate mRNA-1273 as a potential treatment for COVID-19, encoding for a prefusion stabilized form of the Spike (S) protein, conducted at the Kaiser Permanente Washington Health Research Institute Institute in Seattle.
Despite that welcome development, it may take a while before vaccines and other treatments for COVID-19 reach patients who desperately need them.
In a recent note to investors, H.C. Wainwright managing director, senior healthcare analyst Raghuram Selvaraju, PhD, estimated that it would take around 18–24 months to complete the clinical development of a COVID-19 vaccine. Most of the therapy candidates for COVID-19, he noted, were vaccines that are only in animal testing stages.
Another analyst, Damien Conover of Morningstar, offered insight into biopharmas he said could benefit from the COVID-19 outbreak based on their work to advance new treatments. Among companies he cited were biopharma giants with vaccine and/or infectious disease experience, yet whose share prices have lagged behind their value. Among companies Conover cited were GlaxoSmithKline, Merck & Co., Pfizer, and Sanofi, as well as Gilead Sciences, which has generated headlines worldwide through its development of remdesivir.
Gilead’s remdesivir is among five COVID-19 treatment candidates considered furthest along in development and/or most promising based on recent activity. Among other treatments in that top-tier category are AbbVie’s Kaletra® (also marketed as Aluvia; lopinavir/ritonavir); Moderna’s messenger RNA (mRNA) vaccine candidate mRNA-1273, the Regeneron/Sanofi marketed Kevzara® (sarilumab), an arthritis drug now being tested in severe COVID-19 infection; and most recently favipiravir, marketed by Fujifilm as Avigan®.
Those companies, and dozens of other drug developers and research institutions, are behind the 60 active drug development programs in North America, Europe, and China that are highlighted by GEN in this updated A-List. More than two dozen of these treatments have emerged or been made public just in the two weeks since GEN published its original A-List summarizing COVID-19 therapies in the works, How to Conquer Coronavirus: Top 35 Treatments in Development.
Each prospective treatment is listed in alphabetical order by its developer(s), followed by the treatment name or description, the type of treatment including its mechanism, and a brief status update summarizing recent developments. Where applicable, the status updates include links to recent news reports in GEN, as well as to clinical trials pages maintained by U.S. authorities via ClinicalTrials.gov, and by Chinese authorities as the Chinese Clinical Trial Registry.
According to the Chinese registry, numerous Chinese authorities, hospitals, and companies continue to study treatments outside the auspices of their original developers, or any developers. One most recent example of that is the First Affiliated Hospital of Wenzhou Medical University, whose researchers have launched a pair of clinical trials in China assessing thalidomide—one as an adjuvant treatment for prevention or treatment of lung injury caused by COVID-19 (NCT04273529); the other a study assessing thalidomide plus low-dose hormone adjuvant therapy for patients with severe COVID-19 (NCT04273581)—after the drug achieved positive results in the treatment of patients with severe H1N1.
Other COVID-19 related collaborations focus on development of technologies or platforms for future treatment development. Teams at Baylor College of Medicine’s (BCM) National School of Tropical Medicine and Texas Children’s Hospital Center for Vaccine Development have manufactured for clinical use the receptor binding domain (RBD) of the spike protein for SARS and are developing the protein’s RBD from COVID-19, since the spike protein of the coronavirus binds to receptors found deep in the host lung tissue. Additional preclinical tests are being conducted to advance a recombinant protein-based vaccine into clinical trials to determine if it is safe, sufficiently protective, or cross-reactive against COVID-19, BCM said.
Among most recent platform examples is that of Cidara Therapeutics, whose platform aims to develop antiviral Fc-conjugates to treat and prevent severe respiratory infections by targeting the virus directly instead of cells in the lung. On March 9, two researchers for the U.S. Centers for Disease Control and Prevention, Larisa Gubareva, MD, PhD, and Teena Mohan, PhD, published in Cold Spring Harbor Perspectives in Medicine a paper detailing that approach via the identification of monoclonal antibodies (mAbs) targeting neuraminidase (NA) epitopes.
Those and other efforts are taking place in a deadly race against time: As of March 18, 9:53 a.m. U.S. Eastern time, according to the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, 8,244 people in 53 countries had died worldwide, of which 39% or 3,241 were in China. CSSE also recorded 204,264 confirmed cases of COVID-19, of which 40% (81,102) were in China.
Treatment: Kaletra® (also marketed as Aluvia; lopinavir/ritonavir)
Type: HIV-1 protease inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and children 14 days old and older.
Status: AbbVie on March 9 confirmed it was collaborating with health agencies and institutions globally to determine antiviral activity as well as efficacy and safety of Kaletra against COVID-19. The agencies include European health authorities, the FDA, the Centers for Disease Control and Prevention, the NIH, and the Biomedical Advanced Research and Development Authority (BARDA).
On March 16, researchers at the University of Queensland in Australia said they hoped to launch large-scale trials of Kaletra® and chloroquine, marketed by Bayer and other companies (See below), after both drugs successfully treated patients with COVID-19.
China’s National Health Commission authorized Kaletra to treat pneumonia caused by SARS-CoV-2, AbbVie said January 27. AbbVie has donated RMB 10 million ($1.4 million) of Kaletra to Chinese authorities “as an experimental option to support this growing public health crisis.”
The Health Commission of Henan Province announced January 31 that three confirmed cases of patients diagnosed with new coronavirus infections recovered after taking Kaletra, a combination of ritonavir and lopinavir. As of that date, nucleic acid testing of more than 20 confirmed cases of patients infected with new coronavirus, admitted to hospitals in Zhejiang Province turned negative after taking Kaletra, according to Ascletis Pharma, which is evaluating a combination therapy of its own candidates ASC09 and ritonavir (See below).
|2. AIM ImmunoTech
Treatment: Ampligen® (rintatolimod)
Type: Immune modulator indicated for severe chronic fatigue syndrome
Status: AIM ImmunoTech said March 10 in a prospectus that it has 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.
A day earlier, the company said that 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.
Treatment: Single-dose, intranasal vaccine designed to provide systemic immunity
Type: Vaccine based on Altimmune’s proprietary platform vaccine technology, which the company applied in developing NasoVAX, the company’s influenza vaccine candidate that showed positive Phase IIa results.
Status: Altimmune said February 28 that it completed the design and synthesis of the vaccine, and was advancing it toward animal testing and manufacturing. Clinical testing of the vaccine could start as early as August. The company also said it was “actively engaged in discussions with a number of potential partners.”
|4. APEIRON Biologics
Type: Recombinant human angiotensin-converting enzyme 2 (rhACE2) developed for the treatment of acute lung injury, acute respiratory distress syndrome, and pulmonary arterial hypertension.
Status: Vienna-based APEIRON on February 26 launched a pilot investigator-initiated clinical trial in China designed to assess APN01 as a treatment for patients with severe SARS-CoV-2 infection. The randomized, unblinded trial will treat 24 patients for seven days to obtain preliminary data on the impact of rhACE2 on biological, physiologic, and clinical outcomes, as well as safety. Suzhou-based Angalpharma is coordinating the Chinese clinical trial, with support from dMed Pharmaceutical, a CRO based in Shanghai.
|5. Ascletis Pharma
Treatments: Ganovo® (danoprevir) plus ritonavir; ASC09 and ritonavir; ASC09 and oseltamivir; ritonavir and oseltamivir;
Types: HIV protease inhibitors
Status: Ascletis on March 10 trumpeted progress in its clinical research into oral Ganovo and ritonavir, stating that all 11 patients treated with the combination therapy were discharged from hospital after showing positive results in a trial conducted at Nanchang Ninth Hospital (NCT04291729). Ascletis announced the discharge of the study’s first three patients on February 26.
On February 2, Ascletis said it is actively assisting “relevant medical institutions and medical researchers” in clinical trials assessing the combination of Ascletis’ ASC09 and ritonavir for COVID-19, following a request they made to the company. On January 25, Ascletis applied to the National Medical Products Administration and its Drug Evaluation Center to include ritonavir and ASC09 fixed-dose combination into the national emergency channel.
China’s Tongji Hospital is also testing combinations of ASC09 and Tamiflu (oseltamivir), ritonavir and Tamiflu (oseltamivir), and Tamiflu alone in one trial listed on ClinicalTrials.gov (NCT04261270). Tamiflu is distributed in the U.S. by Genentech, a member of the Roche Group, under license from Gilead Sciences. Also, a trial prospectively registered by The First Affiliated Hospital of Zhejiang University School of Medicine is assessing combinations of ASC09 and ritonavir, and lopinavir and ritonavir (ChiCTR2000029603).
|6. Bayer and numerous Chinese manufacturers
Treatment: Chloroquine phosphate (marketed by Bayer as Resochin®)
Type: Phosphate salt of chloroquine, a quinoline compound with antimalarial and anti-inflammatory properties. Resochin was discovered by Bayer and introduced into clinical practice in 1947 to treat malaria.
Status: Chloroquine has “shown fairly good efficacy” according to Sun Yanrong, deputy head of the China National Center for Biotechnology Development under the Ministry of Science and Technology (MOST), the state-owned Xinhua news agency reported on February 17, following clinical trials in over 10 hospitals in Beijing, as well as in south China’s Guangdong Province and central China’s Hunan Province.
On March 16, researchers at the University of Queensland in Australia said they hoped to launch large-scale trials of chloroquine, as well as AbbVie’s Kaletra®(See above), after both drugs successfully treated patients with COVID-19.
Chinese news outlet Shine reported March 10 that Bayer had donated about €1.5 million (about $1.7 million) in medicines and additional financial aid to the Chinese Red Cross to support prevention, diagnosis, treatment, and containment of COVID-19 in China. Bayer’s Kunming, China factory mobilized 50,000 disposable surgical masks and 10,000 R95 medical masks to donate to the Kunming Red Cross Society, in response to a call from the Yunnan Provincial Department of Commerce.
Chloroquine and remdesivir were “highly effective in the control of 2019-nCoV infection in vitro,” a team of Chinese researchers reported in a study published February 4 in Cell Research. After China’s National Health Commission included chloroquine phosphate in its latest treatment guidelines for COVID-19 pneumonia, eight Chinese companies sped up manufacturing and supply of the drug, Shanghai Daily reported February 20.
|7. Beijing Staidson Biopharma and InflaRx
Type: Anti-C5a monoclonal antibody in development for COVID-19 as well as hidradenitis suppurativa, ANCA-associated vasculitis and Pyoderma Gangraenosum.
Status: Chinese authorities approved clinical trials of IFX-1 as a COVID-19 treatment in February. The company however has not listed IFX-1 as a COVID-19 treatment, only stating it is in additional development for “undisclosed chronic inflammatory and autoimmune diseases,” according to a presentation at the SVB Leerink Global Healthcare Conference, held February 25–27.
|8. Beroni Group
Treatment: Nanobody-based treatment
Type: Modified nanobody
Status: Beroni Group said March 9 it is partnering with Tianjin University in China on cytological experiments set to begin this month for a nanobody-based COVID-19 treatment—to be followed by animal experiments, then clinical trials which are expected to occur in April.
Type: Novel oral small molecule T-cell co-stimulator
Status: BeyondSpring said March 11 it submitted a provisional U.S. patent application 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.
Treatment: Galidesivir (BCX4430)
Type: Nucleoside RNA polymerase inhibitor designed to disrupt the viral replication process
Status: Biocryst said March 5 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.
Galidesivir is being assessed for yellow fever in a Phase II trial (NCT03891420) under contracts with the National Institute of Allergy and Infectious Diseases (NIAID) and the U.S. Department of Health and Human Services (HHS).
|11. BioNTech, Pfizer, and Fosun Pharma
Type: Potential first-in-class mRNA vaccine designed to induce immunity and prevent COVID-19 infection
Status: BioNTech and Pfizer on March 17 said they will partner to develop BNT162, which BioNTech announced individually just a day earlier—the first treatment to emerge from its accelerated COVID-19-focused development program, “Project Lightspeed.” The companies said they expect to begin clinical testing for BNT162 in April as part of a global clinical development program in Europe (commencing in Germany), the U.S. and China, to be carried out at multiple sites in the U.S. and Europe. BioNTech and Pfizer said financial terms, and details of development, manufacturing, and potential commercialization will be finalized over the next few weeks.BioNTech is also partnering with Fosun Pharma to jointly develop BNT162 in China, with Fosun agreeing to make a $50 million equity investment for 1,580,777 ordinary shares in BioNTech, and pay BioNTech up to $85 million in additional upfront and milestone payments. The companies will share future gross profits from the sale of the vaccine in China.
Type: Anti-necrosis drug whose glyco-polymer structure consists of hybrid molecules integrating the Hemoglobin molecule and a proprietary polymer chemical structure. BXT-25 is company’s lead product candidate, designed to carry oxygen to tissues when the flow of blood is blocked.
Status: Boston-based Bioxytran said February 5 that it is exploring partnering with “international drug companies” to develop BXT-25 as a treatment for Acute Respiratory Distress Syndrome (ARDS) in end-stage patients with SARS-CoV-2. Since BXT-25 is 5,000 times smaller than red blood cells, the company will use MDX Life Sciences’ MDX Viewer to assess the safety and efficacy of the drug.
|13. CanSino Biologics
Treatment: Vaccine for prevention of COVID-19
Type: Recombinant Novel Coronavirus Disease Vaccine incorporating the Adenovirus Type 5 Vector (Ad5-nCoV)
Status: CanSino said March 18 it has received approval from Chinese authorities to begin human trials of the vaccine, co-developed with China’s Beijing Institute of Biotechnology, Academy of Military Medical Sciences, and was looking for volunteers for the six-month Phase I study, according to reports in Chinese news outlets. According to CanSino, the vaccine candidate is the first novel coronavirus vaccine for COVID-19 to advance to Phase I in China. The company also cited results from preclinical animal studies showing that the vaccine candidate can induce strong immune response in animal models.
Treatment: 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 said March 9 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.
|15. Celularity and Sorrento Therapeutics
Type: Allogeneic, off-the-shelf, placental-derived Natural Killer (NK) cell therapy
Status: In a February 27 company presentation, Celularity stated that its anti-COVID-19 construct had been generated within weeks, and that its DAR-T and DAR-NK cells “will soon be produced for anti-COVID-19 activity testing.” The companies on January 30 launched a clinical and manufacturing collaboration designed to expand the therapeutic use of Celularity’s CYNK-001 to COVID-19. Sorrento and Celularity agreed to assess CYNK-001 as a potential novel therapy for coronaviruses, specifically SARS-CoV-2.
Sorrento—which owns 25% of Celularity—agreed to use current existing capacity in its cGMP cell therapy manufacturing facilities in San Diego to supplement Celularity’s new cGMP facility in Florham Park, NJ. Sorrento said it is already in contact with “leading” scientists and local Chinese experts to discuss clinical validation and logistics requirements for fast-tracking CYNK-001 in China.
|16. Chugai Pharmaceutical and Zhejiang Hisun Pharmaceutical
Treatment: Tocilizumab and favipiravir; tocilizumab
Type: Humanized mAb targeting interleukin-6
Status: On March 16, Peking University First Hospital registered an up-to-150 patient study assessing tocilizumab, marketed in China by Chugai Pharmaceutical, in combination with the Zhejiang Hisun Pharmaceutical-marketed drug favipiravir in adults with COVID-19 (ChiCTR2000030894). A 94-patient trial assessing Tocilizumab alone has been registered with Chinese authorities by The First Affiliated Hospital of University of science and technology of China (Anhui Provincial Hospital) (ChiCTR2000029765).
Chugai, a Roche subsidiary, said February 7 it had donated RMB 1 million (about $143,000) to the Red Cross Society of China to support coronavirus outbreak control efforts in China.
|17. Cocrystal and Kansas State University Research Foundation
Treatment: 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 February 24. Cocrystal said its primary goal was to advance its program into preclinical development, and pursue collaborations as the program progressed through clinical phases.
|18. CSL and The University of Queensland (UQ)
Type: Vaccine based on CSL subsidiary Seqirus’ proprietary adjuvant technology, MF59®
Status: On February 12, CSL said 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.
Nine days later, the University announced that 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.
Type: mRNA-based coronavirus treatment based on company’s vaccine platform.
Status: CureVac on March 17 told reporters in a telephone briefing that it was committed to launching animal trials of its mRNA-based COVID-19 vaccine in April, and clinical trials in humans by early summer. The update came a day after the European Commission offered up to €80 million ($88 million) toward scaling up development and productions of the vaccine. The Coalition for Epidemic Preparedness Innovations (CEPI) awarded the company up to $8.3 million in January for accelerated vaccine development, manufacturing and clinical tests.
During the briefing and in a statement two days earlier, CureVac denied a report in the German newspaper Welt am Sonntag that the administration of President Donald Trump sought to lure German-based CureVac to the U.S. with funding to produce its vaccine exclusively for the U.S. market after then-CEO Dan Menichella visited the White House March 2 with other biopharma executives, while Germany’s government pressed for the company to stay in Tübingen and produce its vaccine for Germany and Europe.
U.S. ambassador to Germany, Richard Grenell denied the report via Twitter, but an unnamed German Health Ministry spokeswoman confirmed Germany’s interest in CureVac developing vaccines there in a statement to Reuters. Menichella resigned on March 11, and was succeeded by former CEO and founder Ingmar Hoerr, who just five days later took a temporary leave of absence for medical reasons “not caused by coronavirus,” the company said.
Treatment: Leronlimab (PRO 140)
Type: Humanized IgG4 monoclonal antibody. Leronlimab is CytoDyn’s lead candidate, and is a CCR5 antagonist with potential for multiple therapeutic indications.
Status: CytoDyn on March 16 that it filed a modified IND and protocol for its Phase II clinical trial assessing leronlimab (PRO 140) in patients who experience respiratory complications as a result of contracting COVID-19. The trial is designed to evaluate 75 patients in up to 10 centers in the U.S. Enrolled patients are expected to have a treatment window of approximately 6 weeks. The company also corrected a March 12 press release to disclose that the first patient had missed one treatment of carboplatin and will continue to be treated with carboplatin and leronlimab.
CytoDyn and Longen China Group said February 12 they will begin exploring leronlimab as a potential treatment for coronavirus as well as cancer.
Leronlimab has successfully completed nine clinical trials in over 800 people, according to CytoDyn, including meeting its primary endpoints in a pivotal Phase III trial in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients. CytoDyn has said it plans to file a BLA with the FDA in HIV during Q1 2020. Leronlimab has the FDA’s Fast Track designation as a combination therapy with highly active antiretroviral therapy (HAART) for HIV-infected patients, and for metastatic triple-negative breast cancer.
|21. Distributed Bio
Treatment: Antibodies bioengineered to fight COVID-19
Type: Broadly neutralizing antibodies based on the company’s SuperHuman platform, which according to the company is the world’s most advanced computationally optimized human antibody library for antibody discovery.
Status: Distributed Bio founding partner, CEO, president, and chairman Jacob Glanville, PhD, told South Korea’s Maeli Business Newspaper that the company is working to extract five SARS-CoV-2 specific antibodies and mutate them into 1 billion different types to see whether any of the antibodies bind to the virus that causes COVID-19.
If a potential antibody is identified by April, it can be mass produced beginning in August or September, said Glanville, who gained fame after being featured in the Netflix docu-series “Pandemic: How to Prevent an Outbreak” in January.
|22. Eli Lilly and AbCellera
Treatment: Antibodies to treat and prevent COVID-19
Type: Anti-SAR-CoV-2 Antibodies based on AbCellera’s rapid pandemic response platform.
Status: Eli Lilly and AbCellera said March 13 that they will partner to co-develop the most promising of 500+ unique fully human antibody sequences identified in a blood sample from one of the first U.S. patients to recover from COVID-19.
AbCellera will tap into the expertise of the Dale and Betty Bumpers Vaccine Research Center of the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), which will identify the antibodies that bind the pandemic strain of SARS-CoV-2 the best. AbCellera and Lilly committed to equally share initial development costs towards a treatment, after which Lilly has agreed to oversee all further development, manufacturing and distribution. If successful, Lilly will work with global regulators to bring a treatment to patients.
|23. Emergent BioSolutions
Treatments: 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 that 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.
|24. Enanta Pharmaceuticals
Treatment: 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.
|25. Fujifilm Holdings and Zhejiang Hisun Pharmaceutical
Treatment: Favipiravir (marketed by Fujifilm as Avigan and by Hisun in China as Favilavir)
Type: Broad spectrum anti-viral agent that is designed to selectively and potently inhibit the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Japan has approved Avigan for novel or re-emergent influenza and was previously used to treat Ebola patients in Guinea.
Status: Zhang Xinmin, an official at China’s Science and Technology Ministry, told reporters March 17 that favipiravir produced positive results in clinical trials in Wuhan and Shenzhen involving 340 patients—including a shortening of the time after treatment that patients tested negative for COVID-19 from 11 days to four, and improved lung conditions in 91% of treated patients vs. 62% of untreated patients, as measured via x-rays.
Japan’s Health Minister Katsunobu Kato said February 22 that his ministry would recommend Avigan, developed by Fujifilm-owned Toyama Chemical, for use as a coronavirus treatment after test dosages appeared effective in mild and asymptomatic cases at least two medical institutions. In China, the National Health Commission on February 17 approved Hisun’s version of the drug as an investigational treatment for SARS-CoV-2 in an upcoming clinical trial being conducted in Shenzhen.
|26. Generex Biotechnology
Treatment: Ii-Key peptide vaccine
Type: Vaccine based on Generex’s Ii-Key immune system activation technology platform.
Status: Generex on March 4 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
Generex said February 27 it has 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.
|27. Gilead Sciences
Treatment: Remdesivir (GS-5734)
Type: Nucleotide prodrug
Status: Rear Adm. Richard Childs, an assistant surgeon general and lung specialist at the NIH, told The Wall Street Journal in a report published March 13 that remdesivir showed a positive effect on 14 Americans who contracted SARS-CoV-2 aboard the Diamond Princess cruise ship, and received the drug during treatment at Japanese hospitals.
The NIH announced February 25 it will run the first U.S. clinical trial evaluating an experimental treatment for COVID-19, by assessing remdesivir in patients at the University of Nebraska Medical Center in Omaha, where some Americans with the disease are being cared for or are under quarantine. Remdesivir showed “no adverse events” when administered to the first American confirmed to be infected with SARS-CoV-2, members of the Washington State 2019-nCoV Case Investigation Team reported in a case study published January 31 in The New England Journal of Medicine.
In China, clinical trials of Gilead Sciences’ remdesivir have begun after China’s National Medical Products Administration approved applications by the China-Japan Friendship Hospital and the Chinese Academy of Medical Sciences to conduct the studies. Remdesivir and chloroquine phosphate were “highly effective in the control of 2019-nCoV infection in vitro,” a team of Chinese researchers reported in a study published February 4 in Cell Research.
|28. GlaxoSmithKline and Clover Biopharmaceuticals
Treatment: 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 February 24, 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.
“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.
|29. iBio and Beijing CC-Pharming
Treatment: Vaccine for preventing infection from SARS-CoV-2
Type: Plant-derived vaccines 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 on March 18 reported progress towards developing vaccine candidates, including creation of the constructs and the filing on March 11 of four provisional U.S. patent applications supporting the VLP platform and other technologies for treating or preventing SARS-CoV-2 infections.
On February 3, 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.
|30. ImmunoPrecise Antibodies
Treatment: Vaccines and coronavirus-neutralizing antibodies
Type: Prophylactic and therapeutic compounds using ImmunoPrecise’s proprietary 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: ImmunoPrecise on March 12 announced its approach to developing a COVID-19 treatment called PolyTope mAb Therapy™, a defined antibody combination designed to target multiple epitopes and mechanisms of viral evasion. PolyTope mAb Therapy applies the company’s discovery platforms and artificial intelligence capabilities through its collaboration partner EVQLV.
On February 20, ImmunoPrecise said it had designated Ilse Roodink, PhD, chairwoman of Talem’s scientific committee, as its Coronavirus Global Project Leader.
|31. Incyte, Shanghai Hengrui Pharmaceutical
Treatment: Camrelizumab and thymosin
Type: Humanized monoclonal antibody targeting PD-1 (Camrelizumab); 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) (ChiCTR2000029806) and Southeast University (NCT04268537).
|32. Impact BioMedical
Treatments: 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 18 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 were shown to block 3 integral viral mechanisms for SARS-CoV-2 replication and infection: the viral spike interaction point, helicase, and protease.
|33. Innovation Pharmaceuticals
Type: Defensin mimetic in Phase II development in oral muscositis in Head and Neck Cancer patients
Status: Innovation said March 10 that tests of Brilacidin as a potential COVID-19 treatment were to start the week of March 16 at an undisclosed U.S. Regional Biocontainment Lab. The company said Brilacidin was a compelling candidate due to its unique qualities to mimic the human innate immune system and a mechanism of action that includes disruption of the membrane of pathogens, leading to cell death.
On February 24 Innovation said that it submitted a Material Transfer Agreement with an unidentified “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).
|34. Inovio Pharmaceuticals and Beijing Advaccine Biotechnology
Type: DNA Vaccine
Status: Inovio on March 12 said it received a $5 million grant from the Bill and Melinda Gates Foundation to accelerate testing and scale-up of CELLECTRA® 3PSP, a hand-held smart device for the intradermal delivery of INO-4800 that runs on AA batteries. Inovio is partnering with Beijing Advaccine Biotechnology on a Phase I trial in China in parallel with the company’s clinical development efforts in the U.S. to develop INO-4800 as a coronavirus treatment.
Inovio said January 30 it will leverage Beijing Advaccine Biotechnology’s expertise to run a Phase I trial in China in parallel with the company’s clinical development efforts in the U.S. to develop INO-4800 as a coronavirus treatment. Inovio has said it will develop INO-4800 through Phase I testing in the U.S., and has launched preclinical testing for clinical product manufacturing. INO-4800 development is also supported by $9 million grant from the Coalition for Epidemic Preparedness Innovations (CEPI).
|35. Janssen Pharmaceutical Cos. (Johnson & Johnson)
Treatment: Prezcobix™ (darunavir and cobicistat); Vaccine to be developed with BARDA
Type: HIV protease inhibitors (Prezcobix); vaccine type to be developed
Status: Janssen said January 29 it has 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 have been provided to the Chinese Center for Disease Control and Prevention for laboratory-based investigations. Prezcobix is under study in a trial sponsored by Shanghai Public Health Clinical Center (NCT04252274), while a Chinese trial is assessing Prezcobix or the lopinavir-ritonavir combination combined with thymosin a1 (ChiCTR2000029541).
Separately, Janssen said February 11 it has expanded an existing collaboration with the Biomedical Advanced Research and Development Authority (BARDA) to develop a vaccine candidate for SARS-CoV-2. The partners agreed to share R&D costs and expertise to help accelerate Janssen’s investigational COVID-19 vaccine into clinical trials. Janssen said it is also working closely with global partners to screen its library of antiviral molecules to accelerate discovery of potential COVID-19 treatments.
|36. Janssen Pharmaceutical Cos. (Johnson & Johnson) + Beth Israel Deaconess Medical Center (BIDMC)
Treatment: Preventive vaccine for COVID-19
Type: Vaccine based on Janssen’s AdVac® and PER.C6® technologies. Janssen noted that research and preclinical collaboration with BIDMC’s Center for Virology and Vaccine Research was foundational to developing vaccines for Zika and HIV.
Status: Janssen Pharmaceuticals said March 13 that it and Beth Israel Deaconess have commenced preclinical testing of “multiple” vaccine prospects, with the goal of identifying a COVID-19 vaccine candidate for clinical trials by the end of March. Janssen expressed optimism that it can launch a Phase I clinical study of a potential vaccine candidate by year’s end “in collaboration with multiple global strategic partners.”
Janssen added that it is preparing to scale-up production and manufacturing capacities to levels required to meet global public health vaccination needs.
|37. Johns Hopkins
Treatment: Antibodies targeting SARS-CoV-2
Type: 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.
Treatment: 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.
|39. LineaRx (Applied DNA Sciences) and Takis Biotech
Treatment: 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 Sciences said March 4 that four DNA vaccine candidates will be produced this month for preclinical animal testing 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 and LineaRx.
Applied’s majority-owned subsidiary LineaRx and Rome-based Takis Biotech said February 7 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.
Treatment: 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 on March 12 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 discussions with the FDA on submitting a pre-IND package in support of the potential use of iNO in coronavirus-associated ARDS.
Treatments: 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: 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.
Treatment: RYONCIL™ (Remestemcel-L)
Type: Allogeneic mesenchymal stem cell (MSC) product candidate, now under FDA review for treating pediatric steroid-refractory acute graft versus host disease (aGVHD). A BLA was filed in January.
Status: Mesoblast said March 10 it is in active discussions with government and regulatory authorities, medical institutions and biopharma companies about its plans to assess remestemcel-L in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19.
The company cited a clinical study published in February which reported that allogeneic MSCs cured or significantly improved functional outcomes in all seven treated patients with severe COVID-19 pneumonia. Mesoblast also cited post-hoc analyses of a study in 60 chronic obstructive pulmonary disease (COPD) patients submitted for presentation at a future conference, showing significantly reduced inflammatory biomarkers, and significantly improved pulmonary function in patients with elevated inflammatory biomarkers. The same inflammatory biomarkers are also elevated in COVID-19.
“Consequently, remestemcel-L could be an effective treatment to reduce the high mortality in patients with COVID-19 who are older, have elevated inflammation biomarkers, and develop moderate to severe ARDS,” Mesoblast CEO Silviu Itescu told GEN. “Clinical trials using remestemcel-L in ARDS associated with COVID-19 disease are expected to be initiated shortly.”
Type: Novel lipid nanoparticle (LNP)-encapsulated mRNA vaccine encoding for a prefusion stabilized form of the Spike (S) protein.
Status: Moderna on March 16 reportedly was to dose the first patient in a Phase I open-label, dose-ranging trial of mRNA-1273 (NCT04283461), occurring at Kaiser Permanente Washington Health Research Institute in Seattle. The study will assess the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults. The first batch of mRNA-1273 was shipped in February to the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC), with partnered with Moderna in designing the vaccine.
Treatment: 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: NanoViricides confirmed January 30 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).
NanoViricides’ 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.
|45. Novavax + Emergent Biosolutions
Treatment: Vaccine candidate to be selected
Types: Vaccines designed to apply company’s proprietary recombinant protein nanoparticle technology platform to generate antigens derived from the coronavirus spike (S) protein. Novavax said it expects to utilize its proprietary saponin-based Matrix-M™ adjuvant with COVID-19 vaccine candidates to enhance immune responses.
Status: Novavax has agreed to use Emergent Biosolution’s molecule-to-market contract development and manufacturing (CDMO) services to support clinical development of Novavax’s COVID-19 vaccine candidate. Emergent said March 10 it agreed to produce the vaccine candidate and has initiated work, anticipating that the vaccine candidate will be used in a Phase I study within the next four months.
On February 26, Novavax cited progress in its development saying it has produced and is currently assessing multiple nanoparticle vaccine candidates in animal models prior to identifying an optimal candidate for human testing.
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 unpublished results from collaborative research with the National Institute of Allergy and Infectious Diseases’ (NIAID) Integrated Research Facility at Fort Detrick, MD. The research 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.
Treatment: Antiviral compounds
Status: Pfizer on March 2 said it recently completed a preliminary assessment of antiviral compounds that were previously in development and that inhibited the replication of coronaviruses similar to the one causing COVID-19 in cultured cells. Pfizer said it was engaging with a third party to screen these compounds under an accelerated timeline and expected to have results back by the end of March.
“Toxicology studies would then need to be completed prior to any clinical development, but if successful, Pfizer hopes to be in the clinic by no later than the end of 2020,” the company added.
Treatment: 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). Six trials including Arbidol were listed on ClinicalTrials.gov. China’s Ruijin Hospital is conducting the monotherapy trial (NCT04260594), while Jiangsu Famous Medical Technology Co. will include 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 (NCT04252885, NCT04273763, NCT04261907, NCT04286503).
|49. 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.
|50. RedHill Biopharma
Treatments: Opaganib (Yeliva®, ABC294640) and RHB-107
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 March 11 that 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.
|51. Regeneron Pharmaceuticals
Treatments: Antibody cocktail therapy; REGN3048 and REGN 3051
Types: Combination of neutralizing monoclonal antibodies leveraging Regeneron’s monoclonal antibody discovery platform called VelocImmune®, part of the company’s VelociSuite™ technologies.
Status: Regeneron on March 17 announced making progress in developing an antibody cocktail therapy against COVID-19, saying that it isolated hundreds of virus-neutralizing, fully human antibodies from its VelocImmune mice, genetically-modified to have a human immune system—as well as antibodies from humans who have recovered from COVID-19. From these antibody candidates, Regeneron said, it will select the top two antibodies for a ‘cocktail’ treatment “based on potency and binding ability to the SARS-CoV-2 spike protein, as well as other desirable qualities.” Regeneron said it is working to produce hundreds of thousands of prophylactic doses per month by the end of summer, and smaller quantities for initial clinical testing at the start of the summer.
Regeneron has also said it is developing the combination of REGN3048 and REGN3051 as a COVID-19 treatment. The combination completed a Phase I trial in MERS-CoV last year (NCT03301090).On February 4, The Biomedical Advanced Research and Development Authority (BARDA) said it was expanding upon an earlier partnership agreement with Regeneron to develop “multiple monoclonal antibodies that, individually or in combination, could be used to treat new treatments.”
|52. Regeneron Pharmaceuticals and Sanofi
Treatment: Kevzara® (sarilumab)
Type: Interleukin-6 (IL-6) receptor antagonist approved by the FDA in 2017 to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
Status: Regeneron Pharmaceuticals and Sanofi on March 16 said they had launched a Phase II/Phase III U.S. clinical trial of Kevzara in patients with severe COVID-19 infection, and will begin recruiting patients immediately. Up to 400 adults hospitalized with serious complications from COVID-19 will be assessed in the study, set to begin in medical centers in New York.
The primary Phase II endpoint is reduction of fever and the secondary endpoint is decreased need for supplemental oxygen. Phase III will evaluate improvement in longer-term outcomes including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization. Regeneron will lead clinical studies in the U.S., while Sanofi will do so overseas.
|53. Roche (Genentech)
Treatment: Actemra (tocilizumab)
Type: Interleukin-6 (IL-6) receptor antagonist approved by the FDA in 2010, with indications in rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.
Status: Genentech said March 13 it was in “active discussions” with the FDA and other government agencies and institutions worldwide to initiate clinical trials for Actemra in severely ill COVID-19 patients, adding: “This is as much detail as we can provide at this time.”
China’s National Health Commission earlier this month included Actemra in its 7th updated diagnosis and treatment plan for COVID-19, to treat patients with high levels of IL-6 and serious lung damage. Three trials assessing Actemra have been registered with the Chinese Clinical Trial Registry: One of 198 patients (ChiCTR2000029765), one of 60 patients with JinYu Bio-Technology Co., which markets the drug as CMAB806 (ChiCTR2000030196), and one assessing the combination of Actemra, , intravenous immunoglobulin (IVIG), and continuous Renal Replacement Therapies (CRRT) (ChiCTR2000030442).
Treatment: Unnamed vaccine
Type: Vaccine based on Sanofi’s recombinant DNA platform, designed to produce an exact genetic match to proteins found on the surface of the virus. Sanofi said the DNA sequence encoding the antigen will be combined into the DNA of the baculovirus expression platform and used for rapidly producing large quantities of the coronavirus antigen, which will be formulated to stimulate the immune system to protect against the virus.
Status: John Reed, MD, PhD, Sanofi’s Global Head of Research and Development, restated March 16 that the Sanofi Pasteur vaccines global business unit plans to quickly develop a COVID-19 vaccine based on previous development work for a SARS vaccine, through a collaboration with the Biomedical Advanced Research and Development Authority (BARDA).
In non-clinical studies, the SARS vaccine candidate was immunogenic and afforded partial protection as assessed in animal challenge models, Sanofi said February 18. That earlier work by Protein Sciences, acquired by Sanofi in 2017, “provides a head start in expediting a COVID-19 vaccine,” Sanofi stated.
|55. Tiziana Life Sciences and Novimmune
Type: Fully human monoclonal antibody targeting the receptor for IL-6, in-licensed from Novimmune in January 2017. TZLS-501—to be administered using a proprietary formulation technology—is designed to bind to both membrane-bound and soluble forms of IL-6R, and rapidly deplete circulating levels of IL-6 in blood.
Status: Tiziana said March 11 it will expedite development of TZLS-501 with Novimmune, with which it entered into a worldwide license in 2017. Tiziana notes that excessive production of IL-6 is a key driver of chronic inflammation, believed to be associated with severe lung damage observed with COVID-19 infections and acute respiratory illness. China’s National Health Commission has recommended the use of anti-IL6-R monoclonal antibodies to treat inflammation and elevated cytokine levels (cytokine storm) in COVID-19 patients.
|56. Tonix Pharmaceuticals Holding
Type: Live modified horsepox virus vaccine for percutaneous administration
Status: Tonix said February 26 it has partnered with Southern Research to develop TNX-1800 as a vaccine treatment for COVID-19. TNX-1800 is under development as a potential smallpox preventing vaccine for the U.S. strategic national stockpile and as a monkeypox preventing vaccine.
|57. Vaxart and Emergent BioSolutions
Treatment: Vaccine based on proprietary VAAST™ Platform
Type: Oral recombinant vaccine administered by tablet
Status: Vaxart on March 9 agreed to use the “molecule-to-market” contract development and manufacturing (CDMO) services of Emergent BioSolutions toward developing and manufacturing Vaxart’s experimental oral vaccine candidate for COVID-19. Development services will begin immediately, and upon Vaxart’s election, Emergent is expected to produce bulk cGMP vaccine allowing Vaxart to initiate a Phase I clinical study early in the second half of 2020. Emergent 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 in January that it plans to generate vaccine candidates based on the published genome of SARS-nCoV-2, and evaluate them in preclinical models based on their ability to generate both mucosal and systemic immune responses.
|58. Vir Biotechnology and Biogen
Treatment: Human monoclonal antibodies
Type: Monoclonal antibodies designed to bind to SARS-CoV-2, and identified through Vir’s antibody platform. Vir engineers the fully human antibodies that it discovers, with the aim of enhancing their therapeutic potential.
Status: Vir said March 12 it signed a letter of intent with Biogen, under which Biogen agreed to carry out cell line development, process development, and clinical manufacturing activities for Vir while they negotiate a formal Clinical Development and Manufacturing Agreement. Vir added that it is conducting research to determine if its antibodies, or additional antibodies it may be able to identify, can effectively treat and/or protect against SARS-CoV-2.
Four days later, Biogen announced that the Biogen Foundation committed $10 million to support global response efforts and communities worldwide that have been impacted by COVID-19.
|59. Vir Biotechnology and NIAID
Treatment: Human monoclonal antibodies
Type: Monoclonal antibodies designed to bind to SARS-CoV-2, and identified through Vir’s antibody platform. Vir engineers the fully human antibodies that it discovers, with the aim of enhancing their therapeutic potential.
Status: Vir said March 11 it will partner with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), Vaccine Research Center, to identify and optimize combinations of antibodies against SARS-CoV-2 and other coronaviruses, including SARS and MERS, as well as antibodies that may be effective across additional types of coronaviruses. The partners will exchange antibodies and other materials for testing in combination and individually and, by mutual agreement, will perform in vivo animal studies to analyze immune responses.
|60. Vir Biotechnology and WuXi Biologics
Treatment: As-yet undisclosed human monoclonal antibodies
Type: Human monoclonal antibodies shown to bind to SARS-CoV-2, isolated from individuals who had survived a Severe Acute Respiratory Syndrome (SARS) infection.
Status: Vir Biotechnology on February 25 announced a development and manufacturing collaboration With WuXi Biologics to advance and produce human monoclonal antibodies as potential treatments for COVID-19. The antibodies were discovered through the company’s antibody platform, which has been used to identify and develop antibodies for pathogens that include Ebola (mAb114, currently in use in the Democratic Republic of Congo), hepatitis B virus, influenza A, malaria, and others. Should the antibodies receive regulatory approvals, WuXi Biologics has rights to commercialize therapies in Greater China and Vir, in all other markets worldwide.