Pipeline: Immunotherapies and Other Investigational Therapies for COVID-19

Updated on 6/16

While no specific treatment for coronavirus disease 2019 (COVID-19) is currently available, several therapies are being investigated globally.*   

AB201 (ARCA biopharma): a selective inhibitor of tissue factor being developed as a potential treatment for COVID associated coagulopathy. Clinical testing is expected to begin in the second half of 2020.

Acalabrutinib (AstraZeneca): a selective inhibitor of Bruton’s tyrosine kinase (BTK) being investigated for the treatment of cytokine storm associated with COVID-19 in severely ill patients. BTK inhibition reduces the production of multiple cytokines and chemokines which may potentially reduce respiratory complications of COVID-19. The Company has initiated an open-label study (CALAVI) to investigate the treatment. An NIH trial showed that the treatment reduced respiratory distress as well as hyperinflammatory immune response associated with COVID-19.

ACE-MAB (Sorrento Therapeutics): a bi-specific fusion protein that binds to the spike protein of coronaviruses. The investigational agent is expected to block SARS-CoV-2 from binding and infecting respiratory epithelial cells or ACE2-expressing cells. 

Anakinra: a recombinant interleukin-1 (IL-1) receptor antagonist being evaluated in patients with COVID-19, acute respiratory distress syndrome and hyperinflammation. High-dose treatment was found to be safe and was associated with clinical improvement.

ATYR1923 (aTyr): a fusion protein composed of the immunomodulatory domain of histidyl tRNA synthetase fused to the FC region of a human antibody. The product candidate will be evaluated in COVID-19 patients with severe respiratory complications. 

Auxora (CalciMedica): a potent and selective small molecule inhibitor of calcium release-activated calcium (CRAC) channels. The investigational agent may prevent pulmonary endothelial damage and lessen the cytokine storm in COVID-19. A phase 2 trial is underway and is expected to enroll 120 patients with severe COVID-19 pneumonia. Interim analysis showed Auxora plus standard of care reduced ventilator use and improved time to recovery compared to standard of care alone.

Aviptadil (RLF-100; Relief Therapeutics): a vasoactive intestinal polypeptide being investigated for the treatment of acute respiratory distress syndrome in patients with COVI-19 infection. The drug has now entered FDA clinical trials at Thomas Jefferson University Hospital. The multicenter trial will enroll patients who are already on mechanical ventilation to see if aviptadil can decrease mortality in this condition.

Baricitinib (Lilly): an oral Janus kinase inhibitor (JAK1/JAK2) being investigated in an NIH study for the potential treatment of hospitalized patients diagnosed with COVID-19.

Brensocatib (Insmed): a small molecule, oral, reversible inhibitor of dipeptidyl peptidase I currently being developed for the treatment of bronchiectasis and other inflammatory diseases. The drug candidate will be studied in patients with severe COVID-19 in an investigator-initiated trial (STOP-COVID19).

Brilacidin (Innovation Pharmaceuticals): a defensin-mimetic that mimics the human innate immune system and causes disruption of the membrane of pathogens, leading to cell death. The investigational agent has already been tested in humans in phase 2 trials for other indications.

Bucillamine (Revive Therapeutics): a cysteine derivative with 2 thiol groups that has the potential, via restoration of glutathione activity and other anti-inflammatory activity, to lessen the negative consequences of SARS-CoV2 infection in the lungs.

CD24Fc (OncoImmune, Inc): a first-in-class biologic that fortifies an innate immune checkpoint against excessive inflammation caused by tissue injuries. The Company has received approval from the FDA for its phase 3 clinical trial evaluating the safety and efficacy of CD24Fc for the treatment of hospitalized COVID-19 patients. A cohort of 230 patients with severe clinical symptoms will be randomized and administered a single dose of CD24Fc or placebo and followed for a 14-day period.

Centhaquine (Pharmazz): an investigational resuscitative agent that is expected to provide hemodynamic stability, improve tissue oxygenation, reduce pulmonary edema, reduce acute respiratory distress syndrome, reduce multiple organ dysfunction score and decrease mortality in patients with COVID-19. The Company is approaching various regulatory agencies regarding use of centhaquine as an adjunct in the management of critically ill patients with COVID-19; the drug has already been assessed in a phase 3 study for hypovolemic shock.

CERC-002 (Cerecor): an anti-LIGHT (homologous to Lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) fully human monoclonal antibody being investigated for COVID-19 cytokine storm induced acute respiratory distress syndrome. Placebo-controlled study expected to begin in June with top-line data anticipated in the 4th quarter of 2020.

Ciclesonide (Covis Pharma): a phase 3 trial has been initiated to treat non-hospitalized patients with symptomatic COVID-19. The inhaled corticosteroid has been shown in case reports to produce favorable outcomes in patients with confirmed infection.

Convalescent plasma: Convalescent plasma therapy for COVID-19 is currently being investigated across the nation by more than 1040 sites and 950 physicians through an expanded access program led by the Mayo Clinic. In addition, several clinical trials are evaluating the safety and efficacy of the therapy. The FDA is also accepting single-patient emergency Investigational New Drug Applications for individual patients.Recovered patients are being urged to donate plasma

Dapagliflozin (AstraZeneca): a phase 3 trial evaluating the sodium-glucose cotransporter 2 (SGLT2) inhibitor as a potential treatment for patients hospitalized with COVID-19 who are at risk of developing serious complications has been initiated in collaboration with Saint Luke’s Mid America Heart Institute.

DAS181 (Ansum Biopharma): a recombinant sialidase protein that cleaves sialic acid located on the surface of epithelial cells lining the human respiratory tract. The Company is enrolling patients in a proof-of-concept study to evaluate the safety and efficacy of the investigational agent for severe COVID-19 infection.

Deupirfenidone (PureTech): a deuterated form of pirfenidone, an approved anti-inflammatory and anti-fibrotic drug, being developed to treat serious respiratory complications associated with COVID-19. Global placebo-controlled trial expected to begin in the third quarter of 2020.

Famotidine: the H2 blocker is being investigated at Northwell Health in New York City following reports from China suggesting that the drug could potentially improve clinical outcomes in COVID-19 patients. Case series involving 10 outpatients showed the treatment was associated with improvements in disease-related symptoms. 

gammaCore (electroCore): an Emergency Use Authorization application has been submitted to the FDA to facilitate the study and clinical use of its gammaCore SapphireTM non-invasive vagus nerve stimulation therapy for respiratory symptoms associated with COVID-19. The hand-held therapy, which is applied at the neck, is currently approved for treating migraine and cluster headache.

Gimsilumab (Roivant Sciences): a fully human monoclonal antibody targeting granulocyte-macrophage colony stimulating factor (GM-CSF) being developed to treat acute respiratory distress syndrome associated with COVID-19. Gimsilumab has demonstrated a favorable safety and tolerability profile based on data collected to date.

HB-adMSC (Hope Biosciences): autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) will be evaluated in a phase 2 trial. The study is expected to enroll 75 patients that are either over 50 years of age, have preexisting health conditions, or are at high-exposure risk.

Ifenprodil (Algernon Pharmaceuticals): an N-methyl-d-aspartate (NDMA) receptor glutamate receptor antagonist that is being prepared for US trials. Animal study results showed the investigational therapy significantly reduced acute lung injury and improved survivability in H5N1 infected mice.

Immune globulin: Octapharma’s Octagam® will be investigated in a phase 3 trial to see if the treatment can stop respiratory deterioration in patients with COVID-19.

IMU-838 (Immunic): an orally available, selective immune modulator that inhibits the intracellular metabolism of activated immune cells by blocking the enzyme dihydroorotate dehydrogenase. A phase 2 trial, CALVID-1, is expected to begin soon with top-line data expected later this year.

Inhaled nitric oxide: the FDA has granted emergency expanded access for use of the INOpulse® system (Bellerophon Therapeutics) and the Genosyl DS tankless system (VERO Biotech) for treatment of COVID-19. In a clinical study of patients infected with SARS-CoV, nitric oxide demonstrated improvements in arterial oxygenation. Phase 3 study evaluating INOpulse has been cleared.

Ivermectin: an FDA-approved anti-parasitic agent that has shown antiviral activity against SARS-CoV-2 in vitro. MedinCell has launched a research initiative on a long-acting injectable formulation of ivermectin for COVID-19.

LB1148 (Leading BioSciences): a broad spectrum serine protease inhibitor designed to neutralize the activity of digestive proteases and preserve gut integrity during intestinal distress (eg, shock, infections, surgery). It is believed that the investigational agent may limit the viral load in patients with COVID-19 as the SARS-CoV-2 virus uses the ACE2 receptor, which is highly expressed in the lung and GI tract to infect epithelial cells of these organs.

LEAPS peptides (CEL-SCI): an immunotherapy being developed using a patented T cell modulation peptide epitope delivery technology, to stimulate protective cell-mediated T cell responses and reduce viral load.

Lenzilumab (Humanigen): an anti-human granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody. Mayo Clinic study in 12 COVID-19 patients (all at high risk of progression) showed that the investigational treatment led to rapid clinical improvement, with a median time to recovery and discharge of 5 days. 

Losmapimod (Fulcrum Therapeutics): a p38 MAPK inhibitor that has been shown to reduce proteins associated with acute inflammatory stress. An IND application to support initiation of a phase 3 trial has been submitted to the FDA.

LY3127804 (Lilly): an investigational selective monoclonal antibody against angiopoietin 2 (Ang2) being developed for pneumonia patients hospitalized with COVID-19 who are at high risk of progressing to acute respiratory distress syndrome. 

LY-CoV555 (Lilly): a potent, neutralizing lgG1 monoclonal antibody directed against the spike protein of SARS-CoV-2. A phase 1 trial has been initiated. 

Mavrilimumab (Kiniksa): a fully-human monoclonal antibody designed to antagonize granulocyte macrophage colony stimulating factor (GM-CSF) signaling by binding to the alpha subunit of the GM-CSF receptor (GM-CSFRα). In a prospective, interventional, single-active-arm, single-center pilot study, patients with severe pulmonary involvement of COVID-19, acute respiratory distress, fever, and clinical and biological markers of systemic hyperinflammation status​ were treated with a single intravenous dose of mavrilimumab. To date, 6 patients have been treated; patients showed early resolution of fever and improvement in oxygenation within 1-3 days. Twenty-eight day clinical outcomes data showed that mavrilimumab-treated patients experienced earlier and improved clinical outcomes than control-group patients, including earlier weaning from supplemental oxygen, shorter hospitalizations, and no deaths.

Multi-antibody cocktail therapy (Regeneron): a novel therapy that could potentially be administered as prophylaxis before exposure to SARS-CoV-2 virus or as a treatment for those already infected; may potentially enter human trials by early summer.

MultiStem therapy (Athersys): a stem cell product candidate for the treatment of acute respiratory distress syndrome induced by COVID-19. First patients have been enrolled in the phase 2/3 MultiStem Administration for COVID-19 Induced ARDS (MACOVIA) study.

Opaganib (RedHill Biopharma): a first-in-class, oral, sphingosine kinase-2 (SK2) selective inhibitor being developed for moderate to severe SARS-CoV-2 infection. Phase 2a study is expected to begin soon.

Pacritinib (CTI BioPharma): an investigational oral kinase inhibitor with specificity for JAK2, IRAK1 and CSF1R. The Company will evaluate the potential of pacritinib in preventing the development of an inflammatory response to COVID-19 in the phase 3 PRE-VENT study. 

PB1046 (PhaseBio): a subcutaneously-injected vasoactive intestinal peptide analogue being assessed in COVID-19 patients at high risk for rapid deterioration and acute respiratory distress syndrome. The investigational treatment will be evaluated in the VANGARD trial starting in June 2020; results are expected late in the 4th quarter of 2020.

Peginterferon Lambda (Eiger BioPharmaceuticals): a type III interferon (IFN) being investigated in a phase 2 study in outpatients with mild COVID-19 at the Stanford University School of Medicine. Administration of IFN lambda has been shown to suppress viral replication while stopping the cytokine storm from developing.

Remestemcel-L (Mesoblast Limited): an allogeneic mesenchymal stem cell (MSC) product candidate being investigated as a treatment for patients with acute respiratory distress syndrome caused by COVID-19. Remestemcel-L, which is composed of culture-expanded MSCs derived from the bone marrow of an unrelated donor, is administered in a series of intravenous infusions and is believed to have immunomodulatory properties to counteract inflammatory processes. A randomized, placebo-controlled trial is being conducted at Mount Sinai hospital in New York City.

Ruxolitinib (Incyte): a phase 3 study evaluating the efficacy and safety of ruxolitinib, a Janus kinase inhibitor, in patients with COVID-19 associated cytokine storm is being initiated. The Company intends to launch an Expanded Access Program to allow eligible patients to receive ruxolitinib, which is marketed under the brand name Jakafi in the US, while it is being investigated for COVID-19. 

Sargramostim: a yeast-derived recombinant humanized granulocyte-macrophage colony stimulating factor (rhuGM-CSF) being assessed in the SARPAC trial (sargramostim in patients with acute hypoxic respiratory failure due to COVID-19) at University Hospital Ghent to treat patients with respiratory illness associated with COVID-19. Sargramostim is marketed under the brand name Leukine (Partner Therapeutics) in the US.

Sarilumab (Regeneron and Sanofi): the interleukin (IL)-6 receptor antagonist is being evaluated in patients hospitalized with severe COVID-19 infection. Preliminary results from the phase 2 portion of an ongoing phase 2/3 trial showed that the drug lowered C-reactive protein, a key marker of inflammation, compared with placebo, meeting the primary end point of the study.

Siltuximab: a study has been initiated at the Papa Giovanni XXIII Hospital, Bergamo Italy, to investigate the use of the interleukin (IL)-6 targeted monoclonal antibody for the treatment of patients with COVID-19 who have developed serious respiratory complications (Siltuximab In Serious COVID-19; SISCO study). Interim data from the first 21 patients show that 7 patients experienced clinical improvement with a reduced need for oxygen support and 9 patients had no clinically relevant changes; worsening was seen in 3 patients and 1 patient died.

ST266 (Noveome Biotherapeutics): a cell-free platform biologic containing hundreds of anti-inflammatory proteins. According to the Company, its lead product candidate has the potential to treat severe inflammatory cytokine storm observed in COVID-19 patients. Human clinical trials are expected by the fourth quarter 2020.

TAK-888 (Takeda): an anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG) being developed for high-risk individuals with COVID-19. Pathogen-specific antibodies from plasma will be collected from recovered patients (or vaccinated donors in the future) and will be transferred to sick patients to improve the immune response to the infection and increase the chance of recovery.

TD-0903 (Theravance Biopharma): a lung-selective nebulized Janus kinase inhibitor in clinical development to assess its utility in preventing the cytokine storm associated with acute lung injury in patients hospitalized due to COVID-19, with the ultimate goal of preventing progression to acute respiratory distress syndrome. A phase 1 study has been initiated.

Tocilizumab (Genentech): a randomized, double-blind, placebo-controlled phase 3 trial is being initiated in collaboration with the Biomedical Advanced Research and Development Authority (BARDA) to evaluate the safety and efficacy of the interleukin (IL)-6 receptor antagonist plus standard of care in hospitalized adult patients with severe COVID-19 pneumonia. A study evaluating toculizumab in combination with remdesivir is expected to begin in June 2020.

Tradipitant (Vanda Pharmaceuticals): a neurokinin-1 receptor antagonist being evaluated for the treatment and prevention of pneumonia associated with COVID-19. The phase 3 ODYSSEY study will include 300 patients with severe infection.

TZLS-501 (Tiziana): the investigational therapy has been shown to rapidly deplete circulating levels of interleukin (IL)-6 in the blood, a key driver of chronic inflammation. Excessive production of IL-6 is believed to be associated with severe lung damage observed with COVID-19 infections.

Umbilical cord mesenchymal stem cells (RESTEM): a phase 1/2a study (Systemic Umbilical Cord Cells to Ease Severe Syndrome) is being initiated at Baptist Health South Florida and Sanford Health.

Vazegepant (Biohaven Pharmaceuticals): an intranasal, high-affinity calcitonin gene-related peptide receptor antagonist that will be evaluated in the treatment of pulmonary complications of COVID-19. The FDA has approved a phase 2 study.

*Not an inclusive list. Updates will be made as more information becomes available.