COVID-19 roundup: Inovio starts vaccine trial; plus updates from RedHill, Hope, CytoDyn, Gilead, Takeda, AACR and UNC-Emory
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Inovio looks to be the second company after Moderna to start a U.S. trial of a COVID-19 vaccine, kicking the study off several months ahead of its previously projected summer trial start date. Outside of vaccines, companies including RedHill, Hope and CytoDyn are moving their coronavirus therapies into more patients.
Inovio Pharmaceuticals Inc. (NASDAQ:INO) said it plans to dose the first patient Monday in a Phase I trial for its DNA-based COVID-19 vaccine, INO-4800. Initial immune responses and safety data are expected by late summer.
Participant screening has begun for the trial, which will enroll up to 40 healthy adult volunteers at the University of Pennsylvania and the Center for Pharmaceutical Research in Kansas City to receive two doses of INO-4800 four weeks apart.
Inovio said that animal models have showed promising immune responses to the vaccine; further preclinical testing, including challenge studies, will continue in parallel with the Phase I trial.
Thus far, Inovio has manufactured thousands of doses to support the Phase I and planned Phase II trials. The biotech is working to further scale up manufacturing and plans to have 1 million doses of the vaccine available by year-end for additional trials and emergency use.
Inovio’s DNA vaccine platform delivers optimized plasmids directly into cells by using a brief electrical pulse to open small pores in the cell to allow the plasmids to enter. Once inside, the plasmids are used by the cell’s own machinery to generate specific coded antigens, stimulating an immune response.
HHS’s Defense Advanced Research Projects Agency allocated $45 million in 2015 to a project led by Inovio to develop a vaccine and therapies for Ebola, including a DNA-based vaccine (see “DARPA’s Gambles Might Have Created the Best Hopes for Stopping COVID-19”).
Inovio’s vaccine enters the clinic about two weeks after NIH’s National Institute of Allergy and Infectious Diseases started dosing in a Phase I trial of mRNA-1273 from Moderna Inc. (NASDAQ:MRNA); data are expected in June.
Inovio was up $0.70 to $8.44 Monday.
Four companies join Takeda-CSL plasma initiative
Biotest AG (Xetra:BIO), Bio Products Laboratory Ltd., LFB S.A. and Octapharma AG joined an alliance formed by CSL Ltd. (ASX:CSL) and Takeda Pharmaceutical Co. Ltd. (Tokyo:4502; NYSE:TAK) to develop a plasma-derived therapy to treat COVID-19 patients with serious complications.
The companies will bring together their respective programs with the aim of developing a single unbranded anti-SARS-CoV-2 polyclonal hyperimmune immunoglobulin medicine, Takeda spokesperson Katie Joyce told BioCentury.
This includes Takeda’s plasma-derived program TAK-888, Joyce said.
In early March, Takeda said it started development of TAK-888 to treat high-risk patients with COVID-19 (see “Biopharma Broads Fight Vs. COVID-19”).
Takeda has reserved manufacturing capacity at its plant in Georgia to begin producing the candidate. At the time, the company told BioCentury TAK-888 could be available to treat patients in 9-18 months.
The alliance will also collaborate on plasma collection, clinical trial development and manufacturing.
Last week, FDA named Mayo Clinic as the lead institution for its convalescent plasma program, with the American Red Cross helping to collect plasma from patients who have recovered from COVID-19 and distribute to patients (see “FDA’s Expanded Access Program for Convalescent Plasma”).
RedHill’s compassionate use programs
RedHill Biopharma Ltd. (Tel Aviv:RDHL; NASDAQ:RDHL) unveiled two compassionate use programs Monday: one in Italy, and one in Israel.
The biotech said it has been cleared by the Italian National Institute for Infectious Diseases and Central Italian Ethics Committee to start an expanded access program for Yeliva opaganib to treat 160 COVID-19 patients in three northern Italy hospitals with life-threatening symptoms.
RedHill said it also treated a COVID-19 patient at a hospital in Israel via a compassionate use program for Yeliva, and expects additional patients to be treated in the coming days.
Yeliva is a SPHK2 inhibitor in Phase I/II testing for various cancers. The compound could block the viral replication complex and pathological inflammation, according to the company.
The company has preclinical data demonstrating antiviral and anti-inflammatory properties of Yeliva and its potential to reduce lung inflammatory disorders and mitigate pulmonary fibrotic damage.
RedHill rose $0.84 (18%) to $5.60.
Gilead Sciences Inc. (NASDAQ:GILD) now has a 1.5 million dose supply of remdesivir, equating 140,000 courses of treatment. The company’s goal is to have 500,000 treatment courses by October and 1 million by year-end.
Chairman and CEO Daniel O’Day said it will make the doses available at no cost for compassionate use, expanded access and clinical trials to treat COVID-19 patients with severe symptoms, and will be donated for broader distribution following regulatory authorization.
To produce remdesivir at those levels, Gilead has reduced end-to-end manufacturing to six months from one year. The company has repurposed some of its facilities to focus on remdesivir and is collaborating with manufacturers to expand global capacity for raw materials and production.
O’Day said Gilead has added new U.S. sites for the antiviral’s expanded access program, and EMA has provided recommendations on implementing expanded access programs in the EU for remdesivir to treat COVID-19.
In March, the company began to work with worldwide regulatory authorities to launch expanded access programs for remdesivir, as individual requests for compassionate use had “flooded” its emergency treatment access system (see “Gilead Looks to Expand Access to Remdesivir”).
Stem cells from Hope
Hope Biosciences Inc. said that FDA approved a Phase II trial of its autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) to provide immune support against COVID-19.
The single arm trial will enroll 75 patients that are either 50 years of age, have preexisting health conditions or are at high exposure risk to receive five IV infusions of HB-adMSCs over a 14-week period. The trial will pretreat patients with the therapy to prepare the immune system to better fight SARS-CoV-2, with the goal of limiting progression and severity of disease if they eventually are infected.
Inflammation is a driving force behind COVID-19 disease progression, the company said. In a Phase I/II trial to treat rheumatoid arthritis, HB-adMSCs were safe and effective in attenuating systemic inflammation.
Hope has also submitted two other INDs to FDA for a trial in those at high risk of infection, including frontline workers, and another to treat hospitalized patients.
Trio of CytoDyn trials
CytoDyn Inc. (OTCQX:CYDY) provided an update Monday on its three clinical trials evaluating leronlimab to treat COVID-19.
In a Phase II trial for those with mild to moderate COVID-19 symptoms, two patients have been treated with the CCR5 antagonist.
As part of an emergency IND, CytoDyn has administered leronlimab to 15 severely ill COVID-19 patients at a New York City medical center and three other hospitals.
The company expects to start this week a Phase IIb/III double-blind, placebo-controlled trial in 342 severely ill COVID-19 patients.
CytoDyn is working with single cell diagnostic company IncellDx Inc., which has created three companion diagnostics to test for CCR5 and two more to monitor patients.
AACR joins virtual meeting trend
After announcing on March 10 that its April meeting will be postponed, the American Association for Cancer Research said Monday it will now hold two virtual meetings instead.
The first meeting, April 27-28, will feature “high-impact” paper presentations, clinical trial plenary sessions and three New Drugs on the Horizon symposia.
On June 22-24, the second meeting will include presentations on the latest developments in tumor biology and genetics, early detection, precision oncology and cancer immunotherapies.
Last month, the American Society of Clinical Oncology said its May 29-June 2 meeting will take place virtually.
EUA for Luminex assay
Luminex Corp. (NASDAQ:LMNX) said FDA granted Emergency Use Authorization for its ARIES SARS-CoV-2 Assay.
The assay runs on the company’s ARIES molecular diagnostic platform, which can give results within two hours and perform 144 tests per day.
The company said it will scale up production of the assay over the next three weeks to provide to labs that already operating on the ARIES system.
Last month, Luminex received EUA for its high-throughput NxTAG CoV Extended Panel, which can be run on its bead-based MAGPIX system to test 96 samples in about four hours.
UNC data for Emory compound
A team lead by University of North Carolina Chapel Hill scientists reported Monday in Science Translational Medicine data supporting COVID-19 treatment with nucleoside analog EIDD-2801, from the Emory Institute for Drug Development.
EIDD-2801 is an orally available prodrug of EIDD-1931, which blocked replication of a Washington state SARS-CoV-2 isolate in cultured monkey kidney cells with an IC50 of 0.3 uM. In human airway epithelial cells, 0.1 uM EIDD-1931 also blocked the strain’s replication and resulted in about a 4-log reduction in viral titers.
Hinting that potency in cell culture may translate to efficacy against COVID-19 in animals an perhaps humans, they showed EIDD-2801 could protect mice from infection by Middle East respiratory syndrome coronavirus (MERS-CoV) and the SARS-CoV-2 relative SARS-CoV.
In mice intranasally infected with MERS-CoV or a mouse-adapted version of SARS-CoV, EIDD-2801 administered two hours before or 12 hours after infection reduced lung injury weight loss and lung viral titers.
But emphasizing the importance of beginning antiviral therapy as early as possible, protective effects began to wane or were lost if EIDD-2801 was administered beginning 24 or 48 hours after infection by either virus.
Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus.
CCR5 (CD195) - CC chemokine receptor 5
SPHK2 - Sphingosine kinase 2