A new U.K. trial evaluating drugs for hospitalized patients in the early stages of COVID-19 has elected to test Evelo Biosciences Inc.'s anti-inflammatory monoclonal microbial, EDP-1815, after an earlier trial found it led to favorable anti-inflammatory activity in psoriasis patients. Interim data from the trial, called TACTIC-E, are anticipated during the fourth quarter. If results of the phase II/III study are positive, Evelo said its team will engage with regulators to determine if the data support registration. Company shares (NASDAQ:EVLO) rose 18.1% to $4.41 on June 22.

The adaptive trial, sponsored by Cambridge University Hospitals NHS Foundation Trust, joins a planned U.S.-based phase II study that's expected to evaluate EDP-1815 in COVID-19 patients, too. As COVID-19 hot spots evolve and change, other potential global trials of the drug could be launched in countries such as India and Brazil, Evelo's chief scientific officer and R&D chief, Mark Bodmer, told BioWorld.

The work, getting underway as the World Health Organization reported total global cases of COVID-19 have approached 8.9 million, could help define a role for EDP-1815, which leverages the connection between the immune system in the gut and inflammatory responses in the rest of the body. By modifying cells in the small intestine, which Bodmer likens to the motherboard of the inflammation system, it can trigger normalization of cytokine levels.

Mark Bodmer, chief scientific officer and R&D chief, Evelo

In the phase Ib trial in psoriasis, EDP-1815 limited the production of multiple inflammatory cytokines, including IL-6, IL-8, TNF and IL-1b, Evelo said. It was also well-tolerated with no overall difference from placebo, the trial found. Preclinical models found the candidate, Evelo's lead asset, resolved inflammation across TH1, TH2 and TH17 pathways, too. That led to down-regulation of cytokines including TNF, IL-4, IL-5, IL-6, IL-12p40, IL-13 and IL-17, several of which have been implicated in the cytokine storm associated with severe complications of COVID-19.

The oral candidate comprises a single strain of the microbe bacterium Prevotella histicola, which was isolated from the duodenum of a human donor. Fermented, then freeze-dried, the white powder product is then put in enterically coated capsules.

"When we compare EDP-1815 to other either oral systemic drugs or injected antibodies, it works just as well and sometimes better while, in the clinic, having a great safety profile," because there's no systemic exposure to the drug, he said.

In TACTIC-E – officially called the Multi-Arm Therapeutic Study in Pre-ICU Patients Admitted With Covid-19 - Experimental Drugs and Mechanisms – investigators are also testing a combination of Astrazeneca plc's approved cardiovascular drugs, Farxiga (dapagliflozin) and Letairis (ambrisentan), a drug co-marketed by Gilead Sciences Inc. and Glaxosmithkline plc, though now available as a generic. Both the combination and EDP-1815 will be tested in addition to standard of care (SOC).

A protocol for the study, which estimates enrollment of more than 1,400 patients, will initially randomize patients 1-to-1-to-1 across three arms, including one in which participants will receive EDP-1815 for up to seven days with an optional 14-day extension on top of SOC. The other two arms will test a combination of 10 mg of dapagliflozin plus 5 mg of ambrisentan and SOC and SOC alone, with the latter being a regimen that could change over time.

While the study's primary endpoint is a comparison to SOC, it also includes 15 secondary endpoints spanning a range of measures, including change in biomarkers thought to be associated with progression of COVID-19 compared to baseline, duration of oxygen therapy and hospitalization, and all-cause mortality.

More studies to get underway

In addition to Evelo's announcement Monday, Gilead provided an update saying that the FDA has given it a green light to start trials of an inhaled version of remdesivir. The Foster City, Calif.-based company will screen healthy volunteers for phase I trials this week and hopes to begin studies in patients with COVID-19 in August, it said.

The inhaled formulation studies could offer one avenue to using remdesivir in the earlier stages of COVID-19. Another approach that might work there is I.V. infusions of the experimental drug in outpatient settings, such as infusion centers and nursing homes. "For patients who are at high risk of disease progression, it could be particularly beneficial to start treatment outside the hospital. Our hope is that earlier intervention could help patients avoid hospitalization altogether," Gilead CEO Daniel O’Day said in a letter posted by the company. Production of the drug is also proceeding, with the company expecting to have more than 2 million remdesivir treatment courses manufactured by the end of the year and many millions more by 2021, he said.

Shares of Gilead (NASDAQ:GILD) fell 2.3% on Monday to $75.67.

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