CEO Mitchell Steiner said Veru Inc. at first downplayed the prospects of oncology candidate VERU-111 in COVID-19 treatment but now, with positive phase II data in hand, the company has a moral obligation to push onward to late-stage research.
“We could see in preclinical models that, in some instances, we had more activity than dexamethasone,” Steiner said. “I’ll be honest with you, I was concerned with standard of care [therapy used at the same time] that we would lose the signal in this small study.”
The opposite happened. Shares of Miami-based Veru Inc. (NASDAQ:VERU) closed at $13.92, up $3.02, or 28% on word of positive results from a double-blind, randomized, placebo-controlled phase II trial testing oral, once-daily VERU-111 at 18 mg vs. placebo in about 40 hospitalized patients at high risk for acute respiratory distress syndrome caused by COVID-19. Treatment for up to 21 days brought a statistically significant and clinically meaningful reduction in the proportion of patients recorded as treatment failures – i.e., dead or alive with respiratory failure. A 30% treatment failure rate turned up in the 20-member placebo group compared to 5.6% in the 18-subject VERU-111-treated group at day 29.
Findings represent an 81% relative reduction in treatment failures and showed statistical significance (p=0.05). Reported another way, the study gained 94.4% treatment success, with no treatment-related adverse events. VERU-111 yielded a statistically significant 82% relative reduction in patient mortality compared to placebo, as well as a statistically significant reduction in days in the intensive care unit. There was a decrease in days on mechanical ventilation, too.
The company said it will consult with the FDA about the design of a phase III trial with the compound, a first-in-class alpha and beta tubulin inhibitor/cytoskeleton disruptor also in the works for taxane-resistant triple-negative breast cancer (TNBC) and prostate cancer. In the latter, a phase III trial remains on track to start this quarter; in TNBC, a phase III experiment should start in the second half of the year.
Specifically, VERU-111 targets the colchicine binding site of alpha and beta tubulin and inhibits tubulin polymerization at low nanomolar concentrations. It disrupts microtubule filaments in a way similar to nocodazole and colchicine (VERU-111’s parent drug). In TNBC, the microtubules’ intracellular networks are disrupted from spindle shape and organized to globular and disorganized.
Phase III in April?
“Think of microtubules as the highway system of the cell,” Steiner told investors during a conference call. “When the virus gets in, it doesn’t just get in and float around to get to the nucleus to make more virus. It has to be transported there on a highway. Interestingly, once the virus gets into the nucleus and it gets replicated, it has to get transported back to the surface of the cell so it can be dumped back out to infect other cells,” which also requires the highway. VERU-111 “doesn’t care if you’re a green car, red car, truck or school bus – that highway gets disrupted. We believe this broad-spectrum antiviral approach will be blind to whether it’s a mutant strain or not.”
VERU-111 might work in a variety of inflammatory conditions. “It’s an anti-inflammatory for the exact same reason that it’s preventing viruses from replicating, from coming in and coming out,” Steiner said. “The vacuoles that contain all the cytokines in any of the immune cells have to be transported in the cell through microtubule trafficking. Those vacuoles, [which] are filled with cytokines, make their way to the surface of the cell and they have to be dumped out.”
When the company first began researching the compound in COVID-19, some predicted the virus would be gone by the time a therapy could be developed, Steiner said. “Here we are, eight months later, and the death rates are the same – if not, they’ve gone up. They’re talking about it being around for a few years like the Spanish flu. I pick up a newspaper and see people burying people all over the world. It just doesn’t feel like we’ve got a handle” on the virus, he said.
Standard-of-care treatment has evolved, albeit not rapidly, Steiner said. Hydroxychloroquine is “gone.” Convalescent plasma has taken “less of a role,” with its emergency use authorization narrowed. Veklury (remdesivir, Gilead Sciences Inc.) has done a good job “getting people home from the hospital, but not necessarily in the critical care situation.” Dexamethasone shows a reduction in death of four to five absolute percentage points. “Antibody therapies are still scratching their heads,” he said, and pointed to “a paucity in the amount of effective drugs available now in the critical care setting.” VERU-111 looks especially intriguing, given that it proved effective even on top of dexamethasone.
“The vaccine rollout is quite slow,” Steiner noted, and “you’ve got 30% or higher of the population that won’t take it. You’ve got mutant strains we’re already seeing that the vaccines are not covering. You’ve got antibody drugs that are going for epitopes that may not be covered in the mutant strains. It may be the new normal to deal with this,” if COVID-19 lingers like influenza and HIV. “I think that until we see something differently, we push ahead strong and fast,” he said.
“We have the resources to get going” with the phase III trial, once the FDA gives its nod, Steiner said. Financial details will be provided Feb. 10, when the company offers results for the fiscal 2021 first quarter, which ended Dec. 31. But Veru lacks the wherewithal to make the number of doses necessary if the phase III succeeds. Hospitalizations have held steadily at the level of 85,000 to 100,000 per week, he said, and “have changed dramatically to patients who are at high risk.” With VERU-111 given daily for 21 days, “it doesn’t take much to get you to about 37 million doses that will be required for the year – 37 million of anything [will cost] a lot of money. We’re going to the U.S. Biomedical Advanced Research and Development Authority and others to help us fund that.” Stockpiling could proceed as the phase III study goes on, he said. The study could start as early as April, and enroll about 200 patients.