Closely-held Arrivo BioVentures is developing novel, first-in-class medicines that target the underlying causes of diseases with high unmet need, aiming to achieve meaningful patient outcomes that extend and improve the quality of lives.
“Our team of experienced drug developers is dedicated to solving complex medical challenges, collaborating with innovators, investors, and pharmaceutical companies to pursue innovative, novel disease-modifying therapies that have the potential to be transformational for patients,” Mr. Steve Butts, co-founder and CEO of Arrivo, says in an interview with BioTuesdays.
The company’s current focus is on two clinical-stage candidates: Forvisirvat (SP-624), a SIRT6 activator that may be the first treatment specifically targeting women with major depressive disorder (MDD); and RABI-767, an FDA Fast-Tracked lipase inhibitor for predicted severe acute pancreatitis. “Each candidate features a novel mechanism of action, offering new treatment options for patients with conditions that currently have high unmet need,” Mr. Butts says.
He explains that Forvisirvat is a first-in-class activator of SIRT6, an enzyme with an epigenetic mechanism that regulates key biological processes—including DNA repair, mitochondrial function, inflammation, and glucose homeostasis—all of which are implicated in depression and other neuropsychiatric diseases such as Alzheimer’s.
According to Mr. Butts, preclinical and clinical studies have demonstrated Forvisirvat’s ability to enhance neural activity associated with mood regulation and cognition, supporting its development for MDD and potential expansion into cognitive disorders.
“We conducted a large Phase 2 study of 319 MDD patients, and very interestingly, found robust efficacy in females with no response in males. When exploring possible reasons for the differences in response by sex, we discovered published research that found that men and women express the same gene in opposite directions when depressed, suggesting an epigenetic mechanism may affect one sex differently than the other.”
Additionally, early efficacy was observed within two weeks, by both the investigator and female patients, with durable effects lasting a week after treatment cessation—findings that Mr. Butts says align with preclinical models.
“Forvisirvat has been very well tolerated,” he added. “Across five clinical trials, we’ve observed a benign side effect profile.”
Recently, Arrivo reported promising results from Cohort 1 of its Phase 1b SP-624-103 study, which evaluated Forvisirvat in 12 healthy participants (eight active, four placebo) who received 20mg of Forvisirvat over a 15-day dosing period. Quantitative EEG (qEEG) and Firefly Neuroscience’s (NASDAQ: AIFF) brain network analytics (BNA) assessments revealed an increase in beta power and a decrease in delta power—the latter being strongly associated with depression.
“These findings provide us with increased confidence that Forvisirvat should alleviate depressive symptoms,” Mr. Butts contends. “By normalizing cortical activity, it has the potential to enhance cognitive processing, attention, and cortical arousal.”
Depression disproportionately affects women, with two-thirds of U.S.-based patients being female. “We know that men and women experience depression differently,” Mr. Butts notes. “While women often exhibit outward symptoms, men tend to internalize theirs.”
Mr. Butts says the company is encouraged by these early data, particularly in females with depression, underscoring Forvisirvat’s potential to address a critical gap in depression treatment. “We are very excited because we’re getting close to personalized medicine—it’s moving in that direction.”
He adds that Arrivo is the first company to use a SIRT6 activator to treat patients with depression. Currently, there are no marketed therapies exclusively to treat MDD in women, despite its prevalence and distinct genetic profile.
Moreover, Mr. Butts emphasizes that Forvisirvat has utility across a number of different therapeutic areas. “We are very encouraged, as we have an active drug in the central nervous system with potential label expansion opportunities into other cognitive disorders, beyond MDD.”
Arrivo is now studying Forvisirvat in a large Phase 2b/3 trial for MDD.
The company’s second lead candidate, RABI-767, is a small molecule pancreatic lipase inhibitor designed to halt the toxic spillover of lipase and fatty acids from the pancreas, a key driver of tissue injury, systemic toxicity, organ failure, and death in severe acute pancreatitis.
“Currently, there are no approved treatments for acute pancreatitis beyond parenteral intravenous fluid management, analgesics, and supportive care,” Mr. Butts points out. “Unfortunately, 20-30% of hospitalized patients progress to severe disease, experiencing extended hospital stays, organ failure, and a 10-30% mortality rate.”
Acute pancreatitis affects more than 300,000 patients annually in the U.S., with 70-90% of cases linked to gallstones, alcohol, hypertriglyceridemia, or idiopathic causes.
“We licensed RABI-767 from the Mayo Clinic, one of the leading institutions in pancreatic medicine,” Mr. Butts notes. “With compelling animal data, we advanced it through Phase 1, demonstrating good tolerability, and we are now conducting a Phase 2a study.”
This Phase 2a proof-of-concept study involves 36 patients at ten U.S. sites and evaluates the impact of a single-dose administered directly to the site via endoscopic ultrasound-guided peripancreatic injection in combination with standard of care compared to standard of care alone in patients predicted to advance to severe acute pancreatitis.
“We’re assessing multiple endpoints—including disease progression, mortality, necrosis, hospitalization duration, and ICU stay—to determine the optimal strategy for Phase 3,” Mr. Butts says.
In July 2024, the FDA granted RABI-767 Fast Track Designation, highlighting its potential to address this critical unmet need. “We are very excited about the potential of this drug to offer hope to patients with this debilitating disease,” he adds.
Arrivo has secured global rights to RABI-767. “This is a major health economic opportunity,” Mr. Butts asserts. “Severe acute pancreatitis patients place a significant burden on healthcare systems, and with an estimated billion-dollar revenue potential, RABI-767 could be a game-changer.”
Looking ahead, Mr. Butts says Arrivo is expecting data readouts on both its Phase 2b/3 study of Forvisirvat and its Phase 2 study of RABI-767 in 2026, followed by a Phase 3 launch.
Since its inception, Arrivo has raised $100 million, including a $45 million Series B round closed in November 2023. “These funds will take us through Phase 2 and into Phase 3, after which we’ll explore strategic options—potentially partnering or pursuing an IPO,” Mr. Butts says.
“We’ve built a successful track record over our 20-year history, identifying promising assets, advancing them in-house, and transitioning them to larger companies—many of which have reached market,” he adds.
Summing up Arrivo’s mission, Mr. Butts concludes, “We have two very promising drugs targeting diseases with high unmet need. If we’re right, they’ll change the way medicine is practiced. It’s an exciting time to be in drug development.”
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