- Author: Kathy Keatley Garvey
EicOsis Human Health LLC, the Davis-based pharmaceutical company developing a non-narcotic drug to relieve chronic pain and inflammation, today announced the next step in its ongoing human clinical trials: the initiation of Phase 1b to test the safety of its drug candidate, EC5026.
The ongoing double-blind, placebo-controlled Phase 1b study is designed to investigate the safety and pharmacokinetics of daily doses of EC5026 over seven days.
EC5026, an inhibitor of the soluble hydrolase enzyme (sEH), was discovered and patented at EicOsis based on previous patents and research papers from the laboratory of UC Davis distinguished professor Bruce Hammock during his half-century of research.
“EC5026 plays a crucial role in regulating the metabolism of signaling lipids and responding to inflammation and other stress responses caused by trauma or disease,” said Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “We found sEH to be a target for treating pain, inflammation, cancer and other diseases.”
By inhibiting sEH, EC5026 alleviates pain by preventing the breakdown of natural analgesic and anti-inflammatory fatty acids. Preclinical studies demonstrate no sedation or other adverse behavioral effects and no signs of addiction.
“Many regulatory molecules are controlled as much by degradation as biosynthesis,” Hammock explained. "The epoxy fatty acids rapidly degraded by the sEH control blood pressure, fibrosis,immunity, tissue growth, depression, pain, and inflammation, to name a few processes.”
“The initial results from Cohort 1 appear to replicate the very favorable safety profile we observed in our previous two Phase 1a clinical studies where there were no adverse behavioral, cardiovascular, or neurological effects over five ascending single-dose levels,” said Dr. William Schmidt, EicOsis vice president of clinical development. “The maximum dose level was 5 to 10-fold higher than the anticipated analgesic dose in humans.”
“If Cohort 2 dosing also proceeds without clinically significant adverse effects and a favorable pharmacokinetic profile for once-a-day dosing,” Schmidt continued, “this provides encouragement for initiating our first analgesic efficacy study in the second quarter of 2024.”
EicOsis plans to initiate its first pain patient study in April 2024 “to evaluate safety and analgesic effects in patients with a spinal cord injury who have failed to achieve satisfactory pain relief with existing non-opioid chronic pain medications,” said Cindy McReynolds, EicOsis chief executive officer and former director of research.
“Initiation of the Phase 1b program represents a significant milestone for EicOsis Human Health and demonstrates the success and dedication of our team to make this happen,” said McReynolds, who holds a doctorate in pharmacology and toxicology from UC Davis. “Demonstrating safety in Phase 1b studies will allow us to evaluate efficacy in patients and bring forward safe and effective treatments for several serious diseases. For example, the sEH inhibitors are being considered for use for treatment of cancer in the UC Davis Comprehensive Cancer Center, and neurological disease through the UC Davis Health's designated Parkinson's Foundation Center of Excellence.”
“As a potential anti-inflammatory fatty acid, EC5026 holds promise in addressing neuroinflammation, a key factor in the manifestation and even progression of Parkinson's,” said Zhang, who holds both an M.D. and a PhD. “Ensuring its safety profile in healthy individuals is fundamental for establishing a foundation for further clinical trials. this investigation provides valuable insights into design and overall safety parameters, paving the way for the next stages in advancing this innovative therapeutic approach for Parkinson's disease."
The FDA granted Fast Track status to EC5026 in April 2020 to support the unmet medical need for safe and effective non-opioid analgesics. EicOsis clinical scientist Irene Cortés Puch, who authored the successful application, commented: “Both our commitment and focus at EicOsis Human Health are guided by a genuine concern for the well-being of patients and recognizing the importance of identifying effective pain management alternatives. Therefore, the initiation of this Phase 1b clinical trial is an exciting step in advancing our mission to provide safer and effective treatments.”
Hammock traces his research on chronic pain to his earlier work on how a caterpillar becomes a butterfly; a key enzyme, epoxide hydrolase, degrades a caterpillar's juvenile hormone, resulting in metamorphosis.
A member of the UC Davis faculty since 1980, Hammock founded ;EicOsis in 2011 and served as its chief executive officer until February 2023 when he transitioned to scientific officer and chairman of the board of directors. Highly honored by his peers, he is a member of the National Academy of Inventors and the National Academy of Sciences and received the 2020 Lifetime Achievement Award in Innovation from UC Davis Chancellor Gary May. Hammock has authored or co-authored more than 1400 peer-reviewed publications and holds more than 95 patents in agriculture, environmental science and medicinal chemistry.
EicOsis (pronounced eye-co-sis), derives its name from eicosanoids, “the major backbone of chemical mediators in the arachidonate cascade,” McReynolds said. “It symbolizes the epoxide group in chemistry, which is key to the anti-inflammatory chemical mediators and where the biochemical target called soluble epoxide hydrolase works.”
Approximately 50 million Americans (20 percent of the population) suffer from chronic pain, according to the Centers for Disease Control and Prevention. The annual economic toll is $560 billion, encompassing direct medical expenses, lost productivity, and disability claims.
More information on the Phase 1b multiple-ascending dose clinical study is available at https://clinicaltrials.gov/study/NCT06089837.
- Author: Kathy Keatley Garvey
It lived--and quite hidden at that--through the freezing cold, the rain, and the wind. It surfaced today on a milkweed in our Vacaville pollinator garden.
Surprise, surprise! We neither saw it as an egg nor as a tiny caterpillar.
"Most larval mortality in monarchs occurs in the first 2 or 3 instars.. so they keep as hidden and low-key as possible," entomologist David James, an associate professor at Washington State University, told us. "Once they make it to the fourth instar, they are emboldened and are more likely to be seen exposed."
James, who studies migratory monarchs, earlier commented on the fall breeding: "The egg laying females you are seeing now are likely migrants that have eschewed reproductive dormancy for reproduction. This has probably always happened to some extent but is likely more significant now because of warmer falls. The lack of activity in summer in Vacaville was probably a function of most of the population having dispersed further east and north, maybe more than usual? They surely did pass through Vacaville in spring on their way north but clearly didnt stop to use your milkweeds. It does seem that some years they are more prone to frequent stopping/oviposition on their way north and east, yet in others they just keep flying. There's evidence that the latter was the case this year... with as many migrants making it to BC as to Washington...Normally they stop in Washington and only a handful make it to BC."
James is the author of a newly published book, The Lives of Butterflies: A Natural History of Our Planet's Butterfly Life (Princeton University) with colleague David Lohman of the City College of New York. The book, released in the UK on Oct. 3, 2023, will be available in the United States starting Jan. 9, 2024.
Irish scientist Éanna Ní Lamhna recently interviewed the WSU entomologist in a podcast on RTÉ, or Raidió Teilifís Éireann. The book, Lamhna said, "showcases extraordinary diversity of world's butterflies, while exploring their life histories, behavior, conservation and other aspects of these most fascinating and beguiling insects." (See Bug Squad blog). Listen to the butterfly podcast here:
https://www.rte.ie/radio/radio1/clips/22294525/
Meanwhile, we checked another milkweed plant in the garden today and spotted another caterpillar, this one a little smaller and less active than the first.
As UC Davis distinguished professor Lynn Kimsey, director of the Bohart Museum of Entomology, commented: "So much for diapause!"
Now our milkweed garden includes scores of hungry aphids, several species of milkweed, two 'cats, and maybe three (one 'cat went missing and is probably j'ing somewhere) and four chrysalids.
Will we have a Merry Chrysalis?
- Author: Kathy Keatley Garvey
The third instar monarch caterpillar we found munching on the remnants of our cut-back milkweed on Jan. 23 in Vacaville, Calif., is now an adult butterfly fluttering around the neighborhood.
We brought the caterpillar in from the bitter cold and heavy rain and reared it in our Bohart Museum of Entomology habitat. Did it like the kitchen? The coffee brewing, the dishes rattling, and NPR sharing information on the declining monarch population?
A strange new world, for sure. But there it was safe and sound. Well, apparently sound.
It pupated on Feb. 4, forming a spectacular jade green chrysalis. Then we waited. And waited. And waited some more. It usually takes 10 to 14 days for a monarch to eclose but this one took 20 days.
We could see our little buddy's iconic orange wings through the transparent chrysalis. We joked about having a gender revealing party. Male? Female?
Finally, on Feb. 24, a healthy male eclosed. We don't usually name the monarchs we rear, but this one we named "Perseverance" after NASA's 2020 Perseverance rover looking for signs of life on Mars.
We released Perseverance on Feb. 25 on an abnormal spring-like day. For 10 minutes, he warmed his wings. Then he fluttered away as if he knew where he was going and what he was going to do when he got there. Monarchs are like that.
"Safe travels, Perseverance," we called after him.
In a previous Bug Squad blog, we likened our "winter monarch caterpillar find" to seeing the Easter Bunny delivering candy in December or Santa Claus handing out candy canes on Easter Sunday.
"Mama Monarch" must have laid the egg in late December, surmised butterfly guru Art Shapiro, UC Davis distinguished professor of evolution and ecology, who has researched butterfly population trends since 1972 and maintains a research website, Art's Butterfly World. "Evidence of inland winter breeding," he commented. "Nothing surprises me any more..." Indeed, he saw and recorded a monarch in Sacramento on Jan. 29, 2020.
In 2020, we collected more than 300 monarch eggs or caterpillars in our pollinator garden, primarily from two of the three milkweed species. We reared and released them or donated them to researchers at the University of California, Davis and the University of Nevada to start their own colonies.
The magical metamorphosis, the incredible transformation from egg to caterpillar to chrysalis to adult, never ceases to amaze. Neither does the Chuang Tzu philosophy: "Just when the caterpillar thought the world was over, she became a butterfly."
Just when Perseverance thought the world was over, he became a butterfly.
Maybe he will meet up with that monarch was saw Feb. 23--23 miles away in Benicia.
- Author: Kathy Keatley Garvey
Some people are born good-looking. Some have the gift of gab. And some are lucky enough to be born smarter than the rest of us. Whether we like it or not, Mother Nature does not dole these characteristics out evenly.--Simon Sinek
How true.
That applies to butterflies, too. Nobody said Mother Nature is perfect.
If you're rearing butterflies, such as Gulf Fritillaries (Agraulis vanillae), expect to see some defects, deformities and death. That chrysalis you've been watching? A butterfly may never eclose. In the cycle of life, the transformation from egg to larva to pupa to adult may never occur.
Nobody said Mother Nature is perfect.
The chrysalis is a withered grayish-brown, perfectly camouflaged on the butterfly's host plant, the passionflower vine (Passiflora). Sometimes you see a burst of reddish-orange wings and sliver spangled underwings, the remains of a butterfly that struggled to eclose.
Then you wait for one that will, one that will eclose.
The next one will take your breath away. Mother Nature is like that.
- Author: Kathy Keatley Garvey
It's Veterans' Day, and after paying tribute to the military veterans (my ancestors have fought in all of our nation's wars, dating back to the American Revolution--and my other half is a U.S. Air Force veteran), I slip out the back door to our pollinator garden to see where the insect action is.
Honey bees and a sole carpenter bee are buzzing on the African blue basil; Gulf Fritillaries are nectaring on the Mexican sunflower (Tithonia); and a cabbage white butterfly is sipping nectar from the Lantana.
But the passionflower vine (Passiflora) steals the show. A Gulf Fritillary has just eclosed from a chrysalis that resembles a thick wad of gum chewed up and spit out and left to mummify; several male Gulf Frits are fluttering around in search of females; and the offspring of previous reunions are crawling on the stems and munching what's left of the leaves.
Overhead, the California scrub jays glance down, as if trying to decide on their luncheon menu: a fat juicy caterpillar or the bird seed scattered in the feeder.
Their choice is clear. They forsake the fat juicy caterpillars for the bird seed. Tomorrow morning, however, there will be several caterpillars missing in action.
