The drug candidate, known as EC5026, targets a novel pathway to block the underlying cause of certain types of pain. Described by EicOsis as a “novel, non-opioid and oral therapy for neuropathic and inflammatory pain,” it is an inhibitor to the soluble epoxide hydrolase (sEH) enzyme, a key regulatory enzyme involved in the metabolism of fatty acids. UC Davis recently licensed certain patents supporting the underlying technology exclusively to EicOsis.
Clinical trials are expected to begin this summer. “The clinical trials would be the world's first clinical evaluation of sEH for pain,” said William Schmidt, EicOsis vice president of clinical development, who has focused his entire professional career on developing novel pain medicines. “I am thrilled that we have a drug candidate lacking the side effects of both opioids and non-steroidal anti-inflammatory drugs that can potentially produce lead to an entirely new way to treat chronic pain.”
“Chronic pain is an enormous emotional and economic burden for more than 100 million people in the United States alone,” said Hammock, a UC Davis a distinguished professor who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. He co-founded EicOsis in December 2011 to alleviate pain in humans and companion animals. “The extreme and poorly treated pain that I observed as a medical officer working in a burn clinic in the Army, is a major driver for me to translate my research to help patients with severe pain.”
National statistics show that as many as eight out of every 10 American adults suffer from chronic pain; three out of four patients consider their therapies for pain ineffective; and as many as a third of the opioid-prescribed patients misuse them.
Every day, more than 130 people in the United States die from opioid overdose, according to the National Institute of Drug Abuse. The Centers for Disease Control and Prevention estimates that the total economic burden of prescription opioid misuse alone in the United States is $78.5 billion a year. That includes the costs of health care, lost productivity, addiction treatment, and criminal justice involvement.
“This completes the fundraising for Phase 1 of the clinical development program of this novel pain therapeutic,” said Hammock. “We are particularly pleased that the support came from Open Philanthropy with its history of both financially successful and socially important investments.”
Dushyant Pathak, UC Davis associate vice chancellor for Research and executive director of Venture Catalyst, lauded the achievement. “We are very pleased to see the achievement of this important business milestone by EicOsis,” Pathak said. “It's especially heartening to see the entrepreneurial persistence of Bruce Hammock being recognized by Open Philanthropy.”
Open Philanthropy identifies outstanding investment opportunities and makes grants based on importance, need, and tractability, according to the organization's scientific advisors Chris Somerville and Heather Youngs. They said Open Philanthropy selected the Davis project because the EicOsis drug “may reduce suffering from chronic pain conditions which are severe in both developed and developing nations.”
On its website, http://www.eicosis.com, EicOsis depicts itself as “a privately held company developing a first-in-class therapy of a once daily, oral treatment for neuropathic and inflammatory pain in humans and companion animals.”
“Our orally active compounds stabilize natural regulatory mediators in the body that reduce endoplasmic reticulum stress, which, in turn, appears to cause a variety of chronic diseases,” said EicOsis neurobiologist Karen Wagner. “The EicOsis compounds represent a new mechanism of action that both resolves inflammation and reduces pain.”
EicOsis (pronounced eye-cosis), derives its name from eicosanoid, “the major backbone of chemical mediators in the arachidonate cascade,” said Cindy McReynolds, an EicOsis project manager and a doctoral student in pharmacology and toxicology at UC Davis. “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.”
The National Institutes of Health (NIH) Blueprint for Neuroscience Research (Blueprint) awarded EicOsis a $4 million grant to advance compounds through Phase 1 clinical trials for diabetic neuropathic pain. A goal of the Blueprint Neurotherapeutics Network is to discover, develop and generate novel compounds that will ultimately be commercialized and benefit humankind.
In addition, EicOsis received support from the NIH's National Institute of Neurological Disorders and Stroke (NINDS), and the support of two small business programs affiliated with the National Institute of Environmental Sciences: the Small Business Innovation Research (SBIR) and the Small Business Technology Transfer (STTR).
“We are fortunate to receive all this support in the development of our oral medication for pain treatment through human Phase 1a trials, and now Open Philanthropy through human Phase 1b trials and beyond,” said Alan Buckpitt, a UC Davis retired professor of veterinary pharmacology and toxicology, and a principal investigator on the grants.
Nationally recognized for his achievements, Hammock is a fellow of the National Academy of Inventors, which honors academic invention and encourages translations of inventions to benefit society. He is a member of the U.S. National Academy of Sciences, a fellow of the Entomological Society of America, and the recipient of scores of awards, including the first McGiff Memorial Awardee in Lipid Biochemistry; and the Bernard B. Brodie Award in Drug Metabolism, sponsored by the America Society for Pharmacology and Experimental Therapeutics.
Hammock, a member of the UC Davis faculty since 1980, received his doctorate in entomology and toxicology from UC Berkeley. He traces the history of his enzyme research to 1969 during his graduate student days in the John Casida laboratory. Hammock was researching insect developmental biology and green insecticides when he and colleague Sarjeet Gill, now a distinguished professor at UC Riverside, discovered the target enzyme in mammals that regulates epoxy fatty acids.
“My research led to the discovery that many regulatory molecules are controlled as much by degradation and biosynthesis,” Hammock said. “The epoxy fatty acids control blood pressure, fibrosis, immunity, tissue growth, depression, pain and inflammation to name a few processes.”
“Basically, I began by trying to figure out how a key enzyme, epoxide hydrolase, degrades a caterpillar's juvenile hormone, leading to metamorphosis from the larval stage to the adult insect,” Hammock. He asked himself these questions: “Does the enzyme occur in plants? Does it occur in mammals?" It does, and particularly as a soluble epoxide hydrolase in mammals.
"It is always important to realize that the most significant translational science we do in the university is fundamental science,” said Hammock, marveling that “this all began by asking how caterpillars turn into butterflies.”
She and colleague Rebecca Rensberg sequenced the genes that encode for the spider glue protein. Their work appears in the April edition of the journal G3-Genes Genomes Genetics.
Stellwagen said she is particularly interested in the "biomechanical properties and genetics of silk, particularly the aggregate glue that orb-weaving spiders deposit on the capture spiral silk of their webs."
"I'll be talking about the biomechanics of spider glue--how droplets of glue on a spiders web stretch, and how environmental variables like humidity, temperature, and ultraviolet light affect that stretch," Stellwagen said. "I'll also be talking about the molecular biology of the glue--discovering the DNA sequences that code for main proteins that make up the glue, and how that sequence relates to the mechanical properties."
Stellwagen said that "most people are unaware of the glue on a spider's web because you can't see the droplets with your naked eye, but it's a really important feature of the web that spiders rely on to capture prey. Spider glue is also a modified silk protein, but has lost its fibrous characteristics that we think of when we hear the word silk. Currently, there are only around 20 full-length silk genes known--but many, many partial sequences--because these genes are really hard to sequence due to their size and repetitiveness. I'll talk about why it's so difficult to sequence silk genes, and what got my research over the hurdles."
An individual orb weaving spider can spin up to seven different types of silk, cach with unique functions and material properties, Stellwagen explained. "The capture spiral silk of classic two-dimensional aéenal orb webs is coated with amorphous glue droplets that function to retain prey that get caught in a web. The glue differs from solid silk fibers as it is a viscoelastic, amorphic, wet material that is responsive to environmental conditions. Humidity causes changes in the glue's maternal properties, like stretchiness and adhesion, while temperature mediates these affects. The glue is more or less resistant to damage caused by ultraviolet radiation depending on a species' habitat."
"At the molecular level, spider glue is a modified silk that is mostly comprised of proteins called spidroins (spider fibroins) encoded by two members of the silk gene family."
Stellwagen, whose postdoctoral research focuses on arachnids, is currently working with Mercedes Burns studying population genetics of Japanese facultative parthenogenic harvestmen. Using Oxford Nanopore, she is sequencing the genome of the polyploid species Leiobunum manubriatum in an effort to understand their mixed ploidy and sexual/asexual reproductive modes.
Stellwagen received her doctorate in biological sciences in July of 2015 from Virginia Polytechnic Institute and State University, Blacksburg, Va. Her dissertation: "Structure and Function of the Viscous Capture Spiral and its Relationship to the Architecture of Spider Orb Webs." She holds two degrees from Clemson University, South Carolina: a bachelor's degree and a master's degree. Her master's thesis: "Spider (Aranea) Diversity, Habitat Distributions and Pitfall Trapping in Kings Mountain National Military Park, South Carolina."
Stellwagen has also published her work on spider glue in the Journal of Experimental Biology and the Journal of Arachnology. She delivered oral presentations on "Towards Spider Glue: Sequencing the Longest Known Silk Family Gene" at the 2019 International Congress of of Arachnology, Christchurch, New Zealand, and the 2018 American Arachnological Society Annual Meeting in Ypsilanti, Mich.
Seminar hosts are Hanna Kahl, UC Davis doctoral student in entomology, and Jason Bond, the Evert and Marion Schlinger Endowed Chair in Insect Systematics, UC Davis Department of Entomology and Nematology.
The seminars, coordinated by medical entomologist/assistant professor Geoffrey Attardo, take place at 4:10 p.m. every Wednesday in Room 122 of Briggs Hall, through June 5. (See list of seminars)
Sarah Stellwagen's website
Hölldobler, an evolutionary biologist based at Arizona State University researches the evolution and social organization in ants. He says that colonies that are "true superorganisms, show great cooperation among their nest mates and exhibit fierce aggression against neighboring conspecific colonies and display complex territorial strategies." His experimental and theoretical contributions cover sociobiology, behavioral ecology, and chemical ecology.
Hölldobler and co-author E. O. Wilson won the Pulitzer Prize for non-fiction writing in 1990 for their book, The Ants. They also co-authored The Superorganism: The Beauty, Elegance, and Strangeness of Insect Societies and Journey to the Ants: A Journey of Scientific Exploration. Hölldobler is also the author of The Leafcutter Ants.
A native of Bavaria, Germany (born June 25, 1936), he studied biology and chemistry at the University of Würzburg. He wrote his doctoral thesis on the social behavior of the male carpenter ant and their role in the organization of carpenter ant societies.
Hölldobler began his academic career at the University of Frankfurt in 1971 as a professor of zoology. From 1973 to 1990 he served as professor of biology and the Alexander Agassiz professor of zoology at Harvard University, Cambridge, Mass. Hölldobler returned to Germany in 1989 to accept the chair of behavioral physiology and sociobiology at the Theodor-Boveri-Institute of the University of Würzburg.
From 2002 to 2008, Hölldobler was an Andrew D. White Professor-at-Large at Cornell University, Ithaca, N.Y. Since his retirement in 2004, he has worked at Arizona State University (ASU) as a professor and research scientist. A Regents' and Foundation professor, he is one of the founders of the Social Insect Research Group (SIRG) and of the Center for Social Dynamics and Complexity.
The seminars are coordinated by medical entomologist/assistant professor Geoffrey Attardo and take place at 4:10 p.m. every Wednesday through June 5 in 122 Briggs Hall. (See list of seminars)/span>
Forensic entomologist and adjunct professor Robert Kimsey, master advisor in the Animal Biology program and a lecturer in the UC Davis Department of Entomology and Nematology, and Elvira Galvan Hack, staff advisor in the Animal Biology major and a member of the Phoenix Cluster, won the 2019 Eleanor and Harry Walker Advising Awards from the College of Agricultural and Environmental Sciences, for faculty advisor and staff advisor, respectively. The awards honor excellence and innovation in academic advising.
They will be honored at a Thursday, May 2 ceremony, along with peer advisor Mirella Lopez of Animal Science, announced Susan Ebeler, associate dean for Undergraduate Academic Programs, CA&ES. The event takes place at 3:30 p.m. in Room 3001 of the Plant and Environmental Sciences Building. Ebeler praised Kimsey: "The committee was especially impressed with your strong student mentorship. Student and faculty nominators noted that you provide an inspiring model to students, helping them to explore diverse career paths and make connections with numerous employers and graduate and professional schools. Your enthusiasm and support for students is contagious!"
Ebeler praised Hack: "The committee was especially impressed with your commitment to and leadership in developing a strong community for students in the majors you advise. Your deep compassion and respect for students was noted by many in the nomination materials."
Picnic Day serves as the university's annual open house for prospective and current students, families, alumni, staff, faculty, and the greater Davis and regional communities. It all begins with the parade opening ceremony at 9:30 a.m. by the grandstands on North Quad Avenue, across from Wickson Hall. The parade begins at 10 a.m. Most Picnic Day events will run from 10 a.m. to 4 or 4 p.m. (See more information on the campus website.)
At Briggs Hall, home of the UC Davis Department of Entomology and Nematology, activities will take place from 9 a.m. to around 4:30 p.m., while the Bohart Museum will be open from 11 a.m. to 2 p.m.--shorter hours to enable the Bohart scientists and volunteers to help at Briggs Hall and with the UC Davis Picnic Day Parade. The UC Davis Entomology Club's parade entry is a gigantic black widow spider.
The Bohart Museum, themed, "Will Travel for Bugs: The Bohart Museum of Entomology's Collections from Around the World," is nominated for a people's choice award, as is the honey tasting at Briggs Hall. QR codes will be at each site. "Visitors will have the opportunity to vote for their favorite exhibits in five award categories," according to Madhuri Narayan, UC Davis Picnic Day exhibits director. Folks can vote by QR or vote here from 8 a.m. to 10 p.m. April 13. The prize for earning the most votes? "An awesome certificate and bragging rights," Narayan said.
Briggs Hall. Among the scheduled events:
- Cockroach Races: Participants can pick their favorite "roach athlete" and cheer it to victory.
- Honey Tasting: Extension apiculturist Elina Lastro Niño is planning on a number of varietals of honey.
- Maggot Art: Participants will dip a maggot into water-based, non-toxic paint and position it on paper and let it crawl. Voila! Maggot art, suitable for framing.
- Virtual Reality Bugs: Medical entomologist Geoffrey Attardo will set up a virtual reality system to enable people to view three dimensional models of insects. In VR, the models can be made to look life size, 40 feet tall or anywhere in between, he says. Here's the link that to view them in your web browser: https://skfb.ly/6xVru
- Bee Observation Hive: Viewers can check out the queen, workers and drones in the bee observation hive and see tools used in beekeeping.
- Bug Doctor: The Doctor Is In: Graduate students will identify insects and arachnids and answer questions
- IPM Booth: UC Statewide Integrated Pest Management Program professionals will discuss and answer questions about insect pests, beneficial insects and pest control. They will display their publications and live insects. In keeping with tradition, they will give away free lady beetles (lady bugs), to be released in gardens to devour aphids and other soft-bodied insects.
- Ants: Graduate students from Professor Phil Ward's lab will talk to visitors about the amazing world of ants.
- Mosquito Abatement: Sacramento-Yolo Mosquito and Vector Control District professionals will staff a booth
- Dr. Death: Forensic entomologist Robert Kimsey will staff his traditional Dr. Death booth, inviting the visitors to ask questions and look through microscopes.
- Davis Fly Fishers: The anglers will demonstrate fly-tying techniques in Briggs 158
- Aquatic Insects: Professor Sharon Lawler's lab will display a number of aquatic insects.
- Scavenger Hunt: Participants will search for and identify insects.
- Insect Face Painting: Entomology Club members will face-paint bees, butterflies, lady beetles and other insects
- T-Shirt Sales: Visitors can take their pick or picks among insect-themed t-shirts (popular t-shirts include beetles and honey bees). Newly printed t-shirts feature the roach races, an American Gothic of entomologists, and a cicada plugged into an amp. Selection and prices are online at https://mkt.com/UCDavisEntGrad/
- Bake Sale: The Entomology Club will offer insect-themed baked goods.
"At the Bohart, we are focusing on the various countries from around the world and some of their insect fauna," said Tabatha Yang, education and outreach coordinator. The 12 countries that the Bohart is highlighting, besides the United States, are Australia, Belize, Democratic Republic of Congo, Korea, Madagascar, Malayasia, Mexico,Papua New Guinea, Peru, Republic of South Africa, and Turkey.
“So for anyone who is from there, has lived there, has visited there, or who wants to visit there, please come and take a peak at some unique insects from around the world,” Yang said. “Some people enjoy traveling to explore cuisine and culture, but traveling for the flora and fauna of the world is equally wonderful. Insects are an important part of nature, so be curious, not afraid.”
The Bohart Museum was founded in 1946 by UC Davis entomologist Richard “Doc” Bohart (1913-2007). It is the home of nearly eight million insect specimens, plus a year-around gift shop and a live "petting zoo" that includes Madagascar hissing cockroaches, stick insects, tarantulas and praying mantids. The gift shop is stocked with books, jewlery, t-shirts, insect-collecting equipment, insect-themed candy, and stuffed animals.
The Bohart Museum is open to the general public Mondays through Thursdays, from 9 a.m. to noon and from 1 to 5 p.m., plus occasional, weekend open houses. Admission is free. Further information is available on the Bohart Museum website.
The UC Davis Department of Entomology and Nematology is chaired by nematologist/professor Steve Nadler. Molecular geneticist/physiologist Joanna Chiu, associate professor, serves as the vice chair.