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Investments led by i2E, keep groundbreaking medical technologies on track to benefit patients worldwide
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or the past 24 years, i2E, Inc. and its investment arm, Plains Ventures, has played a major role in funding Oklahoma researchers and entrepreneurs by investing more than $35 million in Oklahoma bioscience companies that are developing new therapeutics, developing new medical devices, developing new diagnostic tools or providing support technologies for the bioscience industry and industry research and development. i2E’s portfolio companies are working to advance medical technologies that prevent hospital acquired infections, help physicians visualize colonoscopy procedures more clearly, protect against accidental catheter disconnection, provide pain-free therapeutics that combat eye disease, reverse hearing loss and much more. Even as these new technologies edge closer to bringing their life changing outcomes to patients around the world, other promising discoveries continue to emerge from Oklahoma laboratories. Millions of dollars will be required to advance them to the market. In Oklahoma, life science entrepreneurs will continue to turn to i2E for the critical seed funding needed to survive the initial stages of development. In the past 2 years, i2E Inc. has invested nearly $7 million in 8 bioscience or life science companies. The following is a look at some of the bioscience companies that i2E investments have supported over the years. All these diverse medical technologies share a common bond. i2E, Inc., led early investment rounds that provided critical funding ensuring the companies created to advance the new drugs and medical devices have the capital necessary to successfully negotiate the development and testing phase.
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PALDARA, INC., LAUNCHED IN 2019 WITH A CONCEPT Team Paldara celebrates 1st place built around an innovative hydrogel technology that prevents win in the Love’s catheter-associated urinary tract infections. Cup competition But the vision of the founders for their groundbreaking technology was much broader than a single device. “We’re developing a platform technology to prevent medical device infections in the hospital and other health care venues,” said Beau Blanchard, a Paldara co-founder along with William Colton, who developed the gel while a student at Oklahoma State University. The technology was developed in a laboratory the cofounders outfitted with money won through i2E’s Love’s Cup Competition, along with that raised through OSU’s Riata Pre-Seed Fund and was subsequently matched by an OCAST Technology Business Finance Program (TBFP) concept award through i2E. Colton’s innovation lubricates catheters with a patent pending antimicrobial hydrogel coating. That makes it easier to insert the device while destroying disease-causing bacteria and potentially up to 99 percent of infections that plague hospital catheter use. “Since hospitals absorb all costs associated with hospital acquired infections, preventing a single catheter-associated urinary infections could save hospitals an BEING AN OKLAHOMA average of $10,000 per patient,” Blanchard C-CORP HAS HELPED said. “We aim to serve throughout the care US KEEP COSTS continuum such as hospitals, nursing homes, LOW WHILE WE and home-health care organizations.” HAVE FOCUSED ON Next stop on the development DEVELOPING AN timeline for Paldara is preparation to seek INNOVATIVE PRODUCT FDA approval for their patent-pending FOR A WORLD-WIDE technology. ISSUE. WE HAVE BEEN The co-founders are preparing for a preTRULY BLESSED TO consultation meeting with the FDA to gain RECEIVE SUPPORT insight on a roadmap through the regulatory FROM OKLAHOMA approval process. STATE UNIVERSITY “We have been advised by several AND I2E, AND regulatory consultants who have spent time WOULD NOT BE HERE reviewing 510k applications at the Center WITHOUT OKLAHOMA for Devices and Radiological Health that our INVESTING IN ITS product should receive expedited approval ENTREPRENEURS and that we may be able to market our product in the next 2-3 years,” Blanchard said. Before the pair launched their venture to advance Colton’s innovation, they teamed with another OSU student to write a business plan around the concept and pitch it in the 2019 Love’s Entrepreneur’s Cup, which is managed by i2E. Paldara won first place and $20,000 in the High Growth Graduate division. Paldara also scored well in other major business plan competitions, including Rice University, Baylor University and Arizona State University. “The Love’s Cup experience provided critical external feedback and $20,000 to launch Paldara from concept to minimal viable product,” Blanchard said. “ “Over the last three years, we have been advised by David Thomison a George Kaiser Family Foundation Endowed Chair in Entrepreneurship and prior Venture Advisor at i2E,” he said. “The team has also been advised by Dr. Carol Curtis and i2E
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Venture Advisor Rick Rainey, who have helped us validate our company and prepare for a successful fundraise. Based on their incredible support, Paldara is now raising $1 million through a convertible note offering led by i2E.” After the Love’s Cup competition, the company received an OCAST Technology Business Finance Program (TBFP) concept award through i2E. Blanchard said the company used the TBFP award to purchase critical laboratory equipment.
Paldara’s founding as an Oklahoma-based venture has benefitted the company’s development through a supportive startup ecosystem that includes i2E and its partners in what is known as the Oklahoma Innovation Model. “Being an Oklahoma C-Corp has helped us keep costs low while we have focused on developing an innovative product for a world-wide issue,” Blanchard said. “We have been truly blessed to receive support from Oklahoma State University and i2E, and would not be here without Oklahoma investing in its entrepreneurs” They are steadily advancing their technology toward their first market and the problem of catheter-associated urinary tract infections. Paldara has developed a platform technology, and there are many more markets to address. “We have received interest from cardiac surgeons to prevent deep sternal wound infections, infections from inserting pacemakers, bone screws, central venous catheters, hip/knee replacements, etc.,” Blanchard said. Paldara, Inc. has the potential to prevent serious, lifethreatening infections in millions of patients worldwide, all from the determination of two college students who believed enough in their idea to raise external capital and start their own private research and development laboratory.
www.paldara.com
EXCITANT POTENTIAL OKLAHOMA CITY-BASED EXCITANT THERAPEUTICS is a pre-clinical stage pharmaceutical company working to develop an oral medication to treat two major vision conditions that often lead to blindness. Diabetic retinopathy and age-related macular degeneration threaten the vision of millions of people. However, current state-of-the-art treatments involve once-a-month invasive eye injections. “That imposes a high treatment burden on patents, BIO Edition 2022
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and up to 40 percent may not respond well,” said Henry Shin, Ph.D., Excitant’s CEO and co-founder of the company along with Jian-xing “Jay” Ma, MD/PhD, and Adam Duerfeldt, Ph.D. “With our technology, we are developing a first-in-class orally available drug for diabetic retinopathy and age-related macular degeneration, with differentiated disease modification profiles, to alleviate the treatment burden associated with the current standard of care,” Dr. Shin said. The compound Excitant is using to tackle vision damage was discovered in the University of Oklahoma Health Sciences Center laboratory of Dr. Ma, a renowned vision researcher. It was redesigned and improved in Dr. Duerfeldt’s laboratory through a research collaboration. Dr. Shin was a graduate student and post-doctoral fellow in Glow-in-the-dark Dr. Ma’s lab, while Dr. Duerfeldt was protein called a medicinal chemist on OU’s Norman luciferase. Image Credit: Creative campus. “Dr. Ma spent 20-plus years Commons License 2.0 Credit: Oregon investigating diabetic retinopathy, State University. Flickr and the work that culminated in the formation of Excitant revolves around his collaboration with Dr. Duerfeldt, who is now at the University of Minnesota,” Dr. Shin Henry Shin, Ph.D. said. “The collaboration focused on designing and synthesizing new Jian-xing “Jay” Ma chemical entities that selectively activate a protein called PPAR-alpha Adam Duerfeldt, Ph.D. (peroxisome proliferator-activated receptor alpha), which when activated decreases symptoms of diabetic retinopathy.” OU funding supported research by the trio as they sought a compound that showed potential to treat the condition. “We based our scientific approach on two large clinical trials that tested a drug therapy intended to reduce cardiovascular Dr. Robert Holbrook events in Type II diabetic patients,” Dr. Shin said. “The therapy wasn’t so successful for cardio, but there was a robust effect on diabetic retinopathy instead.” They founded Excitant in 2019 to translate their discoveries. Excitant has since received approximately $1 million Small Business Innovative Research grants from the National Eye Institute, which Dr. Shin described as “validation” of their science by peer reviewers. “It also enabled us to identify and develop a promising small molecule that shows therapeutic effects in rodent models of diabetic retinopathy and age-related macular degeneration,” Dr. Shin said. As CEO of a life sciences startup, Dr. Shin not only conducts high level research, but stays current on scientific literature and Insufflation learning about other scientific disciplines that would be helpful Retention Device as the company’s R&D needs evolve. (IRD) “Our tentative plan is to reach Investigational New Drug approval from the Food and Drug administration within the next The IRD is an three years,” he said. add-on device, So, how does the name “Excitant Therapeutics” fit a company intended to make that is immersed in R&D for compounds to prevent vision loss for colonoscopies safer millions of people worldwide – without requiring eye injections. and more efficient. 8
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The term “Excitant” was adopted from the scientific research process and substances that elicit active physiological or behavioral responses, Shin said. The founding scientists used cell-based assays to screen hundreds of newly synthesized compounds. “This assay uses a light-producing enzyme called luciferase, and it generates bioluminescense when provided the right stimulus,” he said. “We imagined this process as a tiny celebration, because we’ve found a molecule that “excites” the cells. As a result, we named our company Excitant Therapeutics.” Now that’s something to get Excitant about. Excithera.com
A LIGHT ON THE SUBJECT Of the more than 20 million colonoscopy procedures done in this country annually, roughly 20 percent of them are disrupted by a common obstacle: the patient’s colon can’t retain air. Why is that a problem? During a colonoscopy, physicians insert a device known as an endoscope – a tiny camera and a long, flexible tubular instrument that transmits an image of the lining of the colon – into the large intestine through the patient’s rectum. But the colon must be inflated for doctors to navigate and look for potential problems like polyps. “It becomes important to the physicians when they need to do something – they’ve identified a polyp or there is some bleeding -- and if we can’t see what we are doing that creates more problems, said Dr. Robert Holbrook, a Norman-based gastroenterologist and inventor. Dr. Holbrook founded a company in 2017 called BPEndo to advance a patented plug device he invented to solve the lack-ofinflation problem that often challenges physicians during the colonoscopy procedure. When the colon won’t inflate, nurses and technicians are called in to assist the physician in manually holding the patient’s body to keep air from escaping. “When we do that, it takes that person essentially out of the room,” Dr. Holbrook said. “They can’t do their normal tasks because they are trying to help us simply visualize the colon, which is normally pretty
easy to do. But when they have this problem, they can be quite difficult.” The two-piece device consists of a plastic handle that remains outside of the body and a balloon that is placed inside the body cavity. The handle snaps over the colonscope so that it doesn’t have to be removed from the body and reinserted. The intellectual property is protected by two “very broad” patents. “The technology BPEndo is developing solves a critical problem physicians face when performing colonoscopies,” said i2E Venture Advisor Rick Rainey, who has worked closely with Dr. Holbrook along his entrepreneurial journey. “New medical products like this tend to have favorable partnering or acquisition events with large manufacturers looking to bolster their current product offerings,” Rainey said. BPEndo’s technology appears so promising that the company attracted 13 gastroenterologists as early investors. Both of Dr. Holbrook’s physician partners at Norman Endoscopy Center are investors. “They know there is a problem, and this may be a good solution,” Dr. Holbrook said. “It’s been really well received.” In addition to investment by medical professionals, BPEndo received a $1.2 million seed round investment in 2019 that was led by i2E. As the device nears FDA approval, Dr. Holbrook anticipates another investment round that will facilitate manufacturing and sales. He continues to work closely with Rainey and his i2E colleagues. “i2E took a lead role in structuring the initial deal and valuation, discussing with me dilution and what my part would be, things like that,” Dr. Holbrook said. “I really relied heavily on their expertise and legal expertise to walk me through this whole process.” With expected FDA approval looming, there is anticipation of big things ahead for BPEndo and its founder. “If you just do the simple math, that’s at least 2 million colonoscopies that will need this device,” Dr. Holbrook said. “I’m excited about the future.” BPEndo.org
LINEAR HEALTH SCIENCES DEVICE SECURES FDA CLEARANCE Oklahoma City-based Linear Health Sciences has received U.S. FDA clearance and Health Canada approval of its Orchid SRV™, a tension-activated breakaway safety release valve designed to reduce the risk of IV catheter failure and replacement in hospitals. The medical device company also announced the simultaneous launch of Orchid SRV Type D, a Class I device based on the same proprietary platform technology for use in surgical/wound, nephrostomy, and abscess drainage. The Orchid SRV is a sterile, single-use connector for needlefree access that, when activated, makes return to treatment fast, simple, and clean, while improving both the patient and clinician experience. Clinical simulation testing of 360 Orchid SRVs showed that the device prevented IV dislodgement by 91.1 percent across all test groups. The Orchid SRV is indicated
Dr. Ryan Dennis
for use during direct injection, intermittent infusion, and continuous infusion. “We designed Orchid SRV to disrupt an area of medicine long overlooked and due for positive change,” said Dr. Ryan Dennis, Linear Health Sciences co-founder and CEO. “We expect our current and future pipeline of platform technology-based products to help change the standard of practice in vascular access and medical tubing applications as a whole.” Orchid SRV is placed between the existing IV extension set and general IV tubing connection intended to be used for delivery of fluids to and from an IV catheter. When tension (of up to 3.25 lbs.) acts on the IV line, the valve separates and seals off both sides of the IV, creating a sterile barrier. The clinician then restores the line simply by removing the separated halves and replacing them with a new, pre-packaged, sterile valve. According to a study published in J-AVA, 95 percent of 1,561 U.S. clinicians surveyed agreed that IV dislodgements continue to pose significant safety risks for patients and hospitals. In fact, reports have shown that, of the 342 million peripheral IVs in the U.S. each year1, up to 10 percent may dislodge2, costing more than $2 billion annually3. Dislodgement is most frequently caused by patient confusion or removal of the catheter, loose dressing or tape, or tubing becoming tangled in bed linens. “Despite great advances in other areas of medicine, there is still a significant unmet need for improved safety in IV therapy,” said Nancy Moureau, PhD, RN, CRNI, CPUI, VA-BC, an internationally recognized expert in vascular access practice who conducted the survey. “With an estimated 90 percent of hospitalized patients requiring treatment using IV therapy and a need to maintain those devices, it is time for a product like the Orchid SRV, not only to increase patient and staff safety but also to reduce cost associated with accidental dislodgment.” “The power of our breakaway safety release valve technology platform has been demonstrated and is now validated by both the FDA’s and Health Canada’s clearance of the Orchid SRV,” said Dan Clark, co-founder, president, and COO of Linear Health Sciences. “Our platform expands with the addition of Orchid SRV Type D, and we look forward to developing new use cases for it in other areas of medical tubing in the future.”
Linearsciences.com
In 2020, Plains Ventures, a subsidiary of i2E, led an $11.535 million Series B investment in Linear Health Sciences. It was a follow-on investment to a 2016 Seed round investment of $1.25 million and a $1.54 million Series A round in 2018, both of which were led by i2E/Plains Ventures.
References: 1 iData research report 2 "The Peripheral Intravenous Catheter Journey: A Prospective Cohort Study of 1000 Patients." Podium presentation by Nicole Marsh, RN, and Claire Rickard, RN, PhD, AVA 2017 ann 3 Helm, et al. “Accepted but unacceptable: peripheral IV catheter failure” J Infus Nurs May-Jun 2015;38(3):189-203. doi: 10.1097/NAN.0000000000000100
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