Principals
Robert
A. Casper, Ph.D
David
L. Gardner, Ph.D
Gastrointestinal
Devices
InteliSite Articles Clinical
Trials/StudiesRespiratory Devices
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email
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| August,
1995 (BT Catalyst) |
Innovative Devices, LLC, Company Profile |
| September
3, 1995 (News & Observer) |
Hillsborough Start-Up Finds A Way To Target The GI Tract "Capsule is New Take on Drug Testing" |
| January
21, 1997 (News Release) |
TheraTech Expands Protein Delivery Capabilities By Acquiring Pulmonary Delivery Technology |
| January
31, 1997 (Triangle Business Journal) |
Hillsborough Firm to Ramp Up After 1st Sale |
| February
15, 1997 (Genetic Engineering News) |
Collaborations and Agreements |
| March
7, 1997 (Triangle Business Journal) |
Signal-Sending Test Pill Benefiting Scientists |
| March/April
1997 (BT Catalyst) |
Innovative Devices Signs Licensing Deal |
| June,
1997 (Start Up Magazine) |
Innovative Devices "A Capsule Tracks Drug Absorption in the GI Tract, and Two Respiratory Inhalers Help Asthmatics Breathe Easier" |
| June,
1997 (Machine Design Magazine) |
A $1200 Pill That's Worth The Price |
| July, 1997 (PPS TV Program) |
Breakthrough Program-Future X Segment on InteliSite® Capsule |
| August
6, 1997 (News Release) |
TheraTech, Inc. and Innovative Devices, LLC Receive Patent for Dry Powder Inhaler Drug Delivery Device |
| September,
1997 (BT Catalyst) |
News Brief on Innovative Devices Allowance of DPI Patent |
from BT CATALYST - AUGUST 1995
section "Company Profile"title "INNOVATIVE DEVICES LLC"
As his two partners recline in matching swivel chairs, David Gardner ponders what he brings to Innovative Devices LLC of Hillsborough. "We split the work around," he says. "I'm probably the computer whiz of the group." Frank Leith and Bob Casper burst into laughter.
"We're both engineers, and Dave's a physiologist," Casper says in between teasing retorts flung at his colleague. To be precise, Casper holds a doctorate in biomedical/biochemical engineering, Gardner, a Ph.D. in physiology. Leith is an electrical engineer with an MBA. Eight months ago this eclectic trio formed Innovative Devices (ID) to develop and manufacture novel medical devices. Their products include a remote-controlled drug-delivery capsule for use in bio-availability studies and breath-actuated inhalors for use in treating pulmonary diseases. They also perform contract research on inhalation devices.
Developing such intricate tools involves a range of skills. Each partner's talents - be they in manufacturing, biomedicine, electronics, (or computers) - complement the others' to yield new, cutting-edge products. Together they've spent the past month cranking out a business plan, marketing documents and funding proposals as well as conducting lab work. "We do try to stimulate each other," Gardner says after the laughter subsides. "I think that's how a lot of things are done here."
One of the fruits of the partners' diverse talents is the InteliSite’ capsule, which combines engineering, physiology and pharmacology into a controlled mechanism for observing how well drugs are absorbed through the intestinal tract. As Casper describes InteliSite, "It's like putting a drug in a submarine and popping the hatch [at the desired location]." A human volunteer swallows the capsule, which carries up to a milliliter of drug in its reservoir. A radiotracer enables the capsule's journey through the gastro-intestinal (GI) tract to be followed. Once the capsule has reached the target spot, a radio pulse triggers InteliSite's inner sleeve to rotate so its apertures align with those on the outer sleeve, releasing the drug.
The capsule offers the only alternative to the current method of inserting tubes down the esophagi of human volunteers to deliver drugs for absorption studies. The capsule measures a little over an inch long - a "horse pill" by industry standards. But, as Casper says, "it's easier to swallow than 30 feet of naso-gastric tubing." Moreover, Gardner points out, subjects do not have to forego eating before studies using InteliSite, thus enabling results to better reflect everyday reality; as Gardner points out, "most people don't fast before they take their medication."
One key advantage for drug developers, Gardner notes, is that the capsule can save clients time and money up front by efficiently demonstrating whether a drug will work in oral formulation. For example, many therapeutic peptides and proteins cannot withstand direct contact with the GI tract. However, drug developers prefer the convenience of oral administration, which yields higher patient compliance. Inhalant formulations are an attractive oral drug-delivery alternative, and ID is developing improved inhalors to help deliver drugs more efficiently.
Inhalors, hand-held pumps that spritz medication toward a user's windpipe with the press of a button, might seem low-tech and mundane compared to "submarine-like" capsules. However, ID's technology again combines engineering with physiology and pharmacology to create an improved product. Metered-dose inhalers (MDIs) are the most commonly used for their speed and convenience, but some studies indicate that up to 90 percent of users-especially pediatric and elderly patients - do not correctly coordinate their inhalation with dosing. ID is securing patents to create automatic, breath-actuated inhalors that measure and respond to individuals' inhalation rates and spritz medication at the peak of breath intake. The automated device could also deliver dry powder formulations of drugs, such as peptides and proteins, that do not mix well with the aerosol propellants used in MDIs.
ID's inhalors are still three to five years from the market, Leith said. In the meantime, the partners will look to revenues from the InteliSite capsules, which will be launched in late October, to help support the company. They are also pursuing federal grants and joint ventures. For now, the company runs on funds from each partners' pocket. They relish the entrepreneurial spirit of sharing equally in the work and the satisfaction of developing innovative technologies.
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THE NEWS & OBSERVER - SATURDAY, SEPT. 3, 1995
"Hillsborough Start-Up Finds a Way to Target the GI Tract""Capsule is new take on drug testing"
Hillsborough - Imagine a miniature submarine floating through the human gastrointestinal tract and - when it reaches just the right spot - popping the hatch and unloading a dose of medication.
That, in effect, is what the brains at Innovative Devices LLC, a Hillsborough start-up, are putting together in their cramped laboratory in a former textile mill.
The company's three founders and sole employees - two former Glaxo scientists, David Gardner and Robert Casper, plus Frank Leith, an electrical engineer with an M.B.A. - expect to be selling such devices before the end of this year.
The threshold question - why would anyone want such a device - actually has a relatively straightforward answer.
When pharmaceutical companies test oral doses of new drugs in humans, they need to determine how quickly the drugs are absorbed. That's because some drugs are rendered ineffective by acids in the stomach. And other drugs, depending on their chemical composition, are more effective at different spots in the GI tract, where the acidic levels and bacteria vary considerably.
The upshot is that the drug companies need to determine how quickly a new drug will be absorbed at various sites along the GI tract.
The best current method of doing that is a nasty one. It involves inserting 30 feet or so of tubing through the nose and down the throat of a paid volunteer, then releasing the drug through the tube at various spots. Blood samples determine how quickly the drug is absorbed at those sites.
Innovative Devices' patented InteliSite capsules, which will cost $1,000 apiece, could change all that. All a paid volunteer would have to do is swallow a large - 35 millimeters long - plastic capsule that is radio-controlled and contains a minute amount of radioactive material. Once the capsule reaches the right spot in the intestinal tract, which researchers can determine by using a special camera that picks up gamma rays, the capsule is activated to release the drug.
In size, "it is a horse pill, basically," Casper said of the InteliSite. "People think it looks big until you show them a coil of 25 feet of neogastric tubing. Then it doesn't look so big."
The InteliSite "is a superb device," said Robert Beihn, a former University of Kentucky research scientist and president of Centiprox Inc., an Indianapolis company. Beihn tested an early version of the InteliSite three years ago and found it to be safe for human use.
Using the InteliSite probably will cost drug companies just as much as the tube system, called intubation. But it obviously is dramatically easier on the paid volunteers. And the InteliSite should provide better data. Beihn said intubaton irritates the GI tract and, therefore, "may warp or alter absorption of the drug, because you have tinkered, if you will, with the anatomy." The InteliSite does a much better job of simulating what happens when a patient swallows a pill or capsule.
Casper co-invented the InteliSite while he was still at Glaxo, now Glaxo Wellcome. Innovative Devices, which was born at the outset of this year after Casper and Gardner left the pharmaceutical giant, licensed the technology from Glaxo.
Glaxo Wellcome decided to license the device because the company is first and foremost a drug company and "isn't in a position to manufacture and sell the device to other companies," said Alan Parr, a senior scientist at Glaxo Wellcome and a co-inventor of the device.
Glaxo plans to use the device for testing its own drugs, according to Parr, who expects the InteliSite to replace intubation eventually.
"My philosophy when we were developing it," Parr said, 'is that I don't ask people to do what I wouldn't do. And I wouldn't swallow a tube."
Innovative Devices' founders say sales of the device ultimately could top $1 million a year. But the InteliSite isn't the company's future.
Instead, the goal is to generate some cash with InteliSite by doing contract research and development work while the company focus on developing two potentially more lucrative products. It also is seeking $1 million from outside investors to help finance research and development.
Both the products it is developing are improved devices for delivering drugs via inhalation. Currently, drugs administered via inhalers are limited primarily to asthma and other respiratory ailments, but Innovative Devices expects that to change rapidly.
The reason: A multitude of biotechnology drugs are being developed, and many of those aren't suitable for taking orally because their effectiveness is destroyed by the GI tract. The most convenient alternative to oral doses is inhalation.
"It is obviously a much larger market," Leith said. "But Ö this is three to five years away."
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THERATECH -- January 21, 1997
THERATECHRESEARCH PARK
417 WAKARA WAY
SALT LAKE CITY
UTAH 84108
News Release
FOR RELEASE AT 8:00AM EST
TUESDAY, JANUARY 21, 1997
By Acquiring Pulmonary Delivery Technology
Salt Lake City, UT and Hillsborough, NC, January 21, 1997 --- TheraTech, Inc. (Nasdaq:THRT) and Innovative Devices, LLC (IDL), announced today that TheraTech has acquired from Innovative Devices exclusive rights to its dry powder inhaler (DPI) respiratory drug delivery device and a breath-activated device for use with metered dose inhalers (MDI). Both devices have patents pending and are in early development.
According to Innovative Devices partner Dr. David L. Gardner, "Each of these devices possesses a number of advantages over competing products. The device for use with MDI inhalers will be compatible with MDIs representing approximately 80% of the drugs used to treat asthma. It will be reusable for up to a year and breath-activated by the patient.
"The DPI device's principle features include inspiratory flow rate activation and a mechanism that provides maximum deaggregation of drug particles. Design features include a replaceable multi-dose cartridge and an expected lower production cost compared with other devices currently on the market," Dr. Gardner said.
"Patient-friendly administration of peptide and protein drugs remains one of the greatest challenges facing the pharmaceutical and biotechnology industries," stated Dr. Dinesh C. Patel, TheraTech's President and Chief Executive Officer. "TheraTech has already demonstrated the feasibility of administering small peptides such as glucagon-like insulinotropic peptide in humans using our proprietary oral transmucosal tablet. Eli Lilly and TheraTech recently announced a multi-product collaborative agreement for the development and marketing of peptide drugs utilizing that patented oral transmucosal delivery system.
"Acquisition of IDL's pulmonary delivery technology complements TheraTech's oral transmucosal delivery technology giving us the added capability to deliver both large peptides and proteins," Dr. Patel added.
Industry records show that the pulmonary drug delivery market is significant and growing. In 1995 the total U.S. pulmonary drug delivery market exceeded $1.9 billion. Industry analysts project that by the year 2005, the worldwide pulmonary drug delivery market could exceed $30 billion, due largely to an anticipated increase in peptide and other biotechnology-developed products.
Innovative Devices is a North Carolina-based company founded in January, 1995 to research, develop and manufacture novel medical devices for more effective drug administration. Specifically, IDL has focused on inhalation devices for use in administering drugs to the respiratory tract and a device (InteliSiteŚ capsule) for studying absorption/bioavailability of drugs in the gastrointestinal tract. Innovative Devices has filed patent applications on two inhalation devices and has two patents covering the capsule.
TheraTech, Inc., headquartered in Salt Lake City, Utah, is a leader in the development of innovative products based on controlled release drug delivery technologies. Working independently, as well with corporate partners, the Company has developed two transdermal products that are on the market and is developing a wide range of drug delivery products, including transdermal patches, oral transmucosal products for the delivery of macromolecules, including peptide drugs, oral controlled-release products, topical preparations and, now, pulmonary products.
This release contains forward looking statements. All statements released by TheraTech, Inc. that are forward looking are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Editors and investors are cautioned that forward looking statements involve risk and uncertainties that may affect the Company's business prospects and performance. This includes economic, competitive, governmental, technological and other factors discussed in the Company's filings with the Securities and Exchange Commission on forms 10-K and 10-Q.
FOR INFORMATION CONTACT:
TheraTech, Inc.
Alexander L. Searl
Alan Behunin
(801) 588-6200
Innovative Devices, LLC
Frank A. Leith
David L. Gardner
Robert Casper
(919) 644-0060
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from TRIANGLE BUSINESS JOURNAL - JANUARY 31, 1997
"Hillsborough firm to ramp up after 1st sale"A small virtual company has closed on its first major deal, signing over exclusive rights for a device that could produce a majority of the company's revenue.
Innovative Devices LLC of Hillsborough last week sold the exclusive rights to two respiratory drug delivery devices to TheraTech Inc., a pharmaceutical development company based in Salt Lake City.
Officials on both sides refused to reveal the monetary value of the contract, but TheraTech's president said that Innovative will receive a portion of the revenues from any commercial use of the devices by TheraTech.
"It's quite early-stage, but the reason we decided to step in was the caliber of the people involved," said TheraTech President Dinesh Patel. "We felt this was something we needed for the direction we're moving in, rather than trying to develop a device ourselves."
The approaching revenue stream has Innovative Devices poised for a move. Next month, the 2-year-old company will move from a cramped, 400-square-foot office in Hillsborough to 2,800 square feet of space in Umstead Industrial Park in West Raleigh.
The company also derives some of its cash flow from contract research and development done for area firms, as well as low-level manufacturing of InteliSite, a research-and-development-oriented capsule device used in testing absorption of drugs delivered to specific sites in the digestive tract. That product was brought to market in May.
The new inhalers, developed about 18 months ago, are similar to traditional inhalers in some respects. A traditional inhaler, however, requires the user to time inhalation with a firm press downward, releasing the medicine into the lungs. That process can be difficult for small children and the elderly, who may not be able to inhale a full dose of medication.
The inhalers developed by Innovative Devices instead are triggered by inhalation, assuring the user of receiving the proper dose of medication. Both devices are still in the research and development phase.
Innovative Devices has filed patent applications on two such inhalers, one designed to work with liquid spray-type medications, the other to work with dry, fine powders. Since dry powders are just now coming into the U.S. market, the approval process for that device may take longer than the spray-type one, company officials said. However, dry powder inhalers are gaining in potential, since they don't utilize chlorofluorocarbons (CFCs) as spray inhalers do.
Other potential uses for the product, however, are what have TheraTech interested. That company hopes to utilize Innovative Devices' technology in delivering peptide and protein drugs via the lungs, Patel said. By delivering drugs in inhalant form, absorption into the system is quicker and more effective.
"The dry powder inhaler would be ideally suited for this purpose," Patel said.
That has the industry thinking big. In 1995, the pulmonary drug-delivery market was $1.9 billion - but by 2005, that number is expected to top $30 billion.
With the deal, TheraTech will fund Innovative Devices' continuing R&D on the two devices. If completed and approved by the Food and Drug Administration, the Salt Lake City company will handle manufacturing of the inhalers.
Although the TheraTech deal marks Innovative Devices' first big score, don't look for the make-up of the company to change quickly. Partners David Gardner, Frank Leith and Bob Casper - all one-third shareholders - said that any ramping up would involve only a handful of temporary workers to help handle the flow of contract research and development work coming in from area companies.
And although the three have, in the past, had preliminary discussions with venture capitalists, a round of VC isn't in the works, the partners say. And any thought of going public or selling out appears to be even more remote.
"Our idea is to stay small, stay R&D, and get a big return on our investment," Leith said.
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FEBRUARY 15, 1997 GENETIC ENGINEERING NEWS
"Collaborations & Agreements"TheraTech Inc. (Salt Lake City, UT) has acquired from Innovative Devices LLC (Hillsborough, NC) exclusive rights to its dry powder inhaler (DPI) respiratory drug delivery device and breath-activated device for use with metered dose inhalers. Both devices are patented and in early development.
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from TRIANGLE BUSINESS JOURNAL - MARCH 7, 1997
section "Onsite: Health care""Signal-sending test pill benefiting scientists"
A Hillsborough-based company has developed a radio-activated capsule that helps pharmaceutical company researchers track a drug's absorption in the gastrointestinal tract.
Innovative Devices LLC, which sells the capsules and the equipment necessary to activate them for $1,200 each, calls the non-disintegrating capsule the InteliSiteŚ Capsule. The company markets the capsules for drug development only, said Frank Leith, one of the firm's three main partners.
Leith said the pill is easily swallowed and is eventually eliminated from the body. Measuring 10 millimeters in diameter and 35 millimeters in length, it is suitable in animal or human volunteer studies, he said. Because the pill is able to be tracked, once a drug is developed and its dosage determined, it can be targeted for a part of the gastrointestinal tract where absorption is best.
A prototype of the capsule had been developed in Research Triangle Park five years ago by pharmaceutical giant Glaxo Wellcome. Two of Innovative Devices' founders, Bob Casper and David Gardner, are former Glaxo employees. Leith at that time was employed by Aerosol Associates and worked as a consultant to Glaxo.
But Glaxo officials didn't view the project as a high priority. So Casper, Gardner and Leith formed their company in January 1995 and bought rights to the capsule.
The InteliSite Capsule consists of a drug reservoir, electronics compartment and a radio-tract reservoir, which can hold gamma isotopes. Once the drug reservoir portion of the capsule is loaded with either a liquid or powder formulation, the capsule is swallowed.
When the capsule reaches the desired location in the gastrointestinal tract, the capsule is activated by means of a magnetic field-induced current.
Since the body of the capsule is essentially a "sleeve valve," the inner sleeve turns inside the outer sleeve, lining up a series of slots in both sleeves. As these slots align, they provide an exit for the drug being tested.
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BT CATALYST - MARCH/APRIL 1997
Section - "Funding Deadlines""INNOVATIVE DEVICES SIGNS LICENSING DEAL"
Innovative Devices LLC of Hillsborough has completed its first major licensing deal, selling exclusive rights to its inhaler technology to TheraTech Inc., a Salt Lake City, Utah-based developer of controlled-release drug-delivery technologies.
Financial terms were not disclosed, but TheraTech will pick up further development costs and Innovative will gain a Portion of revenues from any commercial products developed.
Innovative has developed two types of inhalant devices, a dry powder inhaler and a breath-activated device for use with liquid spray-type inhalers.
While the breath-activated trigger could make significant inroads in the multimillion dollar asthma treatment market, it's the dry powder technology that could bring the real payoff. Pulmonary drug-delivery is projected to be a $30 billion industry by 2005 as more peptide and protein drugs reach the market. Drug makers are eager to find more patient-friendly ways to administer these drugs than the injections used now. For more information, call 919-644-0060.
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from START-UP - JUNE 1997, P. 25
"INNOVATIVE DEVICES - A capsule tracks drug absorption in the GI tract, and two respiratory inhalers help asthmatics breathe easier."6008-101 Triangle Drive
Raleigh, NC 27613
Phone: (919)781-6315
Fax: (919)781-6016
E-mail: devices@mindspring.com
Contact: David L. Gardner, PhD, manager
Industry Segment: Pharmaceuticals
Business: Drug Delivery Devices
Founded: January 1995
Founders: David L. Gardner, PhD, Robert A. Casper, PhD, and Frank A. Leith
Employees: 3
Financing to date: Undisclosed
Patients overwhelmingly prefer taking medication orally, so pharmaceutical companies place great emphasis on developing new oral drug delivery systems whenever possible. Unfortunately, oral delivery has not been a viable option for certain types of medications, such as most peptide and protein drugs, either because of their sensitivity to gastric acids or because they are destroyed by proteolytic enzymes within the gastrointestinal (GI) tract. A better understanding of the rate and extent of drug absorption from different regions of the GI tract would help companies aim their drugs to the best environment for absorption and bioavailablity. The colon may be a favorable site for peptide and protein drugs due to its reduced concentration of proteolytic enzymes.
Absorption data is currently collected by inserting a nasogastric tube through the GI system, and it can take up to two days to monitor the progress of the tube, if delivery is to the colon. In addition, absorption inaccuracies may result if there is shifting of the tube from its intended delivery site. Innovative Devices LLC has developed a non-invasive method of collecting absorption information throughout the GI tract utilizing its InteliSite capsule. "Despite the obvious need for human absorption data, there is a paucity of information," says Robert A. Casper, Ph.D., co-inventor of the capsule and one of the company's three co-founders and managers, "and this stems principally from the lack of a simple, easy-to-use technology that is capable of collecting absorption data under non-invasive conditions."
Casper developed and patented the capsule prior to co-founding the company. Although it was designed as an R&D tool enabling pharmaceutical and biotech companies to study drug absorption/bioavailability within the GI tract, in the future, the capsule may also be used for acute therapeutic delivery of medication or to follow disease progression within the GI system.
InteliSite is an ingestible capsule, 10 mm x 35 mm in size, that can be filled with either liquids (solutions or suspensions) or dry powders, unlike current techniques that work only with liquids. The formulation includes a radio-tracer substance that emits gamma rays enabling the operator to track the capsule on a monitor as it moves through the GI system using either gamma scintigraphy or digital fluoroscopy. The operator uses a remote control which triggers a magnetic field to release the contents of the capsule on demand to specific sites within the GI tract.
The company estimates the US market for the InteliSite capsule to be $5-10 million for pharmaceutical applications and $25-50 million for other types of research investigators. Innovative plans to develop a follow-on capsule that can be targeted to a specific GI site for sampling purposes.
Innovative Devices is also developing inhalation devices for administering medication to the respiratory tract. In 1995, the total US pulmonary drug delivery market exceeded $1.9 billion. By 2005, the worldwide market is projected to exceed $3 billion, due largely to an anticipated increase in the use of the pulmonary route to administer peptides and other biotech products. The company is working on a dry-powder inhaler (DPI) and a breath-activated device for use with metered-dose inhalers (MDI). Both devices have patents pending and are in early development. In January 1997, Innovative sold exclusive rights to both inhalation devices to TheraTech Inc., a drug delivery company that will manufacture and market these products [W#972044].
According to Innovative partner David L. Gardner, PhD, the company's devices possess advantages over competing products. The device for use with MDI inhalers will be compatible with approximately 80% of the drugs used to treat asthma. It will be reusable for as long as a year, and be breath-activated by the patient. The DPI device is also breath-activated and it incorporates a mechanism that provides maximum deposition of the drug particles to the lungs. It also has a replaceable multi-dose cartridge.
Treatment of asthma, a common chronic condition affecting 10-12 million people in the US, 1-2 million in Canada, and 28 million in Europe, exceeds $600 million worldwide. "There are mild, moderate and severe asthmatics," says Gardner. "We are targeting the mild to moderate cases, which make up 80% of the market and our focus is on simplicity. These products are being used by the general public and they need to be easy to operate." In particular, Gardner points out that many asthmatics are pediatric or geriatric patients who frequently have difficulty exerting the strength needed to operate certain inhalers easily.
Prior to founding Innovative, Gardner and Casper worked together as director and associate director, respectively, of Glaxo Wellcome PLC's Allen & Hanburys respiratory division. Gardner, who has four patents, spent 17 years at the Battelle Memorial Institute before joining Glaxo. Casper holds six patents in his 15 years of experience in biomedical product development. Frank A. Leith, the company's third co-founder and manager, holds four patents and previously worked with Aerosol Associates, an aerosol research and consulting firm. Funding has been provided by the firm's own principals.
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from MACHINE DESIGN - JUNE 1997
"A $1,200 pill that's worth the price"Before a pharmaceutical company puts a drug on the market, hundreds of tests must take place to evaluate the drug's efficacy, safety, preferred dosages, side effects, and the best way to administer it. One part of that testing is determining the drug's bioavailability, or how much of the drug is in the patient's bloodstream over time. Most drug bioavailability curves follow a similar path; initially zero to low levels as the drug is absorbed, an initial peak, then a slow reduction as the body metabolizes the drug and excretes it.
A new device, the InteliSite capsule from Innovative Devices, Research Triangle Park, N.C., gives researchers a new way to carry out these tests. Stated simply, once swallowed, the capsule is remotely controlled to open and release its contents. And though each capsule costs about $1,200, it's worth it, especially to the human volunteers used in testing.
Each capsule consists of two shells, with the outer shell made of chlorotriflouride (CTFE) and the inner of polysulfone. Both materials have a long, documented history of good biocompatibility. There are holes in each shell, and when the capsule is activated, the shells turn in relationship to each other, aligning the holes, and releasing whatever is inside. One of the initial design considerations was choosing materials that could slide against each other with relatively low friction. "We wanted low friction so that as little torque as possible was necessary to open the capsule," says David Gardner, a partner in the company. "We also had to adjust the gap between the sleeves so that friction was minimal and there was still no leakage."
Gamma isotopes, usually Indium or Technetium, tucked in the capsule's tracer port, let researchers track the capsule's progress through a volunteer's GI tract with gamma scintigraphy. When the 1.25-in. capsule is seen on the gamma camera in the right location, a 6.78-MHz alternating magnetic field is applied using an antenna applied to the volunteer's skin. A three-axis core in the capsule receives the signal, using tuning capacitors and resistors to transform it into heat, which warms a bent shape-memory allow wire. As the signal is applied for 2 min, the wires slowly return to their original straightened shape, twisting the inner sleeve relative to the outer and exposing the inner chamber to GI fluids. Researchers then know the exact time, place, and amount of drug entering the GI tract. Blood tests taken periodically over the next hours plot a precise bioavailability curve. Eventually, the nondisintegrating capsule passes through the tract.
Because the activation signal is limited in range to about 100 mm, volunteers can be no more than 200-mm "thick." The farther a capsule is from the antenna, the longer it takes to heat. But this is no problem since they recruit from a large pool of college and med students. And it's a pretty sure bet they prefer this method to the alternative, at least comfortwise.
In the traditional intubation process, researchers insert a tube through the volunteer's nose, down through his stomach and through to his intestines or colon, tracking it on X-ray. A small inflated balloon on the end of the tube utilizes gut action to move it through the intestines, a process that takes up to two days. And 25% of the time, a valve in the tract, the illosicheal, prevents reaching the colon. "Putting 20 feet of tubing down the gut probably disturbs normal digestion, which throws off test results since we're looking for normal reactions," says Gardner. "Our capsule, which looks like a dosage pill, even though it is large, gives more realistic results."
Costwise, the capsule compares well, even though it's a one-time use device and requires expensive gamma scintigraphy equipment. Testing three different sites costs $10, $128 with intubation, versus $11,750 with InteliSite. The capsule, however, gives quicker, more accurate results, according to the company. And unlike intubation, it isn't restricted to liquids.
"Ours is the only system that can deliver powders to the intestines," notes Gardner. "And drug companies all want medicines in pill or tablet form, because you get better compliance. Patients are more likely to take them at the proper times and dosages. "The InteliSite is also sized to take a #3 or #4 gel capsule, so drug companies can test coatings and buffering technology, as well as powder versions of drugs.
At first, although the company had a good product, they had a hard time securing a reliable source of the shape-memory alloy. Eventually they found one, Shape Memory Applications in California. "Now we're rethinking how the capsule is assembled and configured," says Gardner. "We want to mass produce them by the hundreds rather than build five or six time at a time."
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THERATECH -- August 1997
THERATECHRESEARCH PARK
417 WAKARA WAY
SALT LAKE CITY
UTAH 84108
News Release
FOR RELEASE AT 8:00AM EST
Wednesday, August 6, 1997
For Information Contact:
TheraTech, Inc.
Alexander L. Searl
Alan Behunin
(801) 588-6200
Innovative Devices, LLC
Frank A. Leith
David L. Gardner
Robert Casper
(919) 781-6315
Patent for Dry Powder Inhaler Drug Delivery Device
The breath-activated device, which TheraTech acquired from IDL in January of this year, incorporates a mechanism designed to maximize the deposition of drug particles in the lungs, according to IDL partner Dr. David L. Gardner. "Other design features, as detailed in the patent, are expected to facilitate patient convenience and provide a lower manufacturing cost relative to other DPI devices under development," Dr. Gardner added.
"The rapid approval of the DPI patent is a result of the truly innovative design features incorporated in this device by IDL," stated Dr. Charles D. Ebert, Senior Vice President of Research and Development at TheraTech. "We are extremely pleased with the progress being made by IDL in the DPI development program."
Widely viewed as the next generation of pulmonary drug delivery devices, DPI's are expected to capture a significant share of the growing inhalation therapy market for asthma drugs. A fairly common disorder, asthma affects 3% to 5% of the population and asthma treatment products generated approximately $1.8 billion in sales worldwide in 1996.
The asthma market is only one of several potential applications TheraTech foresees for its DPI. Of particular interest to the Company is the area of peptide, protein and macromolecule drug delivery.
According to Dr. Ebert, such drugs are currently administered primarily by injection. "The TheraTech DPI technology," he stressed, "complements our existing oral transmucosal drug delivery capabilities and has broad based applicability in both conventional and peptide drug administration."
TheraTech, Inc. is an industry leader in the development of pharmaceutical products based on its controlled-release drug delivery technologies. Working both independently, and with corporate partners, TheraTech is developing a wide range of drug delivery products including: a variety of transdermal patches; oral transmucosal products for the delivery of peptide drugs; oral controlled release products; inhalation systems for local and systemic drug administration; and topical preparations.
TheraTech currently has equity and/or research and licensing agreements with many of the world's leading pharmaceutical companies including Astra, Eli Lilly, Pfizer, Procter & Gamble, SmithKline Beecham, Roche and Wyeth-Ayerst.
For additional information on TheraTech, Inc., visit our Web Site at www.thrt.com, or e-mail us at investor@thrt.com
All statements contained in this release that are not purely historical are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These encompass TheraTech's beliefs, expectations, hopes or intentions regarding the future, including those relative to uses of the DPI. All are based on information available to TheraTech as of such date. TheraTech assumes no obligation to update any forward-looking statement. It is important to note that actual outcomes and TheraTech's actual results could differ materially from those in such forward-looking statements. Factors that could cause actual results to differ materially inlcude risks and uncertainties such as regulatory requirements. Readers should also refer to the risk disclosures outlined in TheraTech's filings with the Securities and Exchange Commission on Forms 10-K and 10-Q.
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BT CATALYST - SEPTEMBER 1997
"NewsBriefs"Innovative Devices LLC of Durham and its licensing partner, TheraTech Inc. of Salt Lake City, Utah, have received a patent on a dry powder inhaler devised by Innovative Devices. The inhaler is designed to deliver a variety of drugs to the lungs for local and systematic therapy.
TheraTech acquired the technology from Innovative Devices in January. Delivery of asthma drugs is one potentially lucrative application, but of even greater interest to TheraTech is the area of protein and other macro-molecule drug-delivery. Currently these drugs can be given only by injection.
Innovative Devices' inhaler should offer greater patient convenience and a lower manufacturing cost than other devices in development, said company Partner David Gardner. For more information, call 919-781-6315.