Capillary Biomedical has raised $2.9 million in an angel round, which it believes will bring its novel infusion set through to FDA clearance. The “SteadiSet infusion set with SteadiFlow technology” will soon begin clinical testing, and if all goes well, the company ambitiously aims for a late 2019 US launch of a first-gen product through pump partners.
SteadiSet will launch with three-day wear and includes three really cool features intended to increase reliability of insulin delivery and consistency of absorption: (i) It is made of a flexible soft polymer to temper the foreign body response (far more flexible than Teflon); (ii) It has three holes along its side to reliably spread the infusion under the skin (a sprinkler-like design); and (iii) A wire coil running along the inside of the cannula renders it “kink-proof.” An ADA poster demonstrated the set’s diminished kinking and greater surface area spread of a bolus infusion vs. Unomedical’s Inset, and the company has submitted data for publication on the body’s wound response. Extended wear beyond three days is the goal of a second-gen product.
Read on for an outstanding Q&A with Capillary Biomedical’s Mr. Mark Estes (a pump industry veteran) and a host of pictures of the SteadiSet and packaging first shown at the T1D Exchange Diabetes Innovation Challenge.
Capillary Biomedical recently informed us that it has closed a $2.9 million angel round, which will support development of its three-day, “kink-proof,” multi-port “sprinkler” design (multiple holes along the side of the catheter) infusion set through FDA clearance. The company tells us that “if all goes well,” the “SteadiSet infusion set with SteadiFlow technology” could hit the market in late 2019, though additional funds will be needed to scale up manufacturing for commercial launch. The company has been conducting JDRF and NIH-funded studies in swine since 2016 and will soon begin human clinical testing.
In a fascinating interview with us, Capillary Biomedical’s VP Marketing Mr. Mark Estes (formerly Chief Product Architect at Asante) explained how the SteadiSet aims to address three factors that contribute to the infusion set’s long-held title of “The Achilles heel of pump therapy.”
To slow the body’s wound response to foreign materials (“an infusion set is like a splinter”), Capillary is making the cannula out of “a soft polymer material,” which is reportedly far more flexible than Teflon.
SteadiSet boasts four holes along its length – “one distal and three proximal…set 2 mm apart in a helical pattern” – which spreads out insulin to a larger surface area of subcutaneous tissue for reliable delivery and to better reach capillary and lymph vessels for consistent absorption.
There is a wire coil reinforcement on the inside of the cannula to prevent kinking (think wire-reinforced flexible ducting).
An ADA 2018 poster hinted at the possible clinical benefit to these features: In swine, boluses delivered by the SteadiSet cannula had greater surface area than did those delivered by a Unomedical’s Inset (~275 mm2 vs. ~175 mm2; p=0.018) , plus the SteadiSet cannula never kinked vs. 18% kinking with the Inset. Nice! Mr. Estes said Capillary and collaborator Dr. Jeffrey Joseph (Thomas Jefferson University) have gathered histology data showing the SteadiSet cannula has a reduced wound response vs. Teflon cannulas – results have been submitted for publication at an upcoming professional meeting.
With respect to user experience, Mr. Estes suggested SteadiSet “would not look out of place next to other recent excellent designs like Abbott’s FreeStyle Libre sensor, Dexcom’s G6 inserter, and/or the MiniMed Mio Advance.” Based on the packaging below, it looks a lot like the round FreeStyle Libre applicator, where a user pulls off the tape, presses the applicator into the body, and pulls it off the body with the needle hidden and retracted. (The best applicator we’ve seen lately is Dexcom’s G6 and the new Medtronic/Unomedical Mio Advance – available in select OUS countries since ATTD.)
Capillary Biomedical intends to ensure broad access to its technology by white labeling its infusion sets for “all the [pump] players.” That is, it will ship infusion sets with appropriate connectors and packaging to pump companies to distribute, similar to how Unomedical currently operates. (And in contrast to BD, which distributed its FlowSmart infusion set exclusively through Medtronic.) The plan is to price similar to current sets and use the existing reimbursement pathway. While integrating the SteadiFlow cannula technology into patch pumps may also be possible, this would be a “a more complicated process” requiring “extensive collaboration.”
A big portion of the research on this set to date – testing in a swine model at Thomas Jefferson University – was funded by a $1.5 million grant from JDRF. At the time, Capillary Biomedical co-founders Mr. Paul Strasma and Dr. Jeffrey Joseph told us that they aimed to develop a catheter that could be worn for 7+ days, reduce trauma upon insertion, heat the skin to increase local circulation, and vibrate to break up tissue obstructions. Mr. Estes noted that the company still intends to extend wear beyond three days in its second-gen product – which could eventually open the door to all-in-one CGM sensor-infusion set combos – but the other features remained areas of ongoing research. Early research on steel needles was funded by an initial NIH SBIR Phase I grant and the company was recently awarded a Phase II grant to investigate insulin absorption over extended durations using the hyperinsulinemia/euglycemic clamp PK-PD study technique.
We are very excited to hear Capillary is eyeing commercialization, as there has been very little innovation on the catheter side of infusion sets in the past decade. The science here seems solid and will address real, tangible issues with sets. While user experience around insertion and detachment has improved a bit – most recently with Medtronic/BD’s MiniMed Pro-set and Medtronic/Unomedical’s Mio Advance – there has been very little in the way of kink-proofing or improving consistency of insulin delivery. As more people move to hybrid closed loop, especially at younger ages, the need for outstanding and reliable infusion sets and cannulas is only going to grow.
Schematic Image of SteadiSet Infusion Set
Wire Coil Reinforcement that Helps Prevent Kinking
“Sprinkler Needle” Design
Infusion Set Packaging
Q&A with Capillary Biomedical’s Mr. Mark Estes
Close Concerns: Can you provide us an update on Capillary Biomedical and the SteadiSet infusion set in particular? What features are you looking to bring to market in a first-gen product?
A: With our Series Seed financing wrapped up, we’ve moved into our first headquarters and shifted our focus to development and commercialization of our first-gen SteadiSettm infusion set product. The Cove incubator hosted by UC Irvine’s Applied Innovation group was a great place to support our initial prototype development and our animal work with Thomas Jefferson University. After testing more than 300 infusion sets in over 30 swine, we figured out what works and what does not. We now have a much better idea of what goes on under the skin with CSII and have a design in process that we hope addresses the issues that have always made infusion sets the weak link in pump therapy.
The short version of what we learned is that an infusion set is like a splinter and the normal wound response of the body over time poses an ever greater challenge day-by-day for insulin to reach intact capillary and lymph vessels where the body can absorb it. We also learned that a bolus infused through a traditional single-port cannula makes a spherical pool of insulin at the tip, which happens to be where the wound response is the greatest. Our answer to that is two-fold: (i) Make the cannula out of a much softer material to reduce the wound response; and (ii) Add additional holes on the side of the cannula to spread out the insulin over a greater surface area of subcutaneous tissue. However, both of these structural changes increase the likelihood of the cannula kinking and collapse. Thus, we added a wire coil reinforcement that is internal to the cannula to make it kink-proof. The result is an infusion set that we believe will more reliably deliver, be more comfortable to wear, and help the body absorb insulin more predictably.
Close Concerns: Where are you in the development process?
A: We are at the point where we have molded parts (vs. 3-D printed prototypes used in prior animal studies) and are preparing to sponsor our first human clinical study.
Close Concerns: What published data supports the idea of “kink-proof” and greater insulin absorption?
A: In our testing at Thomas Jefferson University, we have demonstrated a significant increase in the surface area of a bolus of insulin infused through our multi-port cannula vs. a commercially available Teflon infusion set. This was presented in our 2018 ADA poster. That same study/poster also showed no kinking with our cannula vs. about 20% of the Teflon cannulas developing a kink. The same testing further showed that our softer cannula (far more flexible than Teflon) reduced the wound response significantly vs. a Teflon cannula. This histology data has been submitted for poster presentation at an upcoming professional meeting.
Q: How about the user experience around the set?
A: The rest of our design – packaging, insertion, connecting and detaching – would not look out of place next to other recent excellent designs like Abbott’s FreeStyle Libre sensor, Dexcom’s G6 inserter, and/or the MiniMed/Unomedical Mio Advance. Fewer parts = reduced steps = less to do, less to learn, and less to go wrong. There are even a few small features that might bring a smile to your face.
Q: Do you intend to sell your infusion sets directly, or go through pump companies?
A: We intend to distribute infusion sets with “SteadiFlowtm technology” (our brand) through existing pump companies. We would work with the pump companies to make sets with appropriate pump connections and then pack them up with pump company specific branding and ship them by the pallet to the pump companies for their distribution. We believe our set should be able to use the same reimbursement code and have similar pricing as the current soft cannula sets so as to not disturb the existing infusion pump company business model. We have had positive discussions to lay the groundwork with most players. Our goal is to ensure access to our sets for anyone who wants them, so we believe we eventually will need an agreement with all the players. I believe we can get there if our set works as well as I believe it does.
We have been approached by a number of patch pump developers about integrating our cannula design into their patches. That is a more complicated process and we are very early, but the holy grail of a longer-lasting patch pump with an integrated glucose sensor might soon be within the realm of technological feasibility.
Q: How big of jump do you see SteadiFlowtm technology being in the grand scheme of infusion sets?
A: I am old enough to remember when the differentiation between infusion sets was enough to move the pump market (the first soft cannula set did this, and the first set with a quick disconnect did it again). I am not so bold as to predict a third time, but the data out there suggests current sets are not getting the job done for a lot of people and a quick dive into the FDA’s MAUDE database suggests that infusion sets are a big call generator for the pump companies. A more reliable infusion set could make people happy and cut internal support costs at the same time. That seems like a real win.
Q: What is coming in the pipeline, e.g. extended wear sets?
A: We’ve researched heating, vibrating, and atraumatic insertion and have a few other ideas for the pipeline. But our biggest learning was that these such complicated designs are not needed for a first-gen product to solve real-world problems. The biggest performance difference between our infusion set and others came from the flexible, kink-proof cannula, and when we found that, we focused our efforts on developing a first-gen set for initial commercial launch.
As far as extended wear goes, we see that as a second-gen product release. Our goal is to extend wear to seven days and we’ve gathered data in swine out to fourteen days. Practically, anything beyond three days would be a significant game changer for traditional infusion sets and patch pumps alike. Given the challenge of reliably overcoming the body’s wound response this will not be an easy task. I have not seen anything else that looks like it can get there. We’re going to learn a lot next year with our recently awarded NIH SBIR Phase II study of how insulin gets absorbed day-by-day from our SteadiSet infusion set versus a Teflon control set. This clinical study at Thomas Jefferson University will use the gold standard hyperinsulinemia / euglycemic clamp PK-PD study design.
We hope that the combination of increased surface area and reduced tissue response will allow reliable absorption out beyond three days. Assuming modern tape can do for sets what it has done for glucose sensors and our wire coil reinforcement can eliminate kinking in humans as well as it did in pigs, then we have a good shot at extending duration of use. If that works out, then sensor-set products start to make more sense as they require a very small sensor/transmitter and a very good infusion set with high reliability.
BD/Medtronic, Unomedical, and Medtronic are also driving innovation in infusion sets and catheters.
Medtronic/Unomedical’s Mio Advance launched to great feedback at ATTD in February in three European countries, with other launches expected by April (Canada, Hong Kong and certain EMEA markets) and still others sometime this year. No specific US timing has been shared.
Medtronic’s MiniMed Pro-set with BD’s FlowSmart technology has not been mentioned by either partner company, to our knowledge, since JPM, where we learned that a study was still finishing as the company works to aggregate clinical evidence. A brief limited launch was halted for higher-than-expected rates of kinking and the set has yet to re-launch. There was no update on BD’s 1Q18 call or at Medtronic’s 2018 Analyst Meeting, and per the last update nearly a year ago, the set was slated to re-launch by this September. As a reminder, FlowSmart includes one additional hole along the side and some user experience advantages for insertion.
At ADA, we saw early data from Unomedical’s Lantern catheter, which has several slits along the side to allow insulin to flow out of multiple places (e.g., for occlusion or kinking) plus a coating to suppress the body’s foreign body response over seven days of wear. In the study, 16 type 1s wore the set for seven days, though with a trend toward more hyperglycemia and reduced insulin action over time. No commercialization plans have been shared.
Medtronic also shared on its 2018 Analyst Day call that it intends to launch a sensor-infusion set with extended wear in 2020 or beyond.
-- by Brian Levine, Adam Brown, and Kelly Close