(20 Jun 2016) Following is the final article in a series reviewing emerging advanced wound care and regenerative medicine trends and implications for the future of the industry. Part 1 focused on wound diagnostics approaches. Part 2 analyzed corporate strategy and positioning among the major wound care players. Part 3 will look at emerging innovative therapies, trends, and opportunities.

 

Emerging Innovative Therapies

In my prior post on trends in advanced wound care and regenerative medicine, I stated that the most successful of the next generation of therapies will need to simultaneously deliver high levels of clinical efficacy and cost effectiveness. In this post, I will demonstrate that it is possible for solutions to both meet these criteria and still be highly creative and innovative.

Due to my background in both wound care services management and product commercialization, innovators and entrepreneurs in this space often approach me for clinical, financial, operational, and strategic insights before and during early-stage commercialization. The result is that I get an inside look at many emerging solutions, even before they get a lot of attention. However, for many of those solutions, I have also committed to refrain from discussing material aspects of their business. Although I cannot disclose all of the emerging innovations and therapies I have had the opportunity to be involved with, I will share a few exciting ones (and my thoughts on them) that I have no formal business or financial relationships with and can therefore discuss freely:

 

1) Compression Therapy Meets Smart Materials

Ask any vascular, podiatric, or wound care clinician about compression therapy and they will tell you, “It works great–when the patients use it!” Indeed, chronic venous efficiency and related comorbidities are the causes of many advanced wounds (venous leg ulcers), and can exacerbate treatment of others such as traumatic, surgical, and diabetic leg ulcers. In addition to chronic leg ulcers, swelling, blood clots, and other issues can be mitigated with compression therapy.

Traditional compression stockings can be uncomfortable and difficult for patients to put on without assistance. This can be due to age, arthritis, poor mobility/flexibility/dexterity, and related issues. Pneumatic compression pumps, which use air chambers to squeeze fluid out of the legs, can also be effective. Yet due to their cost, bulk, and cumbersomeness, patients tend to refuse the modality, or use it for just a few days or weeks before compliance drops. Moreover, they cannot easily bring the pump with them to work, vacation, and other places. It’s no surprise that partial or non-compliance with traditional compression is about 79%. Finally, from the point of view of the physician/clinician/case manager/administrator who is usually the one facilitating the order, the multiple specific documentation requirements and order forms can be a huge hassle compared to ordering traditional compression.

(Above: ElastiMed Founder & CEO Omer Zelka demonstrates a prototype of his smart-material-based compression therapy device at the May 2016 IATI Biomed Conference in Tel Aviv)

Enter ElastiMed. ElastiMed is using smart materials to develop a wearable compression therapy device to improve circulation in the lower extremity. The lightweight stocking presents patients with a comfortable, easy-to-wear, highly effective and affordable treatment option. The garment, which can be put on effortlessly like a normal sock, holds a lightweight battery. The battery sends regular pulses of low energy through the stocking, which allows it to contract and “massage” the leg, much like a pneumatic compression/lymphadema pump.

In short, by using nanotechnology, their solution combines the the mobility and cost effectiveness of a traditional compression stocking with the comfort, ease-of-application, and clinical effectiveness of a compression pump.

(Below: a video demonstration of ElastiMed’s technology shows the device and its compression mechanism in action)

According to Founder and CEO Omer Zelka, “I was a student of electrical engineering when I found out about the materials, fell in love with the technology, and constructed an improvised lab at home. When I reached a breakthrough with the materials, I started looking for the right application for it…After talking to countless physicians—and especially to patients—I began to understand the pain that people with these conditions experience: The current compression stockings on the market are uncomfortable and very difficult to put on and take off. With the majority of people being elderly or suffering from arthritis, wearing a compression stocking becomes Mission: Impossible. In most cases, they just stop using the stocking, which leaves them vulnerable to DVT, lymphedema, and other venous diseases or conditions such as chronic wounds.”

Patient-centric? Check. Clinically efficate? Check. Price attractive? Check. I believe that Elastimed’s technology has the potential to disrupt the medical compression therapy industry, and as a result, to have a significant impact on the delivery of advanced wound care and related chronic venous disease.

My industry sources recently informed me of at least one major advanced wound care company that is attempting to develop a similar smart materials compression product as well (launch targeted for 2017). Leading traditional compression therapy firms fighting to differentiate such as BSN Medical (who just announced they are looking to be acquired or listed), Convatec3MmediSigvarisTactile Medical, and even athletic compression firms like Under Armour and Nike will likely take a keen interest in ElastiMed (if they haven’t already).

 

2) Growing & Harvesting Human Collagen from Plants

As of this writing (June 2016), there are something like 60+ soft tissue related allografts / CTP (cellular and tissue products marketed in the US. Generally, I would not advocate that this is an underserved market in need of new entrants. However, sometimes there are innovative approaches to this space, with implications beyond wound care. CollPlant (TLV:CLPT) is such a technology.

CollPlant has developed a method of genetically modifying tobacco plants so that their leaves grow human collagen, which are then harvested and turned into allograft/biological products for chronic, surgical, and related wound care/regenerative medicine applications. Their VergenixFD gel and VergenixWD matrix products were recently awarded CE approval and distribution in some Western European markets. At this time, they are simultaneously working on the necessary clinical trials to gain US FDA approval as well.

Why tobacco plants? In ideal conditions, they can grow to a height of two meters (six feet) in one month. Also, their large leaves allow for relatively large quantities of collagen harvested per plant. Advantages claimed by CollPlant’s solution include:

  • Yielding of recombinant, type I human collagen (rhCollagen), as opposed to denatured collagen from other species that may be less effective in human wound healing.
  • No immunogenic response (i.e. no immune system rejection) due to lower levels of cytokines compared with bovine collagen (no allergic response, either).
  • Lower time and cost to produce (easier and cheaper to grow and harvest plant-grown collagens, compared to obtaining and processing bovine, porcine, or human cadaveric/amniotic/other tissues).
  • More consistent quality and purity compared to other sources (i.e. more homogeneity and fewer discarded lots), resulting in 10 to 100 times higher collagen concentration as compared with tissue derived collagen products.
  • Ability to control the protein at the molecular level (i.e. tensile strength, viscosity, thermal stability, and other characteristics).
  • No need to perform costly disease testing on the genetically modified plants (i.e. hepatitis, HIV, etc.), as is needed to do with other allograft sources such as human amniotic, or cadaveric tissue.

While I have not yet experienced CollPlant’s products in the clinical setting, based on my understanding of the scientific, clinical, financial, and operational implications of the solution, there is disruptive potential. As 3D printing of tissue–even organs–becomes a reality, it will need an organic ink as fuel. For this application, CollPlant has a real chance to shine.

Still, CollPlant’s long term success is far from certain. Just because they grow human collagen in plants does not mean that the per-unit price will be cheaper than other products (a lot of leaves are needed to produce one unit of product). Furthermore, the design and results of their US FDA and other future clinical trials will be crucial. Likewise, even innovative technologies still need proper business execution in order to be successfully commercialized. At its core, CollPlant is still a clinical stage/R&D organization. Its ability to carry out key activities such as pricing strategy, distributor selection and management, launch and marketing plans, physician and clinician education, selection of key opinion leaders (KOLs), and other key business and commercialization strategies and tactics will dictate the firm’s ultimate success or failure.

Historically, very few R&D-focused firms are able to successfully become leaders in global marketing, too. And with 60+ competing products that have already established market share and veteran, US-based sales forces, for CollPlant to quickly develop a strong grasp of the competitive dynamics of this niche industry will be a must. Leveraging industry and on-the-ground insights to form key partnerships in its key markets will be the key to successfully capturing market share once US FDA approval is secured.

All too often, promising companies whose strengths comes from R&D and disruptive innovation are unable to meet the challenge of global commercialization–especially in the biomedical field with its many regulatory, political, reimbursement, and other hurdles to approval and adoption.

Only time will tell what happens with CollPlant, and any projection of their commercial success or failure in the US is still quite premature. Their technology and clinical results thus far have been extremely impressive. With multiple potential applications, including tendon and ligament repair, acute wounds, and the recently announced research in 3D printing of tissue and organs, I look forward to continuing to follow this company closely as it transitions from a pure research organization to an innovation and commercialization firm (with several more promising products still in the pipeline). Whether or not they will succeed in the advanced wound care setting remains to be seen. There exist multiple other competitors that are taking similarly innovative approaches to the similar challenge of effective, yet low-cost allografts other healing stimulants. Still, it is definitely an innovative approach.

 

3) Just Short of Commercialization, Yet Impressive Nonetheless

This industry, like many others, focuses on the solutions that achieve end-game success, but usually does not even hear about the fascinating ones that, had they been commercialized, would have been no less impressive and important.

I would like to take a moment to mention two advanced wound care/regenerative medicine technologies in particular that were extremely innovative and very exciting to follow–yet they each had some recent bumps in the road that will prevent them from being in on formulary in clinical settings anytime soon.

The first firm, Macrocure, focused on taking white blood cells from healthy donors, then activating them through a proprietary process. The resulting product, called CureXCell, could then be superficially injected into a patient’s wound, offering a novel approach to stimulating wound healing.

I especially appreciated this product’s potential to eventually be rolled out in remote locations or markets lacking the logistical infrastructure and reliability to transport sensitive tissue-based allografts and biological-based growth factors. In theory, Macrocure’s solution could eventually be leveraged on demand, at the point-of-care.

Unfortunately, their most recent Phase III clinical study did not meet its endpoints, so CureXCell will not be receiving US FDA approval anytime soon. This was a huge blow to the professionals involved in the company and the development of its technology, with several blaming the clinical trial design itself, not the actual technology or product. This is always a contentious issue within this clinical specialty due to the many comorbidities, complex medical histories, medications, and compliance challenges inherent in the patient population).

Still, the company’s leadership is looking for other medical fields that the technology might be applicable to. If they could, in theory, prove that their activated white blood cells reduced infection or inflammation rates in joint replacement surgery, reduced scarring in cardiothoracic or plastic surgery, or some other unique and valuable application, it could breathe new life into the firm’s underlying technology.

Another firm, ExceeMatrix, is quite interesting as well. They were focused on developing collagen-based tissues harvested from soft corals. As both a wound care industry professional and a scuba diver, I really enjoyed following them!

Unlike CollPlant, which uses genetically modified plants to grow human growth factors, ExceeMatrix took an even more natural approach: They determined that even without being genetically engineered, soft corals are naturally rich in collagen, provide a natural matrix/scaffold, have extremely high tensile strengths, and can be grown at consistent quality and specifications (cadaveric grafts, for instance, are notorious for arriving in the OR in inconsistent, unpredictable shapes, sizes, and elasticities).

If successful, the possibilities were limitless: Tendon, ligament, cartilage and bone repair, chronic and acute wound healing, organ repair, abdominal wall reconstruction, the list goes on. At a recent exhibition, their booth aptly displayed the title: ExceeMatrix: DEEP SEA TREASURES IN REGENERATIVE MEDICINE (see photo below). While ExceeMatrix is not the only wound care company to look to the sea for healing properties (Iceland-based Kerecis has shown success using acellular fish skin matrices in wound care and surgical applications).

In fact, one of ExceeMatrix’s first challenges after receiving funding was to build what was possibly the world’s first coral farm for biomedical purposes (to both ensure quality and also to prevent harm to ocean coral). It was literally a simulated indoor ocean lab where they could control every factor such as mineral content, flow, temperature, light, etc.

ExceeMatrix’s startup team was also really cool, consisting of:

  • A veteran business development manager from J&J,
  • a scientist with a PhD in collagen engineering (who happened to work at Collplant prior to ExceeMatrix, where she honed her collagen focus),
  • a biomedical engineer with an expertise in mechanics,
  • and a marine biologist with a background in aqua-culture and marine farming.

Talk about a complimentary and exciting startup team!

The latest ExceeMatrix animal trial was to assess the effect of the coral matrix on achilles tendon repair surgery in goats. Due to its high consistency and tensile strength, coupled with the rich collagen and natural matrix properties of the soft coral, the team had high hopes for the trial.

Unfortunately, it was determined from the trials that a property of the raw coral causes prohibitive biocompatibility issues when utilized as an implanted medical device. As a result, the company reached the difficult decision to shut down just a few days ago.

Beyond the excitement of new innovations, clinical tools, and business opportunities, I felt it was important to share the stories of Macrocure and ExceeMatrix. But not just because they were recent developments in the field of wound care and regenerative medicine.

Too often, we hear about exciting academic research or regulatory approval of a new device or drug for marketing. But so many industry professionals dedicate countless hours and sacrifice, only for the solution to fall short of commercialization due to an unforeseen clinical setback somewhere in between, or even right at the finish line.

Whether due to a poorly designed trial, unlucky randomization, or an unanticipated biochemical reaction, these innovators and risk takers enhance our understanding of science and the world around us, even if their efforts don’t result in an esteemed award or a lucrative exit.

 

Conclusion

In this post, we looked at the technologies and challenges surrounding four wound care and regenerative medicine-related firms in the pre-commercialization and early commercialization stages. We also saw how, despite the amazing innovation potential, companies can still stumble on or struggle with unforeseen scientific/clinical, marketing, competitive, regulatory, and other challenges.

My advice to innovators in startups, small, or even large companies with a desire to be successful in advanced wound care and regenerative medicine:

  1. Know your customers and end-users. First of all, your customers and end-users are not necessarily the same people–especially in healthcare. These include not just physicians and clinicians who will be applying products–they include the reimbursement managers who can advise on price points and ensure you get paid for it (and approve their use in the practice/company/health system), the administrators who will actually order it and understand its place in their business, and of course the patients, who need to have it fit into the framework of their overall care and lifestyle. Instead of simply asking, “Why would somebody want to use this?” be sure to spend at least as much time asking, “Why wouldn’t somebody want to use this?” and tweak or rethink your solution as appropriate.
  2. Know your competitors. A Google search is not enough. In this field, you need to dig and leverage direct interactions with primary stakeholders to know current and future competitors (medical devices take a long time to commercialize) and off-label uses of other products that might be practical competitors, if not formal ones. And don’t forget about substitute products–they’re competitors, too. I can’t tell you how many times a startup has contacted me to discuss their killer wound care solution and how it’s going to disrupt everything, but then they can’t even name half of the current products/methods being used to solve the “problem” they’re trying to fix in the first place. When I work with startups and investors (usually VCs or private equity firms performing due diligence on a potential investment target), one of the most valuable insights I provide them is an assessment of current or planned competitors/substitutes for their solution. This is crucial, especially since a firm’s solution might not have competition now–but by the time it’s expected to roll out in 12+ months, there could be several others in the market already. When I am approached early enough in the process, we’re often able to tweak or rework the solution to give it a competitive advantage that the others don’t have. Or, in some cases, the investors have determined not to pursue the investment due to the new insights into the competitive landscape.
  3. Follow the money. In a perfect world, solutions that reduce cost for the system as a whole, will generally be better (i.e. if someone develops a better or less expensive mobile display, charger, camera, etc. the mobile phone end-purchaser/user is better off, because the price/experience is all part of the mobile phone package, which the user pays for in the mobile device). Unfortunately, healthcare in most developed markets is totally different. It’s not enough to say, “This product will save the healthcare system $1 billion dollars.” If it will save the hospital operating room $1 billion but will cost the physician clinics $10 million and you expect the clinics to purchase it, it likely won’t happen; If it will save the insurance company $1 billion but will cost the hospitals $1 million, it likely won’t happen, either. Even within most hospitals, saving $1 million for department X via an expense of $100,000 that will hit the budget of department Y is a stretch (because each unit usually has its own P&L that operates in a relative silo). With such an outdated, intertwined system that is anything but value-based (for most treatments and procedures), it is difficult to link the prices stakeholders pay to the outcomes they receive. This is why I believe that generally, non-US and non-Western European markets hold the greatest opportunities for advanced wound care and regenerative medicine innovation…

… but that discussion will be the subject of a future post…

This was Part 3 of a 3-Part series. Check out Part 1 and Part 2 as well.

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