Upgrade Your Medicine: The Tip of the Spear
Bioelectric medicine is an emerging field, with innovation happening at the concept, product, and clinical stages. The previous articles in this series showed how the technology can stretch from implantable pacemakers that have been on the market for decades all the way to cutting edge miniature stimulators that are still in clinical development. To give an idea of the cutting edge of bioelectric medicine, this article will dive into a few examples of the startups who are pushing the limit and the investors who are funding them.
The Startups
Description: early-stage company developing a novel neuromodulation approach to treat heart failure
Core technology: As of early 2019, Axon Therapies is the assignee for multiple patents related to splanchnic nerve ablation. Per patent US10207110B1, the technology works by blocking or inhibiting innervation of organs and vasculature near the heart. This can alter circulating blood volume, pressure, blood flow and overall heart and circulatory system functions, resulting in a novel approach to treat heart failure.
Product pipeline: The company provided some of the funding for a clinical study published in November 2018 exploring the Relation of Volume Overload to Clinical Outcomes in Acute Heart Failure. In October 2018 the company started recruiting for a small (n=10), open-label clinical study in Poland to study the effect of resection of certain nerves around the heart on patients with a particular type of heart failure
Funding: $2M round in 2016; $1.3M in 2017; $7.5M in 2019
Takeaway: Axon Therapies remains in stealth mode from a product perspective, and LinkedIn shows only on full-time employee. That being said, there appears to be strong momentum and a clear product strategy moving into 2019: assignment of key patents, initiation of human trials, and raising a funding round which should support the company through execution of the clinical trial. The market for heart failure therapeutics has a 13.7% CAGR with a predicted market size of $11B+ by 2025.
Description: Minimally invasive implantable brain device that can interpret signals from the brain for patients with paralysis. Development stage.
Core technology: Synchron has multiple patents related to sensing and stimulating tissue. Their leading technology, the Stentrode™, is a stent which is inserted into the motor cortex. The stent captures signals from the motor cortex, then transmits them wirelessly to an external receiver. The goal is to ultimately return bodily control to paralyzed patients.
Product pipeline: Synchron has demonstrated in sheep models that their stent-based electrode can control muscular response in the face and limbs at a level comparable to electrodes implanted via invasive surgery. Critically, this demonstrates that their minimally invasive device can effectively interact with the brain; however it only demonstrated unidirectional control (electrode->brain->muscle). The company launched a human safety and efficacy trial this month to evaluate interaction in the opposite direction. Specifically, Synchron is assessing whether the implanted electrode can communicate outward from the brain to a software platform designed to translate thoughts into control of assistive devices.
Funding: Synchron announced a $10M series A round in April 2017, with participation by the US Defense Advanced Research Projects Agency (“DARPA”) and Neurotechnology Investors
Takeaway: Synchron has a compelling vision that makes an immediate emotional and cognitive impact (“With our product, paralyzed people can walk again”). In addition, their minimally invasive neuro-electrode technology has huge potential as a platform for other bioelectric medicine interventions. That being said, their current leadership team is limited to CEO, CTO, and Business Development; no positions in operations, regulatory affairs, clinical, etc. This, combined with their close and ongoing ties to the University of Melbourne, suggest that the strategy is to develop novel technologies and IP that are then licensed to operational medical device companies.
Description: Implantable platform to power neuromodulation implants. Development stage.
Core technology: Neuspera has multiple patents related to powering an implantable medical device wirelessly using a midfield coupler
Product pipeline: Neuspera’s “Technology” page speaks in generalities about the ability to precisely power implanted devices through layers of air, skin, muscle, and bone. There are no distinct products described, and the only clinical study associated with Neuspera, exploring applications of their technology in urinary incontinence, was closed in January 2018 with no resulting publications.
Funding: $1M seed; $8M A in 2017; $26M B in 2018 (closed Feb 2019 after achieving certain product development and regulatory milestones)
Takeaway: Neuspera has potential as a platform play to support the growing bioelectric medicine field by enabling other device developers to reduce device size through novel power management. This strategy relies on an effective partnership, licensing, and distribution strategy (in addition to simply delivering an effective device), which complicates the business model. With $20M+ in the bank, only twenty employees, and no ongoing clinical trials, Neuspera seems to be planning to optimize their technology, increase partnership and corporate development activities, and position themselves as somewhat of an Amazon Web Services for implantable medical devices.
Description:Non-invasive wearable neuromodulation technology. Clinical stage.
Core Technology: Multiple patents for devices, methods, and systems related to neuromodulation including applications for controlling essential tremor, as well as overactive bladder, osteoarthritis, and cardiac dysfunction.
Product Pipeline: In April 2018, the FDA cleared Cala ONE , an individualized prescription neuromodulation therapy for transient relief of hand tremors in adults with essential tremor. This was supported by two clinical trials. In July 2018 Cala Health initiated the PROSPECT clinical trial, with n=263 participants studying the Cala TWO device for essential tremor. In 2019 licensed tech for Transcutaneous Vagus Nerve Stimulation (cutting-edge technology to improve action control through enhanced GABA and noradrenaline) and Transcutaneous Vagus Nerve Stimulation (hypertension treatment) from Massachusetts General Hospital
Funding:$18M in 2016
Takeaway: Cala Health has a foot in the door with the FDA-cleared Cala ONE device for essential tremor, and an IP portfolio covering the application of this cleared technology for additional potential indications. The technology licensed from MGH suggests that they’re exploring the application of noninvasive neurostimulation for modulation of the Inflammatory Reflex, setting themselves in competition to Setpoint Medical (which has already completed human studies of their technology). Of the 45 Cala Health employees on LinkedIn, only two are involved in manufacturing or operations. Taken together, Cala appears to be a few years from generating meaningful revenue by manufacturing a product and will likely be looking to close a large funding round soon to finance the continued development of their technology.
Description:direct stimulation of the vagus nerve using an electrode in contact with the nerve to provide the most effective and predictable stimulation of the Inflammatory Reflex versus near field stimulators outside the body. This approach has the potential to reduce or completely replace the need for pharmaceuticals or biologics as therapeutic agents. Clinical stage.
Core Technology: Leading platform is a microregulator pulse generator, which is implanted adjacent to the vagus nerve. It regulates stimulation of the nerve to modulate the inflammatory reflex, which has been shown to impact multiple inflammatory diseases. Setpoint has multiple patents related to devices, systems, and treatments of inflammatory disease using neural stimulation.
Product Pipeline: Preclinical testing demonstrating that one dose of bioelectric medicine can reduce and reverse demyelinization in multiple sclerosis. Proof-of-concept study (in humans) showing a significant reduction in disease activity among patients with Crohn’s disease. Proof-of-concept study showing vagus nerve stimulation attenuates symptoms of rheumatoid arthritis, with an ongoing pilot IDE clinical trial in the United States
Funding: Setpoint has raised ~$90M, with the most recent investment a $30M Series D in August 2017.
Takeaway: Setpoint has demonstrated the most clinical evidence among the latest crop of bioelectric medicine startups. It was co-founded by Dr. Kevin Tracey, who characterized the inflammatory reflex while researching at the Feinstein Institute for Biomedical Research, and benefits from being the first mover in this space.
The Investors
APVC is a stage-agnostic venture firm dedicated to advancing bioelectric medicine. It was launched in 2013 with $50M from GlaxoSmithKline; remains funded by GSK however invests independently. APVC has invested in many of the leading bioelectric medicine startups including Setpoint Medical, Cala Health, and Neuspera.
The existence of Action Potential VC demonstrates GSK’s ongoing faith in bioelectric medicine (as does GSK’s joint venture with Google, “Galvani Biosciences”). As of now, APVC is the only venture firm focused entirely on bioelectric medicine. Their portfolio companies range in maturity from product feasibility stage to clinical trials.
Coridea is a medical device incubator based in NYC, focused primarily on interventions for cardiac, pulmonary, and renal disorders. Coridea stepped into the bioelectric medicine game by investing in Axon Therapies, which was attractive based on its heart failure application. As of 2018, Coridea hadissued 120 US patents, raised $100M, and returned more than $1.4B to investors. With a strong engineering and medical pedigree, and a focus on translating medical technology innovation into clinical impact, Coridea has the ability to identify and develop, and commercialize products cutting-edge technology across a range of medical disciplines.
Neurotechnology Investors
Neurotechnology Investors was started by Martin Dieck (Chairman of Synchron) in 2016. The total offering size was $14.5M, with sold $900,000 to 18 total investors. Neurotechnology Investors participated in the Series A round for Synchron, and there have not been any publicized deals since that investment. It remains to be seen if the firm will extend to fund other early-stage companies or remain focused on funding Synchron’s development.
What’s Next
These examples give an insight into the types of technologies being developed within the bioelectric medicine focus, and the range of companies participating in the space. There are several macro issues that will continue to influence its development, including
Advances in electrical engineering, facilitating miniaturization and improved power management
Negative public sentiment toward the pharmaceutical industry stemming from the ongoing opioid crisis
Evolution of the regulatory landscape, making it easier to bring digital health products to market
The next article in this series will explore these factors in greater detail, with the goal of identifying systemic trends that will shape the continued development of bioelectric medicine.