Presidio Medical Files for IPO to Advance ULF™ SCS System for Chronic Pain Affecting 20% of Global Population

According to The Economic Costs of Pain in the United States, approximately 50 million people in the United States alone suffer from chronic pain, with annual treatment and economic costs exceeding $560 billion. Epidemiological surveys indicate that around 20% of the global population suffers from chronic pain, which has become a “global public health priority.” To date, chronic pain remains a leading cause of disability worldwide and a significant factor contributing to reduced quality of life.

Presidio Medical’s ULF™ (ultra-low frequency) SCS system is poised to provide a more effective, safer, and longer-lasting treatment option for the vast population of patients with chronic pain.

Presidio Medical is a clinical-stage medical device company founded in 2017 and headquartered in South San Francisco, California. It is led by CEO and Chairman Michael Onuscheck, who previously served for over seven years as Senior Vice President and President of the Neuromodulation Division at Boston Scientific. With the vision of “building the future of neuromodulation therapies,” Presidio Medical’s core product, the ULF™ SCS System, is dedicated to treating various conditions characterized by aberrant neural activity, with chronic pain as its primary indication.

Chronic pain is defined as pain that persists or recurs for more than three months. In 2018, the World Health Organization (WHO) revised the International Classification of Diseases (ICD-11), listing chronic pain as an independent disease for the first time.

Currently, pharmacotherapy is a major approach to alleviating chronic pain; however, its efficacy is limited for most patients with chronic pain, and it may cause serious adverse effects. For instance, opioids can lead to drug addiction and even pose a risk of death. Despite these risks, clinical practice remains heavily reliant on opioids. According to data from the U.S. Centers for Disease Control and Prevention (CDC), more than 168 million opioid prescriptions were issued in the United States in 2018. Another method for relieving chronic pain is electrical neuromodulation. Direct current can block the propagation of action potentials, thereby producing an analgesic effect. However, prolonged use can result in tissue damage.

The limitations and shortcomings of current analgesic therapies underscore the urgent need for superior treatment options. How can patients be helped to alleviate chronic pain while minimizing side effects and therapeutic risks? Presidio Medical’s ULF™ SCS system offers a novel approach.

Over the past few decades, millions of patients have experienced relief from pain symptoms through neuromodulation devices activated or triggered by short pulses. However, in many cases, neural inhibition—acting as a “brake” rather than an “accelerator”—would represent a more ideal therapeutic solution. Stephen McMahon, Professor of Sherrington Physiology at King’s College London (London, UK), is highly optimistic about the ULF™ SCS system’s ability to inhibit pain neurons in a controlled and reversible manner: “The mechanism of action of this new technology has been studied from the laboratory to the clinic. We now understand that ULF neuromodulation can induce immediate and slowly developing neural inhibition through sodium channel inactivation, which is particularly effective in persistent pain states.”

Presidio Medical’s ULF™ SCS system is an innovative neuromodulation technology for the treatment of various chronic pain conditions, built upon Nobel Prize–winning foundational scientific principles. The ULF™ SCS system leverages the scientific principles of the “ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane,” discovered by British physiologists Alan Hodgkin and Andrew Huxley—namely, the Hodgkin-Huxley model—for which they were awarded the 1963 Nobel Prize in Physiology or Medicine.

The ULF™ SCS system operates by delivering ultra-low frequency (ULF) current waveforms to stimulate nerve fibers in the spinal cord. These ULF waveforms induce sodium channel inactivation, thereby reducing nerve fiber excitability and slowing conduction velocity, which ultimately blocks the transmission of pain signals. The ULF waveform can suppress ectopic activity in sensory neurons, a key driver of clinical neuropathic pain. This mechanism enables reversible inhibition of pain signals without causing damage to nerve fibers.

On August 25, 2021, Presidio Medical announced that research involving its ULF™ SCS system had been published in Science Translational Medicine, under the title “Neuromodulation using ultra low frequency current waveform reversibly blocks axonal conduction and chronic pain.” This breakthrough collaborative study spanned three continents and involved scientists and clinicians from King’s College London (UK), the University of Michigan (US), Hunter Pain Specialists (Australia), and Presidio Medical.

The literature reveals that the ULF™ SCS system can inhibit pain signals in preclinical animal models, computational models, and clinical trials. Its neuromodulation mechanism is unique, capable of controlling and reversibly inhibiting pain neurons through sodium channel inactivation. This differs significantly from existing SCS technologies, which alleviate pain by activating neurons.

The study also evaluated the analgesic effects of epidural ULF current in 20 subjects with chronic leg and back pain. Relevant data showed a 90% improvement in pain levels after two weeks. One week after electrode explantation, pain scores returned to 72% of the pre-treatment screening values. In clinical studies, 95% of patients responded to ULF neuromodulation therapy (≥50% pain relief), and 90% achieved a profound response (≥80% pain relief). During the trial, patients did not experience paresthesia or functional loss, and neurological examinations revealed no stimulation-induced deficits or muscle weakness.

Many subjects clearly reported that pain began to subside approximately 2 to 12 hours after the initiation of ULF delivery, and noted that pain returned within about one day after cessation of ULF and explantation of the device. The study participants also generally indicated an improved ability to engage in physical and leisure activities, such as long-distance walking and car maintenance. In this study, experts stated that “the ULF™ SCS system is a promising novel therapy for chronic pain.”

Previous studies have explored the use of direct current (DC) to block action potential conduction; however, this approach has not been adopted to date due to tissue damage and electrode degradation caused by prolonged DC exposure. From a neuronal perspective, the biphasic waveform of the ULF™ SCS system, featuring both cathodic and anodic plateau phases, effectively simulates DC conditions with alternating polarity. Furthermore, this alternating polarity helps prevent potential tissue or electrode damage associated with high charge-capacity electrode materials. Meanwhile, the power consumption at the electrodes of the ULF™ SCS system is consistent with that of commercially available SCS devices, indicating that power consumption will not be a major barrier to the feasibility of fully implantable systems.

On June 26, 2023, Presidio Medical completed a $72 million Series C financing round., this round of investment was led by Deerfield, an investment firm dedicated to transforming the healthcare industry through information, investment, and philanthropy, with participation from Shangbay Capital, Invus Opportunities, and Action Potential Venture Capital. According to Crunchbase, after three rounds of financing,Presidio Medical's total funding has currently reached $102 million.The financing will be used to continue expanding the team and production scale, and to conduct long-term, pivotal clinical studies on the ULF™ SCS system.

Michael Onuscheck, Chairman and Chief Executive Officer of Presidio Medical, stated, “With this round of financing, we will continue to bring this innovative solution to market and collaborate with leading clinical researchers on large-scale, long-term clinical studies to demonstrate the durability and efficacy of the ULF™ SCS System.” Presidio Medical will remain focused on providing effective pain relief therapies for various types of pain that are not adequately addressed by conventional treatments. The company is also expanding research into new applications of its technology to extend this innovative therapy to additional indications in other therapeutic areas, thereby meeting unmet medical needs in these fields.

Currently, the primary therapies for alleviating chronic pain in China include spinal cord stimulation (SCS), deep brain and motor cortex stimulation, peripheral nerve stimulation, and repetitive transcranial magnetic stimulation. Meanwhile, stem cells are emerging as a promising new option for treating chronic pain, owing to their robust tissue repair capabilities, anti-inflammatory properties, and immunomodulatory effects.

In the field of chronic pain management, Beijing Lingchuang Medical Valley Technology Development Co., Ltd. started with spinal cord stimulation (SCS) and independently developed China’s first wireless, energy-harvesting implantable neurostimulation product. This device overcomes the clinical application limitations of traditional active implantable neurostimulation products and holds promise for delivering more comfortable and effective treatment solutions to hundreds of millions of chronic pain patients worldwide. Hangzhou Shenluo Medical Technology Co., Ltd. is also focused on SCS systems. Dedicated to the independent research, development, and manufacturing of medical devices in the fields of implantable neurostimulation and brain-computer interfaces, Shenluo Medical’s self-developed and manufactured SCS system has successfully completed its first clinical implantation in the Pain Department of the First Affiliated Hospital, Zhejiang University School of Medicine.

As one of the earliest companies to establish a presence in China’s pain management sector, Aipeng Medical has been deeply engaged in this field for many years. Its chronic pain treatment system—the Internal Heating Needle Therapy Instrument—can release and repair spastic and degenerated muscle tissue, promote myocyte regeneration and revascularization, enhance local blood circulation, and reduce myofascial tension and sterile inflammation. Meanwhile, Tuoren Medical, as the leader in China’s analgesic pump market, continues to expand its efforts in the chronic pain domain. Its disposable puncture kit for pain therapy meets the clinical needs for drug administration in the treatment of refractory chronic pain and malignant pain.

In China, the chronic pain market continues to expand in scale. The Blue Book on China’s Pain Prevention and Control and Health Promotion Strategy: Report on the Development of Pain Medicine in China (2020) indicates that there are over 300 million chronic pain patients in the country, with an annual increase of 10 to 20 million, and a trend toward younger demographics. Statistics show that the domestic pain management market is projected to exceed RMB 400 billion in 2023.