ShiraTronics Submits IPO Prospectus Following $66M Series B to Address Global Migraine Epidemic Affecting 1.04 Billion

Migraine is a common chronic, episodic disorder of brain dysfunction. Its long-term, recurrent episodes lead to significant health burdens, reduced quality of life, and loss of productivity, making it one of the major global public health challenges.

According to data from the Chinese Guidelines for the Diagnosis and Treatment of Migraine, approximately 1.04 billion people worldwide are affected by migraine. The lifetime prevalence is approximately 10% in men and as high as 22% in women. In China, the annual prevalence of migraine is approximately 9%, imposing a substantial negative impact on patients and their families, as well as on society as a whole.

In October 2024, ShiraTronics, a clinical-stage medical device company focused on developing neuromodulation therapies for patients with chronic migraine, announced the completion of its $66 million (approximately RMB 460 million) Series B financing round.

This round of financing was led by Norwest Venture Partners, with other new investors including Seroba, OSF Ventures, Global BioAccess Fund, and an unnamed strategic investor. Existing investors U.S. Venture Partners, Amzak Health, Treo Ventures, and Aperture Venture Partners also participated in this round.

In 2018, ShiraTronics was incubated by the renowned medical fund Treo Ventures. In 2021, the company’s self-developed innovative migraine treatment system received FDA Breakthrough Device designation. The first clinical trial was completed in late 2023, and the pivotal RELIEV-CM2 clinical study is currently underway in the United States and Australia.

From the perspective of its etiology, migraine is a recurrent primary chronic headache disorder of neurovascular origin, characterized by recurring moderate-to-severe pulsating headaches, often accompanied by symptoms such as nausea or vomiting, photophobia, and phonophobia. Migraine has a high prevalence and a prolonged course, ranking second in the burden of neurological diseases.

In 2018, the International Headache Society (IHS) released The International Classification of Headache Disorders, 3rd Edition, which categorizes migraine into six types: migraine without aura, migraine with aura, chronic migraine, complications of migraine, probable migraine, and episodic syndromes that may be associated with migraine.

Currently, pharmacological prevention and treatment are the primary clinical approaches for migraine. ShiraTronics primarily targets patients with chronic migraine syndrome (RELIEV-CM) who are refractory to medication and experience severe headaches on at least 15 days per month.

Currently, conventional implantable neurostimulation systems for chronic pain management on the market typically place electrodes within the spinal canal and are primarily used to treat various forms of chronic back and limb pain. In contrast, neuromodulation systems targeting the brain generally involve Deep Brain Stimulation (DBS) for neurological disorders such as Alzheimer’s disease. These systems require electrode implantation into specific deep brain nuclei, such as the subthalamic nucleus or the globus pallidus internus.

ShiraTronics’ neuromodulation therapy system is the world’s first fully implantable brain neuromodulation system utilizing a minimally invasive approach. It comprises an Implantable Pulse Generator (IPG), Integrated Leads, a head-worn device for charging and communicating with the IPG, a charger, ShiraTronics Therapy Software, and a Patient Magnet that can be placed on the skin above the IPG to rapidly suspend therapy.

Minimally Invasive Implantable Cranial Neuromodulation System, Image Source: ShiraTronics.com

From a mechanistic perspective, the implantable pulse generator continuously delivers narrow-pulse electrical currents via leads implanted beneath the scalp to the greater occipital nerve (GON) and supraorbital nerve (SON), thereby blocking and dampening pain signals in the brain to alleviate and prevent symptoms of chronic migraine. Meanwhile, patients can personalize and control the treatment process through a companion app, enabling around-the-clock therapy.

From the perspective of clinical trial procedures, ShiraTronics’ process from implantation to treatment consists of four steps:

First, a 28-day headache diary is completed preoperatively to assess eligibility for surgery. Next, a trial system is implanted by placing a 60-cm temporary lead subcutaneously near the target cranial nerves. This step determines the patient’s suitability for permanent implantation. The temporary lead implantation can be performed under local anesthesia in an ambulatory surgery center. Subsequently, after a 4–10-day trial period, if the patient is satisfied with the therapeutic effects of the temporary leads, the physician will proceed to implant one wireless rechargeable neurostimulator and two permanent leads on each side of the head. The final stage involves device utilization and follow-up.

Implant Localization Map, Image Source: ShiraTronics.com

The third step is the core procedure and a critical metric for evaluating the safety of the implantation surgery and the product. Specifically, during the implantation process, the physician only needs to make a small incision on the patient’s scalp. A 14-gauge, 4-inch curved introducer needle is then used as a sheath for the delivery electrode, gradually advanced from the incision into the subcutaneous tissue along the target neural pathway. After withdrawing the sheath, the minimally invasive implantation of two lead wires is completed. ShiraTronics emphasizes that because the implanted leads are positioned in the subfascial plane and the implantable pulse generator features a curved design, the device does not affect the patient’s appearance or daily life when worn.

Anatomical Localization Diagram. Image source: ShiraTronics.com

Specifically, the occipital nerve lead (OL) is 15.4 cm in length, and the supraorbital nerve lead (FPL) is 26 cm in length, with their distal ends connected to a pulse generator. Each lead contains multiple electrodes distributed along a specified segment, thereby achieving comprehensive unilateral coverage of the frontal, parietal, and occipital regions of the head to fully inhibit and block pain signals.

Wearing Diagram, Source: ShiraTronics.com

In July 2024, ShiraTronics presented the results of its early-stage clinical study in Australia, RELIEV-CM, at the American Society of Pain and Neuroscience (ASPN) conference, demonstrating significant efficacy of its combined neuromodulation technology targeting the occipital nerve and supraorbital/supratrochlear nerves.During the 12-week postoperative follow-up, the mean monthly headache days (MHD) and mean monthly migraine days (MMD) were significantly reduced compared to preoperative baseline levels. Pain intensity was also significantly decreased, with marked improvements in patients’ daily functioning and overall well-being. The implant demonstrated a favorable safety profile, with no significant adverse events reported.

It is worth noting that upon completion of the RELIEV-CM trial, six patients opted for permanent implantation of the ShiraTronics system, representing the strongest endorsement of the product’s efficacy.

It should be noted that although pharmacotherapy remains the mainstay of migraine treatment, ShiraTronics is not the first company to employ neuromodulation—i.e., physical system-based therapy—for migraine management.

Neuromodulation/Neuromodulation（Neuromodulation) is an effective non-pharmacological neuromodulation therapy for migraine and has a history spanning several decades. As early as 2014, the U.S. FDA approved Cefaly (Chinese name: Shifanli), the world’s first electrical neurostimulation device for treating migraine, ushering in the era of electroceutical treatment for migraine.

Cefaly Neuroelectrical Stimulation Device

Image source: Cefaly.com

Unlike ShiraTronics, which opts to stimulate the suboccipital and supraorbital nerves, Cefaly employs a non-invasive technology to develop an external Trigeminal Nerve Stimulation (eTNS) system. Targeting the first branch of the trigeminal nerve, this system features three functional modes: migraine treatment, migraine prevention, and stress relief.

The acute treatment mode is designed for acute migraine attacks, with a recommended duration of 60 minutes. The preventive mode is intended for daily use, once a day for 20 minutes per session; regular use can reduce the frequency of migraine attacks. The stress relief mode is suitable for individuals experiencing high stress, anxiety, or insomnia, particularly for patients who need to reduce medication usage.

Notably, China’s first guideline on non-pharmacological management and prevention of migraine, the “Chinese Expert Consensus on Non-Pharmacological Management and Prevention of Migraine” (2021), reviewed the clinical data on Cefaly for the treatment and prevention of migraine. In summary, Cefaly is an effective and safe therapy for migraine prevention. For acute treatment, mean pain intensity decreased by 57.1% at 1 hour and by 52.8% at 2 hours post-treatment. During the 2-hour observation period, no patients required rescue medication, significantly reducing the use of acute analgesics.

In addition, there is electroCore (Nasdaq ticker: ECOR). The company achieved a technological breakthrough in 2010 by developing a technology for non-invasive vagus nerve stimulation (nVNS) that delivers proprietary signals transcutaneously to the right or left branch of the cervical vagus nerve. This breakthrough ultimately led to the creation of the company’s flagship product, GammaCore Sapphire. The device is compact, handheld, and portable, allowing for quick and easy treatment anytime, anywhere.

 GammaCore Sapphire

Image source: electroCore.com

Unlike traditional vagus nerve stimulation, the GammaCore Sapphire non-invasive vagus nerve stimulator (nVNS) activates the vagus nerve through gentle electrical stimulation via the skin to prevent and relieve headaches without surgery. The company’s official website states that patients can achieve immediate headache relief with just a two-minute treatment per session; furthermore, using the device twice daily, once in the morning and once in the evening, can resolve long-term headache symptoms. This technology is indicated for the treatment of common migraine, cluster headache, and continuous or episodic hemicrania, among other conditions.

In addition, there are non-invasive neuromodulation systems such as Relivion MG, a percutaneous cranial nerve electrical stimulation (PCC) device developed by the Israeli company Neurolief; Nerivio, a remote electrical stimulation device worn on the arm; and SAVI Dual, a transcranial magnetic stimulation system developed by the U.S. company eNeura.

Source: Official websites of respective companies; Graphic by VCBeat

Turning to the domestic market, public data indicate that there are currently no neuromodulation devices specifically indicated for migraine in China. In early 2024, Nerivio announced the successful completion of its first patient use in China at Ruijin Hainan Hospital. Reportedly, Nerivio is a Class II imported medical device. Its successful market entry in the future will provide richer treatment options for individuals who are intolerant to medication side effects, have contraindications to pharmacotherapy, and adolescent migraine patients who currently have very limited therapeutic choices.