Astellas’ focus on technology leads to bioelectronic medicine

by Susan Schaeffer, consulting editor

January 2022 issue, BioElectRx Business Report

A few pharmas have dipped their toes into bioelectronic medicine, but Astellas Pharma Inc. has declared it as a key element of its growth strategy over the next decade. The Japanese pharma says it believes bioelectronic therapies can deliver greater value to patients by improving outcomes and reducing costs, and can also provide its prescription drug business with a competitive advantage derived from new biological insights.

Astellas is every inch a pharmaceutical company today, with about $11.3 billion (¥1.25 trillion) in revenue for its fiscal year 2020, which ended on March 31, 2021. Its marketed products are prescription drugs, with its core offering concentrated in various cancers, kidney disease, overactive bladder, and transplant.

But a change in R&D strategy in 2018 set the company on a path that places more emphasis on technology than its pharma-industry peers. Before that point, Astellas’ R&D strategy was similar to that of other mid-sized pharma companies in the sense that the company concentrated its investment and development efforts in disease areas where it had critical mass.

In 2018, shortly after Kenji Yasukawa was promoted to president and CEO from EVP, chief strategy officer, and chief commercial officer, Astellas shifted to an R&D strategy that is driven by developments in biology and treatment modalities or technologies, regardless of disease area. According to its most recent annual report, the approach continues to drive R&D strategy today.

Consistent with that new philosophy, Astellas also formed a small unit in 2018 called the Astellas Rx+ Business Accelerator to develop new revenue streams outside of the drug business using new technologies that can help patients live healthier and happier lives. These included software, apps, and other digital health technologies; medical devices; and bioelectronic medicine.

The acquisition of iota Biosciences Inc. in 2020 for $127.5 million up front and up to $176.5 in potential milestones remains Rx+ Business Accelerator’s highest-profile bioelectronics deal to date. But Astellas also has positions in at least three neuromodulation companies through direct or indirect investments. The pharma also has tapped into bioelectronic medicine partnerships to develop key insights into neural networks to support its core business of drug development.

The overall goal is for the Rx+ Business Accelerator to reach financial break-even in FY2025, and to become one of the company’s “mainstays” by FY2030. And bioelectronic medicine could be at the core of it all.

In a March 2021 Rx+ Business Accelerator Day for investors, Astellas said the bioelectronic medicine platform it gained by acquiring iota Biosciences, Inc. in October 2020 “could be the platform technology that underpins the Rx+ business” across all its areas of focus.

Building a foundation

The October 2020 acquisition of iota Biosciences followed a multiyear relationship. Astellas had participated in iota’s $15 million series A round in May 2018, and in September 2019 the companies inked a collaborative research and development agreement (CRADA) to co-design detailed specifications of implantable medical devices and conduct preclinical studies for several undisclosed diseases.


The iota platform consists of an implantable device that is only a few millimeters long, and an external ultrasound transducer. The implantable device can sense biological information and send it to the transducer. The transducer can send energy to the device to power it and to enable stimulation of nerves or muscle depending on where it is implanted.

Because ultrasound can reach deep into tissues without interference from muscle and fat, the device can be implanted deep into the body.

The technology has the potential not only to yield novel treatments and diagnostics, but also to generate data and insights that can lead to new drug targets and candidates.

“The acquisition and utilization of biological information deep within the body is a competitive advantage for pharmaceutical companies,” said Kunitake Abe, an executive within the Rx+ Business Accelerator, during the investor presentation last March.


In combination, he said, these properties could enable real-time, at-home measurement of biological parameters that currently can be monitored only in a hospital, as well as measurement of novel parameters that currently cannot be measured at all. One example of the latter might be the ability to monitor pH levels, which Abe said is known to fluctuate in response to inflammation. 


According to Abe, discovery of new parameters that indicate disease status could lead to new methods of monitoring disease, as well as novel treatments.

In addition, more frequent measurement of biological parameters that are currently measured only periodically during hospital visits could enable patients to respond to sudden changes in disease status, help patients and physicians to assess the real-world efficacy of treatments, reduce the need for hospital visits, and possibly even predict and prevent disease exacerbations.

The company has identified multiple potential indications for the technology, including numerous neurology indications; respiratory diseases such as chronic obstructive pulmonary disease; urological indications; rheumatoid arthritis and muscular dystrophy; cancer treatment and monitoring; treatment and monitoring of eye and heart diseases; gastrointestinal diseases including Crohn’s and gastroesophageal reflux disease; and metabolic diseases including diabetes.

Abe said Astellas is aiming to launch its first products that can sense and provide electrical stimulation in the later 2020s. A later iteration will include closed-loop systems, followed by “more complex, multiple closed-loop, auto-controlled projects.”

“iota may be able to do something game-changing if the device becomes so small it’s like a pill,” Chihiro Hosoya, head of venture management and business development in the Rx+ Business Accelerator, told BioElectRx Business Report. “It may be able to achieve less side effects than a systemic drug. I do believe it will be a new modality,” she added.

Building a pipeline portfolio

In addition to partnerships and acquisitions, Astellas’ approach to building a portfolio of bioelectronic medicines candidates includes both direct and indirect investments.


As an example of the former, Astellas invested an undisclosed amount in a series A-2 round for Nēsos Corp. in April 2021. The round was first announced in December 2020, with a $16.5 million close. 


Nēsos is developing a therapy for RA that uses neuroplasticity-altering electrical fields, delivered via earbuds, to the target brain areas that help regulate immune function. The company calls the approach e-mmunotherapy. E-mmunotherapy retrains brain networks by stimulating the cholinergic anti-inflammatory pathway via transauricular vagus nerve stimulation. 


The device has breakthrough device designation from FDA, and clinical data published last February in The Lancet Rheumatology showed a 53% ACR20 response rate after three months, a 37% ACR50 response rate, and a 17% ACR70 response rate in patients with RA who have had an inadequate response or intolerance to disease-modifying anti-rheumatic drugs.

Future applications of e-mmunotherapy may include migraine and post-partum depression.

One of Astellas’ vehicles for indirect investment is Treo Ventures (formerly known as Strategic Healthcare Investment Partners), in which the pharma is a limited partner. Treo’s portfolio includes bioelectronic medicine/neuromodulation plays CVRx, Inc., Neuspera Medical, Inc., and ShiraTronics, Inc.


CVRx markets its Barostim NEO device in the U.S. for improvement of symptoms in patients with heart failure who are not indicated for cardiac resynchronization therapy. Barostim NEO is a subcutaneously implanted wireless device that activates baroreceptors in the wall of the carotid artery and stimulates the autonomic nervous system. The brain responds to the therapy by modulating efferent pathways, to relax blood vessels, slow the heart rate and reduce fluid in the body via improved kidney function. 


Neuspera is developing the Neuspera Implantable Sacral Neuromodulation system to treat the symptoms of urinary urge incontinence. The system comprises a minimally invasive implant and an external wearable transmitter.

ShiraTronics is in the early stages of developing novel neuromodulation technologies to treat migraine.

Supporting the pharmaceutical business

Astellas also is looking for ways to apply insights from bioelectronic medicine approaches to its work in preclinical drug development. In October 2019, the pharma’s Astellas Research Institute of America LLC partnered with Inscopix Inc. to develop preclinical drug screening assays for psychiatric disorders using Inscopix’s fluorescence microscope-based brain-mapping platform. The aim was to help identify new drug targets and help evaluate the efficacy of candidate therapies during preclinical development.

The two-year deal included using Inscopix’s nVoke system to investigate neural activity patterns in animals during the performance of behavioral tasks that reflect clinical features of disease, and characterizing aberrant brain activity in rodent disease models to create a platform for efficacy studies.

nVoke combines real-time in vivo imaging of neuronal activity using a miniature microscope with optogenetic manipulation that can stimulate or suppress circuit activity. The system is capable of imaging thousands of individual neurons simultaneously, with single-cell resolution.

Inscopix was founded in 2011 based on an imaging platform developed by CEO Kunal Ghosh and cofounders Mark Schnitzer and Abbas El Gamal at Stanford University. At the Neurotech Leaders Forum in November 2021, CSO David Gray said the company is beginning to transition into developing therapeutics itself. Gray has spent his career developing small molecule therapeutics for neurology indications, most recently at Pfizer spinout Cerevel Therapeutics Inc.