Japan’s ten hottest biotech companies in healthcare

While historically lacking in foreign investments, Japan’s biotech scene is thriving with global investors showing increasing interest. Here are ten of the hottest Japanese private biotech companies innovating in the healthcare space.

Japan boasts one of the highest life expectancies in the world, and, faced with a rapidly aging population, is witnessing a growing burden of chronic conditions including cardiovascular disease and type 2 diabetes. For this reason, the Japanese healthcare authorities are encouraging research into the treatment and prevention of these diseases, in addition to promoting the potential of regenerative medicine.  

In addition to having a roster of healthcare giants including Takeda, Astellas Pharma and Eisai, Japan is also an Asian hotspot for biotech companies. Upcoming startups have historically been limited in foreign funding and reliant on local venture capital players such as Nippon Venture Capital, Shinsei Capital Partners, and the University of Tokyo Edge Capital Partners.

Chordia Therapeutics

Chordia Therapeutics derives its name from the English term ‘chord’ — referring to a collection of musical notes normally played in harmony. Similarly, the Japan-based biotech company aims to work in harmony with stakeholders and collaborators to develop first-in-class small-molecule treatments for cancer.

Chordia’s lead program is a drug that disrupts the processing of RNA in tumor cells. In a healthy cell, RNA molecules are typically transcribed from a DNA template and spliced together to guide the production of new proteins. Some cancer cells accumulate mutations in the RNA splicing machinery and become vulnerable to Chordia’s drugs that interfere with this process.

Chordia raised $31 million (4 billion yen) in a Series C round in May 2022. The round aimed to push the company’s lead drug, CTX-712, through phase I testing and fund the preclinical development of the rest of its pipeline.

In phase I Chordia’s CTX-712 demonstrated an acceptable safety profile with early signs of clinical antitumor activity, establishing the initial proof of concept of the CLK inhibitor.

Heartseed

Heart failure occurs when the heart muscle is irreparably damaged and is unable to pump blood. While this deadly condition can be treated with a heart transplant, there is a general shortage of donors available, making a pressing need for alternatives.

In June 2021, the stem cell therapy developer Heartseed raised $36.5 million (4 billion yen) in a Series C round. Its mission is to provide a regenerative route to saving the heart via stem cell therapy. The same month the company announced its collaboration with Novo Nordisk to develop its lead candidate, HS-001.

In the lab, Heartseed reprograms skin cells from the patient into a type of stem cell called induced pluripotent stem cells and grows these stem cells into heart muscle cells. The company then injects the muscle cells as a small cluster, or ‘seed,’ into the heart tissue to repair the muscle.

The proceedings from its Series C round allowed Heartseed to take its lead candidate into clinical development, including a phase I/II trial scheduled for later this year. Last year, Heartseed also licensed its treatment to Novo Nordisk in Denmark to co-develop the treatment outside of Japan.

More recently, Heartseed raised $13.3 million in a series D funding round. Earlier in 2023 Heartseed and Novo Nordisk dosed the first patient in phase 1/2 clinical study.

LUCA Science

LUCA Science hit the headlines in 2022 for raising an impressive $30.3 million (3.86 billion yen) in a Series B round. The company is developing an unusual approach for treating a wide range of diseases: delivering a therapy based on mitochondria, the energy production plants in human cells.

One example where the technology could work well is in strokes and heart attacks, where blood flow is blocked to critical tissue in the brain and heart respectively. The reperfusion of blood to these tissues after the blockage can kill the tissue by damaging its mitochondria. Delivering healthy mitochondria could keep the tissue working properly and protect it from harm.

LUCA Science plans to use its recent Series B winnings to accelerate the preclinical development of its mitochondrial therapies and establish its manufacturing process. In May 2022, the Japan-based biotech also inked a collaboration deal with compatriot pharmaceutical company Kyowa Kirin Co., Ltd. to co-develop a mitochondrial therapy for rare genetic diseases.

Recently the company was selected for the Japanese startup support program “J-startup” by the Ministry of Economy, Trade and Industry of Japan.

Modulus Discovery

Based in Tokyo in Japan, biotech Modulus Discovery is a preclinical-stage drug discovery company. The company focuses on developing small-molecule treatments for conditions such as cancer, inflammatory disorders, and rare genetic conditions.

The firm uses a mixture of strategies to speed up the drug discovery process. These include simulating target proteins using a supercomputer; structural protein biology; forming collaborations such as with the peptide drug expert PeptiDream; and tapping into global networks for biological expertise. Modulus’ most advanced drug program is in late-stage preclinical testing for the treatment of chronic inflammatory diseases.

In March 2022, Modulus bagged $20.4 million (2.34 billion yen) in a Series C round. The cash is earmarked to advance the company’s R&D programs by expanding its infrastructure, collaborations, and headcount.

Noile-Immune Biotech

The name Noile-Immune is derived from blending the phrases ‘no illness’ and ‘no immunity, no life.’ This company is developing CAR-T cell therapies for the treatment of cancer, which traditionally consist of extracting the patient’s immune T cells, engineering them in the lab to hunt down cancer cells, and reinfusing them into the patient.

Unlike approved CAR-T cell therapies, which are limited to treating forms of blood cancer, Noile-Immune aims its therapies at treating solid tumors. The company does this by engineering immune T cells to produce proteins that cause immune cells to migrate into the tumor site. Its Proliferation-Inducing and Migration-Enhancing (PRIME) technology features improved local trafficking of CAR-T cells and other immune cells into solid tumors. This technology genetically modifies CART-T cells so they simultaneously produce interleukin-7 (IL-7) and CCL19, immune regulators.

Noile-Immune is testing its lead candidate in phase I in patients with solid tumors. The firm is also co-developing therapies with partners including Takeda and the European cell therapy specialists Adaptimmune and Autolus. Additionally, Noile-Immune has an allogeneic version of its cell therapy in the pipeline — where immune T cells are sourced from healthy donors rather than the patient.

To finance the clinical development of its lead candidate, Noile-Immune raised $21.8 million (2.38 billion yen) in a Series C round in early 2021. In 2023 the company announced its collaboration with Rebirthel. This alliance aims to advance the development of allogeneic CAR-T cell therapy using immune cells derived from pluripotent stem cells. Noila-Immune also has a collaboration with Chugai Pharmaceuticals, a Roche majority-owned company. This collaboration aims to advance CAR-T cell therapy for solid tumors, combining PRIME technology with Chugai’s drug discovery expertise.

PeptiDream

With headquarters in Kawasaki in Japan, PeptiDream is a biotech company specializing in the discovery and development of macrocyclic peptide therapeutics, leveraging its proprietary Peptide Discovery Platform System (PDPS). This technology is a cornerstone of their business model, enabling the generation of peptide libraries for hit finding.

PeptiDream’s pipeline is diverse and spans a range of therapeutic areas, including oncology, CNS disorders, and immunology. With over 120 discovery and development programs, their pipeline encompasses a variety of peptide modalities such as peptide therapeutics, peptide-drug conjugates (PDCs), and multi-functional peptide conjugates (MPCs). This pipeline diversity is part of their strategy to mitigate the inherent high risk of the drug discovery industry by spreading it across numerous projects​​​​.

A key aspect of PeptiDream’s business model is its vast network of discovery and development partnerships, including collaborations with large, mid-, and small-sized pharmaceutical companies worldwide. This network is built around their PDPS discovery platform, with the biotech company licensing this platform to both global and Japan-based pharma partners, thereby solidifying a common platform for drug discovery. Through these collaborations and in-house developments, PeptiDream aims to further expand its network and modality, develop products in-house, and license these products to network partners​​.

In September 2023 the company announced a collaboration with Genentech where they will lead early preclinical development before transitioning products to Genentech for further development and commercialization. PeptiDream retains rights in Japan and will receive an upfront payment of $40 million from Genentech, with potential for further milestone payments of up to $1 billion, plus tiered royalties on net sales outside Japan​​. Other significant collaborations include Eli Lilly, Novartis, Merck, and Bristol Myer Squibb to name a few.

In addition to these collaborative ventures, PeptiDream develops a few projects in-house. 225Ac and 64Cu-CA9 targetting renal cell carcinoma and their myostatin Inhibitor for obesity, spinal muscular atrophy, and other muscle disorders are in their preclinical phase.

Raqualia Pharma

RaQualia Pharma, based in Nagoya, Japan, is a biotech company focused on the research and development of pharmaceutical compounds targetting pain management, gastrointestinal disorders, and cancer​​.

RaQualia Pharma operates with a diverse portfolio of products at various stages of clinical development. Among their notable projects are tegoprazan for gastroesophageal reflux disease, currently in phase 3 clinical trials in the United States, and grapiprant for cancer and pain management, which is in phase I clinical trials in China and the United States. Additionally, the company provides veterinary products, such as grapiprant also used for osteoarthritis in dogs, and is also developing a range of other compounds targeting conditions like cancer-related anorexia/cachexia syndrome, chronic pain, gastrointestinal dysmotility, schizophrenia, and more​​.

RaQualia’s business model is primarily licensing-based, generating revenue through upfront payments, milestone payments, and royalties from the licensing of their developed compounds to pharmaceutical companies. This approach allows them to capitalize on their R&D investments by partnering with larger pharmaceutical entities for the further development and commercialization of their compounds​​.

Recently, RaQualia Pharma announced a significant development with the acquisition of FIMECS, indicating an expansion of its R&D capabilities and portfolio. This move aims to accelerate drug discovery by leveraging FIMECS’ RaPPIDSTM platform for targeted protein degradation.

Restore Vision

Restore Vision is a startup focused on developing a visual restoration gene therapy aimed at treating retinitis pigmentosa, a group of genetic disorders that involve a loss of photoreceptors in the retina, causing vision impairment. In collaboration with the Keio University School of Medicine, Restore Vision has developed a promising product, RV-001.

RV-001 is a gene therapy developed for treating retinitis pigmentosa. This therapy utilizes adeno-associated virus (AAV) vectors to deliver a gene coding for ‘Chimeric Rhodopsin,’ a protein-based optical sensor designed to restore vision. The treatment involves a minimally invasive intravitreal injection, targeting the expression of chimeric rhodopsins in the remaining interneurons, thereby enabling patients to regain sight. Restore Vision is advancing RV-001 towards pre-clinical development, aiming to initiate clinical trials promptly, aspiring to be the world’s first vision restoration gene therapy.

Restore Vision has recently completed a $12.6 million Series A funding round on December 15, 2023, to accelerate global development and announced plans to begin the first-in-human study in 2024. Additionally, the biotech company was selected for a grant by a Japanese Governmental Agency in July 2023.

SanBio

SanBio Co., Ltd. is a Tokyo-based biotechnology company that specializes in the development, production, and sales of regenerative cell medicines. SanBio’s key product in development is SB623, a cell therapy aimed at treating chronic neurological deficits resulting from conditions like traumatic brain injury (TBI) and ischemic stroke​​.

SB623, also known as vandefitemcel, is a cell therapy product derived from the bone marrow of healthy adults. It has been designed to promote the brain’s natural regenerative abilities to restore lost functions by implanting SB623 cells into injured nerve tissues in the brain. This innovative treatment is currently being investigated for several conditions, including chronic neurological motor deficits resulting from TBI and ischemic stroke. SB623 is currently under review for manufacturing and marketing approval in Japan and in phase 2 clinical trial in the U.S. for traumatic brain injury

Some less advanced candidates include SB618 for the treatment of peripheral nerve damage, SB308 for muscle dystrophy, MCS1 for the treatment of cancer, and MCS2 targeting inflammatory diseases and optic neuritis, all in preclinical phases.

StemRIM

Based in Osaka in Japan, biotech company StemRIM is also focused on the development of regenerative medicines for treating intractable diseases. The company’s approach, termed “Regeneration-Inducing Medicine,” aims to induce functional regeneration of tissues and organs within the patient’s body by leveraging the human body’s innate tissue repair capabilities. StemRIM’s innovative strategy involves mobilizing the patient’s own in-vivo stem cells to damaged tissues for functional tissue regeneration without relying on traditional cell therapy methods. This represents a shift towards a new generation of regenerative medicine that could offer solutions for conditions previously considered untreatable​​.

Its development pipeline includes redasemtide, a regeneration induction medicine created from the bioactivity domain of the biologic protein HMGB1 (High mobility group box 1) peptides currently in Phase II clinical trials for various conditions such as epidermolysis bullosa, cerebral infarction, osteoarthritis, chronic liver disease, and cardiomyopathy. According to Nature, HMBG1 is a nonhistone nuclear protein that has multiple functions according to its subcellular location. In the nucleus, HMGB1 is a DNA chaperone that maintains the structure and function of chromosomes. In the cytoplasm, HMGB1 can promote autophagy by binding to BECN1 protein.

Additionally, StemRIM is working on pre-clinical stage products like PJ2 and PJ3 for treating multiple tissue damage diseases, PJ4, an autologous cell sampling device for medical treatment, and PJ5, a stem cell gene therapy​​.

Japan’s strategic investments and collaborative efforts in biotechnology

Japan is taking more space in the international scene than before. During the Bio International Convention 2023 held in Boston, the Ministry of Economy, Trade and Industry (METI) of Japan did a presentation about the government’s initiative and the biotechnology ecosystem as a whole.

The METI talked about a $3 billion plan to support Japan biotechnology and enhance collaborations with the U.S. One of Japan’s strong suits is drug discovery and this will keep improving with the Drug Discovery Venture Ecosystem Enhancement Project, aimed at supporting Japanese biotech startups in this area.  Prime Minister Kishida stated, “Now is the time to invest in Japanese pharmaceutical startups.” As Japan’s biotechnology ecosystem might still lack international investment it is certainly making efforts in the right direction.

Moreover, Japan’s strategic focus on regenerative medicine and cell therapy as part of its growth strategy highlights the country’s ambition to lead in these fields. The supportive regulatory environment, combined with robust intellectual property protections, offers a conducive ecosystem for biotech innovation and commercialization.