Mentoring Promising Life Science Companies from Japan’s Kansai Region
by Crystal Hsu
Powered by entrepreneurs, Japan’s startup ecosystem is poised to take off - Forbes
While cautious investors and strict corporate cultures have traditionally characterized Japan, the Kansai region is quickly emerging as a central hub of innovation. With the country’s growing venture capital base, leading infrastructure, and a highly educated talent pool, Japan’s startups are beginning to blossom.
Last month, six life science startups representing Japan’s Kansai region presented their companies and business plans at the Kansai Pitch Demo Day, aiming to secure financial and/or business partners in the global market. They included programs ranging from novel approaches to AI-based drug discovery to cell and gene therapies.
Through Back Bay’s mentoring program, I had the unique privilege of sitting as one of the panelists, where we were encouraged to ask these startups questions and offer advice.
All the startups were recent participants in the CLSI’s FAST International program - Spotlight Japan, a collaboration with the Kansai Life Science Accelerator Program, which is a new mentoring program for life science startups in Japan that was launched in 2020 by Bayer Yakuhin Ltd and others with the California based non-profit organization California Life Sciences Institute (CLSI).
Back Bay is deeply committed to mentoring young startups. Not only do we enjoy collaborating with them because they have unique challenges and perspectives compared to global-stage pharma companies, but we are always so inspired by the energy and creativity of tech creators.
Our roots go deep in Nordic countries, but our reach is global, and Japan is an exciting development area.
Many thanks to CLSI for the invitation to participate in this event. We look forward to teaming up again in the future and doing more. To learn more about the following companies, connect with the Director of Operations, Innovation Services at CLSI, here.
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HACARUS Inc.
Explainable and lightweight AI-assisted drug discovery tools powered by sparse modeling
Hacarus Inc. founded 2014 in Kyoto, Japan, is the leading provider of explainable lightweight AI Tools, with a company mission of extending human life expectancy to 120 years. Its proprietary engine is based on Sparse Modeling, an AI method that leverages small amounts of data and understands data like a human would, which is more resourceful and efficient than Deep Learning. Their medical & life science AI solution, SALUS, leverages medical imaging data such as CT & MRI scans, time series data such as ECG data, and medical records to create precise, complex tools, that aid caregivers and researchers to help provide better, faster, and safer treatment.
They have several partnerships, including:
OHARA Pharmaceutical: Partnership along with a leading Medical University to digitize specialists’ knowledge, aiming to offer AI-enabled assistance in acute cerebral infarction diagnosis
Kobe University: Joint research for liver cancer diagnosis support tool to: 1) Detect risk areas in MRI images using AI trained by using supervised learning. 2) Perform HCC disease type classification in risk areas. 3) Create an accurate AI type classification and diagnosis support system
Kyoto University: Joint R&D project to build an AI support system (using colposcopy video data) for prevention and early diagnosis of cervical cancer
ITK Engineering: Joint development of a proof of concept for a personalized patient monitoring system, serving to evaluate ECG signals
DS Pharma Animal Health: Collaboration on a non-intrusive ECG measurement and analytics tool for animals, based on a connected sheet that has the ability to capture vital heart data from standing animals paws
Hacarus’s advantages include its AI from human experts and sensor-generated data, its applicability to a broad range of conditions (even rare ones), it is faster and more energy efficient, and integrates with deployed equipment such as Cloud or Edge. HACARUS is currently looking for partners interested in AI-assisted Phenotypic drug discovery. To learn more about the company and its programs, please visit hacarus.com.
HiLung Inc.
iPSC-based drug discovery platform for respiratory diseases
HiLung provides a physiologically relevant respiratory cell system based on iPS-cell technology and is currently focused on developing modeling technologies for COVID-19, idiopathic pulmonary fibrosis, and cystic fibrosis. Its core technologies include regenerated human respiratory cells, respiratory infection models, and alveolar and bronchial disease models. The company has three core pillars to its business:
Cells for research: The goal is to accelerate discovery by providing human respiratory cells that recapitulate human pathophysiology. This includes an air-liquid interface (drug testing for COVID and inflammatory diseases), cell plates for screening (COVID and CF), and organoids systems (CF and IPD)
Drug discovery and development: Aids in development certainty, especially in rare diseases, through in-house collaborative candidate pipeline with high expected success rate validated on human organoid disease models. HiLung’s drug discovery system allows for high accuracy of reconstruction of human cellular components, high-quality disease modeling in vitro, high throughput screening system on “real” lung development, and highly specialized assays
Respiratory cells and organoid therapy: Offers novel regenerated respiratory organoids and tissues for therapeutic offerings for irreversible diseases
In collaboration with Sanford Burnham Prebys Medical Discovery Institute in San Diego, HiLung recently published a study demonstrating how their iPSC model captures COVID-19 pathophysiology and drug effects. This included detection of drug effect of remdesivir and a recapitulation of an innate immune response to SARS-COV2.
For their cells for research, HiLung is currently seeking worldwide distribution with external partners for cell manufacturing and sales, and in-house or collaboration drug discovery with pharmaceutical companies. The HiLung team is led by CEO and co-founder Yuki Yamamoto, MD, Ph.D.
MiCAN Technologies Inc.
Human iPSC-derived blood-like cells for drug discovery research
MiCAN’s goal is to “contribute to the health of all people around the world by providing specialized blood cells using stem cell technology”. The company was founded in 2016 and has locations in Kyoto and Kobe, Japan. They have leveraged joint research to incorporate and utilize advanced technologies to demonstrate that the blood cells can be used in drug discovery research to then develop and provide test kits in partnership with their co-developers. MiCAN’s core offerings include:
High precision artificial blood cells
Young red blood cells: Mpv – as material for R&D for infection diseases etc. affecting red blood cells
Immature dendritic cells: Mylc – as material for evaluation of efficacy and safety of drugs
Contract evaluation services to assess drugs, functional materials, etc.
Efficacy evaluation
Safety evaluation
A phenomenon called antibody-dependent enhancement (ADE) occurs when the antibodies generated during an immune response recognize and bind to a pathogen, but are unable to prevent infection, and instead enhance the entry of the virus. Therefore, it is important to understand and check for the “quality of the antibody” to dictate if and when someone needs a vaccine. Dendritic cells have been shown to be the optimal cells for ADE evaluation. MiCAN’s solution leverages their Mylc product to provide an ADE evaluation tool, which are the best for cytokine production, viral proliferation ability, and ADE evaluation ability.
The company has demonstrated that Mylc cells can detect ADE effect of Dengue virus and plan on utilizing the test to identify and manage the risk of serious illness, along with the risk of illness in the event of a family member becoming infected. They will first target Asia, Middle, and South America, which has an estimated 4 million patients.
MiCAN is currently seeking collaborators and investors. The team is led by founder and President/CEO, Kazuo Miyazaki. Please see micantechnologies.com to learn more.
NextGeM Inc.
AI-based image analysis for infertility treatment
NextGeM’s mission is to “build cross-life science development platforms ranging from AI to Bio, with a special focus on worldwide problems at medical and healthcare space”. They were founded in 2016 in Kobe and are initially focused on leveraging AI for higher quality embryos. NextGeM’s founder identified a social problem of declining birth rates – the number of fertility patients has increased by 97%, birth rates have declined by 13%, and the cost of fertility treatment is soaring with an average cost of $4k. The core issues of fertility treatment include the subjective nature of embryo selection which is dependent on doctor experience and expertise, the invasiveness of the tests, and the lengthy and slow process required to freeze embryos.
NextGeM believes that its AI fertility platform can change this. Their technology is AI-backed and therefore data-driven and objective, includes a non-invasive test of chromosomal aneuploidy, and allows for rapid analytics powered by cloud/SaaS. Patients enjoy improved outcomes over conventional tests and lower risk of embryo damage, and healthcare providers experience improved efficiency and more consistent outcomes.
The product works as follows:
Input from the doctor includes patient information and still or time-lapse images
The AI algorithm and cloud system considers the images, hormonal profiles, and clinical outcomes (e.g., pregnancy, live birth, chromosome aneuploidy)
Output includes rapid outcome forecast based on grading scores for pregnancy/live birth, chromosomal aneuploidy, and morphology
A retrospective study has demonstrated significant improvement with NextGeM’s technology compared with conventional morphology grading. This proof of concept study included 2,000 data sets in Japan, and shows a pregnancy prediction accuracy of 65.2%, compared to the 59.8% with conventional methods. Additionally, the team conducted a pre-marketing study to evaluate potential user engagement with 1k fertility patients in Japan. They asked, “Do you want to use AI-supported / SaaS products for embryo evaluation and selection?”. 63% reported yes, with higher rates reported in younger generations (i.e., >85% of patients in their 20’s and >75% of patients in the 30’s reported yes).
NextGeM is currently seeking a co-development partner in the US. The team is led by co-founder and CEO Masakazu Nakajima.
RAFJIK Inc.
Cancer immunotherapy using artificial adjuvant vector cells
RAFJIK is developing novel cancer immunotherapy using artificial Adjuvant Vector Cell (aAVC). They have developed a partnership with the national RIKEN Institute, and are currently licensing RFK-01 for HPV, as well as two additional assets. The following data has supported ongoing development of this modality:
In a phase 1 investigator-initiated trial with aAVC-WT1 in relapse/refractory AML patients, there was high tolerability as well as an aAVC-triggering immune response.
In humanized mouse studies, it was shown that aAVC resulted in human melanoma regression, suggesting that aAVC would work in human immune systems.
In animal studies, aAVCs have demonstrated a role in the activation of both innate and acquired immunities, followed by the establishment of long-term memory CD8+killer T cells without immune-related adverse effects.
Additionally, aAVC resolves many of the disadvantages and shortcomings of existing cancer immunotherapies:
Existing technologies (DC therapy, CAR-T)
Pros
Tumor-specific acquired immunity
Few adverse events
Cons
Low innate immunity
Short-term immune memory
High processing cost
High medical expenses
Made-to-order
Low potential to solid tumors
aAVC
Pros
No adverse events
High innate immunity
High tumor-specific acquired immunity
Long-term immune memory
Low manufacturing cost
Ready-made
High potential to solid tumors
Cons
Utilization of immune system in patients.
RAFJIK is currently looking for a biopharmaceutical partner to build a more extensive pipeline in additional tumor types. The company is led by CEO Satoru Yamsaki, PhD.
Revorf Inc.
Revolution of open reading frame with full-stack bioinformatics
Revorf Inc. is an RNA focused bioinformatics firm focused on discovery drug discovery leads and developing pharmaceutical agents and genetic analysis instruments. Revorf Inc.’s goal is to tackle the current challenges with bioinformatics, including: 1) Functional analysis of 40% of genes has not been done, 2) RNA is more promising than DNA analysis however most conventional analysis methods use DNA, 3) Disease samples are difficult to obtain, and 4) Bioinformatics is a new field and there is a shortage of skilled bioinformaticians.
Revorf leverages RIKEN’s genome analysis technology which includes RNA detection and analysis techniques. Additionally, they have authorized access to private patient data through partnerships with universities and hospitals, and are conducting additional data analysis and AI development led by frontline doctors and researchers at the University of Tokyo and Kyoto University. Revorf’s technology utilizes various RNA detection/analysis technology for non-coding RNA, high-resolution mRNA detection machine learning algorithm, and Protein Expression Variation Analysis Software (TIGER) which is an exclusive license from RIKEN. It can be used to develop cutting-edge biomarkers, search for drug discover leads by stratifying patients, streamline clinical development process, and devise new genetic analysis instruments.
Revorf is currently looking for strategic partnerships in the following areas:
Diagnostic agent development: Strategic partnership with health tech companies to develop gene diagnostic agents
Drug discovery project: Strategic partnership with pharmaceutical companies to assist in gene discovery and drug formulation
Bio-related data analysis: Analysis of bio-related data and development of AI models
The Revorf team is led by CEO Dr. Sueta Shinichi, MD. For more information, please visit revorf.jp.