JHVS, 2020

Corporate HP
www.kotai-bio.com

KOTAI Bio Analytical Service
www.kotai-bio.com/service/

KOTAI supports R&D (drug/vaccine/diagnostic) by visualizing immune responses
KOTAIは免疫応答の可視化により、医薬品の研究開発をサポートします

KAZUO System

KAZUO System 2Immune repertoire analysis system, a combinationof unique clustering technologies and machinelearning

Feature selection system using machine learning
A system that appropriately selects features
without overfitting

A powerful tool for observing patient's immune
responses with small number of clinical samples

KOTAI provides solutions at every stage
KOTAIはあらゆるステージでソリューションを提供します

Non-clinicalClinical• Finding novel drug discovery targets• Disease-specific biomarkers• Design the more preventive vaccineImmunedataset• Successful clinical trials with low cost
• Clinical development for diseases withfewer patients

KAZUO System

Varioussolutions

Sales・Post Marketing• Expansion of market share by productdifferentiation• Prediction of side effects• Reducing drug costs through proper use

Payment according to thedegree of contribution• Intellectual property sharing• Joint R&D expenses• Licensing fee, milestone• RoyaltyKAZUO System 2

KOTAI Biotechnologies, Inc.

JHVS, 2020

KAZUO System

1. Application in auto immune diseases (TCRβ repertoire analysis of peripheral lymphocytes)
Diagnostic usefulness of selected clusters
Patientlymphocyte

TCRClusters(patients)

SelectedClusters

TCRClusters(healthy)

Disease-related clusters
selected by KAZUO System
to diagnose

AUC** of ROC
curves
0.922
0.994
0.948
0.997

Disease（No. of samples）
Behçet's disease (10)Polymyositis (8)Psoriasis (12)Ulcerative colitis (10)KAZUO System drastically reduces the numberof patients required for prediction
Auto immune diseases: Total 50
Ankylosing spondylitis*, Behçet's disease, Crohn’sdisease, Polymyositis, Psoriasis*, Rheumatoidarthritis, Still’s disease, Ulcerative colitis*:One patient has psoriasis and spondylitis>8～12>100

KAZUO System

ConventionalApproach**AUC of ROC curves➢ Used to verify the cutoff value setting for diagnostic agents➢ Usually takes a value between 0.5 and 1.0➢ AUC = 1: 100% for both positive and negative predictive values (perfect test)➢ AUC = 0.5: Random and invalid model (no value to perform)

Healthy: Total 493 from the public database

2. Prediction of side effect of Immune check point inhibitor
 Nivolumab for NSCLC (2nd-line therapy)
Comparison ofthe clusters

TCR
Ir AE*TCR

Datasets:CD8+ T-cell β-chain from PBMC

Statistically significant
specific clusters

Healthydonors**

Statistical significance-log(P-val)

Bloodsampling

Dosage ofdrugs

VSTCR clusters*Ir AE:Immune-related Adverse Events**Public database

Collaboration with Osaka U Medical School (Unpublished)

KAZUO System 2

3. Application in immune check point inhibitors
Efficacy/Safety prediction of nivolumab for NSCLCAUC of ROC curves *Blood test before dosage ofdrugs（Total 763 features）

No feature selections

Responder*/non-responder

Adverse event

0.72
0.63

⚫ Flow cytometry
Ratio of different cell types⚫ Gene expression
190 genes⚫ HLAClass I (A,B,C)

KAZUO System２
Selection of features(to 5-12 features)
Evaluated randomly generated 300 samples,(training : test) = 4:1.

Responder*/non-responder

Adverse event* RECIST（1.1）

0.92
0.97

Responder(CR, PR, SD), Non-responder (PD)** AUC of ROC curves: described above

Collaboration with Osaka U Medical School (Unpublished)

Highly accurate prediction of drug efficacy and safety!
KOTAI Biotechnologies, Inc.

◆ How KAZUO System works 4
The results using KAZUO System has created the NEXT opportunity!
Joint Research with CiRA**

Joint Research with NCC*

Therapeutic regenerative T cells using iPS cells

Single-cell Analysis of TIL†

Sample collection
from cancer patients

Initialization to iPS cells
Cancer-specificDiverseT cells
T cell population

T-cells in tumor

Large amount of functionallyrejuvenated cancer-specific T cells?
Tumor specificCD8+ T-cell

Separation of T cells reactivewith cancer cells or antigens

Cancer immune celltherapy by transfusion

Non-tumor specificT-cellRedifferentiationof T cells➢ Confirmation of anti-cancer cytotoxic T cells bysingle-cell analysis of TIL from cancer tissue➢ Discovery of surface antigens frequently expressedon the surface of anti-cancer cytotoxic T cells(patent granted)
TIL† : Tumor Infiltrating Lymphocytes

iPS cellswith ability tomultiply infinitely➢ Isolates T cells from cancer tissue to conduct iPS cellinduction followed by T cell redifferentiation.
➢ T cell isolation with the surface antigen discovered by
the Joint Research with NCC described on the left

*NCC: National Cancer Center Japan**CiRA: The Center for iPS Cell Research and Application, Kyoto University◆ KOTAIバイオ受託サービス◼10x Genomics社の日本における最初の認定サービスプロバイダー
10x認定アプリケーション• 3’シングルセルRNA seq解析
認定取得予定• シングルセル免疫プロファイリング解析• 空間的遺伝子発現解析（Visium)
問合せ先: https://www.kotai-bio.com/service/◆ Recent News

DateTitle

Utilization of “Rare Disease Research and Development Program based on
patient-centered principle” and call for patient participation in “Study of Specific
Jul 1 Immune Conditions of Autoimmune Diseases”
https://www.kotai-bio.com/news/post-503/
2019
Completion of the first study of the “Rare Disease Research and Development
Aug 20 Program based on patient-centered principle” https://www.kotaibio.com/news/post-500/
KOTAI Biotechnologies, Inc was granted as Japan’s first 10x Certified Service
Jan 6 Provider. https://www.kotai-bio.com/news/post-1016/
Participation in the Clinical Research on the Coronavirus Disease (COVID-19)
Mar 24 https://www.kotai-bio.com/news/post-1132/
2020
Joint Research on the analysis of immune profile of COVID-19 patients
Aug 5 https://www.kotai-bio.com/news/post-1150/
Joint research on personalized cancer immunotherapy using regenerated T cells
New Oct 1
derived from iPS cells https://www.kotai-bio.com/news/post-1160/*NIID: National Institute of Infectious Diseases**CiRA: The Center for iPS Cell Research and Application, Kyoto University

Partner(s)3H Holdings

3H Holdings
10x Genomics
NIID*
NIID, Shionogi,
Osaka UnivCiRA**

◆ 会社概要■ Academic collaborations

R&D network with top research institutions
Cell Therapy (Solid tumor)

Nagoya U.

■ Company overview
Establishment：May 2016
CEO： Kazuo Yamashita (山下和男)

Capital：100,000,000 JPY (Series A-C：9/2016, 6/2017, 12/2018)
Employees：13 (As of Oct. 2020. incl. 8 R&D staffs.)
Investors： Osaka University Venture Capital, Nissay Capital, Shinkin
Capital, Minato Capital, Ikeda-Senshu Capital

Immuno-Oncology

CEO Biography：
Kazuo Yamashita, the representative director and CEO of KOTAI.
Yamashita was an assistant professor and a Post Doc at Immunology
Frontier Research Center (IFReC), Osaka University, in which he has
published more than fifteen scientific papers in top journals.
He got a Ph. D. degree in Physics from Osaka University in 2012.

U. TokyoAutoimmune

CiRA/Kyoto U.
Immune Cell Therapy

Infectious Diseases

Osaka U.
Cancer (Solid tumor)
Autoimmune

Hiroshima U.

Immunology

Blood Cancer

Infectious Diseases■ Contract service in Japan■ Industry collaborations
Research:(Ongoing) two pharmaceutical companies.
Development: (under consideration) one pharmaceutical company.

• Single-cell RNA sequence Analysis• Single-cell Repertoire Analysis• Bio-informatics Information Analysis• Visium Spatial Gene Expression Analysis◆ 科学アドバイザー

名前役割

審良静男
大阪大学免疫学フロンティア研究センター特任教授

免疫学の権威。研究者時代からの共同研究者。免疫学的な見地から研究結果、進め方、疾患選択についてのアドバイス、共同研究者の紹介。
制御性T細胞の発見者。研究者時代からの共同研究者。がん免疫学の研究にあたり、国立がん研究センターの共同研究者の紹介、シングルセル解析についてのアドバイスを提供。
B細胞研究の第一人者。自己免疫疾患の共同研究、POCのためのデータの提供など。
現在もCOVID-19の共同研究を行っている。

坂口志文
大阪大学免疫学フロンティア研究センター特任教授
黒崎知博
大阪大学免疫学フロンティア研究センター特任教授
理化学研究所 グループリーダー
高木淳一
大阪大学蛋白質研究所教授
Mark Evans
Associate Director, Exact Sciences

構造生物学・生化学の専門家。研究者時代からの共同研究者。分子構造研究に対するアドバイスや、当社のがん免疫共同研究における実験手法選択についてのアドバイス等。
バイオインフォマティクスの専門家。米国のバイオベンチャーでの経歴が長く、米国市場や研究開発の状況情報提供、顧客候補等の紹介など。

◆ 連絡先

www.kotai-bio.com+81-6-6170-5267

contact@kotai-bio.com

2-1, Yamadaoka, Suita,
Osaka, 565-0871, Japan