Based on scientific research results performed by HiPep Laboratories during the last decade a new company, PIPLS PharmaInc., was founded on Aug . 5, 2016, in Kyoto. Fortunately the new company receives investments with the “exit doe

products” in the business model. PIPLS is an abbreviation of “Peptides containing Imidazole and Pyrrole as building blocks-

Large scale Syntheses“. PIPLS Pharma focuses on GMP production of high quality peptide derivatives, especially peptideconjugates and PIPA (peptides consisting of pyrrole and imidazole as major building unites) for clinical applications. PIPA is anovel drugs with novel action mechanisms such as gene controls.

Hence, HiPep laboratories is a research company having the enormous know-how concerning combinatorial compoundlibraries and proteins & peptides science, especially production, separation and characterization has been generated severalconcepts, PepTenChip®, on bead cyclic peptides, Peptide-Vehicle which involved delivery system for drugs. HiPep continuesfurther development for practical applications of the novel Biochip system, PepTenChip®. PIPLS Pharma has been founded asspin off from HiPep for production of API from HiPep in Aug. 2016.

PIPA can bind to specific nucleotide sequences in the minor groove of double-helical DNA with high affinity and specificity,suggesting that PIPA blocks binding of transcription factors inhibiting gene expression, thus PIPA can be applied to gene-therapy. Additionally, PIPA can be also used for specific double strand DNA-visualization for diagnostics. Advantages of PIPAare: stabilities (nuclease resistant); entering into cell nucleus without any DDS-technologies; siRNA causes knockdown ofgenes and side effects are unneglectable; PNA is toxic. Until now no-toxicities of PIPA have been found in animal experiments.

PIPA is difficult to prepare and industrial production has not yet been reported in world wide. Focusing on drug productionindustrial production system has been successfully established by Dr. Nokihara supported by two national grants of Japan(2013-2014 JST and 2014-2015 NEDO) based on Dr. Nokihara’s expertise. Until 2016 a ” Large Scale Syntheses System forPIPA, PIPLS System” has been completed.

Industrial scale GMP-products are indispensable for clinical trial as well as for FDA-approval. In addition to PIPA, GMP gradeof numerous peptides can be produced, angiogenic peptides (AGP) can be also produced for regenerative medicine, ofwhich patent enforcement by PIPLS. Initial investment was ca. 3 million USD by Bio-division of Alpha Holdings. Since PIPLSPharma will not carrying out researches in drug discovery but production of active pharmaceutical ingredients, relativelyshorter term M&A or IPO can be expected. The location of GMP-facility was found in Gumpo-city near Seoul, Korea.

Corporate Profiles

PIPA as a DNA-probes

1. Alternative gene silencer other than siRNA or PNA.2. Stable in cells or bodies because of nuclease resistance.3. Specifically binds to the target double strand DNA.4. Enter into cell nucleus without any DDS.5. Flexible Design against any gene. 6. No-toxicities have been found in animal experiments.7. Target diseases: not possible by small molecules or antibodies

PIPA can be used for therapies for gene-controlwith different mechanisms against conventionalmethods. Recently, HPTH59 was commercializedas the optimal probe for telomere staining, whichis not affected by nuclease, enters into cell nucleiwithout any delivery systems and allows highthroughput quantitative measurement oftelomere length with less disruptive process.Comparing to the other methods, such astelomerase, Southern blotting and/or PNA-fluorescence in situ hybridization method, theprobe HPTH59 can offer simple with lowerbackground staining.

Advantages of PIPA focusing on novel drugs

http://pipls.hipep.com/PIPLS@hipep.com

Biographical Sketch of Kiyoshi NOKIHARA(Doctor of Pharmaceutical Sciences)

The CEO and CSO of the HiPep Laboratories, Dr. Nokihara, initially studied Organic Chemistry and ChemicalEngineering in Tokyo, followed by many years of academic research in Germany. His involvement with bio-molecules commenced at Deutsches Wollforschungs Institute at the Technischen Hochschule Aachen (1973-1979). In 1980-1985, he was Assistant Professor of the Faculty of Pharmaceutical Sciences, Shizuoka PrefecturalUniversity, where he undertook extensive research on brain-gastrointestinal peptides, syntheses as well asimmunochemical and endocrinology studies. He subsequently relocated to the Faculty of Medicine, University ofHeidelberg in the role of visiting Professor, and later at the GBF (German Research Centre for Biotechnology). In1990 he joined the Shimadzu Corporation, as a General Manager in R & D of the Biotechnology InstrumentsDepartment and Head of the Life Science Center. He has developed several novel instruments focusing onapplications, including the simultaneous multiple automated peptide synthesizers, for which his team received aprize bestowed by the Japanese Agency of Science and Technology.

Trade name

PIPLS Pharma .IncAddress(tentative office)

Nakatsukasa-cho, 486-46, Kamigyo-ku, Kyoto, 602-8158, JapanPhone +81-75-813-2101Fax +81-75-801-0280PIPLS@hipep.comFounded 2016 August 5

Capital 61.3 million Yen Home page http://pipls.hipep.com/

Major products: Peptides (cosmeceutical/pharmaceutical), PIPA, Bioconjugates, Peptide-Vehicle, PIPA

GMP facility: PIPLS Pharma Korea CO. Ltd., Gunpo, Gyonggi-do, Korea

His expertise was focused on the biochemical and medical fields, especially proteins and peptides, from isolation, synthesis andcharacterization to biochemical and medical applications. As well as his business commitments he received visiting Professor positions atthe Tokyo University of Agriculture and Technology and the Tokyo Metropolitan Institute for Neuroscience Research to continue hisacademic research. In 1997 he founded Shimadzu Scientific Research Inc. and established a novel research business as the Chief Scientist.In 2002 he has independently founded a new venture company, the HiPep Laboratories, based on his knowledge and experiences inbioscience. Since 2002 he is a visiting Professor in Nanjing Medical University (China). He has more than 250 publications and 130 patentapplications.

PIPLS Pharma Korea (PPK), Gunpo, Korea GMP Production Facility of PPJ

Founded in October 2016 GMP-Facility will be constructed by Aug. 2017

HiPep Korea (HPK), Anyang, KoreaFounder: Y-M. Kim (CEO) & Dr. Nokihara (CSO) HiPep Products for KoreanMarket, and call for investments.Founded in March 2016

PIPLS Pharma Inc. Kyoto, Japan (PPJ)SPIN-OFF from HiPep, A production companyFounder, CEO: Dr. NokiharaAPI-GMP (focusing on PIPA, Peptide-derivatives, Peptide-conjugates)Founded in August 2016

HiPep Laboratories, Kyoto, JAPAN (HPL)Founder, CEO, CSO: Dr. K. NOKIHARA A Research Institute founded in 2002, development of applications for BiomolecularRecognition; Diagnostics (Biochip) and Therapeutics (Drug development).Fundamental Technologies have been completed in 2015. To enlarge the marketsHiPep Korea has been founded in 2016 (below).Non GMP production of peptide conjugates, peptide vehicles, PIPAs etc.

HiPep Laboratories and PIPLS Pharma

Founder, CEO & CSOHiPep Laboratories

http://pipls.hipep.com/PIPLS@hipep.com