New peer-reviewed collaborative publication

Alpha-1 Antitrypsin-Expressing Mesenchymal Stromal Cells Confer a Long-Term Survival Benefit in a Mouse Model of Lethal GvHD Authors: Sabine Geiger,1,5 Emrah I. Ozay,2,3,5 Ulf Geumann,1,5 Marina K. Hereth,1 Terese Magnusson,1 Sudarvili Shanthalingam,3 Daniela Hirsch,1 Stefanie Kälin,1 Christine Günther,1 Barbara A. Osborne,2,3 Gregory N. Tew,4 Felix G. Hermann,1,6 and Lisa M. Minter2,3,6 1apceth Biopharma GmbH, 81377 Munich, Germany; 2Program in Molecular & Cellular Biology, University of Massachusetts Amherst, Amherst, MA 01003, USA; 3Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA 01003, USA; 4Department of Polymer Science and Engineering, University of Massachusetts Amherst, Amherst, MA 01003, USA Molecular Therapy Published: May 15, 2019 DOI: https://doi.org/10.1016/j.ymthe.2019.05.007

apceth will operate as the commercial manufacturer in Europe for Zynteglo, bluebird bio’s gene therapy for β-thalassemia

Munich, Germany, June 4, 2019 – apceth Biopharma GmbH, a leading company for the manufacturing of cell and gene therapeutics, will operate as the commercial manufacturer in Europe for ZyntegloTM, a product of bluebird bio. Yesterday the European Commission (EC) has granted conditional marketing authorisation for ZyntegloTM, a gene therapy for patients 12 years and older with transfusion-dependent β-thalassemia (TDT) who do not have a β0/β0 genotype, for whom haematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available. “We are proud to be the commercial manufacturing partner of bluebird bio and to be part of bringing this life-changing therapy to TDT patients in Europe”, commented Dr Christine Guenther, CEO of apceth Biopharma. “Being one of the very few companies worldwide to manufacture a cell-based gene therapy for commercial use marks a milestone for our company.” “We are looking forward to continue supporting bluebird bio with its other programs”, announced Dr Guenther. apceth Biopharma is bluebird bio’s clinical and commercial manufacturing partner for Europe not only for ZyntegloTM, but also for bluebird bio’s product candidate Lenti-D for cerebral adrenoleukodystrophy. Following a successful long-term manufacturing relationship, apceth Biopharma and bluebird bio entered a commercial drug product manufacturing agreement in 2016.   About apceth Biopharma GmbH apceth Biopharma, a subsidiary of Hitachi Chemical Co., Ltd. is a pioneering company in regenerative medicines and a leading and certified Contract Development and Manufacturing Organization for cell and gene therapeutics with a broad international customer base. apceth owns state-of-the-art manufacturing facilities with Grade B/A, C and D cleanrooms (ISO 5, ISO 7, ISO 8, BSL2) and is certified according to regulatory requirements for cell and gene therapies (Advanced Therapy Medicinal Products, ATMPs). The company has a comprehensive expertise in GMP manufacturing of autologous and allogeneic cell types that are either native or genetically modified. It has long-standing experience with various cell products, including mesenchymal stem cells (MSCs), hematopoietic stem cells (HSC), lymphocytes, monocytes, dendritic cells, cord blood derived stem cells, and has the potential to expand to CAR-T and induced pluripotent stem cell (iPSC) technologies. apceth has successfully obtained manufacturing licenses for multiple cell therapy products for clinical as well as commercial use. apceth’s CDMO team provides fully customized solutions in the development and production of every customer product and process. Located centrally in the heart of Europe, apceth can perform efficient and fast supply for patients all over the continent. For more information on apceth, please visit www.apceth.com   About Hitachi Chemical Co., Ltd. Hitachi Chemical Co., Ltd. (TSE:4217), headquartered in Tokyo, Japan, delivers wide range of innovative products, such as electronic materials, automobile parts, energy storage devices and systems, in global markets. The company’s consolidated revenues for fiscal 2017 (ended March 31, 2018) totaled 669 billion yen (5.4 billion euros*). For more information on Hitachi Chemical, please visit the company’s website at http://www.hitachi-chem.co.jp/english/ *The conversion rate is 1 euro = 124 yen.   About the Hitachi Chemical Regenerative Medicine Business Sector The Hitachi Chemical’s Regenerative Medicine Business Sector provides contract development and manufacturing organization (CDMO) services at current Good Manufacturing Practices (cGMP) standards, including clinical manufacturing, commercial manufacturing, and manufacturing development. The global footprint of the business is over 180,000 square feet and includes operations in North America (Allendale, New Jersey and Mountain View, California), Europe (Munich, Germany), and Japan (Yokohama). The business leverages two decades of experience exclusively focused on the cell therapy industry.   Contact For more information on North America services, please visit www.pctcelltherapy.com. For more information on Europe services, please visit www.apceth.com. For more information on Japan services, please visit www.hitachi-chem.co.jp/english/   apceth Biopharma GmbH Dr Christine Guenther, CEO Max-Lebsche-Platz 30 81377 Munich Germany Phone: +49 (0)89 7009608 0 Email: contact@apceth.com Web: www.apceth.com Press release as pdf: English and German Link to the press release of bluebird bio

Hitachi Chemical Co. Ltd. Completes Acquisition of apceth Biopharma GmbH, Expanding Global Footprint of its Cell and Gene Therapy Contract Development and Manufacturing Services

Munich, April 4, 2019 – We are pleased to announce that Hitachi Chemical Co. Ltd. (Head Office: Chiyoda-ku, Tokyo; President and CEO: Hisashi Maruyama; hereinafter “Hitachi Chemical”) has completed its acquisition of apceth Biopharma GmbH (Head Office: Munich, Germany; CEO: Dr. Christine Guenther; hereinafter “apceth Biopharma”), a contract manufacturer of cell and gene therapy products, adding its capabilities to the Hitachi Chemical’s Regenerative Medicine Business Sector’s offerings. apceth Biopharma manufactures cell and gene therapy products for American and European clients through two manufacturing sites in Munich, Germany, both certified for GMP manufacture since 2010. These facilities are fully compliant with all current EU regulations (ATMP regulation (EC) No.1394/2007) and ICH guidelines. The company’s strength stems from its experience and comprehensive quality management systems allowing the manufacturing and development of a wide range of complex cell and gene therapy products, which will be integrated into the Hitachi Chemical Regenerative Medicine Business Sector. By combining apceth’s gene and cell therapy manufacturing expertise and facilities in Europe to Hitachi Chemical’s capabilities and facilities in North America and Japan, we will enhance our global footprint, while preserving what customers value most: high-quality GMP manufacturing from a trusted partner that is a pioneer in the industry. Existing clients of apceth Biopharma will enjoy continuity of service and executive leadership. In the near future, Hitachi Chemical’s Regenerative Medicine Business Sector aims to offer customers the possibility to manufacture their products throughout Europe, North America, and Japan. Our combined strength will make us a world leader in the field and will allow us to address all of our customers’ manufacturing and process development needs. Our global contract development and manufacturing services platform currently includes two U.S. facilities, in Allendale, NJ and Mountain View, CA, and a recently opened facility in Yokohama, Japan. Construction is underway for a third U.S. facility in Allendale, NJ that will provide manufacturing capability for products after the opening in April 2019. About apceth Biopharma GmbH apceth Biopharma, a subsidiary of Hitachi Chemical Co., Ltd. is a pioneering company in regenerative medicines and a leading and certified Contract Development and Manufacturing Organization for cell and gene therapeutics with a broad international customer base. apceth owns state-of-the-art manufacturing facilities with Grade B/A, C and D cleanrooms (ISO 5, ISO 7, ISO 8, BSL2) and is certified according to regulatory requirements for cell and gene therapies (Advanced Therapy Medicinal Products, ATMPs). The company has a comprehensive expertise in GMP manufacturing of autologous and allogeneic cell types that are either native or genetically modified. It has long-standing experience with various cell products, including mesenchymal stem cells (MSCs), hematopoietic stem cells (HSC), lymphocytes, monocytes, dendritic cells, cord blood derived stem cells, and has the potential to expand to CAR-T and induced pluripotent stem cell (iPSC) technologies. apceth has successfully obtained manufacturing licenses for multiple cell therapy products for clinical as well as commercial use. apceth’s CDMO team provides fully customized solutions in the development and production of every customer product and process. Located centrally in the heart of Europe, apceth can perform efficient and fast supply for patients all over the continent. For more information on apceth, please visit www.apceth.com About Hitachi Chemical Co., Ltd. Hitachi Chemical Co., Ltd. (TSE:4217), headquartered in Tokyo, Japan, delivers wide range of innovative products, such as electronic materials, automobile parts, energy storage devices and systems, in global markets. The company’s consolidated revenues for fiscal 2017 (ended March 31, 2018) totaled 669 billion yen (5.4 billion euros*). For more information on Hitachi Chemical, please visit the company’s website at http://www.hitachi-chem.co.jp/english/ *The conversion rate is 1 euro = 124 yen. About the Hitachi Chemical Regenerative Medicine Business Sector The Hitachi Chemical’s Regenerative Medicine Business Sector provides contract development and manufacturing organization (CDMO) services at current Good Manufacturing Practices (cGMP) standards, including clinical manufacturing, commercial manufacturing, and manufacturing development. The global footprint of the business is over 180,000 square feet and includes operations in North America (Allendale, New Jersey and Mountain View, California), Europe (Munich, Germany), and Japan (Yokohama). The business leverages two decades of experience exclusively focused on the cell therapy industry. Contact For more information on North America services, please visit www.pctcelltherapy.com. For more information on Europe services, please visit www.apceth.com. For more information on Japan services, please visit www.hitachi-chem.co.jp/english/ For more information on North America and Japan services, contact: Eric Powers Director, Marketing and Communications Hitachi Chemical Advanced Therapeutics Solutions, LLC epowers@pctcelltherapy.com Tel: +1 201 786 7941 For more information on Europe services, contact: Dr. Almut Windhager Manager Business Development and Communications apceth Biopharma GmbH a.windhager@apceth.com Tel: + 49 89 665472259

New peer-reviewed collaborative publication

Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells: Results from the phase 1/2 TREAT‐ME‐1 trial Authors: Jobst Christian von Einem, Christine Guenther, Hans‐Dieter Volk, Gerald Grütz, Daniela Hirsch, Christoph Salat, Oliver Stoetzer, Peter J. Nelson, Marlies Michl, Dominik P. Modest, Julian W. Holch, Martin Angele, Christiane Bruns, Hanno Niess, Volker Heinemann International Journal of Cancer, first published 23 February 2019 https://doi.org/10.1002/ijc.32230

New peer-reviewed collaborative publication

Human Stem Cells Promote Liver Regeneration After Partial Hepatectomy in BALB/C Nude Mice Simon Wabitsch, MD,a,* Christian Benzing, MD,a Felix Krenzien, MD,a Katrin Splith, PhD,a Philipp Konstantin Haber, MD,a Alexander Arnold, MD,b Maximilian Nösser,a Can Kamali,a Felix Hermann, PhD,c Christine Günther, PhD,c Daniela Hirsch, PhD,c Igor M. Sauer, MD,a Johann Pratschke, MD,a and Moritz Schmelzle, MDa a Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité Universitätsmedizin, Berlin, Germany b Department of Pathology, Campus Charité Mitte and Campus Virchow-Klinikum, Charité Universitaetsmedizin, Berlin, Germany c Apceth Biopharma GmbH, Munich, Germany Journal of Surginal Research, July 2019,Volume 239, Pages 191–200 To the article: https://doi.org/10.1016/j.jss.2019.02.010

Hitachi Chemical Co. Ltd. to acquire apceth Biopharma GmbH

Munich, Germany, January 31, 2019. apceth Biopharma GmbH, a leading contract manufacturing organization in the field of cell and gene therapy, announces today that Hitachi Chemical Co., Ltd. will enter into an agreement to acquire all shares of apceth Biopharma GmbH. This acquisition is expected to close in April 2019. Founded 2007, apceth is a pioneer in cell and gene therapy and has developed into a leading European contract development and manufacturing organization (CDMO) for Advanced Therapy Medicinal Products (ATMPs). The company has state-of-the-art facilities located in Munich, Germany, which are fully compliant with all current EU ATMP regulations, BSL2 and ICH guidelines. With the acquisition of apceth, Hitachi Chemical will be expanding its business presence footprint in Europe―the world’s second-largest market for regenerative medicine after the United States. “We are very pleased to become part of Hitachi Chemical. Our combined strengths within Hitachi Chemical will allow us to manufacture complex cell and gene therapies for clients in North America, Asia, and Europe. This will allow our clients to supply patients around the world with highly needed innovative and high-quality cell and gene therapies”, said Christine Guenther, MD, CEO of apceth Biopharma. “apceth had been built by a great team and strong support of its shareholders into Europe’s leading independent cell therapy manufacturer. We are very proud that these joint efforts resulted in apceth Biopharma now being chosen as Hitachi Chemical’s hub for cell therapy in Europe,” commented Manfred Ruediger, PhD, Chairman of the Board of apceth. “We are proud having been able to accompany apceth on its successful journey from its foundation in 2007 until today. We are very pleased to have found an excellent partner for apceth’s future endeavors with Hitachi Chemical,” said Helmut Jeggle, Managing Director of Santo Holding (Deutschland) GmbH, majority shareholder of apceth. “The addition of apceth Biopharma to Hitachi Chemical will strengthen our presence in the second-largest cell and gene therapy market in the world, and enable us to offer a truly harmonized global operation, providing our customers with ready access to new markets and maximizing the value we bring to the industry,” said Robert A. Preti, PhD, CEO and President of Hitachi Chemical Advanced Therapeutics Solutions, LLC and General Manager of the Hitachi Chemical Regenerative Medicine Business Sector.   About Hitachi Chemical Hitachi Chemical Co., Ltd. (TSE:4217), is headquartered in Tokyo, Japan, delivers wide range of innovative products, such as electronic materials, automobile parts, energy storage devices and systems, in global markets. The company’s consolidated revenues for fiscal 2017 (ended March 31, 2018) totaled 669 billion yen (5.4 billion euros*). For more information on Hitachi Chemical, please visit the company’s website at http://www.hitachi-chem.co.jp/english/ *The conversion rate is 1 euro = 124 yen.   About apceth Biopharma GmbH apceth Biopharma is a pioneering company in regenerative medicines and a leading and certified Contract Development and Manufacturing Organization for cell and gene therapeutics with a broad international customer base. apceth owns state-of-the-art manufacturing facilities with Grade B/A, C and D cleanrooms (ISO 5, ISO 7, ISO 8, BSL2) and is certified according to regulatory requirements for cell and gene therapies (Advanced Therapy Medicinal Products, ATMPs). The company has a comprehensive expertise in GMP manufacturing of autologous and allogeneic cell types that are either native or genetically modified. It has long-standing experience with various cell products, including mesenchymal stem cells (MSCs), hematopoietic stem cells (HSC), lymphocytes, monocytes, dendritic cells, cord blood derived stem cells, and has the potential to expand to CAR-T and induced pluripotent stem cell (iPSC) technologies. apceth has successfully obtained manufacturing licenses for multiple cell therapy products for clinical as well as commercial use. apceth’s CDMO team provides fully customized solutions in the development and production of every customer product and process. Located centrally in the heart of Europe, apceth can perform efficient and fast supply for patients all over the continent.   Contact apceth Biopharma GmbH Dr Christine Guenther, CEO Max-Lebsche-Platz 30 81377 Munich Germany Phone: +49 (0)89 7009608 0 Email: contact@apceth.com www.apceth.com   Press release as pdf: German and English

Phacilitate 2019

Miami, USA, Jan 22-25, 2019: Phacilitate Leaders World & World Stem Cell Summit 2019. Meet apceth at the world’s largest advanced therapies partnering event – visit us at booth no. 13.