apceth Biopharma GmbH manufactures DCprime’s cell-based cancer vaccine for phase II clinical study

Munich, Germany, November 16, 2018. apceth Biopharma GmbH, an established contract manufacturing organization in the field of gene and cell therapy, has started supplying clinical batches of DCprime’s cell-based cancer vaccine DCP-001 to a phase II clinical study for the treatment of Acute Myeloid Leukemia (AML). AML is a haematological cancer characterized by high risk of relapse, even after initial response to chemotherapy. Cancer vaccination with dendritic cells could be a successful strategy to boost the patient’s immune system and result in lasting disease control. DCprime announced yesterday that the first patient has been treated with the product DCP-001 at the Amsterdam University Medical Center (UMC). “We are proud to be the manufacturing partner of DCprime for DCP-001, the first off-the shelf dendritic cell vaccine in a cancer indication with high unmet medical need”, explained Dr Christine Günther, CEO of apceth Biopharma. “Our long-term collaboration with DCprime has always been constructive and cooperative, from technology transfer to the large-scale manufacturing process.” Dr Erik Manting, CEO of DCprime, commented: “Based on the recently published encouraging results of the phase I trial with our lead product DCP-001, we aim to confirm these results in the phase II ADVANCE-II trial and we are happy with the enrollment of the first patient. We would like to thank the apceth Biopharma team for their important contribution to the manufacturing of our product.” About apceth Biopharma GmbH apceth Biopharma is a pioneering company in cell therapies and regenerative medicine with an innovative portfolio of drug candidates for the treatment of inflammation, autoimmunity and solid tumors. apceth is developing two proprietary next generation gene therapy products, which are based on the introduction of therapeutic transgenes into mesenchymal stem cells (MSCs). apceth-201 expresses the immunomodulatory protein alpha-1 antitrypsin for the treatment of graft-versus-host disease. The company’s second program, apceth-301, expresses a potent immunostimulatory “cocktail” of cytokines, which locally activates the immune system to eradicate tumor cells. apceth-301 is currently being developed for glioblastoma as well as for other solid tumors. apceth Biopharma is also 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. Press release as pdf (English) Press release as pdf (German) 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

apceth Biopharma presents positive data demonstrating efficacy of apceth-201 in preclinical models of acute GvHD

Munich, Germany, Oct 19, 2018 – apceth Biopharma GmbH, a company with the mission of improving patients’ lives with next generation cell therapies, announced today positive results for apceth-201 in mouse models for acute graft-versus-host disease (aGvHD). The data was highlighted in a poster presentation at the Annual Congress of the European Society of Gene and Cell Therapy in Lausanne on October 16-19. “We are very excited with these results that clearly show the transformative therapeutic potential of apceth-201 in an immune-mediated disease with high unmet medical need and few treatment options”, said Dr Christine Guenther, CEO of apceth Biopharma. “Based on these promising and impressive data, we are currently preparing to initiate a phase 1/2 clinical study assessing the safety and efficacy of apceth-201 in adult steroid-refractory GvHD patients.” Acute graft-versus-host disease is a frequent complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). Immunosuppressants are used to manage aGvHD; however, steroid-refractory aGvHD develops in many cases and has an extremely poor prognosis. apceth-201 significantly improved clinical score and overall survival in two aGvHD models apceth-201 are allogeneic human mesenchymal stromal cells (MSCs) that have been genetically modified to express alpha-1 antitrypsin (AAT), a protease inhibitor exerting potent anti-inflammatory and tissue-protective functions to further augment the immunomodulatory potential of MSCs. In vitro assays demonstrated that apceth-201 efficiently suppresses T-cell proliferation, the maturation of dendritic cells, and also polarizes macrophages to an anti-inflammatory M2 type. The in vivo efficacy of apceth-201 was assessed in two different mouse models for aGvHD. In a humanized model vehicle-treated control animals succumbed quickly to GvHD, whereas median survival was doubled in apceth-201-treated animals. Mice receiving apceth-201 showed significantly improved clinical scores, a striking amelioration of bone marrow cellularity, and reduced levels of inflammatory markers. apceth-201 was further tested in a GvHD model system which closely mimics haploidentical HSCT. Vehicle-treated control animals again succumbed quickly to GvHD, whereas treatment with apceth-201 resulted in long-term survival of 57 % of the mice. Initially, all apceth-201-treated animals exhibited clinical scores comparable to the control animals. However, within a period of 25 days after the second cell injection, the clinical scores had returned to baseline, indicating complete resolution of GvHD. This promising data has led to planning of a phase 1/2 study using apceth-201 for the treatment of steroid-refractory aGvHD in adults.   Press release as pdf   About apceth Biopharma GmbH apceth Biopharma is a pioneering company in cell therapies and regenerative medicine with an innovative portfolio of drug candidates for the treatment of inflammation, autoimmunity and solid tumors. apceth is developing two proprietary next generation gene therapy products, which are based on the introduction of therapeutic transgenes into mesenchymal stem cells (MSCs). apceth-201 expresses the immunomodulatory protein alpha-1 antitrypsin for the treatment of graft-versus-host disease. The company’s second program, apceth-301, expresses a potent immunostimulatory “cocktail” of cytokines, which locally activates the immune system to eradicate tumor cells. apceth-301 is currently being developed for glioblastoma as well as for other solid tumors. apceth Biopharma is also 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

apceth to manufacture first potential one-time gene therapy for transfusion dependent β-thalassemia

Munich, Germany, Oct 5th, 2018 – apceth Biopharma GmbH, a leading company for the development and manufacturing of cell and gene therapeutics, congratulates its partner bluebird bio on the acceptance and validation of its market authorization application (MAA) by the European Medicines Agency (EMA). bluebird bio has applied for market authorization of its investigational LentiGlobin™ gene therapy for the treatment of adolescents and adults with transfusion-dependent β-thalassemia (TDT) and a non-β0/β0 genotype. “We congratulate our partner bluebird bio on this recent success”, commented Dr Christine Guenther, CEO of apceth Biopharma. “These are exciting times also for apceth, as we are now in the position to become one of the very few companies worldwide to manufacture a cell-based gene therapy for commercial use.” apceth has supported and will continue to support bluebird bio for obtaining the market authorization for LentiGlobin™. Following a successful long-term manufacturing relationship, apceth Biopharma and bluebird bio entered a commercial drug product manufacturing agreement in 2016. apceth Biopharma is bluebird bio’s clinical and commercial manufacturing partner for Europe not only for LentiGlobin, but also for bluebird bio’s product candidate Lenti-D for cerebral adrenoleukodystrophy.   Press release as pdf (English)  or pdf (German) Press release from bluebird bio     About apceth Biopharma GmbH apceth Biopharma is a pioneering company in cell therapies and regenerative medicine with an innovative portfolio of drug candidates for the treatment of inflammation, autoimmunity and solid tumors. apceth is developing two proprietary next generation gene therapy products, which are based on the introduction of therapeutic transgenes into mesenchymal stem cells (MSCs). apceth-201 expresses the immunomodulatory protein alpha-1 antitrypsin for the treatment of graft-versus-host disease. The company’s second program, apceth-301, expresses a potent immunostimulatory “cocktail” of cytokines, which locally activates the immune system to eradicate tumor cells. apceth-301 is currently being developed for glioblastoma as well as for other solid tumors. apceth Biopharma is also 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 (MSC), 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 (iPSCs) 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

apceth Biopharma receives an extended general manufacturing authorization for cell and gene therapeutics

Munich, Germany, Aug 7, 2018 – apceth Biopharma GmbH, a leading company for the development and manufacturing of cell and gene therapeutics, announced today that it has received an extended general manufacturing authorization by the District Government of Upper Bavaria. This manufacturing authorization for cell and gene therapeutics is now regulated on an activity-related and no longer product-related basis. The previously obligatory inspection by the regulatory authority becomes optional. “We are very pleased with the trust and confidence shown by the regulatory authority”, commented Dr Christine Guenther, CEO of apceth Biopharma. “I am very proud of the entire apceth team, which has successfully completed every inspection by the District Government of Upper Bavaria and the Paul-Ehrlich-Institute since the foundation of the company. This kind of regulatory approval is rarely found for cell and gene therapeutics.” The extended general manufacturing authorization includes the clinical as well as commercial supply of cell products with different manufacturing techniques. It allows the production of cell therapeutics from various starting materials, for example bone marrow and umbilical cord blood, the production of native and genetically modified cells as well as the autologous or allogeneic administration. “This gives us more flexibility, streamlines the manufacturing approval process and shortens the timelines for our new customers”, explains Dr Andreas Schmiede, head of the Contract Development and Manufacturing department (CDMO). In 2018, apceth has also expanded its manufacturing capacities with two new class B clean rooms and is continuously strengthening its Manufacturing and Quality Control teams. “Due to the high demand for capacity for the CDMO business, we are significantly enhancing our capabilities to meet the growing need of our customers”.   About apceth Biopharma GmbH apceth Biopharma is a pioneering company in cell therapies and regenerative medicine with an innovative portfolio of drug candidates for the treatment of inflammation, autoimmunity and solid tumors. apceth is developing two proprietary next generation gene therapy products, which are based on the introduction of therapeutic transgenes into mesenchymal stem cells (MSCs). apceth-201 expresses the immunomodulatory protein alpha-1 antitrypsin for the treatment of graft-versus-host disease. The company’s second program, apceth-301, expresses a potent immunostimulatory “cocktail” of cytokines, which locally activates the immune system to eradicate tumor cells. apceth-301 is currently being developed for glioblastoma as well as for other solid tumors. apceth Biopharma is also 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 (ISO 5, ISO 7, ISO 8, BSL2 cleanrooms) 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 (MSC), 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 (iPSCs) 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 Download the  press release (pdf, English or German)

apceth Biopharma to Present new data for apceth-201 and apceth-301

apceth Biopharma to Present new data for apceth-201 and apceth-301 at the American Society of Gene and Cell Therapy (ASGCT) 2018 Annual Meeting apceth Biopharma GmbH, a company with the mission of improving patients’ lives with next generation cell therapies, announced today that it has been selected for 2 oral presentations on apceth-201 and apceth-301 at the American Society of Gene and Cell Therapy (ASGCT) 2018 Annual Meeting that will take place in Chicago on May 16-19, 2018. apceth’s first presentation is titled “Intracerebral Immunomodulation Using Genetically Engineered Mesenchymal Stem Cells Induces Long-Term Survival and Immunity in Glioblastoma” and will be given by Prof. Dr. Nils Ole Schmidt from the University Clinic Hamburg-Eppendorf. Prof. Schmidt will present the latest results regarding apceth-301 which is being developed for the treatment of solid tumors. The presentation will take place on Wednesday May 16 between 11:15 AM – 11:30 AM in Salon A-1/2 (abstract number 22). The second presentation is titled “Human Mesenchymal Stem Cells Genetically Engineered to Express Alpha-1 Anti-Trypsin (apceth-201) Confer a Long-Term Survival Benefit in a Lethal, Haplo-Identical Mouse Model of Graft-Vs-Host-Disease” and will be given by Dr. Ulf Geumann of apceth. The presentation will take place on Thursday May 17 between 5:00PM – 5:15PM in the International Ballroom North (abstract number 351). “We are honored to have been invited by ASGCT to present the most recent data on apceth-201 and apceth-301”, said Dr. Christine Guenther, CEO of apceth Biopharma. “We are very excited about the data and are currently preparing to move into clinical development.” About apceth Biopharma GmbH apceth Biopharma is a pioneering company in cell therapies and regenerative medicine with an innovative portfolio of drug candidates for the treatment of inflammation, autoimmunity and solid cancers. Through introduction of therapeutic transgenes into Mesenchymal Stem Cells (MSCs), apceth is developing two potent next generation MSC-based gene therapy products. apceth-201 expresses the immunomodulatory protein alpha-1 antitrypsin for the treatment of graft-vs-host disease. The company’s second program, apceth-301, expresses a potent immunostimulatory “cocktail” of cytokines which locally activates the immune system to eradicate tumor cells. apceth-301 is currently being developed for glioblastoma as well as for other solid tumors. apceth is also a leading and certified Contract Development & Manufacturing Organization for Advanced Therapy Medicinal Products (ATMPs) with a broad international and transactlantic customer base. The company has state-of-the-art manufacturing facilities (ISO 5, ISO 7, ISO 8, BSL2 cleanrooms) and is certified according to regulatory requirements for ATMPs. The company has a comprehensive expertise in GMP manufacturing of autologous and allogeneic cell types that are either native or genetically modified, including mesenchymal stem cells (MSC), 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 (iPSCs) technologies. apceth has successfully obtained manufacturing licenses for multiple cell therapy products and 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 of the client’s products across the continent. Download this Pressrelease

apceth Biopharma to Present at EHA-SWG Scientific Meeting

apceth Biopharma is proud to announce that it will be presenting its latest results on apceth-201 in graft-vs-host-disease (GvHD) during the European Hematology Society (EHA)-SWG Scientific Meeting in Amsterdam on November 23-25, 2017. apceth’s presentation will take place on November 24, 2017 between 16:00 – 17:00. For more information, please consult the full press release. Download Press Release_EHA-SWG Meeting

apceth Biopharma Appoints a New Supervisory Board

apceth Biopharma is proud to announce the appointment of a new Supervisory Board. The Supervisory Board will be responsible for advising and supporting the company on its corporate and business strategies. The Board is composed of highly experienced members with successful track records in the pharma and biotech industry. For more information, please consult the full press release: Download Press Release_Supervisory Board

DCPrime and apceth Biopharma GmbH announce manufacturing partnership

apceth Biopharma is proud to announce a new manufacturing partnership with DCPrime. The collaboration involves clinical batch production and the development of a commercial scale manufacturing process of cancer vaccines based on DCPrime’s technology platform DCOne®. The companies also announce that apceth has recently successfully passed an inspection by the District Government of Upper Bavaria and the Paul-Ehrlich-Institute for the manufacturing license for production of DCP-001, DCPrime’s lead program. This will enable DCPrime to enter into a Phase II Proof of Concept study in Acute Myeloid Leukemia. For more information, please consult the full press release: Download Press Release_DCPrime and apceth Biopharma

apceth Biopharma appoints Dusan Kosijer as Chief Financial Officer

apceth Biopharma GmbH (www.apceth.com), a cell therapy company with a proprietary portfolio of genetically modified mesenchymal stem cell therapeutics for the treatment of inflammatory diseases and cancer, and a successful Contract Development and Manufacturing Organisation (CDMO) for cell and gene therapy products, announced today the appointment of Mr Dusan Kosijer as new Chief Financial Officer, effective immediately. Download Press Release ENG (PDF)

bluebird bio and apceth Biopharma Establish Commercial Drug Product Manufacturing Agreement

bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer and apceth Biopharma GmbH (www.apceth.com), the global innovator and leader in the development of engineered mesenchymal stem cell (MSC) therapeutics and a successful and established contract development and manufacturing organization in the field of cell and gene therapy, announced today that they have entered into a strategic manufacturing agreement providing for the future European commercial production of bluebird bio’s Lenti-D™ product candidate for cerebral adrenoleukodystropy and its LentiGlobin™ product candidate for transfusion-dependent β-thalassemia. Downolad Press Release ENG, DE (PDF)