Promethera Biosciences established Branch Office in Tokyo×
Promethera Biosciences established Branch Office in Tokyo
“Today, we took another significant step as a global innovator in the liver disease space and are consistently pursuing our vision and strategy. Adding a local presence in Japan, in addition to our corporate headquarters and growing product development organization in Belgium, our US operations and manufacturing center of excellence in the North Carolina Research Triangle, as well as our newly announced Swiss subsidiary Baliopharm AG represents a key milestone for Promethera in continuing to establish an international footprint,” commented John Tchelingerian, PhD, President & CEO of Promethera Biosciences SA.
Promethera Biosciences presents novel data on HepaStem’s Ability to reduce key disease parameters in advanced stage NASH×
Promethera Biosciences presents novel data on HepaStem’s Ability to reduce key disease parameters in advanced stage NASH
In the current study, the NASH STAM™ model for advanced stage NASH was used to evaluate the therapeutic effect of the liver-derived cell-based treatment HepaStem. The data showed a significant and dose-dependent decrease in the commonly used NAFLD activity score (NAS) following one (22.4% NAS reduction) or three intravenous injections of HepaStem (32.6% NAS reduction versus the control arm). This effect was mainly attributed to a significant reduction in inflammation, thus supporting the proposed mechanism of action of HepaStem.
Promethera Biosciences Raised additional EUR 9.3 Million to advance a broad product Pipeline in Severe Liver Diseases×
Promethera Biosciences Raised additional EUR 9.3 Million to advance a broad product Pipeline in Severe Liver Diseases
Promethera Biosciences raised EUR 9.3 million (approx. USD 11.5 million) through the issuance of convertible bonds to existing and new investors. Major existing shareholders renewed their commitment and participated in the convertible bonds issued. New investors subscribing the bonds from Japan were Shibuya Corporation and Shinsei Corporate Investment and from Switzerland some high-net-worth individuals (HNWI) linked to Baliopharm. The proceeds will be used to accelerate the progression of Promethera’s clinical pipeline and to continue expanding the company’s research and development activities in addressing liver disease indications with significant unmet medical need such as acute-on-chronic liver failure (ACLF), nonalcoholic steatohepatits (NASH) and fibrosis.
Promethera Acquires Baliopharm AG to Strengthen its Therapeutics Strategy in NASH with a unique Tumor Necrosis Factor Receptor 1 (TNF-R1) Antibody Drug Candidates×
Promethera Acquires Baliopharm AG to Strengthen its Therapeutics Strategy in NASH with a unique Tumor Necrosis Factor Receptor 1 (TNF-R1) Antibody Drug Candidates
The transaction complements Promethera’s pipeline with an innovative antibody-based drug candidate that specifically binds to the tumor necrosis factor receptor 1 (TNF-R1). Combining this novel therapeutic strategy with Promethera’s unique liver cell-based therapies could provide improved treatment option for patients suffering from Nonalcoholic steatohepatitis (NASH) and potentially other severe liver diseases. Financial details of the transaction were not disclosed.
With the TNF-alpha pathway and its Receptor 1 (R1) being implicated in the progression of many inflammatory diseases, including chronic liver diseases leading to fibrosis, a therapeutic antibody approach is a valuable strategy in its own right as well as in combination with Promethera’s cell-based medicines such as the HepaStem technology. Through today’s transaction, Promethera gains control over Baliopharm’s entire antibody development programs in particular the one focused on establishing a unique next-generation and selective TNF-R1 inhibitor including the novel, antibody based monovalent drug candidate Atrosimab.
Promethera Biosciences and Shibuya Announce Strategic Collaboration to Establish Breakthrough Cell Therapy Manufacturing Platform×
Promethera Biosciences and Shibuya Announce Strategic Collaboration to Establish Breakthrough Cell Therapy Manufacturing Platform
Both companies signed a strategic collaboration to establish a high-throughput, commercial-scale and clinical-grade cell therapy and regenerative medicine manufacturing platform. For Promethera, the collaboration will act as a cornerstone to optimize and expand the manufacturing capabilities for its current and future portfolio of liver-derived cell therapies to treat Non-Alcoholic Steatohepatitis (NASH), acute-on-chronic liver-failure (ACLF) and other indications.
Promethera Announces Review Acceptance of Heparesc New Drug Submission for Neonatal Onset Urea Cycle Disorders by Health Canada×
Promethera Announces Review Acceptance of Heparesc New Drug Submission for Neonatal Onset Urea Cycle Disorders by Health Canada
“This achievement is a recognition of our dedication to working with the Canadian regulatory bodies as a start to build a path for innovative cell therapies for patients worldwide and a validation of our approach for severe liver diseases,” said John Tchelingerian, CEO of Promethera. “While our strategic focus remains on our stem/progenitor cell products such as HepaStem and H2Stem and the larger indications ACLF and NASH, I am very proud of this joint effort which is a prime example of the successful integration of the Cytonet and Promethera teams.”
Promethera Biosciences Presents Preclinical Data on Novel H2Stem Cell Therapy at EASL International Liver Congress×
Promethera Biosciences Presents Preclinical Data on Novel H2Stem Cell Therapy at EASL International Liver Congress
Novel in vitro and in vivo data were presented on Promethera's preclinical pipeline program H2Stem were presented at the European Association for the Study of the Liver (EASL), International Liver Congress.
“The preclinical results we have generated so far with H2Stem demonstrate that these hepatobiliary progenitor cells, isolated from human livers, have the ability to engraft and repopulate rodent livers and exhibit hepatic functionality in vivo,” commented Etienne Sokal, MD, PhD, Chief Innovation and Scientific Officer of Promethera. “At Promethera, we are committed to bringing innovation to the treatment of severe liver diseases and other indications through novel cell-based approaches. H2Stem strengthens our portfolio with its potential to provide an effective, safe and cost-effective treatment option for patients with severe liver diseases.”
Promethera Biosciences Announces Key Additions to its Executive Management Team×
Promethera Biosciences Announces Key Additions to its Executive Management Team
Henrik L. Luessen, Ph.D., appointed as Chief Business Officer, Nancy Veulemans appointed as VP Clinical & Medical Affairs, Decebal Bora, Pharm. D, MPH, appointed as VP Regulatory Affairs
Promethera Biosciences and LifeLiver Sign Strategic Alliance to Develop Liver Disease Therapeutics in South Korea×
Promethera Biosciences and LifeLiver Sign Strategic Alliance to Develop Liver Disease Therapeutics in South Korea
Both companies will collaborate on the clinical development and commercialization of Promethera's cell-based liver-focused therapeutics portfolio in Korea.
This alliance initially includes:
- a licence agreement for HepaStem and H2Stem to develop and commercialize these platforms in Promethera’s main indications in NASH and ACLF in Korea and
- a supply agreement to provide Heparesc® for LifeLiver’s proprietary bioartificial liver (BAL) system.
Promethera Biosciences raised EUR 10 million in a Series C-extension Financing×
Promethera Biosciences raised EUR 10 million in a Series C-extension Financing
All major existing shareholders including Vesalius Biocapital, SRIW, Fund+, MGI Global Fund (Mitsui & Co), Boehringer Ingelheim Venture Fund and SMS Investments supported this round. New investors joining the financing round were Mitsubishi UFJ Capital Co., Ltd. and Cell Innovation Partners, L.P. (CIP) from Japan and LifeLiver Co., Ltd. from South Korea. The proceeds will be used to expand Promethera’s product development focus to include larger liver disease indications such as acute-on-chronic liver failure (ACLF), nonalcoholic steatohepatits (NASH) and Fibrosis and to accelerate these developments towards the clinic.
Promethera awarded Pharma Deal of the Year×
Promethera awarded Pharma Deal of the Year
Promethera Biosciences has been awarded Germany Healthcare & Pharma Deal of the Year for the acquisition of Cytonet Assets by Acquisition International Magazine.
Promethera Biosciences appointed world-class Scientific and Medical Advisory Board×
Promethera Biosciences appointed world-class Scientific and Medical Advisory Board
Six independent, renowned and international key opinion leaders in hepatology/liver research on advisory board
Strengthens Promethera’s relationship to the international clinical and academic liver disease community to receive broader strategic, scientific and medical advice The opinion leaders appointed are Massimo Pinzani, MD, PhD, FRCP, FAASLD, Anil Dhawan, MD, FRCPCH, Sanjeev Gupta, MBBS, MD, FRCP, FACP, FAASLD, Michael Ott, MD, Andreas Nuessler, PhD and Patrice Cani, RD, MSc, PhD. In addition, Promethera has appointed Professor Massimo Pinzani as the Chairman of the SMAB.
Promethera Biosciences appointed New Chairman of the Board of Directors and expansion of the Executive Management Team×
Promethera Biosciences appointed New Chairman of the Board of Directors and expansion of the Executive Management Team
Promethera appointed Prof. Dr. Christof Hettich to the board as Chairman. Dr. Hettich replaced Dr. John Tchelingerian who held the Chairman position from December 2014 and was subsequently appointed as Chief Executive Officer of Promethera in September 2015.
Dr. Torsten Hombeck, Ph.D. was appointed Chief Commercial and Strategy Officer. Dr. Hombeck was appointed to lead Promethera’s commercial and pre-commercialization activities and general strategy of Promethera Biosciences, which includes market access, pricing and re-imbursement and regulatory filing strategies.
Promethera Biosciences acquired key assets of Cytonet to create the global leader in regenerative medicine and cell therapy for liver diseases×
Promethera Biosciences acquired key assets of Cytonet to create the global leader in regenerative medicine and cell therapy for liver diseases
Acquisition of Cytonet’s key assets enabled Promethera access to:
- Leading liver sourcing at an industrial level through the U.S. Organ Procurement Organization network relationship
- A U.S. presence with a highly qualified team of 18 people and manufacturing facilities ready for commercial use under GMP conditions
- An additional cell therapie product, Heparesc®, a pre-commercial cell therapy for the treatment of early onset Urea Cycle Disorders and a unique cell therapy technology
- A prospect of near term income generation potential both with tissue placement in the U.S. and supply of cryopreserved human liver cells to third parties
Promethera Biosciences strengthened and completed its management team with two key senior appointments×
Promethera Biosciences strengthened and completed its management team with two key senior appointments
Dr Jürgen Beck appointed as VP Clinical and Medical Affairs and Patrick Stragier as VP Operations.
Promethera Biosciences appoints Dr John Tchelingerian as CEO×
Promethera Biosciences appoints Dr John Tchelingerian as CEO
Promethera Biosciences appointed Dr John Tchelingerian as its new Chief Executive Officer. John Tchelingerian joined the company as Chairman of the Board on 8 December, 2014, and has acted as its interim CEO since 23 January, 2015.
Promethera Biosciences opened "Plateforme Wallonne de Thérapie Cellulaire"×
Promethera Biosciences opened "Plateforme Wallonne de Thérapie Cellulaire"
Promethera opens its affiliate Hepatic Cell Therapy Support, integrated into the new Plateforme Wallonne de Thérapie Cellulaire.
From Phase I/II to next clinical trial manufacturing: from open to a closed system using ATMI’s XP bioreactor technology×
From Phase I/II to next clinical trial manufacturing: from open to a closed system using ATMI’s XP bioreactor technology
Clinical batches for the first multicentric phase I/II clinical trial (HEP001) for the treatment of Crigler-Najjar syndrome and Urea Cycle Disorders in a pediatric setting were produced under aseptic conditions using cellbind-treated CellStacks.
Promethera developed a fully closed system to further upscale the process, minimize manual operations and related-risks, as well as reduce overall costs for future clinical trials. This new production process is based on ATMI’s Xpansion bioreactor technology. This offers a similar surface treatment and area, allows for an easy transfer from the existing multi-tray stacks process and a fully controlled environment via real-time monitoring of temperature, dissolved oxygen, pH and media flow rate, reducing in-process variations.
The Xpansion™ 2-D multiplate bioreactor offers a valuable technology for large-scale production. Using this single-use technology, Promethera Biosciences is able to increase the yield of its production process by 20-fold and reduce manpower by 50 %.
Promethera Biosciences partner with EMD Millipore to deliver a pre-clinical liver pharmaco-toxicological testing assay×
Promethera Biosciences partner with EMD Millipore to deliver a pre-clinical liver pharmaco-toxicological testing assay
Promethera Biosciences identified a novel adult human hepatic progenitor cell population that can be maintained in vitro in two- and three-dimensional cell culture conditions providing new models for testing in vitro drug metabolism: H2Screen and H3screen. These cell-based models are derived from healthy human livers and might acquire a metabolic capacity within the range of primary hepatocytes. They have long-term stability in culture as well as potential for large-scale production and reproducibility across batches.
Promethera Biosciences and EMD Millipore collaborated to develop a ready-to-use microfluidic perfusion liver assay. This new product has been designed to perform more robust studies in preclinical toxicity and drug metabolism.
EMD Millipore’s ‘Pearl’ microfluidic technology maintains hepatocyte functionality by mimicking the liver microenvironment. When liver cells are cultured in the ‘Pearl’ format they recover key metabolic functions and could display phenotypic profiles of the intact organ for over a month.
Promethera Biosciences appoint Frank Hazevoets as chief financial officer
Promethera Biosciences receives approval in Belgium to enrol patients in the Phase IIb/III (HEP002) clinical trial×
Promethera Biosciences receives approval in Belgium to enrol patients in the Phase IIb/III (HEP002) clinical trial
Belgian authorities approved the phase IIb/III HEP002 clinical trial. Belgian patients were recruited and treated in Cliniques Universitaires Saint-Luc in Brussels. HEP002 was a prospective, open label, multicenter, efficacy and safety study with HepaStem. The primary objective was to assess the efficacy of HepaStem in patients with urea cycle deficiencies during the year following treatment.
Promethera Biosciences Series C financial round - €25.33 million ($31.4 million)×
Promethera Biosciences Series C financial round - €25.33 million ($31.4 million)
Promethera Biosciences raised €20.33 million in capital and €5 million in loans and subsidies from the Walloon region (Belgium) in a Series-C fundraising. Promethera Biosciences attracted two new investors in this round - SFPI-FPIM, the Belgian Federal Holding and Investment Company, and SMS Investments, a Luxemburg based subsidiary office of the German SMS group. They joined the company’s historical international investors: Vesalius Biocapital and Boehringer Ingelheim Venture Fund (the venture capital fund of the German pharmaceutical group) the lead investors; SRIW; Shire, a leading UK biopharmaceutical company; Mitsui Global Investment, the venture capital fund of Japanese industrial conglomerate Mitsui & Co Ltd. and Pall-ATMI LifeSciences; Vives-Louvain Technology Transfer Office Fund; as well as several business angels.
In addition, the Walloon region of Belgium, which has backed the company since its inception, granted loans and subsidies of €5 million to support the clinical development of HepaStem and the collaborative program with EMD-Millipore.
Phase I/II: Promethera Biosciences opened the French part of its clinical trial in cell therapy×
Phase I/II: Promethera Biosciences opened the French part of its clinical trial in cell therapy
Promethera treated a 14-year-old adolescent suffering from Ornithine Transcarbamylase Deficiency (OTCD, one of the Urea Cycle Disorders) was treated with HepaStem. The patient was the first to have been treated in France. The administration of the cells took place at Hôpital Jeanne de Flandre in Lille (France). The treatment was successfully applied over three days. The cell formulation was performed both on clinical site in Promethera’s mobile formulation unit and at the premises in Mont-Saint-Guibert (Belgium).
Phase I/II: Promethera Biosciences opened the United Kingdom part of its clinical trial in cell therapy×
Phase I/II: Promethera Biosciences opened the United Kingdom part of its clinical trial in cell therapy
Promethera treated a 2.5-year-old toddler suffering from Ornithine Transcarbamylase Deficiency (OTCD) with HepaStem. The administration of the cells took place at the Birmingham Children's Hospital (UK).
Phase I/II: Promethera Biosciences opened the Italian part of its clinical trial in cell therapy×
Phase I/II: Promethera Biosciences opened the Italian part of its clinical trial in cell therapy
Promethera treated a 6-year-old girl suffering from Carbamoylphosphate Synthetase I Deficiency (CPS-ID) with HepaStem in a phase I/II trial studying the safety and preliminary efficacy of this innovative cell-therapy. The patient received the higher dose of HepaStem. The administration of the cells took place at the Bambino Gesu Hospital (Rome) and was performed by the teams of Drs Torre and Dionisi-Vici.
The treatment was successfully applied over four days. The cell formulation was performed at the hospital using the closed formulation system installed in a room near the patient. This system was validated and approved by Italian Competent Authorities to prepare the cells in a non-aseptic environment.
Phase I/II: Promethera Biosciences successfully enrols twenty patients in its multicentric Phase I/II trial×
Phase I/II: Promethera Biosciences successfully enrols twenty patients in its multicentric Phase I/II trial
Promethera Biosciences is conducting the trial in five countries: Belgium, France, United Kingdom, Italy and Israel. In total, 11 clinical centers actively participate in the study: Cliniques Universitaires Saint-Luc, Belgium, Universitair Ziekenhuis Antwerp, Belgium, Hopital Jeanne de Flandre in Lille, France, Centre Hospitalier Universitaire Bicetre in Paris, France, Centre Hospitalier Universitaire de Toulouse, France, Birmingham Children’s Hospital, UK, Great Ormond Street Hospital, UK, IRCCS Ospedale Pediatrico del Bambino Jesu, Italy, Meyer Children’s Hospital at Rambam Health Care Campus, Israel, Hadassah Ein-Kerem Medical Center, Israel, Schneider Children’s Medical Center of Israel.
Belgian Authorities granted GMP accreditation of the manufacturing facility located in Mont-Saint-Guibert×
Belgian Authorities granted GMP accreditation of the manufacturing facility located in Mont-Saint-Guibert
GMP certification of Promethera’s facilities was delivered for the manufacture and the quality control of Promethera’s product HepaStem. Promethera’s GMP facilities cover 327 m² including three grade B aseptic rooms, dedicated Quality Control areas and warehouses.
This accreditation of Promethera's high level quality system allowed the initiation of the manufacturing campaign for the clinical lots that will be used in the phase I/II clinical trial.
Belgian authorities (AFMPS) and British authorities (MHRA) approved HepaStem Phase I/II clinical trial involving Crigler Najjar and Urea Cycle Disorders patients×
Belgian authorities (AFMPS) and British authorities (MHRA) approved HepaStem Phase I/II clinical trial involving Crigler Najjar and Urea Cycle Disorders patients
Promethera® Biosciences obtained the first authorizations from the British (MHRA) and Belgian (AFMPS) regulatory authorities to begin the phase I/II clinical study of HepaStem. As part of the clinical study, the cell therapeutic product was assessed in a paediatric setting involving children suffering from Crigler-Najjar syndrome or urea cycle disorders. Most young patients have few therapeutic options and many die at an early age.
Promethera Biosciences raised EUR 23.6 million (~ USD 31.4 million) in Series-B financing round in March 2012×
Promethera Biosciences raised EUR 23.6 million (~ USD 31.4 million) in Series-B financing round in March 2012
Promethera Biosciences secured new investors in the second investment round, resulting in a further capital increase of EUR 17 million. In addition, the Walloon Region, which has backed the project since its inception, granted a loan of EUR 6.6 million to support the clinical development of HepaStem.
Five new investors have acquired equity in Promethera: Boehringer Ingelheim Venture Fund, the venture capital fund of the pharmaceutical giant; Shire, a leading biopharmaceutical company; Mitsui Global Investment, the venture capital fund of Japanese industrial conglomerate Mitsui & Co Ltd.; ATMI, a global leader in semiconductors and innovative culture systems.
In addition to these four groups of international scope and reputation is Sambrinvest, the investment fund of the Gosselies region in Wallonia. This Series-B fundraising has been successful thanks to the major achievements made by Promethera Biosciences since its Series-A fundraising in 2009.
Promethera develops of a mobile unit for the formulation and distribution of HepaStem×
Promethera develops of a mobile unit for the formulation and distribution of HepaStem
HepaStem, the cell therapy product developed by Promethera, is a hepatic progenitor cell suspension that must be infused to the patient in a medical setting within 6 hours after its final formulation. By transposing the aseptic and temperature-controlled formulation process performed at Promethera’s unique plant at Mont-Saint-Guibert into a mobile unit brought near the clinical site, it would deliver the product within its shelf-life.
A closed formulation system, where the product does not come into contact with the environment, was designed and validated to aseptically prepare the final product in a non-aseptic environment. A temperature controlled production room was designed and fitted on a truck frame. It was used to both transport the required equipment to the clinical site and to perform the formulation.
This innovation enabled the delivery of the cell therapy product to remote patients who cannot be reached within 6 hours from Promethera’s facilities. The process and the equipment was inspected and approved by the Belgian authorities (AFMPS).
The closed system ability to maintain the aseptic conditions in an uncontrolled environment was fully demonstrated and, as part of the validation process, a specification-compliant batch of HepaStem was successfully formulated in the mobile unit at the Birmingham Children Hospital (UK) as well. Several patients were then treated with HepaStem formulated in the mobile unit in the Cliniques Universitaires Saint-Luc (Brussels, Belgium) and in the Hôpital Jeanne de Flandre (Lille, France).
Phase I/II: Promethera Biosciences treated first patients with Promethera HepaStem×
Phase I/II: Promethera Biosciences treated first patients with Promethera HepaStem
Promethera Biosciences treated its first four patients with its innovative treatment based on allogeneic adult liver stem cell technology (Promethera HepaStem). These patients were treated at the Cliniques Universitaires Saint-Luc (Brussels, Belgium). Two patients with Crigler-Najjar syndrome and two patients with a deficiency in ornithine transcarbamylase deficiency received the low dose. Patients were aged from 9 months to 17 years old at the time of cells administration. The trial, a prospective, open label, multicentre, phase I/II study was designed to evaluate the safety and the preliminary efficacy of Promethera HepaStem in Urea Cycle Disorders and Crigler-Najjar Syndrome patients.
Patent granted by the European Patent Office×
Patent granted by the European Patent Office
The first international patent application for HHALPC was submitted in December 2005. The patent (EP 1969118) was granted by the European Patent Office.
Successful technology transfer of manufacturing process from UCL into Promethera’s large scale facility×
Successful technology transfer of manufacturing process from UCL into Promethera’s large scale facility
The technology was successfully transferred and scaled up from the university laboratory to the Promethera Biosciences facilities. These include clean rooms and with capability of producing progenitor cells for clinical trials.
Pre-clinical proof of concept in three different models×
Pre-clinical proof of concept in three different models
10 GLP/non GLP animal studies with HHALPC were conducted. These studies assessed HHALPC engraftment as well as activation of the deficient enzyme (proof of concept studies), risk of tumorigenicity and biodistribution.
Three pre-clinical studies were undertaken in two immunodeficient mice models with and without liver regeneration stimulus. These studies demonstrated that HHALPCs, once injected in animals, are able to engraft and differentiate in the host liver parenchyma despite a xenogeneic environment. In addition to engraftment, successful hepatic differentiation in situ was also demonstrated.
Another study demonstrated the functional proof of concept through restoration of in vivo enzyme activity on Gunn rats. These were selected because it was an animal model homologous to Crigler Najjar Syndrome. Gunn rats present a high level of unconjugated bilirubin in blood due to a mutation in UGT1A1 gene similar to the human condition. Transplanted Gunn rats responded to Promethera® HepaStem therapy with a significant decrease of unconjugated bilirubin in blood after 6 months.
World first proof of concept in man - treating three patients with HHALPCs×
World first proof of concept in man - treating three patients with HHALPCs
Test doses of human adult liver stem cells HHALPC (Heterologous Human Adult Liver Progenitor Cells) were injected in three patients at St Luc Hospital (Brussels, Belgium). The cells were produced in the Liver Stem Cell Tissue Bank of Saint-Luc Hospital.
Patient 1 - suffering from ornithine transcarbamylase deficiency, one of the 6 Urea Cycle defects. -
Patient 2 - presented a Crigler-Najjar syndrome
Patient 3 - suffering from Glycogenosis type 1a.
The infusion of the liver progenitor cells occurred safely and was well tolerated by all the patients
Promethera Biosciences was founded in February 2009. The company raised €5.3 million through series A financing end of October 2009 complemented by an additional €4 million in loans and grants from the Walloon region. Vesalius Biocapital was the lead investor of the Series A round.