Amsterdam, The Netherlands, April 26, 2012 – Amsterdam Molecular Therapeutics (AMT) Holding N.V. (in liquidation) (Euronext: AMT), today reported its results for the year to December 31, 2011.
Jörn Aldag, Liquidator of AMT, commented: “We believe that the gene therapy business developed by AMT offers significant promise. We are very disappointed that whilst the majority of CHMP members voting followed the advice of the experts at the CAT and the SAG, there were still a sufficient number of blocking votes to prevent Glybera advancing for the benefit of patients. Nevertheless we are encouraged that no safety of manufacturing issues were raised in the latest CHMP assessment. We believe that, under uniQure’s ownership, the future of gene therapy development is very encouraging.”
The progression of AMT’s lead product, Glybera® through the assessment process was the key focus of the Group’s activities during 2011 until the outcome of the reexamination process of the CHMP in October. Thereafter, the Group went through a strategic reorganization to reduce costs and secure additional funds. This resulted in a 50% reduction in headcount and the transfer of AMT’s operations and programs to a newly created company uniQure BV. uniQure received an initial € 6.0 m in new financing from one of AMT’s investors, Forbion. Since completion of the transaction, on April 5, 2012, another of AMT’s investors, Gilde Healthcare, has invested a further € 1.0 m into uniQure.
Lipoprotein Lipase Deficiency (LPLD)
AMT has developed Glybera for the treatment of Lipoprotein Lipase Deficiency (LPLD), a rare and very severe disease. In patients with mutations in the LPL gene, dietary fat (triglyceride molecules) cannot be broken down and so causes chylomicrons, which carry triglycerides around the body, to accumulate in the blood. This may result in recurrent extremely painful and life-threatening episodes of pancreatitis. Pancreatitis, or inflammation of the pancreas, is a major clinical symptom of LPLD. It causes severe abdominal pain and often leads to hospitalization of patients as well as other complications such as diabetes and early atherosclerosis.
AMT submitted the Marketing Authorisation Application (MAA) for Glybera in December 2009; in June 2011 the CHMP published its opinion that Glybera was not approvable at that time. In July 2011, AMT filed for reexamination of the dossier. Two new rapporteurs examined the application for approval under exceptional circumstances, and both issued positive assessments. The Scientific Advisory Group (SAG), an expert panel specifically selected to evaluate clinical results and the science of the product, and the Committee for Advanced Therapies (CAT), which provides guidance on advanced therapeutics such as gene and cell therapy, after extensive review and analysis of the data advised the CHMP that Glybera should be approved now under exceptional circumstances. The CHMP Rapporteurs, SAG and the CAT concluded that data from three Glybera clinical trials demonstrated meaningful evidence of clinical efficacy, without any major safety concerns. However, the CHMP was not bound to follow this advice, and maintained its negative opinion.
In January 2012 AMT announced that the European Commission Standing Committee, which makes the final determination on approvability of novel therapies, requested further information from CHMP, which resulted in a further assessment of Glybera in a limited patient population. In April 2012 AMT announced that the CAT remained positive and that a majority of CHMP voting members were also positive on Glybera. However the CHMP vote was only 16 – 15 in favour and consequently Glybera failed to achieve the level of 17 positive votes required for an approval.
Since originally submitting the MAA, AMT has generated significant additional data, including results from a long-term efficacy study of Glybera showing that improved chylomicron metabolism could be used as a biomarker for increased LPL activity in those patients missing the gene that produces this protein. Data showed that breakdown of chylomicrons produced after meals was greatly and significantly improved at both 14 and 52 weeks following one-time Glybera administration.
It was also shown that Glybera significantly reduces the risk of pancreatitis in LPLD patients. By reducing the incidence of pancreatitis episodes substantially, Glybera has the potential to help “normalize” the day to day lives of patients affected by this disease and prevent the often frequent trips to hospital that patients otherwise experience.
The application will now go back to the European Commission Standing Committee for further consideration.
During the period until the transfer to uniQure, AMT took steps to bring in non-dilutive financing to cover some or all of the costs associated with its remaining programs, in order to reduce its cash expenditure.
AMT continued to work with St Jude’s Children’s Hospital in the USA, which is currently financing and conducting a clinical study in US and UK. Initial results are promising, with patients showing stable and persistent expression of the Factor IX clotting protein, and able to reduce or stop their administrations of protein replacement therapy, which is the current standard of care and requires intravenous infusion up to three times per week.
By contrast, the hemophilia B gene therapy requires a single administration to provide lasting benefit – the earliest patient was treated almost 24 months ago and so far has shown no detectable lessening of the benefit from this treatment. This is the second gene therapy program that AMT was involved with to show clinical benefit from a single treatment and established AMT as the leading gene therapy company worldwide. The initial results of the study were described in the New England Journal of Medicine in December 2011.
Acute Intermittent Porphyria
This program, in collaboration with the University of Navarra and Digna Biotech in Spain, is making encouraging progress. Earlier this year, the consortium won a significant EU grant worth approximately €1 million to AMT, which covers the majority of AMT’s expenditure at this time for this program.
In August 2011, the consortium began enrolling patients into a pre-observation study. This initial study will provide baseline data for the subsequent treatment study, which involves administering patients with a one-time gene therapy and is expected to begin in 2012.
AMT conducted pre-clinical research and successfully completed a proof of concept study in a disease model of Parkinson’s disease in collaboration with the University of Lund, Sweden. Data generated for AMT by the University of Wisconsin (USA) in a further pilot study using large animals also showed effective delivery, distribution and expression at levels that are expected to correlate with clinical efficacy; overcoming these challenges is one of the major challenges to clinical development. Taken together, these positive data provide encouragement for the continued development of GDNF gene therapy and its extension to other neurodegenerative indications such as multiple system atrophy (MSA) and Huntington’s disease.
Under an agreement signed at the beginning of 2011, AMT collaborated with a consortium led by Institut Pasteur in the clinical development of a novel gene therapy to treat Sanfilippo B. This rare genetic disease affecting new-born children leads to progressive neuronal degeneration and death. There is no approved therapy currently available.
On behalf of the Consortium, Institut Pasteur will lead the development program and will also sponsor the initial Phase I/II clinical study. AMT’s successor, uniQure, has taken on manufacturing and supplying the adeno-associated virus, serotype 5 (AAV5) gene therapy product to the Consortium. The overall manufacturing contract entails payments to AMT (and its successor uniQure) of up to € 1.8 million. If the Consortium successfully demonstrates proof of concept in the Phase I/II study, uniQure will have an option to acquire full commercial rights for the program. The Phase I/II clinical study is scheduled to begin in 2012.
Other Research and Development
AMT demonstrated the advantage of its AAV vector delivery technology for the efficient delivery of short and micro RNA to inhibit disease by RNA interference in two further pre-clinical disease models, for hypercholesterolemia and Huntington’s disease. RNAi-based therapeutic strategies are considered highly promising in the industry, but so far, effective delivery has been elusive. Two other important research projects are intended to greatly enhance the value of the platform developed by AMT: gene expression control and re-administration.
Duchenne Muscular Dystrophy
Following the strategic reorganization announced in October 2011, AMT postponed further investment into this program until additional resources could be obtained.
The result for the year from continuing operations for the period ended December 31, 2011 amounted to € 0.0 million (2010: € 0.0 million). The result for the year from discontinued operations amounted to a loss of € (17.3) million (2010: loss of € (19.1) million), a reduction of € 1.8 million or 9%.
Cash and cash equivalents amounted to € 1.1 million at December 31, 2011, a decrease of € 16.8 million compared to € 17.9 million at December 31, 2010. The decrease in cash and cash equivalents mainly stems from the operational cash outflow from discontinued activities which amounted to € 16.7 million for the period ended December 31, 2011 (compared to an operating cash outflow of € 4.8 million for the period ended December 31, 2010).
On December 29, 2011 AMT announced that it had entered into a subscription agreement to raise an additional € 2.5 million in new equity. These funds were received on 4 January 2012 and are therefore not shown within the figures set out above.
On February 17, 2012, AMT announced the transaction with uniQure BV described above. This transaction completed on April 5, 2012.
On February 17, 2012 AMT announced a major corporate restructuring and financing transaction involving the disposal of AMT's entire business and operations to uniQure B.V. and the subsequent dissolution, liquidation and delisting of AMT. On March 30, 2012, an extraordinary general meeting of shareholders approved the transaction and on April 5, 2012 completion of the disposal of AMT's entire business and operations to uniQure B.V. took place. Immediately following the completion of the disposal and consequently as per 5 April 2012, the dissolution of the company as resolved by the EGM became effective, with Mr. Jörn Aldag and Mr. Piers Morgan being the liquidators that shall liquidate the company's dissolved property.
About Amsterdam Molecular Therapeutics
AMT and the AMT shares will continue to exist until the liquidation is finalised, which is expected to occur in the summer of 2012. AMT and its shares ceasing to exist upon the ending of the liquidation shall effectively also result in AMT's delisting, to the extent the delisting cannot be achieved at an earlier date in consultation with Euronext Amsterdam and subject to such conditions as Euronext Amsterdam may propose.
More information on the advance distribution and the further upcoming events and steps in the AMT’s liquidation process and delisting and the timing thereof can be found in the overview of the key transaction elements and the transaction timetable that is available via AMT's website and in AMT’s press releases of 6 and 17 April 2012.
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