story of TGN1412

March 15, 2006
Volunteers taking part in a clinical trial involving TeGenero’s study drug monoclonal antibody TGN1412 have experienced adverse events. The study, sponsored by TeGenero, involves TeGenero’s TGN1412, an immunomodulatory humanized agonistic anti-CD28 monoclonal antibody that is being developed for the treatment of immunological diseases with a high unmet medical need, such as multiple sclerosis, rheumatoid arthritis and certain cancers.“These events were completely unexpected and do not reflect the results we obtained from initial laboratory studies which enabled us to progress investigations into human volunteers”, commented Dr. Benedikte Hatz, Chief Executive Officer, TeGenero AG. The clinical trial performed by the contract research organization, PAREXEL International, adhered to standard clinical research guidelines.” The clinical trial was approved by the Medicines and Healthcare products Regulatory Agency, the UK regulatory authority responsible for clinical trial approval, and the local Ethics Committee. “The drug was developed in accordance with all regulatory and clinical guidelines and standards. In pre-clinical studies, TGN1412 has been shown to be safe and the reactions which occurred in these volunteers were completely unexpected,” said Dr. Thomas Hanke, Chief Scientific Officer of TeGenero AG.
March 15 2006
Thomas Hanke, Chief Scientific Officer of TeGenero; “Our first concern right now is for the patients and families and that they get all treatment possible. We are confident in the excellent treatment at this hospital and have made ourselves available to answer any questions from the doctors about the drug. The drug being tested, TGN1412, is an innovative new treatment for the devastating illnesses of leukaemia, rheumatoid arthritis and multiple sclerosis.The investigation must proceed as quickly as possible into these shocking developments in the testing of a new medicine which showed no signs of any safety problems in previous testing.Our thoughts are with the patients and the families.”Notes:Parexel was conducting the first human testing of TGN1412 for TeGenero AG. The trial was approved by the MHRA and the local ethics committee.There is no further human testing of TGN1412 being pursued.
March 17 2006
“We are encouraged by the signs of progress in the conditions of the patients but remain deeply concerned for them and their families. They are receiving excellent treatment at Northwick Park Hospital in London. We are working closely together with the doctors and have made ourselves available to answer any questions on the drug and to support them in choosing the most suitable treatment.At the same time we have offered every support possible to the institutions in charge of investigation, the MHRA in the UK and the German authorities. We will respond to any questions and provide information beyond the material already available. We are doing everything we can to unravel as quickly as possible how these unexpected symptoms could have developed.The tested substance TGN1412 is a new treatment for the devastating illnesses of leukaemia, rheumatoid arthritis and multiple sclerosis. We are shocked about the symptoms we have seen in the volunteers. Extensive pre-clinical tests showed no sign of any risk. We observed strict standards for this clinical test and we obtained all required approvals both in Germany and Great Britain. The drug was tested extensively in laboratories and has been tested on rabbits and monkeys. We saw no drug related adverse events and there were no drug related deaths. Our thoughts are with the patients and their families.”
March 29 2006
Northwick Park Hospital has yesterday (28th March) confirmed that two of the volunteers in the trial of TGN1412 have been discharged from hospital having responded well to treatment. They will continue to visit the hospital for check ups.Three other volunteers have left Critical Care and are making a good recovery, although they continue to receive specialist care and observation. One volunteer remains in a critical condition but is continuing to respond to treatment. TeGenero remains in close contact with the doctors treating the volunteers to provide all possible assistance to them.Everyone at TeGenero is pleased at the improvement in the conditions of the volunteers and is grateful for the excellent work of all the staff at the hospital. Our thoughts remain with all the volunteers and with their families. We are continuing to do all we can to support the investigations into what went wrong in the trial but have received no update from the investigators at this time.TeGenero will issue further statements when there are significant developments.For the latest updates on the condition of the volunteers please visit the website of the North West London Hospitals Trust, www.nwlh.nhs.uk
April 5 2006
Statement from TeGenero AG responding to the report of the MHRA’s findings on 5th April 2006“We are grateful to the MHRA for their conduct of this investigation.”“We are of course saddened that preliminary findings suggest that the unforeseen side effects resulted from the drug itself. For a company dedicated to developing medicines to help millions it is devastating that such events could occur.”“The preliminary findings of the investigation underline that we observed the highest standards in developing this drug and that these symptoms were both unexpected and unforeseeable. The information released today shows that there was no sign of risk from the pre-clinical tests of TGN1412.”“The animal study results show that there were no drug related deaths in the tests with just one animal sadly having to be put down during the trial after suffering severe diarrhoea caused by an unrelated bacterial infection.”“The announcement of a new expert commission to supervise future trials of monoclonal antibodies challenges all of us in the biotechnology industry to think again about the safest way to develop new medicines in the future.”“Everyone at TeGenero is extremely pleased that 5 of the 6 volunteers have now been discharged from hospital and that the sixth is making steady progress and is no longer in critical care. We are grateful for the excellent work of all at the hospital.”For the latest updates on the condition of the volunteers please visit the website of the North West London Hospitals Trust, www.nwlh.nhs.ukFor further information of the MHRA please visit the website of the MHRA, www.mhra.gov.uk

About TeGenero AG TeGenero AG is a privately held biopharmaceutical company dedicated to the development of innovative, highly effective and broadly applicable therapeutic drugs for the treatment of severe immunological disorders. The company was founded in 2000 and is located in Würzburg, Germany.Contact:TeGenero AG Science Park Würzburg Friedrich-Bergius-Ring 15 D-97076 Würzburg Phone: +49 (0) 931-35 96 2-0Fax: +49 (0) 931-35 96 2-11Email: info@tegenero.com