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Biotech / Medical : Micromet Inc (MITI) -- Ignore unavailable to you. Want to Upgrade?

To: Biomaven who wrote (60)	3/13/2009 12:33:55 AM
From: rkrw	Respond to of 196

The replacement candidate is a new BiTE antibody that the companies will develop to treat hematological cancers. MedImmune has rights in North America, while Micromet has rights elsewhere. Micromet will receive reimbursement fees for performing preclinical development and is eligible for milestones and royalties. A spokesperson for MedImmune said the company believes the replacement compound has an "increased chance" of success in North America. Micromet was down $0.15 to $2.79 on Thursday.

To: Biomaven who wrote (60)	3/13/2009 11:12:50 AM
From: ejgopher	Respond to of 196

MEDI has been trying to recruit 45 pts since June 2004 for the P1 Blinatumomab (MT103)for relapsed NHL. If MT103 is as great as what MITI is saying, why has MEDI taken that long (5 years) to run this trial? That's the main motivation that got me curious as to the real reason behind this long trial and MT103. clinicaltrials.gov MITI had disclosed the following AE's (where 1 pt had died from MT103) at ASH 2008: micromet.de Results: To date 39 patients have been treated. Most common adverse events (AEs) included lymphopenia, pyrexia, and leukopenia. The majority of AEs (>95%) improved or resolved during treatment. Permanent treatment discontinuation due to AEs occurred in a total of 8 patients, of which 6 had fully reversible CNS events. One patient with a history of nearly fatal sepsis, pre-existing hypogammaglobulinemia and bone marrow affection by chemotherapy, experienced a fatal sepsis 5 weeks after treatment start. Dose-dependent activity was observed in mantle cell lymphoma, follicular lymphoma and CLL with responses observed in 11 out of 27 patients treated at doses of 0.015 mg/m2/24 h and higher. I have some slides from clinical data published in ‘Science’ magazine and poster presentation at ICML meeting in Lugano in 2008 showing the following: (sorry about the format, I can send you the original slides upon request) Safety and Tolerability Most Frequent AE (irrespective of relationship) Adverse Event All Events; Grade ¾ Events; (%) (%) Lymphopenia 68.4 68.4 Pyrexia 68.4 5.3 Leukopenia 57.9 23.7 CRP increased 52.6 34.2 Headache 39.5 2.6 Chills 36.8 0 D dimer increased 36.8 13.2 Thrombocytopenia 36.8 13.2 Weight increased 36.8 0 ALAT increased 34.2 0 Diarrhoea 34.2 0 Neutropenia 34.2 15.8 ASAT increased 31.6 0 Gamma-GT increased 31.6 10.5 Anaemia 28.9 10.5 Fatigue 28.9 2.6 Haematuria 28.9 0 Hyperglycaemia 26.3 5.3 Hypokalaemia 26.3 5.3 Oedema peripheral 26.3 2.6 Weight decreased 26.3 0 Taken from Bargou et al., Science, 2008 & Poster at ICML meeting in Lugano, 2008 Safety and Tolerability Summary of Observations • No significant cytokine release observed – No patient with clinical CRS – Only at highest dose cohort some cytokines detected • Most frequent adverse events were mode of action-related: leukopenia and lymphopenia, and short episode of fever and chills • Some events are believed to be transient bystander effects (i.e., transiently elevated liver enzymes, margination of CD19-negative blood cells) • Some patients showed CNS symptoms including transient confusion, disorientation, tremor, convulsions, and speech disorders – Most effects appear to be linked to initial and transient endothelial stress – All patients fully recovered without sequelae • The majority of adverse events normalized under treatment Dose-Dependent Objective Responses Cheson Criteria – Confirmed by Independent Review Dose levels Patients(n=38)OverallResponses CR PR* ResponseRate 0.0005 – 0.005mg/m2/24 h 12 0 0 0 0 0.015 & 0.030 mg/m2/24 h 19 4 2 2 21 0.060 mg/m2/24 h 7 7 2 5 100 CR: Complete Response PR: Partial Response Taken from Bargou et al., Science, 2008 Clinical Activity in Mantle Cell Lymphoma MCL patients (> 2nd Line) treated at Higher Doses Dose levels Patients Overall Responses CR PR* 0.030 mg/m2/24 h 3 1 1 0 0.060 mg/m2/24 h 2 2 1 1 CR: Complete Response PR : Partial Response *Taken from Bargou et al., Poster at ICML meeting in Lugano, 2008 2008-03-14 10K page 32 sec.gov We previously terminated three other phase 1 clinical trials for MT103, which involved a short-term infusion, as opposed to a continuous infusion dosing regimen of MT103, due to adverse side effects and the lack of observed tumor responses. Serious adverse events included infections, dyspnoea, hypersensitivity and various symptoms of the CNS. CNS-related side effects led to termination of the treatment in a total of six patients in these short-term infusion trials. All of these side effects fully resolved within a period of a few hours to a few days, with the exception of one patient, who suffered from seizures and a myocardial ischemia, or loss of blood flow to the heart. This patient ultimately died 49 days after receiving the last dose, and the cause of death was determined to be pneumonia.

To: Biomaven who wrote (60)	3/13/2009 12:20:50 PM
From: ejgopher	Read Replies (1) \| Respond to of 196

MITI URL correction: MITI had disclosed the following AE's (where 1 pt had died from MT103) at ASH 2008: abstracts.hematologylibrary.org Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract 267 © 2008 American Society of Hematology Nov 2008 Articles by Bargou, R. C Articles by Zugmaier, G. Articles by Bargou, R. C Articles by Zugmaier, G. Oral Session Targeted Therapies and New Agents in Lymphoma Sustained Response Duration Seen after Treatment with Single Agent Blinatumomab (MT103/MEDI-538) in the Ongoing Phase I Study MT103- 104 in Patients with Relapsed NHL Ralf C Bargou, MD1,, Peter Kufer, MD2,, Mariele Goebeler, MD3,, Stefan Knop, MD4,, Hermann Einsele, MD5, Richard Noppeney, MD6,, Andreas Viardot, MD7,, Patrick A Baeuerle, PhD2,, Carsten Reinhardt, MD2,, Margit Schmidt, PhD2,, Petra Klappers2,, Dirk Nagorsen, MD2,* and Gerhard Zugmaier, MD2,* 1 Internal Medicine II, University Hospital Würzburg, Würzburg, Germany, 2 Micromet AG, Munich, Germany, 3 Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, 4 Hematology & Oncology, Medical Center University of Wuerzburg, Wuerzburg, Germany, 5 Medizinische Klinik II, Wurzburg, Germany, 6 Center for Internal Medicine, Hematology, University Hospital Essen, Essen, Germany, 7 Internal Medicine III, Hematology, University Hospital Ulm, Ulm, Germany Abstract Introduction: Blinatumomab (MT103/MEDI-538), a BiTE antibody targeting the CD19 antigen, is a member of a novel class of molecules that redirect T cells for lysis of target cells. A Phase 1 dose escalation study is being conducted in patients with advanced NHL. Methods: Relapsed NHL patients requiring treatment were included. Most patients were pre-treated, with a median of 3 previous chemo/immunotherapy regimens. To date, 7 dose levels ranging from 0.0005 to 0.09 mg/m2/24 h have been tested. Blinatumomab was continuously infused as single agent over a period of 4–8 weeks. Objective responses were assessed by Cheson criteria and centrally reviewed. Results: To date 39 patients have been treated. Most common adverse events (AEs) included lymphopenia, pyrexia, and leukopenia. The majority of AEs (>95%) improved or resolved during treatment. Permanent treatment discontinuation due to AEs occurred in a total of 8 patients, of which 6 had fully reversible CNS events. One patient with a history of nearly fatal sepsis, pre-existing hypogammaglobulinemia and bone marrow affection by chemotherapy, experienced a fatal sepsis 5 weeks after treatment start. Dose-dependent activity was observed in mantle cell lymphoma, follicular lymphoma and CLL with responses observed in 11 out of 27 patients treated at doses of 0.015 mg/m2/24 h and higher. Five of those patients had complete and six had partial responses. At the dose level of 0.060 mg/m2/24 h, 7 out of 7 patients have shown objective responses. Beside one relapse after 14 months, no treatment failure has so far been observed for responders at dose levels of 0.030 mg/m2/24 h and 0.060 mg/m2/24 h. Five patients at these dose levels have ongoing responses for more than 6 months. Interestingly, partial remissions converted into complete remissions in two patients four weeks after end of infusion suggesting either reduction in lesion size due to efflux of a previously expanded T cell pool or prolonged T cell activity. Conclusions: Blinatumomab as single agent induced apparently durable responses in pre-treated B-NHL patients with the highest response rate at a dose level of 0.06 mg/m2/24 h. Recruitment is ongoing. Footnotes Corresponding author Disclosures: Bargou: Micromet: Consultancy. Kufer: Micromet: Employment. Baeuerle: Micromet: Employment. Reinhardt: Micromet: Employment. Schmidt: Micromet: Employment. Klappers: Micromet: Employment. Nagorsen: Micromet: Employment. Zugmaier: Micromet: Employment.