mt103 science paper presentation final aug 18 2008...

Micromet, Inc.

Slide Kit for Analyst Call(August 18, 2008)

Blinatumomab (MT103/MEDI-538) Data As Published

in Science Magazineg

Science 321: 974-977 (2008)

Forward-Looking StatementsForward-Looking StatementsThis presentation contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. These forward-looking statements include expressed or implied by such forward looking statements. These forward looking statements include statements regarding the efficacy, safety and intended utilization of our product candidates, the development of our BiTE antibody technology, the conduct, timing and results of future clinical trials, expectations of the future expansion of our product pipeline and collaborations, and our plans regarding future presentations of clinical data. You are urged to consider statements that include the words "ongoing," "may," "will," "believes," "potential," "expects," "plans," "anticipates," "intends," or the negative of those words or other similar words to be uncertain and forward-looking. Factors that may cause actual results to differ materially from any future results expressed or implied by any forward-looking statements include the risk that product candidates that appeared promising in early research, preclinical studies or clinical trials do not demonstrate safety and/or efficacy in subsequent clinical trials, the risk that encouraging results from early research, preclinical studies or clinical trials may not be confirmed upon further analysis of the detailed results of such research preclinical study or clinical trial the risk that further analysis of the detailed results of such research, preclinical study or clinical trial, the risk that additional information relating to the safety, efficacy or tolerability of our product candidates may be discovered upon further analysis of preclinical or clinical trial data, the risk that we or our collaborators will not obtain approval to market our product candidates, and the risks associated with reliance on collaborator MedImmune for the funding or conduct of further development and commercialization activities relating to our product candidates. These factors and others are more fully discussed in activities relating to our product candidates. These factors and others are more fully discussed in Micromet’s Annual Report on Form 10-K for the fiscal year ended December 31, 2007, filed with the SEC on March 14, 2008, as well as other filings by the company with the SEC.

Any forward-looking statements are made pursuant to Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934 as amended and as such speak only

© Micromet, Inc. 2008

amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and, as such, speak only as of the date made. Micromet, Inc. undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.

Cancer and TherapyCancer and TherapyBiTE Antibodies Offer a Unique Opportunity

O t Di O lt DiOvert Disease(Primary Tumor, Metastases)

Occult Disease(Micrometastatic = MRD Status)

ChemotherapySurgery

Antibodies


SurgeryRadiationAnti-Angiogenesis

BiTE Antibodies Use Patients Own Immune Cells to Eliminate Cancer

T Cell

CD3ε

BiTE

CD3ε

BiTEBiTE®

Master Switch CD3

TAA

BiTE

TAA

BiTE

Tumor Associated Antigen

Tumor Cell


BiTE® Antibodies Engage T Cells to Eliminate Tumors

i ib d i liBiTE Antibody Pipeline

BiTE MT110 EpCAM GI & Lung

BiTE Blinatumomab (MT103) CD19 NHL and ALL AZ/MedImmune

Preclinical Phase I Phase IIResearch Collaboration

BiTE MT110 EpCAM GI & Lung

BiTE MT111 CEA AZ/MedImmuneBiTE MCSP

--

--

BiTE EGFR

BiTE CD33

BiTE EphA2 AZ/MedImmune

--

--

BiTE HER-2 --BiTE Renal Ca --BiTE IgE --


BiTE IgE --

Blinatumomab (MT103)Anti-CD19 Lymphoma BiTE Antibody

• MT103 is targeting most B-cell derived Non-Hodgkin‘s lymphomas (NHL) and leukemias

• MT103 engages T cells to kill B cell tumors

• Phase 1 clinical trial in late-stage NHL patients elapsed/ ef acto to Rit an and chemothe aprelapsed/refractory to Rituxan and chemotherapy

– Most patients had stage III or IV mantle cell lymphoma (MCL) or follicular lymphoma (FL)

– Dose-dependent objective responses

– Clearance or reduction of tumor cells from tumor-infiltrated organs

• Phase 2 in ALL patients started early 2008


Phase 2 in ALL patients started early 2008

• Study Population

Blinatumomab Phase 1 Study

Study Population- Relapsed incurable NHL patients requiring treatment (MCL, FL, MZL, IC)

- Median of 3 previous therapies (87% pretreated with Rituximab, 47% with Fludarabine)with Fludarabine)

• Study Design- Conventional 3+3 dose escalation (0.5 to 60 µg/m2 per day were tested)

- Continuous infusion over a period of 4-8 weeks

- Mitigation of first infusion reactions by initial steroid coverage

• T A t• Tumor Assessment- Tumor responses assessed by Cheson criteria (centrally reviewed)

- Anti-tumor activity in bone marrow and liver assessed by histochemical


analysis of biopsies obtained before and after treatment

Safety and TolerabilityMost Frequent AE (irrespective of relationship)

All Events; Grade 3/4 Events; Adverse Event All Events; (%)

Grade 3/4 Events; (%)

Lymphopenia 68.4 68.4 Pyrexia 68.4 5.3

Leukopenia 57.9 23.7 CRP increased 52 6 34 2 CRP increased 52.6 34.2

Headache 39.5 2.6Chills 36.8 0

D dimer increased 36.8 13.2 Thrombocytopenia 36.8 13.2

Weight increased 36 8 0 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 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

© Micromet, Inc. 2008*Taken from Bargou et al., Science, 2008 & Poster at ICML meeting in Lugano, 2008

Hypokalaemia 26.3 5.3 Oedema peripheral 26.3 2.6 Weight decreased 26.3 0

Safety and TolerabilitySummary 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 • Some events are believed to be transient bystander effects (i.e., transiently elevated liver enzymes, margination of CD19-negative blood cells)

• S ti t h d CNS t i l di t i t f i • 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


All patients fully recovered without sequelae

• The majority of adverse events normalized under treatment

Rapid Depletion of B Lymphoma Cells

Peripheral B Cell Count Annexin V Expression on B Cells

© Micromet, Inc. 2008*Taken from Bargou et al., Science, 2008

ff hEffects on T LymphocytesProliferation Induced in Effector Memory T cells

Total CD4+ and CD8+ Counts Effects on CD8+ Subpopulations


Sh i k f T L iShrinkage of Tumor LesionsExample of a Patient with Complete Response

+ Blinatumomab

+ Blinatumomab

S

S


Dose-Dependent Objective ResponsesCheson Criteria - Confirmed by Independent Review

Dose levels Patients(n=38)

OverallResponses

CR* PR* ResponseRate

0.0005 – 0.005 mg/m2/24 h

12 0 0 0 0

0.015 & 0.030 19 4 2 2 21mg/m2/24 h

0.060 mg/m2/24 h

7 7 2 5 100

*CR: Complete Response*PR: Partial Response

g/ /


Clinical Activity in Mantle Cell LymphomaMCL patients (> 2nd Line) treated at Higher Doses

Dose levels Patients OverallResponses

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* l

g/ /

*PR: Partial Response

© Micromet, Inc. 2008*Taken from Bargou et al., Poster at ICML meeting in Lugano, 2008

Durable Remissions Observed (as of 06/08) Follow-up of Responding Patients

Pat. 102003 (CLL) (3 weeks, 15 µg)

3 Months 12 Months6 Months 9 MonthsDuration of Response

Pat. 102003 (CLL) (3 weeks, 15 µg)

3 Months 12 Months6 Months 9 MonthsDuration of Response

+

+

Pat. 109002 (FL) (8 weeks, 15 µg)

Pat. 105003 (FL) (8 weeks, 15 µg)

Pat. 109009 (MCL) (12 weeks, 30 µg)

P 109011 (MCL) (2 k 60 )

+

+

Pat. 109002 (FL) (8 weeks, 15 µg)

Pat. 105003 (FL) (8 weeks, 15 µg)

Pat. 109009 (MCL) (12 weeks, 30 µg)

P 109011 (MCL) (2 k 60 )

+

+Pat. 109011 (MCL) (2 weeks, 60 µg)

Pat. 109012 (MCL) (4 weeks, 60 µg)

Pat. 109013 (FL) (12 weeks, 60 µg)

Pat 109014 (FL) (8 weeks 60 µg) CR

+ Ongoing+

+

+

+Pat. 109011 (MCL) (2 weeks, 60 µg)

Pat. 109012 (MCL) (4 weeks, 60 µg)

Pat. 109013 (FL) (12 weeks, 60 µg)

Pat 109014 (FL) (8 weeks 60 µg) CR

+ Ongoing+

+

as of 06/08

+

+

Pat. 109014 (FL) (8 weeks, 60 µg)

Pat. 109015 (FL) (5 weeks, 60 µg)

Pat. 109017 (FL) (5 weeks, 60 µg)

Pat 109- 018 (FL) (8 weeks 60µg)

SD

PR

CR+

+

+

+

Pat. 109014 (FL) (8 weeks, 60 µg)

Pat. 109015 (FL) (5 weeks, 60 µg)

Pat. 109017 (FL) (5 weeks, 60 µg)

Pat 109- 018 (FL) (8 weeks 60µg)

SD

PR

CR+

+

© Micromet, Inc. 2008*Taken from Bargou et al., Poster at ICML meeting in Lugano, 2008

Pat. 109- 018 (FL) (8 weeks, 60µg) +Pat. 109- 018 (FL) (8 weeks, 60µg) +

Elimination of Lymphoma Cells in Bone Marrow

Blinatumomab

Tumor Cells: BlueT Cells: Brown

8 out of 9 patients had a bone marrow improvement

5 patients had complete bone marrow clearance


Elimination of Lymphoma Cells from Infiltrated Organs (Liver Parenchyma)

Blinatumomab

Tumor Cells: Brown

dl)

6

7200

Bil

iru

bin

(m

g/

d

U/

L A

P

1

2

3

4

5

6

50

100

150


00 5 10 15 20 25 30

Treatment Day

0

*Taken from Bargou et al., Poster at ICML meeting in Lugano, 2008

Summary of Phase 1 in Relapsed NHL

• D l l t t d f 0 0005 t 0 060 / 2 d • Dose levels tested from 0.0005 to 0.060 mg/m2 per day –study ongoing

• Safety• Safety– Majority of AEs have been fully reversible and in many cases resolved

without discontinuation of MT103 administration

– Most common AEs were lymphopenia pyrexia leukopenia and increase Most common AEs were lymphopenia, pyrexia, leukopenia, and increase of C-reactive protein

• Anti-tumor activity– Dose-dependent complete and partial responses observed in MCL, FL

and CLL patients

– Total doses of < 10mg sufficient to induce durable remissions


– Complete removal or reduction of tumor load in bone marrow and other infiltrated organs

Blinatumomab Summary

• Highly encouraging data on clinical activity in various B cell • Highly encouraging data on clinical activity in various B cell lymphomas

• Co-development with MedImmune Inc.– Shared development costs

– MITI retains all rights outside of North America

• Current clinical data suggests strong clinical activity in Current clinical data suggests strong clinical activity in established lesions and micrometastatic disease– Development plan covers both advanced and early disease settings

– Phase 2 in consolidation of MRD positive ALL – Phase 2 in consolidation of MRD-positive ALL

– Phase 1 in advanced NHL

• Commercial opportunity in most NHL indications, including


DLBCL, FL, MCL, CLL, ALL

Blinatumomab Outlook2008 and Beyond

• Update on blinatumomab activity in Q4/2008– Annual Meeting of the American Society of Hematology (ASH) on g y gy ( )

Dec 6-9, 2008 in San Francisco (abstracts submitted)

– Update on the response duration from the Phase 1 trial in NHL

Fi t d t f th i Ph 2 t i l i ALL (MRD tti )– First data from the ongoing Phase 2 trial in ALL (MRD setting)

• Expect the start of additional trials in 2009– Clinical activity observed in MCL patients strongly supports

accelerated development in this indication

– Opportunity in other indications (CLL, DLBCL, FL) is currently


pp y ( , , ) yunder investigation

mt103 science paper presentation final aug 18 2008...

Documents