........about TGN1412, a fully humanized CD28-SuperMAB®,

[Guest guest]

Drug Development

http://www.tegenero.com/research__development/drug_development/index.

php

TeGenero's CD28-SuperMAB® have been generated to therapeutically

balance the immune system in diseases associated with life-

threatening abnormalities in T lymphocyte number and function. The

company's most advanced product candidate TGN1412, a fully humanized

CD28-SuperMAB®, is far advanced in pre-clinical development. It has

shown exquisite and unique ex vivo and in vivo T lymphocyte

activating capacity and great therapeutic potential for a number of

autoimmune/inflammatory as well as oncological diseases.

Development of TGN1412 for the treatment of B-CLL

Despite clinical benefits from chemo-or monoclonal antibody therapy,

B-cell chronic lymphocytic leukaemia (B-CLL) is still an incurable

disease and the development of novel additional immunotherapies for

the treatment of B-CLL is highly requested by hemato-oncologists.

TGN1412 represents a novel class of immunomodulatory antibody and

has demonstrated the potential to be effective in the treatment of B-

CLL in pre-clinical trials.

Several features of this disease suggest that immune-based

strategies have therapeutic potential. Whereas the clinical course

of B-CLL often remains stable for years, the total leukemic cell

burden tends to expand at variable speed without any apparent

reaction of the immune system against the tumor. It has been shown

that this is related to an impaired T cell mediated immune response.

Despite expressing high levels of major histocompatibility complex

(MHC) class I and II molecules, CLL B-cells are ineffective antigen-

presenting cells (APC). Moreover, CLL B cells tend to be resistant

to activation-induced cell death, (apoptosis).

It has been shown by the Company that activated T cells can induce

CLL B-cells to become effective APCs, making these cells " visible

targets " for endogenous, tumor-antigen specific T cells. In

addition, TGN1412 has the potential to increase susceptibility of

CLL tumor cells to induction of apoptosis. In summary, TGN1412 is

seen as an attractive new immunotherapeutic approach that promises

to enhance both cell-mediated anti-tumor immunity and induction of

tumor-cell apoptosis.

Development for the treatment of rheumatoid arthritis

There is growing evidence that autoreactive T cells are involved in

the pathogenicity of chronic inflammatory diseases such as

rheumatoid arthritis (RA). RA is a debilitating, chronic

inflammatory disease of the joints that affects approx. 1% of the

population. Despite recent advancements with novel therapies such as

TNF-á-blockers aiming at neutralization of inflammatory mediators,

complete remission is rarely gained. Thus, there is still a high

medical need for efficacious and well-tolerated novel treatment

options in RA.

A pronounced T-cell activation and expansion mediated by CD28-

SuperMAB® in animal models is accompanied by the expression of anti-

inflammatory cytokines, like IL-10, rather than by the toxic

cytokine storm of pro-inflammatory mediators induced by other agents

that address the TCR complex. CD28-SuperMAB® over-proportionately

expand regulatory T cells, a specialized T-cell subset that

suppresses auto-aggressive T-cells present in the body and which has

only recently been appreciated as important guardians of immune

tolerance. Based on their functional potency in suppression of organ-

specific as well as systemic autoimmune diseases, regulatory T-cells

have been widely accepted as attractive targets for

immunotherapeutic intervention. However, attempts to expand and

activate this subset of CD4 T-cells in vivo and, ultimately, in

autoimmune/inflammatory diseases have been hampered so far by the

lack of therapeutic agents.

The pronounced regulatory T-cell expansion and induction of anti-

inflammatory cytokines by CD28-SuperMAB® are mechanistic

explanations for beneficial effects of CD28-SuperMAB® in animal

disease models for human autoimmune/inflammatory diseases. Multiple

preclinical results indicate that CD28-SuperMA® are capable of

inhibiting clinical signs, surrogate parameters and

pathophysiological characteristics of autoimmune/inflammatory

diseases in a well-tolerated fashion.

Thus, TGN1412 is a promising novel approach to addressing the

medical need in chronic autoimmune/inflammatory diseases, which

require long-term therapy without severe side effects.

[Guest guest]

Drug Development

http://www.tegenero.com/research__development/drug_development/index.

php

TeGenero's CD28-SuperMAB® have been generated to therapeutically

balance the immune system in diseases associated with life-

threatening abnormalities in T lymphocyte number and function. The

company's most advanced product candidate TGN1412, a fully humanized

CD28-SuperMAB®, is far advanced in pre-clinical development. It has

shown exquisite and unique ex vivo and in vivo T lymphocyte

activating capacity and great therapeutic potential for a number of

autoimmune/inflammatory as well as oncological diseases.

Development of TGN1412 for the treatment of B-CLL

Despite clinical benefits from chemo-or monoclonal antibody therapy,

B-cell chronic lymphocytic leukaemia (B-CLL) is still an incurable

disease and the development of novel additional immunotherapies for

the treatment of B-CLL is highly requested by hemato-oncologists.

TGN1412 represents a novel class of immunomodulatory antibody and

has demonstrated the potential to be effective in the treatment of B-

CLL in pre-clinical trials.

Several features of this disease suggest that immune-based

strategies have therapeutic potential. Whereas the clinical course

of B-CLL often remains stable for years, the total leukemic cell

burden tends to expand at variable speed without any apparent

reaction of the immune system against the tumor. It has been shown

that this is related to an impaired T cell mediated immune response.

Despite expressing high levels of major histocompatibility complex

(MHC) class I and II molecules, CLL B-cells are ineffective antigen-

presenting cells (APC). Moreover, CLL B cells tend to be resistant

to activation-induced cell death, (apoptosis).

It has been shown by the Company that activated T cells can induce

CLL B-cells to become effective APCs, making these cells " visible

targets " for endogenous, tumor-antigen specific T cells. In

addition, TGN1412 has the potential to increase susceptibility of

CLL tumor cells to induction of apoptosis. In summary, TGN1412 is

seen as an attractive new immunotherapeutic approach that promises

to enhance both cell-mediated anti-tumor immunity and induction of

tumor-cell apoptosis.

Development for the treatment of rheumatoid arthritis

There is growing evidence that autoreactive T cells are involved in

the pathogenicity of chronic inflammatory diseases such as

rheumatoid arthritis (RA). RA is a debilitating, chronic

inflammatory disease of the joints that affects approx. 1% of the

population. Despite recent advancements with novel therapies such as

TNF-á-blockers aiming at neutralization of inflammatory mediators,

complete remission is rarely gained. Thus, there is still a high

medical need for efficacious and well-tolerated novel treatment

options in RA.

A pronounced T-cell activation and expansion mediated by CD28-

SuperMAB® in animal models is accompanied by the expression of anti-

inflammatory cytokines, like IL-10, rather than by the toxic

cytokine storm of pro-inflammatory mediators induced by other agents

that address the TCR complex. CD28-SuperMAB® over-proportionately

expand regulatory T cells, a specialized T-cell subset that

suppresses auto-aggressive T-cells present in the body and which has

only recently been appreciated as important guardians of immune

tolerance. Based on their functional potency in suppression of organ-

specific as well as systemic autoimmune diseases, regulatory T-cells

have been widely accepted as attractive targets for

immunotherapeutic intervention. However, attempts to expand and

activate this subset of CD4 T-cells in vivo and, ultimately, in

autoimmune/inflammatory diseases have been hampered so far by the

lack of therapeutic agents.

The pronounced regulatory T-cell expansion and induction of anti-

inflammatory cytokines by CD28-SuperMAB® are mechanistic

explanations for beneficial effects of CD28-SuperMAB® in animal

disease models for human autoimmune/inflammatory diseases. Multiple

preclinical results indicate that CD28-SuperMA® are capable of

inhibiting clinical signs, surrogate parameters and

pathophysiological characteristics of autoimmune/inflammatory

diseases in a well-tolerated fashion.

Thus, TGN1412 is a promising novel approach to addressing the

medical need in chronic autoimmune/inflammatory diseases, which

require long-term therapy without severe side effects.

[Guest guest]

Drug Development

http://www.tegenero.com/research__development/drug_development/index.

php

TeGenero's CD28-SuperMAB® have been generated to therapeutically

balance the immune system in diseases associated with life-

threatening abnormalities in T lymphocyte number and function. The

company's most advanced product candidate TGN1412, a fully humanized

CD28-SuperMAB®, is far advanced in pre-clinical development. It has

shown exquisite and unique ex vivo and in vivo T lymphocyte

activating capacity and great therapeutic potential for a number of

autoimmune/inflammatory as well as oncological diseases.

Development of TGN1412 for the treatment of B-CLL

Despite clinical benefits from chemo-or monoclonal antibody therapy,

B-cell chronic lymphocytic leukaemia (B-CLL) is still an incurable

disease and the development of novel additional immunotherapies for

the treatment of B-CLL is highly requested by hemato-oncologists.

TGN1412 represents a novel class of immunomodulatory antibody and

has demonstrated the potential to be effective in the treatment of B-

CLL in pre-clinical trials.

Several features of this disease suggest that immune-based

strategies have therapeutic potential. Whereas the clinical course

of B-CLL often remains stable for years, the total leukemic cell

burden tends to expand at variable speed without any apparent

reaction of the immune system against the tumor. It has been shown

that this is related to an impaired T cell mediated immune response.

Despite expressing high levels of major histocompatibility complex

(MHC) class I and II molecules, CLL B-cells are ineffective antigen-

presenting cells (APC). Moreover, CLL B cells tend to be resistant

to activation-induced cell death, (apoptosis).

It has been shown by the Company that activated T cells can induce

CLL B-cells to become effective APCs, making these cells " visible

targets " for endogenous, tumor-antigen specific T cells. In

addition, TGN1412 has the potential to increase susceptibility of

CLL tumor cells to induction of apoptosis. In summary, TGN1412 is

seen as an attractive new immunotherapeutic approach that promises

to enhance both cell-mediated anti-tumor immunity and induction of

tumor-cell apoptosis.

Development for the treatment of rheumatoid arthritis

There is growing evidence that autoreactive T cells are involved in

the pathogenicity of chronic inflammatory diseases such as

rheumatoid arthritis (RA). RA is a debilitating, chronic

inflammatory disease of the joints that affects approx. 1% of the

population. Despite recent advancements with novel therapies such as

TNF-á-blockers aiming at neutralization of inflammatory mediators,

complete remission is rarely gained. Thus, there is still a high

medical need for efficacious and well-tolerated novel treatment

options in RA.

A pronounced T-cell activation and expansion mediated by CD28-

SuperMAB® in animal models is accompanied by the expression of anti-

inflammatory cytokines, like IL-10, rather than by the toxic

cytokine storm of pro-inflammatory mediators induced by other agents

that address the TCR complex. CD28-SuperMAB® over-proportionately

expand regulatory T cells, a specialized T-cell subset that

suppresses auto-aggressive T-cells present in the body and which has

only recently been appreciated as important guardians of immune

tolerance. Based on their functional potency in suppression of organ-

specific as well as systemic autoimmune diseases, regulatory T-cells

have been widely accepted as attractive targets for

immunotherapeutic intervention. However, attempts to expand and

activate this subset of CD4 T-cells in vivo and, ultimately, in

autoimmune/inflammatory diseases have been hampered so far by the

lack of therapeutic agents.

The pronounced regulatory T-cell expansion and induction of anti-

inflammatory cytokines by CD28-SuperMAB® are mechanistic

explanations for beneficial effects of CD28-SuperMAB® in animal

disease models for human autoimmune/inflammatory diseases. Multiple

preclinical results indicate that CD28-SuperMA® are capable of

inhibiting clinical signs, surrogate parameters and

pathophysiological characteristics of autoimmune/inflammatory

diseases in a well-tolerated fashion.

Thus, TGN1412 is a promising novel approach to addressing the

medical need in chronic autoimmune/inflammatory diseases, which

require long-term therapy without severe side effects.

[Guest guest]

Drug Development

http://www.tegenero.com/research__development/drug_development/index.

php

TeGenero's CD28-SuperMAB® have been generated to therapeutically

balance the immune system in diseases associated with life-

threatening abnormalities in T lymphocyte number and function. The

company's most advanced product candidate TGN1412, a fully humanized

CD28-SuperMAB®, is far advanced in pre-clinical development. It has

shown exquisite and unique ex vivo and in vivo T lymphocyte

activating capacity and great therapeutic potential for a number of

autoimmune/inflammatory as well as oncological diseases.

Development of TGN1412 for the treatment of B-CLL

Despite clinical benefits from chemo-or monoclonal antibody therapy,

B-cell chronic lymphocytic leukaemia (B-CLL) is still an incurable

disease and the development of novel additional immunotherapies for

the treatment of B-CLL is highly requested by hemato-oncologists.

TGN1412 represents a novel class of immunomodulatory antibody and

has demonstrated the potential to be effective in the treatment of B-

CLL in pre-clinical trials.

Several features of this disease suggest that immune-based

strategies have therapeutic potential. Whereas the clinical course

of B-CLL often remains stable for years, the total leukemic cell

burden tends to expand at variable speed without any apparent

reaction of the immune system against the tumor. It has been shown

that this is related to an impaired T cell mediated immune response.

Despite expressing high levels of major histocompatibility complex

(MHC) class I and II molecules, CLL B-cells are ineffective antigen-

presenting cells (APC). Moreover, CLL B cells tend to be resistant

to activation-induced cell death, (apoptosis).

It has been shown by the Company that activated T cells can induce

CLL B-cells to become effective APCs, making these cells " visible

targets " for endogenous, tumor-antigen specific T cells. In

addition, TGN1412 has the potential to increase susceptibility of

CLL tumor cells to induction of apoptosis. In summary, TGN1412 is

seen as an attractive new immunotherapeutic approach that promises

to enhance both cell-mediated anti-tumor immunity and induction of

tumor-cell apoptosis.

Development for the treatment of rheumatoid arthritis

There is growing evidence that autoreactive T cells are involved in

the pathogenicity of chronic inflammatory diseases such as

rheumatoid arthritis (RA). RA is a debilitating, chronic

inflammatory disease of the joints that affects approx. 1% of the

population. Despite recent advancements with novel therapies such as

TNF-á-blockers aiming at neutralization of inflammatory mediators,

complete remission is rarely gained. Thus, there is still a high

medical need for efficacious and well-tolerated novel treatment

options in RA.

A pronounced T-cell activation and expansion mediated by CD28-

SuperMAB® in animal models is accompanied by the expression of anti-

inflammatory cytokines, like IL-10, rather than by the toxic

cytokine storm of pro-inflammatory mediators induced by other agents

that address the TCR complex. CD28-SuperMAB® over-proportionately

expand regulatory T cells, a specialized T-cell subset that

suppresses auto-aggressive T-cells present in the body and which has

only recently been appreciated as important guardians of immune

tolerance. Based on their functional potency in suppression of organ-

specific as well as systemic autoimmune diseases, regulatory T-cells

have been widely accepted as attractive targets for

immunotherapeutic intervention. However, attempts to expand and

activate this subset of CD4 T-cells in vivo and, ultimately, in

autoimmune/inflammatory diseases have been hampered so far by the

lack of therapeutic agents.

The pronounced regulatory T-cell expansion and induction of anti-

inflammatory cytokines by CD28-SuperMAB® are mechanistic

explanations for beneficial effects of CD28-SuperMAB® in animal

disease models for human autoimmune/inflammatory diseases. Multiple

preclinical results indicate that CD28-SuperMA® are capable of

inhibiting clinical signs, surrogate parameters and

pathophysiological characteristics of autoimmune/inflammatory

diseases in a well-tolerated fashion.

Thus, TGN1412 is a promising novel approach to addressing the

medical need in chronic autoimmune/inflammatory diseases, which

require long-term therapy without severe side effects.