Gyre Therapeutics 8K Other Events | GYRE 4 Apr 11

ICOSR, April 2011

The Alpha7 Nicotinic Receptor Agonist TC-5619

had Beneficial Effects with Favorable

Tolerability in a Phase 2 Trial in Cognitive

Dysfunction in Schizophrenia

G Dunbar, D Hosford, JA Lieberman, A Segreti

Exhibit 99.1

This

presentation

includes

“forward-looking

statements”

made

under

the

provisions

the

Private

Securities

Litigation

Reform

Act of 1995. Forward-looking statements include statements that are not purely historical in nature regarding, without

limitation: any future development of TC-5619, including the indication(s) for which TC-5619 may be developed; the

commercial opportunity in any particular indication; the benefits that may be derived from TC-5619; the competitive position of

TC-5619; the timing for a decision by AstraZeneca as to whether to license TC-5619; or Targacept's plans, expectations,

objectives,

prospects

future

operations,

financial

position,

revenues,

costs

expenses.

The

words

“may,”

“will,”

“could,”

“would,”

“should,”

“expect,”

“intend,”

“plan,”

“anticipate,”

“believe,”

“estimate,”

“predict,”

“project,”

“forecast,”

“potential,”

“continue,”

“ongoing,”

“scheduled”

and similar expressions are intended to identify forward-looking statements. Actual results,

performance or experience may differ materially from those expressed or implied by any forward-looking statement as a result

of various important factors, including, without limitation, risks and uncertainties relating to: whether any future clinical trials of

TC-5619

that

may

conducted

will

sufficient

obtain

approval

for

cognitive

dysfunction

schizophrenia,

residual

phase

schizophrenia

any

other

indication;

the

timing

and

success

submission,

acceptance

and

approval

regulatory

filings;

AstraZeneca’s discretion in determining whether to license TC-5619; whether a filing under the Hart-Scott-Rodino Antitrust

Improvements

Act

will

required

connection

with

any

license

TC-5619

AstraZeneca

and,

so,

whether

all

required

clearances

will

obtained;

and

the

risks

and

uncertainties

described

greater

detail

under

the

heading

“Risk

Factors”

Targacept's most recent Annual Report on Form 10-K and in other filings that Targacept makes with the Securities and

Exchange Commission. As a result of the risks and uncertainties, the results or events indicated by the forward-looking

statements may not occur. In addition, any market or industry statistics contained in this presentation are based on

information available to Targacept that it believes to be reliable but has not independently verified.

All forward-looking statements included in this presentation speak only as of the date the presentation is made and should not

be relied upon as representing Targacept's views as of any date after the presentation is made. Targacept specifically

disclaims any obligation to update any forward-looking statement, except as required by applicable law.

Cautionary Note re:

Forward-Looking Statements

Significant Unmet Medical Need:

“Residual Phase Schizophrenia”

Cognitive

Dysfunction

(CDS)

Negative

Symptoms

Dr. Tom Laughren has suggested the term “residual phase

schizophrenia”

encompass

both

CDS

and

negative

symptoms.

Current antipsychotics have little effect against cognitive

dysfunction or negative symptoms.

These residual symptoms are a large unmet medical need.

Laughren and Levin 2011. Schiz Bull. doi:10.1093/schbul/sbq162

TC-5619:

A Selective Alpha7 NNR Modulator

Promising preclinical results

Complete profile with repeat tox, genotox, reprotox, safety

pharmacology

Beneficial effects in preclinical models of memory and of sensory

gating (schizophrenia)

Completed single and multiple ascending dose studies

Maximum tolerated dose between 406mg and 609mg (free base)

No clustering of AE signals through 406mg

Positive signal in Power of Attention measured at 6.8mg

Half-life 20-24 hrs

Phase 2 study objectives to assess the efficacy, safety and

tolerability of TC-5619 as augmentation therapy to quetiapine or

risperidone to improve cognition in stable outpatients with

schizophrenia

Key Inclusion/Exclusion Criteria

Male or female subjects ages 18 –

60 years

Stable outpatients with DSM-IV criteria for schizophrenia

Lack of psychiatric hospitalization for 2 months before Screening

On unchanged dose of quetiapine or risperidone for 2 months before

Screening

Score </= 4 on PANSS items of delusions, hallucinations, conceptual

disorganization, unusual thought content at Screening and at Baseline

No other co-morbid Axis 1 or Axis 2 psychiatric disorder

No unstable medical disorder

Clinical Trial Design

Subjects enrolled at sites in India (12) and US (7)

Goal to enroll approximately 200 subjects with 120 to

complete

2 treatment cohorts

TC-5619 (1mg, 5mg, 25mg each for 4 weeks)

Placebo

Primary Outcome Measure: Change from Baseline (Day 1) in

Groton

Maze

Learning

(GML)

test

score

function

treatment over 3 time points (Weeks 4, 8 and 12)

Pre-defined success: p < 0.10 (one-tailed) against the 3 time points

(Weeks 4, 8 and 12) using the Hochberg adjustment for multiplicity

Target for each cohort:

50% tobacco-users &

50% non-users

Clinical Trial Schematic

(F/U)

-4

TC-5619

1 mg

GML of CSB

CSB

Composite

SANS

CGI-I

CGI-S

SGI-Cog

Day 1

TC-5619

5 mg

TC-5619

25 mg

Placebo + quetiapine or risperidone

Screening

WEEK

TC-5619 + quetiapine or risperidone

Demographics of Randomized Subjects

(N=185)

Placebo: n (%)

TC-5619: n (%)

Variable

91 (49%)

94 (51%)

Age

36.3 yrs

Gender

Male

63 (69%)

65 (69%)

Female

28 (31%)

29 (31%)

Race

Asian

60 (66%)

61 (65%)

African-American

25 (28%)

26 (28%)

Hispanic / Latino

2 (2%)

1 (1%)

Caucasian

4 (4%)

6 (6%)

Tobacco status

User

41 (45%)

45 (48%)

Non-user

50 (55%)

49 (52%)

BMI

24.9

25.0

Completed HS or above

60 (66%)

62 (66%)

Disposition of Subjects

Subjects Screened

N = 242

Randomized Placebo

N = 91

Randomized TC-5619

N = 94

Screen-Failed

N = 57

Discontinued

N = 13

Completed

N = 78 (86%)

Completed

N = 76 (81%)

Discontinued

N = 18

Reasons for placebo discontinuation

•

Adverse event: n = 3

•

Consent withdrawn: n = 2

•

Positive illicit drug screen: n = 1

•

Non-compliance: n = 3

•

Lost to follow-up: n = 2

•

Other: n = 2

Reasons for TC-5619 discontinuation

•

Adverse event: n = 4

•

Consent withdrawn: n = 7

•

Positive illicit drug screen: n = 3

•

Non-compliance: n = 0

•

Lost to follow-up: n = 3

•

Other: n = 1

TC-5619: Generally Well Tolerated -

Most Common Adverse Events

Adverse Event

(preferred term)

Placebo: Subject N (%)

TC-5619: Subject N (%)

Constipation

2 (2%)

4 (4%)

Nausea

5 (5%)

(4 mild, 1 moderate)

Body temperature

increased

2 (2%)

3 (3%)

Decreased appetite

5 (5%)

4 (4%)

Somnolence

2 (2%)

3 (3%)

Schizophrenia

3 (3%)

Headache

2 (2%)

3 (3%)

Insomnia

3 (3%)

No Clinically Meaningful Changes or

Cohort Differences in Other Safety Measures

Both SAEs were deemed by the investigator to be unrelated to study drug:

gastritis (placebo); and acute exacerbation of schizophrenia (TC-5619)

several weeks after a subject stopped taking quetiapine

AEs

leading

discontinuation

(all

deemed

the

investigator

unrelated to study drug ): 3 in placebo cohort and 4 in TC-5619 cohort

Physical exam, vital signs, clinical chemistry, hematology or urinalysis

assessments unchanged from baseline

There were no abnormal involuntary movements as a function of

treatment, assessed by AIMS

QTcF unchanged within and between cohorts after dosing began

No evidence of suicidality after treatment began as assessed by the

Columbia Suicide Severity Rating Scale

No signs of depression after treatment began as assessed by the Calgary

Depression Scale for Schizophrenia

Primary Outcome Measure: Groton Maze

Learning (GML)

All Patients

GML (Total Error) LOG

Visit

Treatment

Adjusted

Mean

Standard Error of

Adjusted Mean

Mean Difference ±

SE between

TC-5619 and Placebo

(Placebo-TC5619)

One-sided 90%

Confidence Interval

for

Mean Difference

One-sided P-

Value

Week 1

Placebo

-0.02

0.01

TC-5619

-0.01

0.01

-0.01 ±

0.02

(-0.03

)

0.6709

Week 4

Placebo

0.02

TC-5619

-0.03

0.02

0.05 ±

0.02

(0.02

)

0.0180

Week 8

Placebo

-0.02

0.02

TC-5619

-0.05

0.02

0.02 ±

0.02

(-0.00

)

0.1308

Week12

Placebo

-0.02

0.02

TC-5619

-0.06

0.02

0.04 ±

0.02

(0.01

)

0.0405

Primary outcome measure, log (10) transformed due to skew, is statistically

significant based on Hochberg adjustment for 3 comparisons (at Weeks 4, 8 and

12; one-sided p = 0.054)

CDS

0.8523

0.0143

0.0858

0.0016

Tobacco

users

Secondary Outcome Measure:

Negative Symptoms

TEST

WEEK 4

WEEK 8

WEEK 12

SANS:

ALL SUBJECTS

0.255

0.118

0.015

SANS:

TOBACCO USERS

0.098

0.054

0.033

One-tailed p-values

This effect on the SANS was driven by statistically significant

scores on 3 of 5 items:

Anhedonia

Avolition / Apathy

Affect

Negative

Symptoms

Secondary Outcome Measures:

Clinical and Subject Global Impressions

TEST

WEEK 4

WEEK 8

WEEK 12

CGI-I

ALL SUBJECTS

TOBACCO USERS

0.049

0.047

0.253

0.075

0.150

0.189

SGI-COG

ALL SUBJECTS

TOBACCO USERS

0.428

0.607

0.491

0.313

0.046

0.109

CGI-S

ALL SUBJECTS

TOBACCO USERS

0.674

0.434

0.544

0.224

0.450

0.307

One-tailed p-values

CogState Item Scores

TEST

WEEK 4

WEEK 8

WEEK 12

Composite score *

0.838

0.821

0.326

[0.098, tobacco users]

Detection *

(psychomotor processing)

0.693

0.650

0.567

[0.265, tobacco users]

Identification *

(attention)

0.311

0.111

0.063

[0.057, tobacco users]

Card Learning *

(visual learning)

0.660

0.899

0.841

[0.338, tobacco users]

1-Back *

(working memory)

0.691

0.647

0.042

[0.020, tobacco users]

Int’l Shopping List

(verbal memory)

0.970

0.813

0.177

[0.027, tobacco users]

Social-Emotional Cognition *

0.259

0.217

0.546

[0.752, tobacco users]

One-tailed p-values

*Analyzed in dataset meeting integrity criteria predefined by CogState

Summary of Results

Statistically significant results favoring TC-5619 on:

GML

primary outcome measure

executive function (objective measure)

SANS, CGI-I and SGI-Cog

secondary outcome measures

negative

symptoms

Week

12,

and

global

improvement

Week

(clinician measures)

global cognitive improvement -

Week 12 (subject measure)

Other CogState outcome measures

attention

and

working

memory

Week

(objective

measures)

These results were driven by tobacco users and often better in the

TC-5619 was generally well tolerated, without any clinically

noteworthy changes in physical examination, vital signs, ECG,

laboratory findings, or suicidality

Conclusion and Opportunity

Cognitive

Dysfunction

(CDS)

Negative

Symptoms

TC-5619 represents a novel mechanism with unique

potential to treat “residual phase schizophrenia”:

Cognitive dysfunction

Negative symptoms

ICOSR, April 2011

The Alpha7 Nicotinic Receptor Agonist TC-5619

had Beneficial Effects with Favorable

Tolerability in a Phase 2 Trial in Cognitive

Dysfunction in Schizophrenia

G Dunbar, D Hosford, JA Lieberman, A Segreti

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