Year: 2015

TC-5619 Cli ical Devel pment

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Overview

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SEC Filli gs Status

Amount

Amount

Targacept entered into collaborative research and license agreement with AstraZeneca AB.

Notice served by Targacept under agreement offering AstraZeneca the right to license its product candidate TC-5619 for specified conditions characterized by cognitive impairment.

DECEMBER 2005

Targacept started focusing on Cognitive disorders. JANUARY 2006

OCTOBER 2007

ASTRAZENECA AB

Amount $ 2,000,000 As Revenue

TARGACEPT Inc.

In accordance with a mutually acceptable development plan, Targacept agreed to develop TC-5619 independently through the completion of Phase I and Phase II proof of concept clinical trial.

Amendment to cognitive disorders agreement with AstraZeneca AB APRIL 2010

ASTRAZENECA AB

$ 11,000,000 Deferred Revenue

TARGACEPT Inc.

ASTRAZENECA AB

Amount $ 2,000,000 Deferred Revenue

TARGACEPT Inc.

Targacept recognized all payment amounting $11,000,000 from AstraZeneca as Revenue. JUNE 2011

ASTRAZENECA AB

$ 11,000,000 Deferred Revenue

TARGACEPT Inc.

ASTRAZENECA AB

Amount $ 2,000,000 Deferred Revenue

TARGACEPT Inc.

Under the agreement, AstraZeneca had an option for an exclusive license to TC-5619 for various cog-nitive disorders. In late April 2011, the Company received notice from AstraZeneca that it had deter-mined not to exercise its license option.

Precli ical i for aio

urement and Treatment Research to Improve Cognition in Schizo-phrenia, or MATRICS initiative of 46 cognitive neuroscientists and neuro pharmacologists have indi-cated alpha7 NNR and cognitive functions are closely associated and compounds that selectively target the alpha7 NNR may have application in the treatment of conditions such as schizophrenia,

cognitive impairment and in-flammation.

TC-5619 is a compound that selectively act on the alpha7 NNR, being developed for the treatment of conditions charac-terized by cognitive impairment such as Schizophrenia, Alzhei-mer's disease etc. A number of published studies and a survey conducted in connection with National Institute of Mental Health initiative known as Meas-

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Mechanism of Action Modulation of activity of the alpha7 NNR

Selective Target alpha7 NNR

Therapeutic Area of

Focus

Schizophrenia, cognitive impairment or

inflammation

Target Indication (s) Conditions characterized by cognitive im-

pairment such as Schizophrenia, Alzhei-

mer's disease etc.

Route of Administra-

tion

Oral

TC- 19 JOURNEY SO FAR...

JULY 2007

APRIL 2011

SINGLE RISING DOSE STUDY

SEQUENTIAL MULTIPLE ASCENDING DOSE STUDY

MULTIPLE RISING DOSE STUDY

SCHIZOPHRENIA

ATTENTION DEFICIT HYPERACTIVE DISORDER

SCHIZOPHRENIA

ALZHEIMER’S DISEASE

ATTENTION DEFICIT HYPERACTIVE DISORDER

PHASE I

PHASE II

TC-5619

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August 8, 2008 Targacept, Inc

FORM 10-Q, For the quarterly period ended June 30, 2007 (Pg 14)

…TC-5619. TC-5619 is a preclinical product candidate that modulates the a7 NNR for which we are currently

conducting a Phase I single rising dose clinical trial. We believe compounds that selectively target the a7 NNR may

have application in the treatment of conditions such as schizophrenia, cognitive impairment and inflammation…

(Pg 15)

…We also announced in July 2007 our initiation of a Phase I clinical trial of TC-5619. The trial is a double blind,

placebo controlled study with single escalating doses administered orally to healthy volunteers. The trial, which is

being conducted in France, is designed to evaluate the safety and tolerability of TC-5619 and to assess its

pharmacokinetic profile…

ASSIGNED TREATMENT: In a single rising dose trial, each subject in a dose group receives a single

dose of the agent being evaluated, with subjects in each subsequent dose group receiving a pre-determined

higher dosage than subjects in the preceding dose group .

May 8, 2008 Targacept, Inc

FORM 10-Q, For the quarterly period ended March 31, 2008

(pg17)

… We have completed a Phase 1 single rising dose clinical trial of TC-5619 and plan to initiate a Phase 1 multiple

rising dose clinical trial of TC-5619 in the third quarter of 2008…

STUDY TITLE: Phase 1 multiple rising dose clinical trial of TC-5619 in healthy volunteers STUDY ID: TC-238-CLP-002

PHASE: I

INITIATION: JULY 2008

COMPLETION: MAY 2008 ACCRUAL: NA

INDICATION: Schizophre ia, Cog iive I pair e t or I la aio

PATIENT SEGMENT: Healthy

STATUS: COMPLETED

OBJECTIVES: To evaluate the safety and tolerability of TC-5619. To assess the pharmacokinetic profile of TC-5619.

ASSIGNED TREATMENT: In a multiple rising dose clinical trial, each subject in a dose group receives a dosage of the agent being evaluated multiple times, with subjects in each subsequent dose group receiving a pre-determined higher dosage than subjects in the preceding dose group.

STUDY TITLE: Double blind, placebo controlled, Phase I study of TC-5619 with single escalating doses

administered orally to healthy volunteers

STUDY ID: NA

PHASE: I

INITIATION: JULY 2007

COMPLETION: MAY 2008 ACCRUAL: NA

INDICATION: Schizophrenia, Cognitive Impairment or

Inflammation PATIENT SEGMENT: Healthy

STATUS: COMPLETED

OBJECTIVES: To evaluate the safety and tolerability of TC-5619. To assess the pharmacokinetic profile of TC-5619.

SINGLE RISING DOSE

STUDY

MULTIPLE RISING

DOSE STUDY

November 6, 2008

Targacept, Inc Form 8-K

…Completed dosing in a Phase 1 multiple rising dose clinical trial of TC-5619, a

highly-selective alpha7 NNR-targeted

product candidate planned for develop-

ment for cognitive dysfunction in schizo-

phrenia and potentially one or more oth-

er conditions characterized by cognitive

impairment…

LOCATION: FRANCE

LOCATION: UNITED STATES

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RESULTS: In the trial, the results on the Groton Maze Learning task met the pre-defined success criteria (adjusted p-value = 0.054), as well as at two of the trial’s

three measurement dates (at 4 weeks, unadjusted p-value = 0.018; and at 12 weeks, unadjusted p-value = 0.041), and were favorable for tobacco users as compared to

non-tobacco users and for subjects at study sites in the United States as compared to subjects at study sites in India. There was no activity in non-tobacco users. Estimates

of the prevalence of smoking amongst schizophrenia patients vary, with one study indicating as high as 80%. Each of the p-values noted above was derived after data log

transformation, a commonly utilized technique where the data does not follow a normal distribution. In addition, positive signals were observed in the trial on several sec-

ondary efficacy outcome measures, including Scale for Assessment of Negative Symptoms, an investigator assessment of improvement on the negative symptoms of schizo-

phrenia, Clinical Global Impression – Global Improvement, an investigator assessment of overall response, and Subject Global Impression – Cognition scale, a patient self-

assessment of cognitive change. Other secondary outcome measures of the trial, including a composite measure of the CogState Schizophrenia Battery, did not demon-

strate a drug effect in the dataset that included all subjects. TC-5619 exhibited a favorable tolerability profile in the trial. There were two serious adverse events in the trial, one in the placebo dose group and one in the TC-5619 dose group. Both were considered by the applicable investigator as not drug related.

PRIMARY OUTCOME: Measure of the trial is change from baseline on the Groton Maze Learning item of the Cog State Schizophrenia Test Battery, a computerized battery of neuropsychi-atric tests that assess specific cognitive domains, on each of three measurement dates as compared to placebo.

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STUDY TITLE: Two-Part, Sequential Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TC-5619-238 in Elderly Subjects With and Without Alzheimer's Disease.

STUDY ID: TC-5619-238-CLP-003, NCT01254448

PHASE: I INITIATION:

SEP-2010 COMPLETION:

MAR-2011 ACCRUAL: 38

INDICATION: Alzheimer’s Disease

PATIENT

SEGMENT: Elderly Subjects With and Without Alzheimer's Disease

STATUS: COMPLETED

OBJECTIVE: To examine the safety, tolerability and pharmacokinetics of TC-5619 in elderly

subjects with and without Alzheimer's disease

November 6, 2009 Targacept, Inc FORM 10-Q, For the quarterly period ended September 30, 2009 (pg17)

... We have completed a Phase 1 single rising dose clinical trial and a Phase 1

multiple rising dose clinical trial of TC-5619 in healthy volunteers. We expect to

initiate a Phase 2 clinical proof of concept trial of TC-5619 in cognitive dysfunction

in schizophrenia in the fourth quarter of 2009. Following completion of the

planned Phase 2 trial, AstraZeneca has the right to license TC-5619 on terms

specified in our agreement.

May 10, 2010 Targacept, Inc FORM 10-Q, For the quarterly period ended March 31, 2010 (pg17-18) …As part of the expanded TC-5619 development program, the Company has agreed to conduct a Phase 2 clinical proof of con-cept trial in adults with ADHD in addition to its ongoing Phase 2

clinical proof of concept trial in cognitive dysfunction in schizo-phrenia, or CDS. (pg20) TC-5619. TC-5619 is a novel small molecule that modulates the activity of the a7 NNR. We initiated a Phase 2 clinical trial of TC-5619 in cognitive dysfunction in schizophrenia, or CDS, in the fourth quarter of 2009 pursuant to a development plan that we agreed upon with AstraZeneca. (pg21) Under our 2005 agreement with AstraZeneca: ...we are responsible for conducting and funding the ongoing Phase 2 clinical trial of TC-5619 in CDS, the planned Phase 2 clini-cal trial of TC-5619 in adults with ADHD and planned specified clinical and non-clinical studies to support the potential advance-ment of TC-5619 into Phase 2 clinical development for Alzheimer’s disease, and AstraZeneca is responsible for conducting and fund-ing other specified non-clinical studies to support the potential advancement of TC-5619 into Phase 2 clinical development for Alzheimer’s disease...

STUDY ID: TC-5619-238-CRD-001, PRO-05619-CRD-001 , NCT01003379

STATUS: COMPLETED

INDICATION: Schizophrenia

COMPLETION: JAN-2011

INITIATION: MAY-2010

PHASE: II

LOCATION: UNITED STATES(7),

INDIA (12)

ACCRUAL: 200 (Planned) 184 (Actual)

STUDY TITLE: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Fixed Dose Study to Assess Efficacy, Safety, and

Tolerability of TC-5619 as Augmentation Therapy to Improve Cognition in Outpatients With Cognitive Dysfunction in Schizophrenia.

PATIENT SEGMENT: Outpatients With Cognitive Dys-function

TRIAL DESIGN & TREATMENT ASSIGNMENT : Double Blind, Placebo Controlled, Randomized, Parallel Group Study Subjects are were randomly assigned to receive either TC-5619 or placebo, together with continued treatment with the atypical anti-psychotic, for 12 weeks. As planned, approximately half of the subjects were users of tobacco products. Subjects who received TC-5619 received a 1mg daily dose for the first four weeks, a 5mg daily dose for the next four weeks and a 25mg daily dose for the last four weeks.

INCLUSION CRITERIA: Subjects meeting DSM-IV criteria for schizophrenia, with stable psychotic symptoms and taking a stable dose of an approved medication from the drug class known as atypical anti-psychotics (either quetiapine, marketed as Seroquel, or risperidone, marketed as Risperdal)

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May 10, 2010 Targacept, Inc

FORM 10-Q, For the quarterly period ended March 31, 2010 (pg17-18) …As part of the expanded TC-5619 development program, the Company has agreed to conduct a Phase 2 clinical proof of concept trial in adults with ADHD in addition to its ongoing Phase 2 clinical proof of concept trial in cognitive dysfunction in schizophrenia, or CDS… (pg20) ... As part of an April 2010 amendment to our 2005 agreement with AstraZeneca, we have also agreed to conduct a Phase 2 clinical proof of concept trial of TC-5619 in adults with ADHD and we and AstraZeneca have each agreed to conduct specified studies to support the potential advancement of TC-5619 into Phase 2 clinical development for Alzheimer’s disease… (pg21) Under our 2005 agreement with AstraZeneca: ...we are responsible for conducting and funding the ongoing Phase 2 clinical trial of TC-5619 in CDS, the planned Phase 2 clinical trial of TC-5619 in adults with ADHD...

STUDY DESIGN & TREATMENT:

Double blind, placebo controlled, forced titration, multi-center, 12-week study Adult subjects are randomly assigned to one of two cohorts, TC-5619 or placebo, and dosed over a 12-week period. Subjects in the

TC-5619 cohort receive 1mg doses of TC-5619 for the first four weeks, 5mg doses of TC-5619 for the next four weeks and 25mg

doses of TC-5619 for the last four weeks.

RESULTS: TC-5619 did not meet the primary outcome

measure of the trial, but showed encouraging signals on some of the trial’s efficacy measures in the subpopulation of subjects with ADHDi.

August 9, 2011

Targacept, Inc. FORM 10-Q, For the quarterly period ended June 30, 2011

...Preparations for a planned Phase 2b clinical trial of TC-5619 as a

treatment for negative symptoms and cognitive dysfunction in schizo-phrenia, as well as potential additional development in either or both

of Alzheimer’s disease and ADHD, are ongoing...

PRIMARY OUTCOME MEASURE: Change from

baseline on the inattention subscale of the Conners’ Adult ADHD Rating Scale—Investigator-Rated, or CAARS-INV, after

four weeks of treatment with TC-5619 as compared to

placebo.

May 9, 2011

Targacept, Inc FORM 10-Q, For the quarterly period ended March 31,

2011 (pg16)

...The Company has completed two Phase 2 clinical proof of concept

trials, one in cognitive dysfunction in schizophrenia and one in adults

with ADHD...

STUDY TITLE: A Double-blind, Randomized, Placebo-controlled, Multicenter, Fixed Dose Titration Study to Assess Efficacy, Safety,

and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)

STUDY ID: TC-5619-238-CRD-002, PRO-05619-CRD-002, NCT01124708

ACCRUAL: 135

INDICATION: Attention Deficit Hyperactivity Disorder (ADHD) PATIENT SEGMENT: Non-tobacco-using adults with ADHD

PHASE: II

INITIATION: MAY 2010

COMPLETION: FEBRUARY 2011

STATUS: COMPLETED

LOCATION: UNITED STATES

STUDY ID: TC-5619-238-CRD-003, NCT01488929 LOCATION: UNITED STATES, HUNGARY, ROMANIA, RUSSIAN

FEDERATION, SERBIA, UKRAINE

PRIMARY OUTCOME MEASURE: Change from baseline on the Scale for the Assessment of Negative Symptoms, or SANS, at the end of

the treatment period with TC-5619 as compared to placebo.

INDICATION: Schizophrenia PATIENT SEGMENT: Negative Symptoms and Cognition in Outpatients With Schizophrenia

ACCRUAL: 450 (Planned); 603 (Actual)

PHASE: II

INITIATION: DECEMBER 2011

COMPLETION: NOVEMBER 2013

STATUS: COMPLETED

STUDY TITLE: A Double-Blind, Placebo-Controlled, Multicenter, Parallel Group Study to Assess Efficacy, Safety, and Tolerability of

TC-5619 as Augmentation Therapy to Improve Negative Symptoms and Cognition in Outpatients With Schizophrenia

STUDY DESIGN & TREATMENT:

Double-Blind, Placebo-Controlled, Multicenter, Parallel Group Study

The trial design provided for a four-week screening period, followed by a 24-week treatment period during which subjects received either one of two daily doses of TC-5619 (5mg or 50mg) or placebo together with continued treatment with an atypical antipsychotic.

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INDICATION: Attention Deficit/Hyperactivity Disorder (ADHD)

STUDY ID: TC-5619-238-CRD-004, NCT01472991

STATUS: COMPLETED COMPLETION: JULY 2012 INITIATION: NOVEMBER 2011 LOCATION: UNITED STATES

ACCRUAL: 152 (Planned), 250 (Actual)

STUDY TITLE: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Fixed Dose Study

to Assess Efficacy, Safety, and Tolerability of TC-5619 in Adults with Inattentive

-Predominant Attention Deficit/Hyperactivity Disorder (ADHD)

PATIENT SEGMENT: Adults with Inattentive-Predominant ADHD

March 14, 2014

Targacept, Inc. FORM 10-K, For the fiscal year ended December 31,

2013

(pg 3) TC-5619 and TC-6987

TC-5619 and TC-6987 are novel small molecules highly selective for the a7 NNR. The a7 NNR has been shown to

play a role in a variety of biological pathways associated with various diseases and disorders. We previously con-

ducted clinical studies of TC-5619 as a potential treatment for schizophrenia, Alzheimer’s disease and attention deficit hyperactivity disorder and exploratory studies of TC-6987 as a treatment for inflammatory disorders. We do not have

plans to pursue additional development of these com-pounds in these therapeutic areas.

PRIMARY OUTCOME MEASURE: Change from

baseline on the inattention subscale of the Conners’ Adult ADHD Rating Scale—Investigator-Rated, or CAARS-INV, after four weeks of treatment with TC-5619 as compared to

placebo.

STUDY DESIGN A 3-arm, fixed dose, double blind, placebo controlled, parallel

group, multi-center, 12-week study

STUDY TREATMENT: Subjects in the trial were randomly assigned to receive a daily

dose of 5mg TC-5619, 25mg TC-5619 or placebo.

RESULTS: TC-5619 did not meet the primary outcome measure of the trial, but showed encouraging signals on some of the trial’s efficacy measures in the subpopulation of subjects with ADHDi.

March 15, 2013 Targacept, Inc.

FORM 10-K, For the fiscal year ended December 31, 2012

(pg 3)

TC-5619 TC-5619 is a novel small molecule that modulates the activity

of the a7 NNR. We are currently conducting a Phase 2b clinical trial of TC-5619 as a treatment for negative

symptoms and cognitive dysfunction in schizophrenia. We are

also currently evaluating potential additional Phase 2 clinical development of TC-5619 as a treatment for Alzheimer’s disease.

PHASE II (ALZHEIMER’S DISEASE)

STATUS: COMPLETED

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PHASE: II

RESULTS :

TC-5619 did not meet the primary outcome measure and did not demonstrate improvement on the key secondary measures.

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