Jefferies Global Healthcare Conference June 2015

2

Developing Novel Treatments For Serious Brain Diseases

3

Clinical drug candidates

TPI 287 CRT 001

TPI 287 3rd generation taxane;

Brain-penetrable; well-tolerated

Encouraging ORR and OS signal in recurrent glioblastoma clinical trials

Clinical trials underway in secondary brain metastases

Oncology Neurology

TPI 287 Preclinical activity

observed in Alzheimer’s disease mouse model

Proof-of-concept clinical trials underway

CRT 001 Previously

marketed heart disease drug; potentially Phase 2 ready

Compelling preclinical activity in models of Alzheimer’s disease and Down syndrome

4

Preclinical Phase 1 Phase 2

Oncology – TPI 287

Recurrent GBM (Avastin naive)

Recurrent GBM (Avastin exp.)

Breast cancer brain metastases (mono)

Secondary brain metastases (+radiation)

Neurology – TPI 287

Alzheimer’s disease

PSP/CBD

Oral formulation

Neurology – β1-ADR modulators

CRT 001 – cognitive impairment

Prodrug follow-ons – cognitive impairment

Pipeline

Update 4Q/15

Update 4Q/15

2016

2016

5

TPI 287 – Oncology

TPI 287 3rd generation taxane Mechanism identical to paclitaxel and

docetaxel Safety profile consistent with the class Readily penetrates the blood-brain barrier

Lead indication: recurrent GBM 53% ORR; 12.9 mo. OS w/Avastin

standard-of-care MTD not yet reached

Secondary brain metastases Phase 1 studies on-going +/- radiation

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GBM standard-of-care

Chinot et al., New Engl. J. Med. (2014); Gilbert et al., New Engl. J. Med. (2014) FDA Briefing Documents, ODAC March 2009 Rahman et al., Neuro-oncology (2014)

Recurrent Disease First Recurrence

Avastin (+/- other therapies)

PFS: 4 mo. OS: 7 – 9 mo.

Second Progression

Avastin (+ other therapies)

NovoTTF

PFS: 1.5 mo. OS: 3 – 4 mo.

Newly Diagnosed Front-line

Temodar Radiotherapy Surgery

PFS: 6 – 7 mo. OS: 16 – 17

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CB-017: TPI 287 in recurrent GBM

Avastin +

TPI 287 dose escalating

Avastin

+ TPI-287 (MTD)

Avastin

RANDOMIZE

Determine MTD Endpoints TBD

# US sites actively enrolling patients: 8

Avastin-naive

Recurrent GBM post TMZ + radiation

2 1

8

TPI 287 adverse event profile typical of taxanes

CB-017 adverse events as of April 17, 2015

Mild-moderate adverse events possibly associated with TPI 287 (n=16)

Peripheral neuropathy 12 (75%) Fatigue 5 (31%) Nausea 5 (31%) Neutropenia 5 (31%) Headache 3 (19%) Diarrhea 3 (19%) Lymphopenia 2 (13%) Alopecia 2 (13%) Back pain 2 (13%) Rhinorrhea 2 (13%)

G 3/4 adverse events regardless of causality (n=16)

Lymphopenia 1 (6%) Neutropenia 1 (6%) Fatigue 1 (6%) Seizure 1 (6%) Hypertriglyceridemia 1 (6%) Confusion 1 (6%) Dysphasia 1 (6%) Lymphopenia 1 (6%)

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CB-017: Updated response analysis June 3, 2015

17 patients evaluable for response per RANO evaluation criteria 9 objective responses (2 CR, 7 PR) → 53% ORR 7 stable disease → 94% disease control rate

months

Dos

e –

patie

nt #

PR

CR PR

PR PR

PR PR PR

CR SD

SD SD

SD SD

SD

PD SD

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RANO response in CB-017

T1 (enhancing)

FLAIR (non-enhancing)

Baseline Post 2 cycles

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TPI 287/Avastin beats Avastin monotherapy

CB-017 ReACT 2 BELOB CABARET BRAIN NCI ‘64E AVAREG

Regimen TPI 287 + Avastin

Avastin alone

Avastin alone

Avastin alone

Avastin alone

Avastin alone

Avastin alone

# patients 19 30 48 62 85 56 59

ORR 53% # 17% 38% 13% 26% 20% 26%

PFS (med) 5.5 mo. # 4.1 mo.** 3.0 mo. 4.0 mo.** 4.2 mo. 3.9 mo. N/A

OS (med) 12.9 mo.* 9.3 mo. 8.0 mo. 6.4 mo. 9.2 mo. 7.1 mo. 7.3 mo.

OS-1 year 73% ^ 31% 26% 20%** 38% 33%** N/A

CB-017 results as of June 3, 2015; ReACT results from Q2/15 CLDX presentation; CABARET 31(15) May 20 Supp, 2013: 2017; AVF3708g and NCI 06-C-0064E data per FDA Briefing Documents, ODAC March 31, 2009; BELOB: Taal et al. Lancet Oncol. (2014); AVAREG: Brandes et al., Annals Oncol. (2014); N/R: not available; # n= 17; ^ n=11; * based upon occurrence of 37% of total events to date and 12.4 mo. median follow-up; ** estimate

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TPI 287 + Avastin beats ASCO rGBM Avastin comps

CB-017 ASCO #2004 ASCO #2005 ASCO #2012

TPI 287 + Avastin

Avastin alone

Avastin alone

Avastin alone

# patients 19 38 34 41

ORR 53% (n=17) 27% NR NR

Median OS 12.9 mo. 7.9 mo. 8.8 mo. 7.0 mo.

Source: CB-017 as of June 3, 2015; ASCO 2015 abstracts

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0%

25%

50%

75%

100%

0 2 4 6 8 10 12 14 16 18

months

CB-017 responders driving the OS median O

S pr

obab

ility

BRAIN trial CB-017

Avastin Avastin + CPT-11

Avastin + TPI 287

# patients 85 82 19

Med OS 9.2 mo. 8.7 mo. 12.9 mo. [95% CI 12.2 - NR]

Source: Friedman et al., JCO (2009)

Survival (mo.) Status Response Dose

(mg/m2)

16.3 + alive PR 140

15.3 + alive PR 140

15.1 deceased SD 140

12.9 deceased PR 140

12.6 + alive PR 160

12.6 deceased PD 150

12.4 + alive CR 160

12.2 deceased SD 150

7.6 deceased SD 170

6.9 + alive PR 170

6.9 + alive PR 180

6.6 deceased SD 170

5.5 + alive PR 180

5.2 deceased SD 160

4.1 + alive CR 170

4.1 + alive SD 180

2.8 + alive SD 180

0.5 + alive N/A 200

0.5 + alive N/A 200

Avastin + TPI 287 Avastin + CPT-11 Avastin alone

CB-017 as of June 3, 2015

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0%

25%

50%

75%

100%

0 2 4 6 8 10 12 14 16 18

months

CB-017 responders driving the OS median O

S pr

obab

ility

BRAIN trial CB-017

Avastin Avastin + CPT-11

Avastin + TPI 287

# patients 85 82 19

Med OS 9.2 mo. 8.7 mo. 12.9 mo. [95% CI 12.2 - NR]

SD CR, SD

PR, PR

CR

PR

PR PR

Source: Friedman et al., JCO (2009)

Survival (mo.) Status Response Dose

(mg/m2)

16.3 + alive PR 140

15.3 + alive PR 140

15.1 deceased SD 140

12.9 deceased PR 140

12.6 + alive PR 160

12.6 deceased PD 150

12.4 + alive CR 160

12.2 deceased SD 150

7.6 deceased SD 170

6.9 + alive PR 170

6.9 + alive PR 180

6.6 deceased SD 170

5.5 + alive PR 180

5.2 deceased SD 160

4.1 + alive CR 170

4.1 + alive SD 180

2.8 + alive SD 180

0.5 + alive N/A 200

0.5 + alive N/A 200

Avastin + TPI 287 Avastin + CPT-11 Avastin alone

PR

CB-017 as of June 3, 2015

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0%

25%

50%

75%

100%

0 2 4 6 8 10 12 14 16 18

CB-017: Objective responders living longer

CR and PR SD and PD # patients 9 8

# events 1 6

median not reached 12.2 mo [95% CI 6.6 - 12.6]

OS @ 9 mo. 100% 50%

OS @ 12 mo. 100% 50%

Surv

ival

pro

babi

lity

CR and PR

SD and PD

p = 0.007

months

CB-017 results as of June 3, 2015

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CB-017 Post-progression therapies – June 3, 2015

Treatment # Patients bevacizumab 9

CCNU 4

carboplatin 3

pembrolizumab 2

no treatment 2

BCNU 1

etoposide 1

NovoTTF 1

radiation 1

temozolomide 1

ipilumumab 1

ICN280/buparlisib 1

surgery 3

# Progressed # On-Study 14 5

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CB-017: TPI 287 in recurrent GBM

Avastin +

TPI 287 dose

escalating

Endpoints Primary: overall response rate Secondary: Safety, PFS, OS

# US sites actively enrolling patients: 11

Avastin-experienced

Avastin +

TPI 287 (expansion)

N=TBD

Recurrent GBM post TMZ

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CB-018: Response and stable disease observed

Dose Patient Best response Duration (mo.)

140 mg/m2

1 SD 4.1

2 PD -

3 PD -

160 mg/m2

1 CR 6.9 +

2 PD -

3 SD 2.8

170 mg/m2

1 SD 1.4 +

2 Not yet evaluated

3 Not yet evaluated

CR: complete response

SD: stable disease

PD: progressive disease

CB-018 (n=8)

CABARET (n=23)

Rahman et al. (n=42)

Median PFS 2.8 mo. (n=7) 1.8 mo. 1.4 mo.

Median OS 5.6 mo. 3.4 mo. 4.3 mo.

CB-018 results as of May 28, 2015; Hovey et al., #2003, ASCO 2015; Rahman et al., Neuro-Onc. 2014

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CB-018: Complete Response

6/6/14 first progression

9/19/14 second progression

10/15/14 baseline

12/4/14 post Cycle 1

T1

FLAIR

TMZ

Avastin

TPI 287

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TPI 287 clinical and regulatory timeline in GBM

2015 2016 2017 2018 1H 2H 1H 2H 1H 2H 1H 2H

CB-017 Phase 1 dose escalation

Phase 2 dose expansion

FDA meeting proposal

CB-018 Phase 1 dose escalation

Phase 2 dose expansion

Phase 3 pivotal

NDA filing

For potential accelerated approval

Follow-up

Follow-up

Meeting Proposal

Follow-up

Follow-up

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Glioblastoma

~ 23K malignant brain tumors/year; 48% GBM

No effective treatments in recurrent disease

$500 - $700M market opportunity

Secondary metastases to brain

~400K patients/year in the US

Radiation therapy and surgery only standards of care

$2 - $3B market opportunity

Pipeline market potential

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Form the spindles on which chromosomes pair and line up

Taxanes ↔ mitotic spindle mitotic catastrophe

Form the “tracks” for trafficking and distribution of cellular cargo

Two major roles of microtubules (MTs)

TPI 287 - Neurology

Taxanes ↔ axonal MTs restore disrupted axonal transport

Adapted from Brunden et al. Nature Rev. Drug Discovery (2009)

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“flame-shaped” NFTs Alzheimer’s disease

“globose” NFTs PSP

“Pick bodies” Pick’s disease

“filamentous” NFTs FTPD-17

Dickson, Brain Pathology (1999)

NFTs in tauopathy indications Alzheimer’s disease Myotonic dystrophy

Amyotrophic lateral sclerosis/parkinsonism–dementia complex * Niemann-Pick disease, type C Argyrophilic grain dementia * Non-Guamanian motor neuron disease with NFTs Corticobasal degeneration * Pick’s disease * Creutzfeldt-Jakob disease Postencephalitic parkinsonism Dementia pugilistica * Prion protein cerebral amyloid angiopathy Diffuse neurofibrillary tangles with calcification Progressive subcortical gliosisa * Down’s syndrome Progressive supranuclear palsy * Frontotemporal dementia with parkinsonism - chr. 17 * Subacute sclerosing panencephalitis Gerstmann-Straussler-Scheinker disease Tangle only dementia Hallervorden-Spatz disease * tau+ NFTs are the most predominant pathologic feature

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TPI 287 vs. other anti-tauopathy therapies

anti-tau antibodies

TPI 287

Infectious aberrant tau

Adapted from Brunden et al. Nature Rev. Drug Discovery (2009)

kinase inhibitors

Tangled clumps of Tau Proteins

Microtubule subunits fall apart

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TPI 287 in PS19: P-tau reductions with TPI 287

Defensor et al., Abst. 691.12, Society for Neuroscience 2014 Tangled clumps of tau Proteins

p-tau (AT8)

t-tau (Tau5)

0 1 3 mg/kg TPI 287

n=5 n=5 n=4

Microtubule subunits fall apart

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TPI 287 in PS19 mice: Morris Water Maze

Escape latency – learning and memory improvements

Probe test – confirmation of spatial working memory improvements

Defensor et al., Abst. 691.12, Society for Neuroscience 2014

WT + TPI 0, 1, 3 mg/kg TPI 287 in PS19 vs. untreated WT

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TPI 287 tauopathy Phase 1 trials

#1 TPI 287 #2 CRT 001

Primary endpoint: safety

Three dose cohorts randomized to placebo 8:3 (n=33)

Secondary endpoints: early efficacy, tau levels in CSF, MR imaging

Funding from CBD Solutions

Primary endpoint: safety

Three dose cohorts randomized to placebo 8:3 (n=33)

Secondary endpoints: early efficacy, tau levels in CSF

Funding from the AD Foundation

3 dose cohorts: 2, 7, 20 mg/m2 every 3 weeks

“Pure” tauopathies

Progressive Supranuclear Palsy Corticobasal Degeneration

Alzheimer’s Disease

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CRT 001 - Neurology

Xamoterol Approved in the 1980’s in select

European territories for the treatment of cardiovascular disease

Clinical data from over 3,500 patients available in over 70 research publications

Intellectual property filed by Stanford University covering:

• methods for enhancing learning and memory with CRT 001

• composition of matter for back-up compounds and analogues

Potentially Phase 2 ready

β1 adrenergic receptor partial agonist

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Adrenergic receptor signaling in the brain

Bondareff, W., et al., Alzheimer Dis Assoc Disord, 1987; Tejani-Butt, et al. Brain Res, 1993; Murchison et al., Cell. 2004

Multi-receptor neurotransmitter pathway distinct from cholinergic system Critical role in learning and memory retrieval Significantly impaired in Alzheimer's disease and other CNS diseases

Noradrenaline

α1A,B,D α2A,B,C β1,2,3 receptors

cAMP

Long-term memory gene expression

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CRT 001 enhances social recognition Alz mouse

Social learning Both normal and APP mice respond equally to the introduction

of Intruder A

Social recognition Normal mice have heightened interest in new Intruder B vs.

prior Intruder A

However, APP mice do not recognize Intruder A and show equally high interest in A and B

APP mice treated with CRT 001 display enhanced recognition of Intruder A without losing interest in Intruder B

inte

rest

leve

l

normal APP

normal APP APP w/ CRT 001

Coutellier et al., Annals of Clinical and Translational Neurology (2014)

Intruder A is removed from the cage Intruder A is reintroduced or new Intruder B is

introduced...

inte

rest

leve

l

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Oncology – TPI 287 CB-017 Phase 1/2 Recurrent GBM: Avastin-naïve Update 4Q/15

CB-018 Phase 2 Recurrent GBM: Avastin-experienced Update 4Q/15

IST Phase 1 Lung/breast cancer brain mets w/FSRT Update 2H/15

IST Phase 1/2 Breast cancer brain mets (mono) Update 2015

Expected milestones

Neurology – TPI 287 and CRT 001 IST Phase 1 TPI 287 in Alzheimer’s disease Interim data 2016

IST Phase 1 TPI 287 in PSP/CBD Interim data 2016

CRT 001 Clinical development plan Finalized 2H/15

32

Management

George Farmer, PhD – Chief Executive Officer

Synta Pharma, Canaccord, Wachovia, DuPont, MSKCC, UCSF, Columbia Univ.

Don Picker, PhD – Chief Operating Officer

Johnson Matthey, Tapestry Pharma, Genta, LXR Biotech, Synergy Pharma, Univ. Washington, SUNY Albany

Sandra Silberman, MD, PhD – Consultant (Chief Medical Officer)

Pfizer, Novartis, Eisai, Tapestry Pharma, Dana Farber, Johns Hopkins Univ., Cornell Univ.

33

Novel approaches for treatment of serious brain diseases

TPI 287: 3rd generation brain-penetrable taxane

Efficacy observed in Phase 1 and 2 GBM clinical trials

Preclinical data provides proof-of-concept for ongoing tauopathy Phase 1 studies

CRT 001: beta1 adrenergic receptor partial agonist

Preclinical data supports proof-of-concept for treatment of cognitive impairment

Potentially Phase 2-ready supported by deep regulatory history

Catalyst-rich over 2015-16

Conservative cash management model

Summary

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CorticeBiosciences.com