Corporate Presentation June 20 June 2013 Safe Harbor Statement - - PowerPoint PPT Presentation

Corporate Presentation

June 20 June 2013

Safe Harbor Statement

During the course of this presentation we will make statements that constitute forward-looking statements. These statements may include operating expense projections, the initiation, timing and results of pending or future clinical trials, the actions or potential action of the FDA, the status and timing of ongoing research, corporate partnering activities and other factors affecting Adherex Technologies’ financial condition or operations. Such forward looking statements are not guarantees of future performance and involve risk, uncertainties and other factors that may cause actual results, performance or achievements to vary materially from those expressed or implied in such

• statements. These and other risk factors are listed from time to time in reports

filed with the SEDAR and the Securities and Exchange Commission, including but not limited to, reports on Forms 10-Q and 10-K. Adherex does not intend to update any forward looking information to reflect actual results or changes in the factors affecting forward-looking information.

Company Overview

Biopharmaceutical company dedicated to the discovery and development of novel cancer therapeutics Two late stage oncology clinical products: Sodium Thiosulfate (STS) and Eniluracil (EU) STS: pending favorable data will file for NDA EU: pending partnering discussions advance to Phase III US based management team Headquarters in Research Triangle Park, NC Ticker: ADHXF – USA, AHX – Toronto Market Cap: $10 MM; 25.1 MM shares outstanding $1.9 MM in cash at 3/31/13, no debt Large insider ownership with aligned shareholder incentives

Management and Board of Directors

Ro Rosty Raykov – CEO Bear Stearns, Tiedemann Group, John Levin & Co., Alchem and DCML Co. Ro Robert A Andrade – – CFO FO Bear Stearns, JP Morgan, CIBC, Caxton Associates, Millennium Partners and DCML Co. Da David Lieberman vid Lieberman – – Chair hairman man Donaldson, Lufkin & Jenrette, Tiedemann Group. Currently, an analyst with Southpoint Capital, Company’s largest shareholder. Ch Chris Rallis – Rallis – Direc ector 30 years of business development, legal and operating experience at Wellcome and Triangle

• Pharmaceuticals. Currently, executive in residence with Pappas Ventures.

St Steve Sk e Skol

• lsky

sky – Direc Director

• r

30 years of operating experience, including Head of Glaxo Welllcome’s Division of HIV/Oncology, Chief Executive at Trimeris and Sequoia Pharmaceuticals. Currently, Global Head of Clinical and Data Operations at Quintiles.

STS Investment Highlights

ST STS is a chemo-protectant agent being developed exclusively in children to prevent hearing loss caused by cisplatin Received Orphan Drug Designation in 2004 with 7 years exclusivity upon approval Phase III trial conducted by Children’s Oncology Group is fully enrolled with data on 135 patients expected in 3Q 2013 Phase III trial conducted by SIOPEL6 in children with liver cancer 76/102 patients enrolled Clinical trial costs covered by government grants Adherex has exclusive rights to data from both studies Potential f ntial for R r Rare P re Pediatric D atric Disease V sease Voucher: her: upon approval of STS 6 month priority review to any other new NDA or BLA application Voucher can be transferred or sold with no restrictions Int Intellect llectual pr ual proper

• perty:

: Use-patent as chemo-protectant in-licensed from OHSU Issued European and Japanese patents expire 2021, US pending prosecution

Platinum Hearing Loss is Frequent, Severe and Irreversible

Platinum drugs are Platinum drugs are major major anti cancer anti cancer agents in agents in pediatric oncol pediatric oncology gy Produce profound, irreversible, cumulative hearing loss Destroy the cochlear hair cells of inner ear Effect can be seen after as little as the second or third dose Hearing loss (ototoxicity) is a dose-limiting side effect Up t to three thousand three thousand children receiv children receive platinum e platinum based chemo based chemotherap herapy ever ery y year in the US: ar in the US: 40-90% 40-90% de develop lop irre irreversible ible ototoxicity icity Loss of high frequency hearing sensitivity - loss of high frequency consonants (s/f/th/p/k/h/t) Background noise compounds disability in critical settings - distance hearing and hearing in the classroom Infants and young children at critical stage of development lack speech language development and literacy Older children and adolescents lack social-emotional development and educational achievement

Ot Ototoxicity icity in Children T

in Children Treat eated with Cisplatin d with Cisplatin and/or nd/or Carboplatin Carboplatin

61% bilateral hearing loss (ASHA criteria) at the end

• f treatment

41% required hearing aids that only partially restore hearing 22% of patients had dose reductions due to

• totoxicity

N=67 age 8 m -20 years

Gilmer-Knight et al., Journal of Clinical Oncology

10 20 30 40 50 60 70 80 90 100 Medulloblastoma Osteosarcoma Neuroblastoma PNET Germ cell

Ot Otot

• toxicity (%)

icity (%)

88 88 75 75 67 67 50 50 11 11

Hearing Loss Diagnosed Hearing Loss Diagnosed Hearing Loss Diagnosed Hearing Loss Diagnosed

Det Detectable hearing loss generally ctable hearing loss generally begins af begins after about tw r about two or

• or three

three cy cycle cles

• f cispla
• f cisplatin,

tin, and ma and may continue y continue t to occur

• ccur

for months (or longer) af r months (or longer) after use is r use is discontinued discontinued

Switch therapi Switch therapies Dose Modi Dose Modify Cont Continue Cours Course

Hearing Loss Hearing Loss De Detect cted or

• r

Communicat Communicated d by Pat Patient ent Less ef Less effectiv ctive dosing/treatment, e dosing/treatment, po potentially shor entially shortening sur ning survival al Lead Leads t s to more more se severe re hearing loss hearing loss

Current Approach to Platinum Induced Hearing Loss

Pt Cl NH3 NH3 Antitumor Effect Ototoxicity Effect Pt Cl Cl

NH3 NH3 Protein

Cl

STS

Pt Cl Cl NH3

NH3 Protein

Requires both Cl unbound to crosslink DNA Binding to plasma proteins

• ccurs within first hour which

inactivates one binding site Free cDDP (unbound) short t1/2 :1.5 hr Requires one Cl unbound to affect cochlear hair cells Binding to plasma proteins

• ccurs within first hour which

inactivates one binding site STS will bind second site preventing ototoxicity

Target and Proposed STS Mechanism

STS Protects Against Cisplatin Ototoxicity in the Rat

Change from baseline hearing threshold. Effect of STS (8 g/m2 IV) 4 hrs, 8 hrs, or 12 hrs after administration of cisplatin (6 mg/kg IA) Delayed administration of STS after platinum agents in animals reduces ototoxicity

Cisplatin and STS animal PKs

Cis Cisplati latin clearance is com learance is comple lete b by 6 hr 6 hrs with ith or

• r without

without S STS, when S S, when STS le S levels are at or higher ls are at or higher than clinically achie than clinically achievable le able levels ls

Cisplatin Pharmacokinetics nu/nu mice administered 4 mg/kg CDDP i.p. STS Pharmacokinetics nu/nu mice administered 3.5 g/kg STS i.p.

ST STS L Leve vel 1 min 15 min Mouse # 1 222.0 mg/dL 941.0 mg/dL Mouse # 2 180.0 mg/dL 5.85 mg/dL Mouse # 3 133.5 mg/dL n/a Mouse # 4 145.8 mg/dL 1131.0 mg/dL Mouse # 5 not detectable 1246.0 mg/dL Mouse # 6 177.1 mg/dL 975.0 mg/dL

*Clinical peak STS level 15 min post-drug administration is approximately 330 mg/dL.

Time-Dependent Tumor Protection of STS after Administration of Cisplatin in Nude Mice

STS allo S allows f ws for anti r anti-t

• tumor activit
• r activity when giv

when given pr n prop

• perly

erly

Harned TM et al. Clin Cancer Res 2008;14:533-540

COG ACCL0431: Randomized Study of STS for Prevention of Cisplatin-induced Hearing Loss

Newly diagnosed children with hepatoblastoma, germ cell tumor,

• steosarcoma, neuroblastoma, and medulloblastoma

Study Chair: David Freyer, DO, MS 135 randomized patients fully enrolled and study completed in 1Q 2012 Futility analysis conducted and reviewed by COG DSMC August 2011 with recommendation at the time to continue study Expect data in 3Q 2013

COG ACCL0431: Randomized Study of STS for Prevention

• f Cisplatin-induced Hearing Loss

Audiology done with each cycle of therapy 80% power to detect 22.5% vs 45% change in hearing 80% power to rule out >12% difference in 3 yr EFS Secondary objectives measurement of nephrotoxicity and neurotoxicity

Note Note: Patient must first be enrolled on the COG hearing assessment study, ACCL05C1 Diagnosis Planned treatment program includes  200 mg/m2 cisplatin (administered according to the disease-specific regimen) Study entry onto ACCL0431 Randomization Sodium thiosulfate given intravenously over 15 minutes starting 6 hours after completion

• f each cisplatin infusion (STS Arm)

No sodium thiosulfate treatment given (Observation Arm) Protocol therapy ends when patient completes planned treatment regimen containing cisplatin Newly diagnosed germ cell tumor, hepatoblastoma, medulloblastoma, neuroblastoma, or osteocarcoma

SIOPEL 6: Efficacy of STS in Reducing Ototoxicity in Patients

Receiving Cisplatin for Standard Risk Hepatoblastoma

Newly diagnosed children with standard risk hepatoblastoma Study Chair: Peppy Brock, MD 78 randomized patients fully enrolled out of 102 Interim evaluations of efficacy of the chemotherapy carried out and reviewed by IDMC after 20, 40, 60 and 80 patients are evaluable for response Early stopping will be considered in case of concerns on efficacy of chemotherapy in either treatment arm The first two interim safety analysis after 20 and 52 patients were conducted with IDMC recommending study to continue Two interim and one final efficacy analyses planned for early stopping in case of a greater than expected difference between treatment arms in terms of hearing loss

*Next interim analysis expected by mid-2014

SIOPEL 6: Efficacy of STS in Reducing Ototoxicity in Patients

Receiving Cisplatin for Standard Risk Hepatoblastoma

Diagnostic biopsy Tumour storage Radiological staging RRR if required Registration to remote data entry site via web 80% power to detect 60% vs 35% hearing loss Two interim and one final efficacy analyses planned for early stopping in case of a greater than expected difference between treatment arms in terms of hearing loss

cDDP: 80 mg/m2 STS: 10-20 gm/m2 depending on age/weight

 

R A N D O M I S A T I O N

CDDP CDDP CDDP CDDP CDDP CDDP CDDP STS CDDP STS CDDP STS CDDP STS CDDP STS CDDP STS

D E L A Y E D S U R G E R Y

STS: Development Timeline

Ev Event ent Timing iming

FDA Type C Clinical Development Meeting  March 2011 Presented to Pediatric ODAC 

ODAC recognized challenge of demonstrating STS does not reduce efficacy of cisplatin and agreed adult study would not be appropriate

Nov 2011 COG ACCL0431 Clinical Data 3Q 2013 FDA Type C Clinical Meeting – Agree COG Data Acceptable for NDA H1 2014 FDA Pre NDA Meeting mid 2014 NDA Submission 1Q 2015

STS Market Opportunity

Pediatric atric M Mark rket O et Opportunity unity 12,000 children develop cancer in the US every year 2,000 children will receive platinum-based chemotherapy, 3x ROW Pricing to be determined based on available therapies in the market Com Competitive P e Posi sition

• n

Significance of injury increases value of STS Limited competition – hearing aids and cochlear implants do not prevent hearing loss Hearing aids cost $2000 to $6000 each Cochlear implants cost up to $75,000 each Thir Third par party mar market resear research sho ch shows str strong adopti adoption

• n charact

characteris ristics Physician approval very high Payors feedback positive

Summary

STS S has T has Two P

• Potential Near T

ntial Near Term V rm Value Driv lue Drivers ers Positive data from COG Phase III trial will support filing of NDA Upon approval of NDA, receipt of Rare Pediatric Disease Voucher Eniluracil Eniluracil is is activ active and w and well t ll tolerat lerated d Indications where 5-FU is administered potentially in excess of $1 BLN market Seek partnership for further development of Eniluracil Thir Third par d party mar y market rese resear arch sho ch shows str s strong adop ng adoption tion charact characteristics ristics With convincing data from COG Phase III trial submit for NDA Further development of Eniluracil