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 olsky sky – Direc Director or 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 operty: : 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
Ototoxicity Ot icity in Children T in Children Treat eated with Cisplatin d with Cisplatin and/or nd/or Carboplatin Carboplatin 100 61% bilateral hearing loss 90 (ASHA criteria) at the end 88 88 80 of treatment otoxicity (%) icity (%) 75 75 70 41% required hearing aids 67 67 60 that only partially restore 50 hearing 50 50 40 Otot 22% of patients had dose Ot 30 reductions due to 20 ototoxicity 10 11 11 N=67 age 8 m -20 years 0 Medulloblastoma Osteosarcoma Neuroblastoma PNET Germ cell Gilmer-Knight et al., Journal of Clinical Oncology
Current Approach to Det Detectable hearing loss generally ctable hearing loss generally begins af begins after about tw r about two or o or three three cy cycle cles Platinum Induced of cispla of cisplatin, tin, and ma and may continue y continue t to occur occur for months (or longer) af r months (or longer) after use is r use is Hearing Loss discontinued discontinued Hearing Loss Hearing Loss Detect De cted or or Hearing Loss Diagnosed Hearing Loss Diagnosed Hearing Loss Diagnosed Hearing Loss Diagnosed Communicat Communicated d by Pat Patient ent Continue Cours Cont Course Dose Modify Dose Modi Switch therapi Switch therapies Leads t Lead s to more more se severe re hearing loss hearing loss Less ef Less effectiv ctive dosing/treatment, e dosing/treatment, po potentially shor entially shortening sur ning survival al
Target and Proposed STS Mechanism Requires both Cl unbound to crosslink DNA Antitumor Effect Binding to plasma proteins NH 3 occurs within first hour which inactivates one binding site Cl Pt Free cDDP (unbound) short NH 3 t1/2 :1.5 hr Cl Requires one Cl unbound to Ototoxicity Effect affect cochlear hair cells Binding to plasma proteins NH 3 occurs within first hour which STS NH 3 Cl inactivates one binding site Pt NH 3 STS will bind second site Cl Pt NH 3 preventing ototoxicity Cl Protein Cl Protein
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 or 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 STS Pharmacokinetics nu/nu mice administered 4 mg/kg CDDP i.p. nu/nu mice administered 3.5 g/kg STS i.p. STS L ST 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 or activity when giv when given pr n prop operly 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, osteosarcoma, 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 of Cisplatin-induced Hearing Loss Audiology done with Newly diagnosed germ cell tumor, Note Note: Patient must first be each cycle of therapy hepatoblastoma, enrolled on the COG hearing Diagnosis medulloblastoma, assessment study, ACCL05C1 80% power to detect neuroblastoma, or osteocarcoma 22.5% vs 45% change in hearing Planned treatment program includes 200 mg/m 2 cisplatin (administered according to the disease-specific regimen) 80% power to rule out >12% difference in 3 yr EFS Study entry onto ACCL0431 Secondary objectives measurement of Randomization nephrotoxicity and Sodium thiosulfate given intravenously over No sodium thiosulfate treatment neurotoxicity 15 minutes starting 6 hours after completion given (Observation Arm) of each cisplatin infusion (STS Arm) Protocol therapy ends when patient completes planned treatment regimen containing cisplatin
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