Fennec Pharmaceuticals Inc. · NASDAQ:FENC
Fennec Pharmaceuticals — Investor Presentation (2013)
23 slides from Fennec Pharmaceuticals's investor presentation, 2013
Slide 1: Eniluracil Summary
de PHARMA Eniluracil Summary
Slide 2: Product Candidate: Eniluracil (EU)
Product Candidate: Eniluracil (EU) Oral Chemotherapy for Solid Tumors • Irreversible inhibitor of DPD, the enzyme responsible for the rapid breakdown of 5-FU • Developed as a potentiator of 5-FU in the 1990s by Burroughs Wellcome and then by GlaxoWellcome (now GSK) 2
Slide 3: Fluorouracil Market Overview
Fluorouracil Market Overview 5-FU (5-Fluorouracil) Xeloda® (capecitabine) Discovered in 1957, widely available as generic Oral, prodrug of 5-FU IV only On the market since 1998, expected generic in the US by Principal uses: colorectal, breast, gastric, pancreatic, 2013/2014 head and neck, ovarian an
Slide 4: 5-FU Metabolic Pathways
5-FU Metabolic Pathways • 5-FU must be activated to kill cancer cells • The enzyme, DPD, prevents activation and degrades 5-FU to F-BAL DPD problems: F-BAL problems: Highly Variable levels >80% of dose = F-BAL Unpredictable 5-FU PK Decreases 5-FU Efficacy 5-FU t1/2 = 10-20 min Neurotoxic 5-FU MTD co
Slide 5: The Solution: EU Inactivates DPD
The Solution: EU Inactivates DPD EU Eliminates DPD & F-BAL Problems 5-FU is not destroyed: F-BAL formation is minimal: Half-life = 5 hr. No interference with efficacy Highly predictable linear PK Minimize neurotoxicity Oral dosing HFS is negligible 5
Slide 6: Burroughs Wellcome Preclinical Studies
Burroughs Wellcome Preclinical Studies Rats Bearing Advanced Colon Carcinoma Cure Rate EU:5-FU ratio < 1:5 EU/5-FU = 100% 5-FU = 13% Therapeutic Index EU/5-FU = 6 5-FU = 1 EU improves 5-FU antitumor activity and therapeutic index 6
Slide 7: EU Clear Advantages
EU Clear Advantages Enable oral 5‑FU dosing Well tolerated, Negligible HFS 100% Oral Bioavailability Improve antitumor efficacy Yield highly predictable 5‑FU dosing Encouraging Preclinical and Phase I & II (see above graphs oral 5-FU with EU vs. iv 5-FU) Decrease toxicity *Source: Baker SD. In
Slide 8: GSK Pivotal CRC Phase III Results and MBC Phase II Results
GSK Pivotal CRC Phase III Results and MBC Phase II Results Results of the North American Pivotal Phase III Trial Colorectal Cancer PFS Survival Treatment (weeks) (months) EU (10 mg/m2) + 5-FU (1 mg/m2) oral: every 12 hr for 28 days, then 7 days off 20.0 13.3 5-FU + Leucovorin iv: daily for 5 days 22
Slide 9: High EU:5-FU Ratio Decreases Efficacy
High EU:5-FU Ratio Decreases Efficacy Adherex licensed EU from GSK, based on the following study results of rats with large tumors: EU:5-FU ratio 5:1 ratio excess EU present <1:5 ratio excess EU avoided A high ratio of EU to 5-FU was less effective than a low ratio Data: Spector T, Cao, S. A Possibl
Slide 10: Adherex New Weekly Schedule: Avoids Excess EU
Adherex New Weekly Schedule: Avoids Excess EU when 5-FU is administered Dr. Grem’s Phase I Weekly Schedule vs. Xeloda®’s Phase 2 in Advanced Colorectal Cancer Refractory to iv 5-FU/Lv Outcome EU/5-FU/Lv Xeloda® 20mg/29mg/m2/30mg 1,250mg/m2 Treatment weekly every 12 hr for 3 weeks for 14 days Tumor R
Slide 11: Phase II: Oral 5-FU Regimens Comparison in MBC
Phase II: Oral 5-FU Regimens Comparison in MBC Weekly EU/5-FU/Lv schedule (all oral regimen) • Administers a higher EU dose to eliminate all DPD, including DPD in nervous tissue to minimize neurotoxicity. Allows excess EU to be cleared before dosing with 5‑FU • Administers 5‑FU when the EU:5‑FU rati
Slide 12: Phase II: Study Design
Phase II: Study Design Other Reasons Arm 1 80 Subjects EU/ 5-FU / Lv PD X-over Assessment of Randomization: Option Primary Endpoint: N = 140: first- or second-line therapy for MBC patients who had Progression-Free previous treatment with an PD Survival anthracycline and a taxane Arm 2 60 Subjects Xe
Slide 13: Interim Study Efficacy Results
Interim Study Efficacy Results* Arm 1: EU/5-FU/Lv vs. Arm 2: Xeloda® Evaluated CR PR SD CR + PR + SD1 Median PFS Arm patients n (%) n (%) n (%) n (%) (days) EU/5-FU/Lv 74 1 (1) 18 (24) 38 (51) 57 (77) 125 Xeloda 61 0 (0) 18 (30) 27 (44) 45 (74) 126 Arm X: patients who failed Xeloda® and crossed over
Slide 14: Main Study PFS Interim Results
Main Study PFS Interim Results Arm 1: EU/5-FU/Lv vs. Arm 2: Xeloda® (capecitabine). At the time of data cutoff, EU had at least 16 patients with PFS of greater than 250 days vs 8 patients for Xeloda 14
Slide 15: Unexpected Activity in Arm X
Unexpected Activity in Arm X Arm 2 Patients Who Rapidly Failed Xeloda® and Crossed Over to Take EU/5-FU/Lv in Arm X Adjuvant/ Patient Arm 2: Xeloda Arm Xa: EU/5-FU/Lv Ratio PFS2:PFS1 Neoadjuvant 5-FU Treatment(s) PFS1 Best PFS2 Best (Days) Response (Days) Response 1 42 PD 37 PD 0.9 1 2 63 SD 51* SD
Slide 16: Crossover Arm PFS in Rapid Xeloda Failures
Crossover Arm PFS in Rapid Xeloda Failures Arm 2: Xeloda® (capecitabine) vs. Arm X: EU/5-FU/Lv 16
Slide 17: Triple Negative Patients in Arms 1, 2 and X
Triple Negative Patients in Arms 1, 2 and X Unexpected durable responses in triple negative patients Patient Arm 1: EU/5-FU/Lv Arm 2: Xeloda Arm X: Crossover PFS1 Best PFS2 Best PFSX Best (Days) Response (Days) Response (Days) Response 1 41* SD 41 PD 34 PD 2 41 PD 41 PD 63 SD 3 44 PD 42 PD 79 SD 4 4
Slide 18: Serious Adverse Events
Serious Adverse Events* SAE Diagnosis EU/5-FU/Lv Xeloda Arm X Neutropenia 1 Anemia 1 Generalized tonic-clonic convulsions 1 Brain Concussion 1 Pulmonary edema or failure 1 1 Pulmonary embolism 1 1 Metrorrhagia 1 C. Difficile Diarrhea 1 Urosepsis 3a Fractures 3 Disease Progression 2 2 1 Acute pneumon
Slide 19: Interim Adverse Events
Interim Adverse Events* Arm 1: EU/5-FU/Lv Arm 2: Xeloda All Grades Grades 3&4 All Grades Grades 3&4 Adverse Event N (%) N (%) N (%) N (%) Diarrhea 31 (42.5) 0 (0) 9 (16.4) 0 (0) Asthenia 14 (19.2) 2 (2.7) 7(12.7) 1 (1.8) Fatigue 13 (17.8) 2 (2.7) 2(3.6) 0 (0) Hand-Foot Syndrome 9 (12.3) 0 (0) 17(32.
Slide 20: EU Clinical Benefit vs Xeloda
EU Clinical Benefit vs Xeloda® The possible mechanisms for rapid Xeloda® failure and subsequent clinical benefit from EU/5-FU/Lv may include any of the following: 1. Low Xeloda® absorption (highly variable with possible extended lag periods) 2. Low or deficient levels of one or more of the three enz
Slide 21: EU Advantages Over Teysuno and UFT
EU Advantages Over Teysuno® and UFT® DPD inhibitor (5-Chloro, 2,4- dihydroxypyridine) used in Teysuno® (S-1) is a simple competitive reversible inhibitor. Accordingly, it must be present when 5-FU is administered to inhibit 5-FU breakdown by DPD. Therefore, it is likely to interfere with the antitum
Slide 22: FDA Feedback and Development Options in MBC
active and well tolerated in MBC 22 FDA can not endorse a single arm pivotal trial in rapidly failed Xeloda patients in MBC since there ® are other approved therapies available such as Halaven and Ixempra ® ® Discussed with Adherex the following development options in MBC: One superiority study vs X
Slide 23: EU Development Plan Forward
23 Future studies of EU/5-FU/Lv regimen in MBC require large number of patients EU/5-FU/Lv active and well tolerated in refractory 23 iv 5-FU and Xeloda populations ® Encouraging results from Dr. Grem Phase I study in mCRC and Adherex Phase II study in MBC Potential development options in mCRC: EU/5
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