TLC BioSciences Corp · TPEX:7924
TLC BioSciences — SinoPac Q4 Forum 2015
50 slides from TLC BioSciences's conference presentation, December 2015
Slide 1: TLC
TLC George Yeh, President
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward-looking statements regarding future events and the future performance of Taiwan Liposome Company that involve risks and uncertainties that could cause actual results to differ materially. These statements are based on management’s current beli
Slide 3: LDDS Differentiation
LDDS Differentiation Cost/Unit 1st Gen Liposomes PLGA Microspheres Hydrogel Microspheres Next Gen & Targeted Nanoparticles Sustained Release Complexes Cumulative Units Produced TLC competes on scale and complexity advantages 3
Slide 4: Innovating Novel Capabilities
Innovating Novel Capabilities Aqueous Core • Proprietary loading Lipophilic Domain • Toxicity/solubility Route of administration • Intravenous • Intraarticular • Intravitireal • Subcutaneous Design delivery strategies for small & large molecules 4
Slide 5: Rapid Nanoparticles Identification
Rapid Nanoparticles Identification Physicochemical evaluation Proprietary screening studies in vivo PK study confirmation 1-3 months to establish feasibility of nanoparticles formulation 5
Slide 6: TLC Payloads Library
TLC Payloads Library For 505(b)2/Hybrid MA Development Molecule MoA Approved Indications Afatinib EGFR/Her2 inhibitor NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution Crizotinib ALK/ROS1 inhibitor NSCLC with ALK+ Lapatinib EGFR/Her2 inhibitor ER+/HER2+ breast cancer Dasatinib BCR/Ab
Slide 7: Core Competency Growth
Core Competency Growth Non-Biological Sustained Targeted Complex Release Delivery Drugs TLC177 (liposomal doxorubicin) TLC399 (retinal vein occlusion) TLC178 (orphan indication) TLC166 (liposomal amphotericin B) TLC599 (arthritis) TLC388 (liver cancer orphan) 7
Slide 8: Development Pipeline
Development Pipeline Discovery Development Phase 1 Phase 2 Phase 3 Launch Oncology Hepatocellular Carcinoma TLC388 Rectal cancer TLC178 CTCL/NHL/HL TLC520 Various cancers Ophthalmology ProDex Macular Edema Pain/Osteoarthritis TLC599 Osteoarthritis-related pain TLC198 Long acting local anesthetic
Slide 9: Overcoming Camptothecins' Limitations
Overcoming Camptothecins’ Limitations Lactone ring hydrolysis O O A B C N N OH- OH D N N E O + E O- H OH O OH O lactone carboxylate • Insoluble in aqueous media • Inactive • Possesses antitumor activity • Toxic • Intrinsic instability of lactone above pH 4
Slide 10: Toxicity
Toxicity Species MTD of TLC388 MTD of Topotecan 480 mg/m2/single 96 mg/m2/single Mice injection* injection* 48 mg/m2/day* 4.7 mg/m2/day*** Rat (5-day study) (5 -28 days study) 20 mg/m2/day** 1.3 mg/m2/day*** Dog (5-day study) (5 -28 days study) Human 50 mg/m2/week 4-5mg/m2/week *: TLC in-house study
Slide 11: Hep3B HCC Model
Hep3B HCC Model Saline Lipotecan 42.6 mg/kg q3dx3 3000 Mean tumor volume (mm3) 2500 2000 1500 1000 500 0 0 5 10 15 20 25 30 35 40 Post drug injection days Mean Treatment Drug dose (mg/kg) Dosing schedule % T/C (day) a Max. % BW change (day) b TDT c Saline 0 - - 16.8 (18) 13.8 ± 3.5 q3d x 3 Lipotecan
Slide 12: Huh-7 HCC Model
Huh-7 HCC Model Antitumor efficacy of Lipotecan in Huh-7 human hepatocellular carcinoma model 5000 Saline Lipotecan 42.6 mg/kg q3dx3 4000 Mean tumor volume (mm3) 3000 2000 1000 0 0 5 10 15 20 25 30 35 Post drug injection days Treatment Drug dose (mg/kg/injection) Schedule (day) % T/C (day) a Max. %
Slide 13: TLC388 + RT in Huh-7 HCC Animal Model
TLC388 + RT in Huh-7 HCC Animal Model Antitumor efficacy of RT + Lipotecan in Huh-7 human HCC model 4000 Saline Lipotecan 25.6 mg/kg RT 2 Gy RT + Lipotecan Mean tumor volume (mm3) 3000 2000 1000 0 0 5 10 15 20 25 30 35 Post drug injection days As tumor volume reached ~ 270 mm3, tumor bearing mice we
Slide 14: Phase I Data
Lipotecan Dose (mg/m?) Prostate x Prostate 12 16 20 24 #28 «#32 «#36 «©6400 «}6«44©«€©648 ~~ «(52 Duration on the study (week) 14
Slide 15: HCC with PVTT
HCC with PVTT Hepatocellular Carcinoma • Sixth most prevalent cancer and third most frequent cause of cancer-related death worldwide • Poor response to systemic chemotherapy HCC with PVTT • Poor prognosis of PVTT HCC patient population lacking adequate treatment • >30% incidence of estimated 600,000
Slide 16: Pilot Study Patients Data
Pilot Study Patients Data 1A1001 • Male, Oriental, 60 years • HCC stage III • Prior Treatment : none • Metastasis: none • 6 weeks at 15 mg/m2 with 3DCRT 50 Gy • PVTT response: PR • Overall response: PD • AE: cough, fever, fatigue, influenza virus B infection, malaise, abdomen pain, abdomen distensio
Slide 17: Pilot Study Patients Data
Pilot Study Patients Data 1A1002 • Male, Oriental, 59 years • HCC stage IIIb • Prior Treatment : Surgery • Metastasis: none • 6 weeks at 15 mg/m2 with 3DCRT 50 Gy • PVTT response: CR • Overall response: PR • AE: fever, herpes simplex on left lip angle, constipation, teethache, hyperglycemia, cough,
Slide 18: Pilot Study Patients Data
Pilot Study Patients Data 1A1003 • Male, Oriental, 73 years • HCC stage IIIb • Prior Treatment 1: Surgery • Prior Treatment 2: Sorafenib, 3 weeks • Metastasis: none • 6 weeks at 15 mg/m2 with 3DCRT 50 Gy • PVTT response: SD • Overall response: SD • AE: anaphylactic shock, fatigue, headache, cough, e
Slide 19: Patient Imaging Data
Patient Imaging Data • PVTT Response Signal • Overall Response Signal
Slide 20: RT Accepted Asian HCC Practice
RT Accepted Asian HCC Practice • Suggests improved local control and OS • Planning global expansion from China to Korea Jiang, W. and Z. C. Zeng Oncology 2013
Slide 21: Supportive China Clinical Guidance
Supportive China Clinical Guidance • Radiotherapy is an integral part of HCC clinical practice in China • Applicable to both metastatic and non-metastatic patients • Potential to expand and replace platinum-based CCRT therapy 21
Slide 22: Rectal Cancer
Rectal Cancer • Colorectal cancer is the 3rd most common cancer worldwide, 4th most common cancer in China • High mortality, with estimated 50,000 deaths in the US annually • Treatment options may include surgery, radiation or chemotherapy • (~10%) pathological complete response rate 22
Slide 23: Cross-Strait MRCT Strategy
Cross-Strait MRCT Strategy Phase I Phase II Phase III Rectal Cancer NEC Taiwan Other indications NDA HCC PVTT Rectal Cancer China Category 1.1 China NCE Other Indications Tech transfer to in China CMO 23
Slide 24: Sustained Release
Sustained Release • Multilamellar and multivesicular • Entraps both small and large molecules • Functions of protein drugs are not compromised • Drug and lipid membrane complex to enhance drug entrapment 24
Slide 25: Lipid-Extended Release Technology (L-ERT)
Lipid-Extended Release Technology (L-ERT) Intravitreal application • Indications: Age-Related Macular Degeneration, Diabetic Macular Edema, Retinal Vein Occlusion • Targeting 1 injection/6 months • Phase I/II in progress Intraarticular application • Indications: Osteoarthritis, Rheumatoid Arthritis,
Slide 26: Development Pipeline
Development Pipeline Discovery Development Phase 1 Phase 2 Phase 3 Launch Oncology Hepatocellular Carcinoma TLC388 Rectal cancer TLC178 CTCL/NHL/HL TLC520 Various cancers Ophthalmology ProDex Macular Edema Pain/Osteoarthritis TLC599 Osteoarthritis-related pain TLC198 Long acting local anesthetic
Slide 27: Competitive Landscape
Competitive Landscape Caused by leakage of Age-related macular Diabetic macular edema fluid from small blood degeneration (AMD) (DME) vessels in the eye. An increased expression of Visudyne Lucentis VEGF can escalate the A progressive eye Macugen Eylea leakage and vascular condition affecting as Luc
Slide 28: Competitive Analysis
Competitive Analysis * Based on BCVA 15 letters Product Stage Technology • Efficacy* Safety • Durability TLC399 Phase I/II Multilamellar • Non-inferior • IOP superior Lipid Complex to Ozurdex to Ozurdex Dexamethasone • Targeting 6 • No cataracts Steroid months observed targeted at Ozurdex Approved
Slide 29: Current Treatment: Ozurdex
esign.com. Implant Ozurdex Implant Inside an. Eye
Slide 30: Target Market
Target Market • Superior than Ozurdex – Better safety profile – Better durability – Non-inferior efficacy • Combinational use with anti-VEGF* – Mean visual acuity improvement: 11 letters 25 letters – Reinjection was prolonged to 125.9 days after the initial injection, with 18% of patients not need
Slide 31: BCVA – Vision Improvement
BCVA – Vision Improvement Average Change from Baseline 25 20 2 mths 9 mths 15 3 mths 6 mths 10 5 D14 0 -5 1 mth -10 ** D14 & 1 mth – 4 subjects / 2 mths – 6 mths – 3 subjects / 9 mths – 2 subjects 31
Slide 32: OCT – Degree of Edema
OCT – Degree of Edema Average Change from Baseline 0 -50 -100 -150 6 mths -200 9 mths -250 2 mths -300 1 mth 3 mths -350 D14 -400 ** D14 & 1 mth – 4 subjects / 2 mths – 6 mths – 3 subjects / 9 mths – 2 subjects 32
Slide 33: IOP – Possible side effect of Steroid
IOP – Possible side effect of Steroid Actual Measurement 30 1 mth 25 D14 9 mths 20 6 mths 15 2 mths 3 mths 10 5 0 ** D14 & 1 mth – 4 subjects / 2 mths – 6 mths – 3 subjects / 9 mths – 2 subjects 33
Slide 34: Premium Pricing
Premium Pricing • 16 million worldwide 1 • Ozurdex: $1,300/implant every 3-4 months 2 • Lucentis: $1,950/dose 3 • Eylea: $1,850/dose 3 Once/6 months TLC399 could be priced similar to Lucentis/Eylea 1 International Eye Disease Consortium 2010 estimate 2 2013 estimate 3 2011 estimate
Slide 35: Development Pipeline
Development Pipeline Discovery Development Phase 1 Phase 2 Phase 3 Launch Oncology Hepatocellular Carcinoma TLC388 Rectal cancer TLC178 CTCL/NHL/HL TLC520 Various cancers Ophthalmology ProDex Macular Edema Pain/Osteoarthritis TLC599 Osteoarthritis-related pain TLC198 Long acting local anesthetic
Slide 36: OA Pain Treatment Regime
OA Pain Treatment Regime * Musculoskeletal injections in orange Severe TLC599 Surgery Hyaluronic Acid Pain Steroids Oral NSAIDs Opioids Physical Therapy Mild Early End Post-Op • Targeting intraarticular steroids injection segment for market entry • Soluble steroid for fast efficacy onset efficacy (h
Slide 37: Musculoskeletal Pain Market
Musculoskeletal Pain Market HA Knee 1,319,613 Hip Steroid 379,991 Knee Steroid 3,169,537 Shoulder Steroid 488,217 Ankle Steroid 318,887 • $2B Global Market, >8% CAGR 2013-18 • United States ~$900M, Japan ~$700M • >10M other musculoskeletal injections o Carpal tunnel, rotator cuff, lower back pain, e
Slide 38: Market Needs
Market Needs • Significantly prolonged pain management – Steroids cannot be injected more often than every 12 weeks – At most 2~3 injections per year • Manageable chondrotoxicity – Crystalized formulation of TA – Damage to the cartilage
Slide 39: Competitive Analysis
Competitive Analysis Product Stage Technology Durability Onset TLC599 Phase I Multilamellar Targeting 12 Targeting Lipid Complex wks based improvement over Dexamethasone on WOMAC Triamcinolone scoring Acetonide (TA) Steroid FX006 Phase III PLGA 8-10 wks Same as TA encapsulated based on (TA) WOMAC sc
Slide 40: Result of the Comparison Study
Result of the Comparison Study Clinical Arthritis Score saline 8 TLC599-1.2mg Celestone Soluspan-1.2mg Kenalog-6mg 6 Clinical Score 4 2 0 0 5 10 15 20 25 30 35 Study Day • Although Kenalog group was terminated before study end, recurred symptoms were observed on Day 25-27. • Pain score of TLC599 is
Slide 41: Clinical Significance
Clinical Significance ry N 1-12 weeks AUC Analysis (p=0.0382) | & ce) \ w N & Nu >1 unit on 10 point scale LS Mean Change from Baseline (+SE), 0-10 Scale | p=0.051 Wk 2 Wk 3 Wk4 Wk5 Wk6 Wk7 Wk8& Wwk9 = Wk10 Wk11l Wk12 Weeks Post Treatment . Note: 2-sided t-test TCA IR 40mg =i FX006 40 mg
Slide 42: TLC599 Rabbit IntraArticular PK
TLC599 Rabbit IntraArticular (IA) PK 1e+5 DP in 599 group Two groups of rabbit were 1e+4 DEX in 599 group administered TLC599 and DP in DSP group DEX in DSP group Dexamethasone Sodium 1e+3 Phosphate (DSP) solution respectively via a single IA injection in both hind knee Conc. (ug/ml) 1e+2 joints. Co
Slide 43: TLC599 GLP Study
TLC599 GLP Study 2 wks 4 wks 8/9 wks Rat OA Safranin O Yellow brackets indicated cartilage damage and chondrocyte loss BioSeizer Vehicle Toluidine Blue GLP Study TLC599 Toluidine Blue High Dose (1.2mg) GLP Study No proteoglycan and cartilage damage from GLP study, signaling lack of TLC599 or vehicle
Slide 44: TLC599 Lack of Chondrotoxicity
TLC599 Lack of Chondrotoxicity • Day 91 • TLC599 1.2mg single-dose • No proteoglycan loss • Day 91 • TLC599 1.2mg x 2 doses • No proteoglycan loss
Slide 45: Premium Pricing
Premium Pricing • 27 million patients in the US alone 1 • $2,600/yr direct treatment cost 2 • $5,700/yr annualized (direct + indirect) 2 • Oral Celebrex once/day cost monthly = $145; 3 months supply = $435 3 • Injectible Synvisc Hyaluronic Acid $620 once/6 months 4 Once 3-4 months TLC599 should be p
Slide 46: Status
Status • 10+ products, over half are at late stage of development / on market • Marketed x 2; Approved x 1; ANDA applied x 1; Phase II x 1; Phase I/II x 2 Products • Fast screening & development platform • >70 patents granted and under review Technology • Lipid based DDS platforms: expanding disease
Slide 47: Achievements in 2015
Achievements in 2015 • TLC599 IND application approved, commenced Phase I/II trial • Received NT$17M through "Industrial Technology Development Program" from MOEA for ProDex Phase I/II Clinical Trial • Out-licensed AmBiL distribution rights for Hong Kong and Macau territories to Main Life Corporatio
Slide 48: Product Screening & Development
Product Screening & Development Clinical Trial in TW Meet / Exceed EU / US Product Didn’t meet but Quick Pre- Emerging IND better than Screening Clinical Target Profile Market existing product Same as existing product 48
Slide 49: Future Outlook
Future Outlook Short Term Mid-Term 2016 (~ 2017) (~ 2020) • IND – TLC178 • IND – TLC198… • IND – TLC520, TLC198… • EU ANDA - Doxisome • ANDA Approval • NDA – TLC178, TLC599… • Data readout - Phase • Data readout – Phase II • Data readout – Phase R&D I/II, BE • Payloads library II/III • Payloads libr
Slide 50: Thank You
Thank You +886.2.2655.7377 +886.2.2655.7366 www.tlcbio.com