Recommended
Recommended
More Related Content
Similar to Presentation the 38th jp morgan healthcare conference chinese
Similar to Presentation the 38th jp morgan healthcare conference chinese (20)
Recently uploaded
Recently uploaded (20)
Presentation the 38th jp morgan healthcare conference chinese
- 1. 張念慈博士 董事長&執行長 OBI Pharma, Inc. 腫瘤免疫與標靶抗癌療法 全球創新者 38th Annual J.P. Morgan Healthcare Conference January 15th, 2020
- 2. Safe Harbor Statement This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes,’ ‘expects,’ ‘anticipates,’ ‘projects,’ ‘intends,’ ‘should,’ ‘seeks,’ ‘estimates,’ ‘future,’ or similar expressions or by discussion of, among other things, strategy, goals, plans, or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1. Pricing and product initiatives of competitors 2. Legislative and regulatory developments and economic conditions 3. Delay or inability in obtaining regulatory approvals or bringing products to market 4. Fluctuations in currency exchange rates and general financial market conditions 5. Uncertainties in the discovery, development, or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side effects of pipeline or marketed products 6. Increased government pricing pressures 7. Interruptions in production 8. Loss of or inability to obtain adequate protection for intellectual property rights 9. Litigation 10. Loss of key executives or other employees 11. Adverse publicity and news coverage OBI Pharma cautions that this foregoing list of factors is not exhaustive. There may also be other risks that management is unable to predict at this time that may cause actual results to differ materially from those in forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date on which they are made. OBI undertakes no obligation to update publicly or revise any forward-looking statements. Any statements regarding earnings growth is not a profit forecast and should not be interpreted to mean that OBI’s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed published earnings or earnings per share forecasts of OBI Pharma, Inc. 2
- 4. 4 San Diego USA Shanghai CHINA Global HQ Taipei TAIWAN Hong Kong CHINA Melbourne AUSTRALIA 設立日期: April 29, 2002 上櫃日期: March 23, 2015 市值 Jan 10, ’20: ~US$805M (~NT$24.2B) 上櫃募資金額: ~US$200M (~NT$6.2B) 帳上淨現金: ~US$154M 員工人數: 117 台灣浩鼎生技 (TPEx: 4174) www.obipharma.com
- 5. 陳志全 財務長 Mitch Che 營運長 David Hallinan, PhD 法規副總 具豐富國際經驗的管理團隊 5 張念慈 博士 董事長暨執行長 黃秀美 OBI Pharma China執行長 Tillman Pearce, MD 醫務長 賴明添 博士 研發長 Kevin Poulos 商務長
- 6. 科學與醫學顧問群 6 Stephan Landisch, MD 石全, PhD 陳鈴津, MD, PhDRussell Greig, PhD 陳紹琛, MD, PhD 翁啟惠, PhD 閻雲, MD, PhD 楊泮池, MD, PhD
- 7. OBI創新專利技術 一鍋法／醣類化學合成法（OPopS™ ）& 酵素合成法Enzymatic Synthesis 7 Barrier to Carbohydrate- Based Drug Discovery Barrier to Efficient Large-Scale Manufacturing Conventional OPopS™ Chemistry Large-Scale Enzymatic Synthesis Inefficient synthesis High COGS Weak affinity ligands High yield Lower COGS Create novel high affinity ligands Highly efficient Minimal purification required Further reduced COGs Suitable for large-scale manufacture
- 8. Adagloxad Simolenin (anti Globo H vaccine) Demonstrated immunogenicity with little toxicity in Phase I MBC and Prostate Cancer studies at MSKCC Applied to the development of the cancer vaccine Adagloxad Simolenin by Optimer and OBI Pharma First-in-Class anti-Globo H therapeutic vaccine licensed from MSKCC (NYC, USA) License transferred to OBI Pharma, Inc. in 2009 Applied to the development of the antibiotic DIFICID (fidaxomicin) by Optimer First-in-class narrow spectrum macrocyclic antibiotic approved by FDA in 2011 for the treatment of Clostridium difficile- associated diarrhea OPopSTM Invented by Prof. Chi-Huey Wong at The Scripps Research Institute San Diego, USA. OPopS™ 實現醣科學運用於研發&製藥之可能 8 Gilewski et al., 2001. PNAS 98 (6), 3270–3275.
- 9. Improved Chemotherapies Novel Tumor-Specific Modalities Continued Growth of Targeted Therapy Driven by CAR T Explosion in Immunotherapy Driven by PD1/PD-L1 and Novel Antigens/MOAs OBI 站在癌症創新治療的最前線 9 CAR T, chimeric antigen receptor T-cell therapy; IV, intravenous; MOA, mechanism of action; PD-1, programmed death 1; PD-L1, programmed death ligand 1. Drivers of Innovation in Oncology Monoclonal Antibodies (mAbs) Bispecific Antibodies Cancer Vaccines Therapeutic Modalities OBI Pipeline Antibody-Drug Conjugates (ADCs) Targeted Prodrugs CAR T ✓ ✓ ✓ ✓ ✓ ✓
- 10. OBI：擁有癌症療法多元化組合的新藥公司 10 mAb: monoclonal antibodies ADC: Antibody Drug Conjugates BiAb: Bi-specific antibodies CAR-T: Chimeric Antigen Receptor T cell mAbVaccine Targeted Prodrug ADC BiAb TARGETS: Globo H (+), SSEA-4 (+), AKR1C3 (+) Tumors CAR T
- 11. OBI 持續擴展策略 務求產品開發極大化 11 mAb: monoclonal antibodies ADC: Antibody Drug Conjugates BiAb: Bi-specific antibodies CAR-T: Chimeric Antigen Receptor T cell 台灣浩鼎 圓祥生命科技 上海浩鼎 67% stock Fully-owned mAb Vaccine Targeted Prodrug ADC BiAb CAR T mAbVaccine ADC China Rights
- 13. OBI 台灣浩鼎 目前全球唯一 開發Globo Series醣分子免疫療法 進入中後期階段的生技公司 Globo H & SSEA-4 13
- 14. Globo系列醣：對腫瘤存活有獨特意義的糖鞘脂(GSL) 14 Diabetes & metabolism journal 35(4):309-16 ·August 2011 Globo H SSEA-4 Cer ββ4α4 β3 Cer Cer β3 α2 Cer α3 Cer SSEA-3 globoside Gb3Cer Sialic AcidFuc GalNAcGalGlcA eukaryotic cell membrane. It composed of the lipid bilayer, consisting of hydrophobic tails and hydrophilic heads.
- 15. Globo H：對腫瘤存活、免疫抑制、血管增生均扮演重要角色 15 1Tsai YC, et al. J Cancer Sci Ther 2013;5:264-270 2Cheng JY, et al. Cancer Res 2014;74:6856-6686 3Chuang PK, et al. PNAS 2019;116:3518-3523 Promotes Immunosuppression1 Promotes Angiogenesis2 Promotes Tumor Survival Signaling3 Tumor Shedding of Globo H Ceramide TRAX Ca2+ Endothelial Cells Notch 1 Ub Ub Degradation Tumor Cells Lymphocytes Kinase Tumor Survival Kinase Kinase
- 16. Pancreatic Esophageal Gastric Breast Lung Colon Liver 0 50 100 150 200 250 300 Globo H IHC H-score of various tumor tissues Hscore Globo H：在多種常見癌症均見高度表現 16 Resections + TMAs + 822-001 Samples. TMA: tissue microarray. Red bar: median score. OBI Data on File. 癌症種類 # Evaluable Specimens # H-score ≥100 Prevalence at H-score ≥100 胰臟癌 72 36 50.0% 食道癌 64 11 17.2% 胃癌 73 18 24.7% 乳癌 131 17 13.0% 肺癌 77 8 10.4% 結腸直腸癌 75 12 16.0% OBI’s Globo H Expression Assay (NeoGenomics) IDE-Approved by FDA
- 18. OBI癌症新藥產品線：四項產品進入國際臨床研究階段 ALL, acute lymphoblastic leukemia; CRPC, castration-resistant prostate cancer; HCC, hepatocellular carcinoma; TNBC, triple-negative breast cancer. 18 作用靶點 潛在適應症 新藥探索 臨床前研究抗癌新藥 臨床一期 OBI-888 OBI-999 OBI-898 OBI-866 Globo H 乳癌 (三陰性乳癌) 肝癌 Globo H Globo H SSEA-4 SSEA-4 OBI-3424 AKR1C3 Adagloxad Simolenin 疫苗 單株抗體 ADC* 疫苗 單株抗體 小分子化 療前驅藥 類型 OBI-998 SSEA-4ADC* 數種癌症 數種癌症 數種癌症 數種癌症 數種癌症 數種癌症 OBI-833 Globo H 數種癌症疫苗 臨床二期 臨床三期 * ADC 抗體小分子藥物複合體
- 20. Adagolaxad Simolenin (OBI-822)+OBI-821 20 Adagloxad Simolenin (OBI-822) Comprises a fully synthetic tumor antigen (Globo H) conjugated to a protein carrier (KLH) Potent Adjuvant (OBI-821) Saponin-based adjuvant Induces humoral and cell-mediated immune responses + OBI-822 + 皂苷佐劑 OBI-821 可針對多種上皮細胞癌標靶Globo H的治療性疫苗
- 21. Higher anti-Globo H IgG levels following vaccination correlated with improved PFS No difference in PFS was seen, however… Higher Globo H tumor expression correlated with improved PFS Adagloxad Simolenin 從臨床二期試驗的學習與經驗 21PFS, progression-free survival. Clinicaltrials.gov. Trial of Active Immunotherapy With Globo H-KLH (OPT-822) in Metastatic Breast Cancer Subjects. NCT01516307 Patients receiving ≥9 injections had improved PFS Ph 2 trial included a broad range of tumor subtypes (HR+/HER2-,TNBC, HER2+) No screening for Globo H expression 這些學習成果已應用於全球三期試驗 選擇Globo H有表現的TNBC患者受試
- 22. Adagloxad Simolenin 全球臨床三期試驗 以早期高復發風險之三陰性乳癌病人為受試對象 ECOG PS, Eastern Cooperative Oncology Group Performance Status. Clinicaltrials.gov. Study of Adagloxad Simolenin (OBI-822) and OBI-821 Versus Placebo Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients (TNBC) Following Neoadjuvant or Adjuvant Chemotherapy. NCT03562637 R 1:1 實驗組 Adagloxad Simolenin (Adagloxad Simolenin 30 μg + OBI-821 100 μg) 334位受試者 對照組 Placebo (phosphate-buffered saline) 334位受試者 22 主要試驗指標: 無「侵襲性疾病」存活期 (Invasive Disease-Free Survival, IDFS) 次要試驗指標: 整體存活期、生活品質、安全性、耐受性 預估試驗期間: 兩年受試者給藥期、三年無侵襲性疾病存活期評估，加上兩年整體存活期評估 用藥期間約兩年（共21針） 早期高復發風險之三陰性乳癌 共 668 位受試者 Neoadjuvant patients with residual disease, or adjuvant patients with 4 axillary nodes Globo H positive (H score ≥15) ECOG PS 0-1
- 23. Adagloxad Simolenin 全球臨床三期試驗地點分布 23 Russia Ukraine USA CHINA Hong Kong Korea EU Enrolling Sites: United States, Australia, Taiwan, Hong Kong, Russia, Ukraine Taiwan Australia Pending Sites: European Union, China, Korea
- 25. OBI-888 具高度腫瘤特異性 25 OBI Data on File. MCF7- tumor Bearing MiceNormal Mice Distribution of labeled Globo H mAb (OBI-888) in the tumor of the MCF7 mouse Eppendorf tubes for reference purposes Distribution of labeled Globo H mAb (OBI-888) in the tumor of the MCF7 mouse
- 26. 癌症種類 動物模型 劑量 (mg/kg) 給藥方式 在最高劑量之腫瘤 生長 抑制 (TGI) 乳癌 MCF7 1, 3, 10 Q2W x 6 85% 乳癌 HCC-1428 3, 10, 30 Q2W x 6 55% 胰臟癌 HPAC 5, 20, 80 Q2W x 5 47% 結腸直腸癌 SW480 100 Q2W x 4 49% 肺癌 NCI-H526 10, 30, 100 Q2W x 5 43% OBI-888 在五種癌症動物模型所展現的抑制效果 26Q2W, every 2 weeks; TGI, tumor growth inhibition. OBI Data on File.
- 27. OBI 888-001 臨床試驗 Part 1: 劑量遞增階段 27 * Number of patients who completed the 4-week DLT assessment A Phase I/II, Open-Label, Dose Escalation and Cohort Expansion Study Evaluating the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Therapeutic Activity of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors. ClinicalTrials.gov Identifier: NCT03573544 劑量遞增階段(3+3) Endpoints: Safety, efficacy, PK/ADA, Tumor and CTC exploratory biomarkers Results • No drug-related SAEs • No DLTs at 20 mg/kg • OBI-888 was well tolerated 20 mg/kg (N = 3*) 10 mg/kg (N = 3*) 5 mg/kg (N = 3*)
- 28. OBI 888-001 臨床試驗 Part 2: 族群擴增階段 28 *The basket cohort includes all other epithelial cancers. A Phase I/II, Open-Label, Dose Escalation and Cohort Expansion Study Evaluating the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Therapeutic Activity of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors. ClinicalTrials.gov Identifier: NCT03573544 Stage 2 Study Centers • 6-9 sites in the US (MDAAC, OSU) • 3-6 sites in Taiwan (TBD) 胰臟癌 胃癌 食道癌 結腸直腸癌 籃型族群 * • OBI-888 monotherapy at 20 mg/kg weekly • Advanced cancer; no effective SOC available; measurable disease; PS 0-1 • Patient tumor sample must have an H score of ≥100 for Globo H in an FDA IDE-approved assay (NeoGemonics) • H0 5%; H1 25%; alpha 0.5%; power 90%; ≥1/9; ≥4/30
- 30. OBI-999 以具腫瘤特異性之Globo H抗原為作用標的 30 OBI data on file. 0 20 40 60 80 100 0 1 2 3 4 5 6 7 8 % DAR Species OBI-999 0 20 40 60 80 100 0 1 2 3 4 5 6 7 8 % DAR Species Adcetris OBI-999 Adcetris Target / Linker / Payload Globo H Ab / Thiobrige / vc-PAB-MMAE CD30 Ab / Maleimide / vc-MMAE Linker Thiobridge (proprietary) Maleimide (generic) Conjugation technology Site specific Random Proprietary Novel Site-Specific Linker Technology ThioBridge® DAR4>95% DAR2 & DAR4 (majority) Improved Homogeneity vs Adcetris
- 31. OBI-999 四種動物模型顯示抑制腫瘤生長之效果 31PDX, patient-derived xenograft; TGI, tumor growth inhibition; QW, every week; Q3W, every 3 weeks. OBI Data on File. 癌症種類 動物模型 劑量（mg/kg) 給藥方式 在最高劑量之腫瘤反應或腫 瘤生長抑制 (TGI) 乳癌 MCF7 1, 3 QW x 6 or Q3W x 2 完全反應 胰臟癌 HPAC 10 QW x 4 完全反應 胃癌 NCI-N87 1, 3, 10 QW x 4 完全反應 (CR achieved at both 3 and 10 mg/kg) 肺癌PDX LU-01-0266 1, 3, 10 QW x 4 完全反應 完全反應 = 腫瘤消失
- 32. once per 3 weeks for two doses once per for four weeks Latent day: 7 day Cell inoculation 2x107 with matrigel (1:1) OBI-999 TGI%: QWK 100%, Q3WK 85% OBI-999 在MCF7乳癌模型隨給藥間隔延長， 依然顯示很強的抗癌效果 32 OBI data on file. Female nude mice (n = 8 per group) were bearing MCF-7 breast cancer cells were dosed as indicated Globo H expression: 81%. MCF7 Xenograft (AB67837)
- 33. QWK x4 Latent day: 7 days Day 0: Start treatment day Cell inoculation 3x106 Tumor Free OBI-999 at 3 mg/kg: TGI 36.1% on Day 36 OBI-999 在HPAC胰臟癌異種移植模型 顯示極強的腫瘤抑制作用 33OBI data on file. Female BALB/c nude mice (n = 8 per group) were implanted subcutaneously with HPAC pancreatic cancer cells. Complete response defined as tumor free. Globo H expression: 97% HPAC Xenograft (OBI-20180927) 2019獲FDA 核准孤兒藥資格
- 34. OBI-999 臨床試驗 34 IDE, Investigational Device Exemption. Clinicaltrials.gov. A Phase 1/2, Open-Label, Dose-Escalation and Cohort-Expansion Study Evaluating the Safety, Pharmacokinetics, and Therapeutic Activity of OBI-999 in Patients With Advanced Solid Tumors. NCT04084366. 多種實體腫瘤 胰臟癌,乳癌,胃癌,食道癌,結腸 直腸癌,肺癌等….. Part 1 劑量遞增階段 OBI-999 Part 2 族群擴增階段 OBI-999 Patient recruitment initiated 以IDE-Approved Assay量測Globo H的表現量
- 36. OBI-3424 具腫瘤特異性之小分子前驅藥物 36 OBI-3424 Tumor Cell AKR1C3 Active drug Prodrug Tumor Cells Killed AKR1C3 Enzyme Present No AKR1C3 Minimal Impact on Healthy Cells Healthy Cell AKR1C3 Active drugOBI 3424 Prodrug OBI-3424經腫瘤內AKR1C3酵素活化後，會釋放出細胞毒殺劑
- 37. OBI-3424 致力開發具高度醫療需求且 AKR1C3>50%之癌症適應症 37 *AKR1C3 Expression: Guise CP, et al. Cancer Res. 2010;70(4):1573-1584. CRPC, castration-resistant prostate cancer; IND, Investigational New Drug Application; n/a, not applicable; NCI, National Cancer Institute; PPTC, Pediatric Preclinical Testing Consortium; T-ALL, T-cell acute lymphoblastic leukemia. 癌症種類 臨床發展進度 AKR1C3表現率* 肝癌 持續開發中 89% 對去勢療法產生抗性之 攝護腺癌 （CRPC） 持續開發中 58% T細胞急性淋巴性 白血病 （T-ALL） P1 IND planned (NCI funded PPTC) 86% 腎臟癌 n/a 64% 膀胱癌 n/a 66% 胃癌 n/a 59%
- 38. OBI-3424 在原位肝癌動物模型顯示令 人印象深刻的臨床前數據 38 Duan et al., AACR Annual Meeting 2016, Abstract #1369 0 4 7 11 14 18 21 25 28 32 35 Days TumorArea(mm2) 2 4 6 8 10 12 14 Saline Sorafenib OBI-3424 2.5mpk OBI-3424 5mpk Significant Separation Achieved
- 39. OBI-3424 在PDX動物模型（T-ALL 31） 明顯降低白血病之骨髓浸潤 39 PB, peripheral blood; PDX, patient-derived xenograft. OBI Press Release 30 Oct 2017: OBI Pharma announces OBI-3424 results from the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Days Post-treatment Initiation %huCD45+inthePB Prof Richard B. Lock Head of the Leukemia Biology Program Children’s Cancer Institute in Australia Control Group OBI-3424 Group Significant Difference in Event-Free Survival (EFS) OBI-3424 is one of the most effective drugs we have ever tested against T-ALL in over 12 years of evaluating drugs at the Children’s Cancer Institute using preclinical models of childhood ALL “ “
- 40. OBI-3424 臨床試驗 40Clinicaltrials.gov. This Study is to Evaluate OBI-3424 Safe and Effective Treatment Dose in Subjects With Hepatocellular Carcinoma or Castrate Resistant Prostate Cancer. NCT03592264 在劑量遞增試驗中已轉 移或不可切除的實體瘤 Part 1 劑量遞增階段 OBI-3424 Part 2 族群擴增階段 OBI-3424 (HCC, CRPC) 以IDE-Approved Assay量測AKR1C3酵素的表現量 Ongoing – Completed 6 Cohorts
- 41. CAR T Anti-SSEA4 Anti-Globo H SSEA4 Targeted Therapies OBI-998 ADC OBI-898 mAb OBI-866 Vaccine OBI開發中的臨床前創新產品 41 Bispecific Antibody Novel IO Targets Globo Series Targets
- 43. 43 Includes Patents Held By Licensors. Approved Patents Patents in Review 68 84 155 186 2019 20202019 2020 浩鼎產品線 完善的全球智財權保護
- 44. 2019臨床試驗里程碑 44 OBI-999 • Commenced Phase 1a Safety and MTD study at MD Anderson CC • FDA granted orphan drug designation for the treatment of pancreatic cancer • Presented poster at AACR meeting OBI-3424 • Commenced Phase 1a Safety and MTD study in Solid tumors at MD Anderson CC and Ohio State University • Peer reviewed article published in Clinical Cancer Research: OBI-3424, a novel AKR1C3-activated prodrug, exhibits potent efficacy against preclinical models of T-ALL OBI-888 • Completed Phase 1a Safety and MTD study - Safe and dose selected • Initiated Phase 1b expansion cohort study in multiple cancers in US • IDE approved for Globo H screening • Presented poster at AACR meeting Adagloxad Simolenin • Enrollment ongoing in the Global Phase 3 GLORIA clinical trial in patients with Triple- negative breast cancer at high risk of recurrence • Presented trial progress Poster at SABCS meeting (San Antonio, TX)
- 46. 2020 2021 2022 20232019 2024 2020~2021臨床試驗預期獲致之成果 46 Adagloxad Simolenin OBI-888 OBI-999 OBI-3424 Initiated Global Phase III Triple-Negative Breast Cancer Trial Enrollment Ends IND Approved Phase 1 DATA IND Approved Phase 1 DATA Stage 2 DATA Phase 1 DATA Phase 2 Stage 1 DATA Phase 2 Stage 2 DATA IND Approved Stage 2 DATA
- 47. THANK YOU Please visit our website: www.obipharma.com