Document 448344
NASDAQ: CASI www.casipharmaceu6cals.com PRESENTATION November 17, 2014 Forward-‐Looking Statements This presenta6on contains forward-‐looking statements within the meaning of the Private Securi6es Li6ga6on Reform Act with respect to the outlook for expecta6ons for future financial or business performance, strategies, expecta6ons and goals. Forward-‐looking statements are subject to numerous assump6ons, risks and uncertain6es, which change over 6me. Forward-‐ looking statements speak only as of the date they are made, and no duty to update forward-‐ looking statements is assumed. Actual results could differ materially from those currently an6cipated due to a number of factors. Such factors, among others, could have a material adverse effect upon our business, results of opera6ons and financial condi6on. Addi6onal informa6on about the factors and risks that could affect our business, financial condi6on and results of opera6ons, are contained in our filings with the U.S. Securi6es and Exchange Commission, which are available at www.sec.gov. Slide 2 Company Overview • We are a U.S. based, NASDAQ-‐listed company and plan to become an integrated biopharmaceu6cal company with significant market share in China, while establishing partnerships for global development and commercializa6on • Our business model is to leverage our exper6se and resources in North America and China for cost-‐ effec6ve drug development and commercializa6on • Our product pipeline includes ENMD-‐2076, a proprietary, novel, first-‐in-‐class oncology drug candidate that has demonstrated ac6vity in several cancer indica6ons; ENMD-‐2076 is currently in three inves6gator-‐ini6ated Phase II clinical trials with ongoing biomarker analysis; we expect to ini6ate an advanced trial in fibrolamellar carcinoma (FLC) in 2015 • Our product pipeline also includes commercial rights to ZEVALIN®, MARQIBO® and Cap6sol Enabled™ melphalan in the greater China region; we are currently preparing to launch ZEVALIN® in Hong Kong, and preparing our market authoriza6on registra6on filings in China and Taiwan • Our corporate headquarters and strategic opera6ons are located in Rockville, Maryland, with a wholly owned subsidiary and local R&D and marke6ng opera6ons in Beijing, China Slide 3 Inflec6on Points in 2015 • ENMD-‐2076: We plan to ini6ate an advanced-‐stage clinical trial for ENMD-‐2076 in fibrolamellar carcinoma (FLC) • FDA IND allowance received • Orphan drug designa6on received for hepatocellular carcinoma (HCC), which includes FLC • Strong science and clinical and regulatory support for trial – Discovery of gene6c altera6on beher defines targeted therapy for FLC • ZEVALIN ® : We plan to launch ZEVALIN® in Hong Kong in 2015 • A product launch allows Company to transi6on from development-‐stage to commercial-‐stage • Also allows Company to accumulate clinical experience in Hong Kong popula6on to support market approval in China Slide 4 Pipeline Proprietary Drug Candidates For Global Market Slide 5 Pipeline In-‐licensed Products For Greater China Market Slide 6 ENMD-‐2076 A Proprietary Orally Ac>ve Mul>ple Kinase Inhibitor with An>angiogenic and An>prolifera>ve Mechanism of Ac>on Orally available protein Kinase Inhibitor Unique combina6on of mul6ple targets Address cancer cell prolifera6on, angiogenesis Slide 7 ENMD-‐2076 Induces Cell Cycle Arrest at G2/M (4N) Consistent With Inhibi>on of Aurora A 5 Days 20 µM 24 hours 1 µM ENMD-2076 HCT-116 No drug 20 µM Cell Numbers (HCT116) 2N 4N Control 20 µM Slide 8 1 µM MK-0457 8N 5 µM ENMD-2076 1 µM MK-0457 2N 4N 8N ENMD-‐2076 Inhibits FGF-‐Driven Angiogenesis in Matrigel In Vivo Inhibits Formation of Blood Vessels Slide 9 Regresses Newly Formed Blood Vessels - bFGF Control –bFGF d13 + bFGF Control +bFGF d7 25 mg/kg PO BID +bFGF d13 50 mg/kg PO BID 150 mg/kg bid d7- d13 ENMD-‐2076 Pre-‐Clinical Summary First in class, poten>ally a novel targeted therapy for mul>ple cancer indica>ons • Orally ac6ve, mul6-‐kinase inhibitor that inhibits Aurora A and several important receptor tyrosine kinases to avoid development of resistance • Dose-‐dependent ac6vity in ectopic & orthotopic tumor models • Can be combined effec6vely with chemotherapy in preclinical models • Acceptable/manageable toxicity profile • PK-‐PD correla6on for kinase targets of ENMD-‐2076 – Ac6vity demonstrated towards VEGFRs, Aur A, FGFRs, SRC, c-‐Kit, Flt3 in vivo at efficacious doses • Excellent drug proper6es & long patent life Slide 10 ENMD-‐2076 has poten6al use in a variety of & hematological cancers solid ENMD-‐2076 Completed Clinical Trials ENMD-‐2076 Phase I 2076-‐CL-‐001: Open-‐Label, Dose-‐Escala6on, Safety, and PK Study of ENMD-‐2076 Administered Orally to Pa6ents with Advanced Cancer Completed (67) Dr. Wells Messersmith, UCHSC Dr. Geoffrey Shapiro, DFCI Slide 11 2076-‐CL-‐002: Study of ENMD-‐2076 in Pa6ents with Relapsed or Refractory Mul6ple Myeloma Correla6ve Studies Completed (30) Dr. Sherif Farag, IUPUI Phase II 2076-‐CL-‐003: Study of ENMD-‐2076 in Pa6ents with Relapsed or Refractory Hematological Malignancies Correla6ve Studies Completed (27) Dr. Karen Yee, PMH 2076-‐CL-‐004: Study of ENMD-‐2076 in Pa6ents with Pla6num Resistant Ovarian Cancer Completed (54) Dr. Ursula Matulonis, DFCI Dr. Kian Behbakht, UCHSC Dr. William Tew, MSKCC Dr. Daniela Matei, IUPUI Dr. Gini Fleming, UCMC Dr. Amit Oza, PMH ENMD-‐2076 Phase I Data Demonstrated Good Safety Profile and Promising Preliminary An>tumor Ac>vity in Mul>ple Types of Solid Tumors 60% 60 mg/m2/d 50% 40% 30% Data supports further Phase II clinical trials Slide 12 120 mg/m2/d 200 mg/m2/d 160 mg/m2/d 20% Par6al Response/Progression 10% Free Survival 6 months pa6ents 0% include: -10% ‒ Ovarian cancer ‒ Triple-‐Nega6ve Breast -20% Cancer -30% ‒ Sop Tissue Sarcoma -40% ‒ Fibrolamellar Carcinoma 80 mg/m2/d -50% colorectal colorectal ovarian pancreatic colorectal cervical ovarian rectal colorectal colorectal trachea colon colon ovarian melanoma renal cell ovarian cervical gastric colorectal ovarian rectal pancreatic breast colorectal colon ovarian ovarian carcinoid urachal ovarian ovarian colorectal bladder sarcoma breast colorectal colorectal colorectal colorectal renal cell renal cell ovarian renal cell ovarian ovarian colorectal ovarian ovarian neuroend colorectal melanoma neuroend ovarian ovarian hepatocell ovarian ovarian Recommended dose: ‒ 160 mg/m2/d Overall response rate ‒ Par6al Response: 3% ‒ Stable Disease: 85% (30% reduc6on in tumor size) ENMD-‐2076 Current Ongoing Trials ENMD-‐2076 Phase II Phase II Study of ENMD-‐2076 in Pa6ents with Previously Treated Locally Advanced and Metasta6c Triple-‐Nega6ve Breast Cancer Currently enrolling Dr. Jennifer Diamond, University of Colorado Dr. Kathy Miller, Indiana University Bren Simon Cancer Center Slide 13 Phase II Study of Oral Phase II Study of Oral ENMD-‐2076 Administrated to ENMD-‐2076 Administrated to Pa6ents with Ovarian Clear Cell Carcinoma Advanced and Metasta6c (OCCC) Sop Tissue Sarcoma (STS) Currently enrolling Currently enrolling Dr. Albiruni R A Razak Dr. Amit Oza Princess Margaret Hospital, Princess Margaret Hospital, Toronto, Canada Toronto, Canada Phase II Study of Oral ENMD-‐2076 Administrated to Advanced Fibrolamellar Carcinoma (FLC) FDA IND open Dr. Ghassan Abou-‐Alfa Memorial Sloan-‐Kehering Cancer Center New York, New York ENMD-‐2076 Clinical Summary A drug candidate with good safety and poten>al efficacy in niche indica>ons • Phase I – Ac6vity shown in a variety of solid and hematological cancer pa6ents – Responses in pla6num refractory/resistant ovarian cancer – Par6al Response in FLC-‐HCC pa6ent – Par6al Response in Triple Nega6ve Breast Cancer, Sop Tissue Sarcoma, and myeloma pa6ents and CRi in AML pa6ent • Phase II – Phase II trials currently ongoing in Triple Nega6ve Breast Cancer, Sop Tissue Sarcoma and Ovarian Cancer Clear Cell – Goal is to iden6fy a niche indica6on and reach clinical inflec6on point – Correla6ve biomarker analysis ongoing using advanced technology We plan to move forward with an advanced stage clinical trial in Fibrolamellar Carcinoma (FLC) • Slide 14 ENMD-‐2076 A Poten>al Targeted Therapy for Triple-‐Nega>ve Breast Cancer (TNBC) Pre-‐clinical • Robust single agent an6-‐TNBC ac6vi6es were demonstrated in vitro and in vivo including mdr human TNBC xenograp models • p53-‐based genomic profiling was iden6fied as a candidate for predic6ve biomarker for pa6ent selec6on of clinical trials • Synergis6c effects with chemotherapy with increased objec6ve response rate were observed Phase I • In our completed Phase I study in solid tumors, a TNBC pa6ent who had failed mul6ple chemotherapy regimens had clinically significant stabiliza6on of disease for 41 weeks • Effec6ve doses between 150 mg and 325 mg/day have been tolerated by a number of pa6ents in the ovarian study over several months and were associated with stable disease or par6al responses • Data support further clinical trials Phase II • Phase II trial in the U.S. is underway • To assess clinical benefit of ENMD-‐2076 in locally advanced and metasta6c TNBC pa6ents • To test in clinical seung the correla6on between p53 based genomic profiling predic6ve biomarker and sensi6vity of the drug to TNBC • To provide guidance on pa6ent selec6on and trial design for more advanced clinical trials Slide 15 ENMD-‐2076 A Poten>al Targeted Therapy for SoX Tissue Sarcoma (STS) Pre-‐clinical Phase I Phase II Slide 16 • Inhibi6on of Aurora kinases abrogates tumor development and progression of sop 6ssue sarcoma in animal model as published in literature • Inhibi6on of angiogenesis delayed the progression of the disease as demonstrated in clinical trials of Pazopanib • The unique inhibi6on to both Aurora A kinase and angiogenesis renders ENMD-‐2076 an ahrac6ve drug candidate for the treatment of sarcomas • An6-‐tumor effects of ENMD-‐2076 against mul6ple sarcoma cell lines demonstrated in pre-‐clinical study • Phase I trial of ENMD-‐2076 in solid tumors observed 1 advanced/metasta6c sarcoma pa6ent prolonged progression free survival (PFS) for 21 months aper ENMD-‐2076 single agent treatment • The median disease PFS for advanced/metasta6c pa6ents is less than 2 months without treatment or less than 5 months with treatments available. • Phase II trial underway in Canada • To assess safety and efficacy of ENMD-‐2076 in advanced and metasta6c STS pa6ents • To test in clinical seung the correla6on between genomic profiling predic6ve biomarker and sensi6vity of the drug in STS pa6ents • To provide guidance on pa6ent selec6on and trial design for more advanced clinical trials ENMD-‐2076 A Poten>al Targeted Therapy for Clear Cell Ovarian Cancer Pre-‐clinical Phase I Phase II Slide 17 • Aurora A is open over expressed in ovarian cancer cells • VEGF is frequently expressed in ovarian clear cell carcinoma • Demonstrated single agent ac6vity in tumor models of human ovarian cancer • Synergis6c effect of ENMD-‐2076 with paclitaxel has been demonstrated in pre-‐clinical studies • Phase I study at the maximum tolerated dose (MTD), ENMD-‐2076 was used to treat 12 ovarian cancer pa6ents (in addi6on to 8 ovarian pa6ents in the dose escala6on por6on) who had failed mul6ple chemotherapy regimens • 40% of the pa6ents have had a Par6al Response either by RECIST or CA-‐125 criteria. Addi6onal 15% have shown clinical benefit, including reduc6ons in tumor size, improvement in symptoms, or both • 1 pa6ent had been on drug for over 5 years with stable disease (SD) • 64 pa6ents of pla6num resistant were enrolled in completed Phase II clinical trial in ovarian cancer. The progression free survival (PFS) rate at 6 months was 22% with a median 6me to progression of 3.6 months • 1 pa6ent had been on drug for over 2 years with stable disease • Stronger ac6vity in clear cell ovarian cancer observed: 3 pa6ents enrolled in the Phase II study with 2 pa6ents having longer progression free survival than the median • Phase II clinical trial in clear cell ovarian cancer currently ongoing ENMD-‐2076 A Poten>al to treat Fibrolamellar Carcinoma (FLC) • Fibrolamellar carcinoma (FLC) is a rare malignant neoplasm of the liver, represen6ng 0.6% to 8.6% of all hepatocellular carcinomas.* • FLC has a dis6nct clinical and histological prognosis, and generally occurs in young individuals. It is open advanced when diagnosed due to lack of symptoms. Surgical resec6ons are the op6mal treatment for localized tumor, but it has a very high recurrence rate. In cases of postopera6ve recurrence, resec6on is not open possible. Overall prognosis remains poor because of its primary chemo-‐resistance and early recurrence of metastasis. • There is no standard first-‐line systemic treatment op6on available for FLC pa6ents. • The absence of any treatment op6ons highlights the need for new compounds with ac6vity in this pa6ent popula6on. • We believe ENMD-‐2076 has poten6al to treat FLC. We observed a pa6ent in our Phase I solid tumor trial who achieved stable disease at Cycle 2, a par6al response at Cycle 12, and maintained stable disease for a total of 17 months aper treatment. * 1986 to 1999 SEER data and various interna>onal series Slide 18 Scien6fic Ra6onale Role of Aurora A in Fibrolamellar Carcinoma (FLC) A Recurrent DNAJB1-‐PRKACA Chimeric Transcript is Detected in FLC* • The chimeric transcript is expressed in FLC but not in adjacent liver • The chimeric RNA is predicted to code for a protein containing the amino-‐terminal domain of DNAJB1, fused in frame with PRKACA, the cataly6c domain of protein kinase A • Immunoprecipita6on and Western blot analyses confirmed that the chimeric protein is expressed in tumor 6ssue, and a cell culture assay indicated that it retains kinase ac6vity, which results in over expression of both protein kinase A and down stream Aurora A kinase • Evidence supports the presence of the DNAJB1-‐PRKACA chimeric transcript in 100% of the FLC examined (15/15) , sugges6ng strongly that this gene6c altera6on contributes to tumor pathogenesis of FLC Aurora A kinase suggested to poten;ally be a primary target in FLC *28 FEBRUARY 2014 VOL 343 SCIENCE www.sciencemag.org Slide 19 Scien6fic Ra6onale Role of VEGF and FGFR in Fibrolamellar Carcinoma (FLC) • VEGF is one of the main inducers of liver tumor angiogenesis. Increased levels of VEGF have been observed in HCC. • Hepatoma cells are believed to possess a prolifera6on mechanism regulated by an autocrine mechanism, a paracrine mechanism, or both, which are mediated by FGF-‐1/ FGFR or FGF-‐2/FGFR (or both). • In addi6on, a gain of FGF-‐R2 (IIIb), -‐R2 (IIIc), and -‐R3 (IIIb) may be associated with malignant transforma6on of liver tumor and may eventually serve as useful diagnos6c and prognos6c indicators. VEGF and FGFR inhibi;on may also play a role in target therapy for FLC pa;ents Slide 20 Clinical Ra6onale Evidence of ENMD-‐2076 Efficacy in Fibrolamellar Carcinoma (FLC) Pa>ent FLC Par;al Response Observed in Phase I Trial of ENMD-‐2076 April 2007 Pa6ent received diagnosis of FLC Jan 2008 Pa6ent received TACE therapy with Doxorubicin/Cispla6n Jan -‐ Jun 2009 Pa6ent received sorafenib treatment for 5 months, relapsed Aper being on ENMD-‐2076 treatment, pa6ent achieved stable disease (SD) at Cycle 2, a par6al response (PR) at Cycle 12, and maintains stable disease for a total of 17 months aper treatment Slide 21 Oct 2007 Pa6ent received TACE therapy with Doxorubicin/Cispla6n May 2008 Pa6ent underwent a liver transplanta6on, relapsed Jul 2009 Aper relapse from sorafenib, pa6ent enrolled in ENMD-‐2076 clinical trial. He starts a dose of 345mg/day in cycle 1 and maintains at 200mg/day most of the cycles of treatment ENMD-‐2076 A Poten>al to be First Drug to Treat Fibrolamellar Carcinoma (FLC) • ENMD-‐2076: targe6ng VEGF, FGFR, and Aurora A • Preclinical animal data demonstrated ac6vity in hepatocellular carcinoma (HCC) models • Clinical evidence supports ra6onale for further clinical trials • FDA: granted Orphan Drug Designa6on in HCC, including for FLC • FDA: IND allowed and now open • We are currently in prepara6on of an advanced clinical trial in FLC, with lead site and inves6gator at Memorial Sloan-‐Kehering Cancer Center, New York Slide 22 ZEVALIN® Launch in Hong Kong in 2015 A Dual-‐Commercializa6on Approach: • A CD20-‐directed, isotope labeled McAb, approved and currently marketed by partner (Spectrum) for follicular non-‐Hodgkins lymphoma (NHL), with ongoing Phase III trial in diffuse large B cell lymphoma (DLBCL) • Launch in Hong Kong in 2015; File Import Drug Registra6on in China and Taiwan in 2015 • The retail cost of ZEVALIN in the U.S. per dose is approximately $40,000 – Treatment cycle is one dose • Annual incidence of NHL is es6mated at 46,563 new cases with a mortality of 29,201 cases in China in 2015* • The five-‐year prevalence is es6mated at 69,200 cases*, including 13% of cases (or 8,996) in fNHL and 30% of cases (or 20,760) in DLBCL *hhp://globocan.iarc.fr/Pages/online.aspx Slide 23 MARQIBO® File for Marke>ng Approval in greater China in 2015 A Dual-‐Commercializa6on Approach: • Liposome encapsulated formula6on of vincris6ne, approved and currently marketed by partner (Spectrum) for second line (Ph-‐) adult acute lymphocy6c leukemia (ALL), with ongoing Phase III trial in untreated adult ALL and ongoing Phase III trial comparing R-‐CHMP to R-‐CHOP in adult untreated NHL • File Import Drug Registra6on in China and Taiwan in 2015; launch in Hong Kong in 2015; • The retail cost of MARQIBO in the U.S. per dose is approximately $11,700 – Treatment cycle is 28 days, 4 doses per cycle, mul6ple cycle regimen • Annual incidence of leukemia is es6mated at 70,240 new cases with a mortality of 58,746 cases in China in 2015* • The five-‐year prevalence is es6mated at 73,694 cases* including about 10,000 Ph-‐ adult ALL *hhp://globocan.iarc.fr/Pages/online.aspx Slide 24 Cap6sol-‐Enabled™ Melphalan A Dual-‐Development Approach: • Cap6sol-‐Enabled formula6on of an alkyla6ng chemotherapy agent for mul6ple myeloma, indicated for condi6oning agent prior to stem cell transplant • NDA filing expected by partner/Spectrum in 2014 " • File Import Drug Applica6ons aper partner’s NDA approval • The retail cost for branded Alkeran injec6on in the U.S. per dose is approximately $1,971/50mg – Treatment cycle is 4 treatments given every 2 weeks, followed by treatments given in 4-‐week intervals • Annual incidence of mul6ple myeloma is es6mated at 12,197 cases with a mortality of 9,038 cases in China in 2015* • The five-‐year prevalence is es6mated at 14,100 cases* *hhp://globocan.iarc.fr/Pages/online.aspx Slide 25 2ME2 (2-‐Methoxyestradiol) An Orally Ac>ve Compound that has An>-‐Prolifera>ve, An>-‐ Angiogenic and An>-‐Inflammatory Proper>es • Significant efficacy in animal models of mul6ple cancers and autoimmune disorders, including rheumatoid arthri6s and mul6ple sclerosis • Addi6onal preclinical studies ongoing in collabora6on with research ins6tutes in North America • Completed mul6ple Phase I and Phase II trials in cancer pa6ents with solid tumors and mul6ple myeloma • Phase I also conducted in healthy volunteers • Excellent safety profile OH • Open IND with the FDA for rheumatoid arthri6s H 3C O HO Slide 26 Experienced Board and Management Determined to Deliver Results BOARD OF DIRECTORS Dr. Wei-‐Wu He, Chairman Chairman & CEO, Origene Technologies, Inc. Dr. Tak W. Mak, Chief Scien>fic Advisor Director, Campbell Family Research Ins6tute/Princess Margaret Hospital; University Professor, University of Toronto James Huang General Partner, Kleiner Perkins Caufield & Byers China Rajesh C. Shrotriya, MD Chairman & CEO, Spectrum Pharmaceu6cals, Inc. Dr. Y. Alexander Wu Franklin C. Salisbury, Jr. President, Na6onal Founda6on for Cancer Research CEO, Crown Biosciences, Inc. OFFICERS Dr. Ken K. Ren Chief Execu6ve Officer Cynthia W. Hu Chief Opera6ng Officer, General Counsel & Secretary Sara B. Capitelli VP, Finance, Principal Accoun6ng Officer Slide 27 2013-‐2014 A Year of Accomplishments Clinical Achievements ! ! ! ! ! ! Ini6ated Phase II clinical trial for ENMD-‐2076 in ovarian clear cell carcinoma at Princess Margaret Hospital CFDA approves applica6on to start a China trial for ENMD-‐2076 in triple-‐nega6ve breast cancer Filed clinical trial applica6on with CFDA for ENMD-‐2076 in advanced ovarian clear cell carcinoma Ini6ated Phase II clinical trial for ENMD-‐2076 in sop 6ssue sarcoma at Princess Margaret Hospital Filed clinical trial applica6on with the CFDA for ENMD-‐2076 in sop 6ssue sarcoma Ini6ated crossover bioavailability study of dosage form for ENMD-‐2076 to be used for pivotal/registra6on clinical trials Infrastructure and Corporate Achievements ! Completed $10 million follow-‐on financing with fundamental investors, including IDG-‐ACCEL and Kleiner Perkins Caufield & Byers China ! Established wholly-‐owned subsidiary and R&D Center in Beijing, built from ground up with a strong team in CFDA regulatory affairs, clinical trial management and local drug development Valida;on Achievements Received U.S. Orphan Drug designa6on for ENMD-‐2076 to treat Hepatocellular Carcinoma (HCC) Received patent allowance in China for 2ME2 in rheumatoid diseases Received patent allowance in China for ENMD-‐2076 Poster presenta6on at ASCO en6tled “Phase II Study of Oral ENMD-‐2076 Administered to Pa>ents with Ovarian Clear Cell Carcinoma: A Trial of the Princess Margaret Phase II Consor>um” ! Poster presenta6on at ASCO en6tled “Phase II Study of Oral ENMD-‐2076 Administered to Pa>ents (pts) With Advanced SoX Tissue Sarcoma (STS)” ! ! ! ! Slide 28 2014-‐2015 Milestones ! Complete crossover bioavailability formula6on study for ENMD-‐2076 ! File clinical trial applica6on with the CFDA for ENMD-‐2076 in ovarian clear cell carcinoma ! June 2014 ASCO poster for sop 6ssue sarcoma trial ! June 2014 ASCO poster for ovarian clear cell carcinoma trial ! Implement company name change ! CFDA approval to start ENMD-‐2076 triple-‐nega6ve breast cancer trial in China ! CFDA approval to start ENMD-‐2076 sop 6ssue sarcoma trial in China ! Acquired greater China rights for 3 oncology drugs from Spectrum Pharmaceu6cals, Inc. ! FDA IND allowance for ENMD-‐2076 Phase II trial in fibrolamellar carcinoma (FLC) " Ini;ate advanced clinical trial for ENMD-‐2076 in FLC pa;ents in the U.S. " Launch commercial ac;vi;es for ZEVALIN in Hong Kong " File import drug registra6on (IDR) for ZEVALIN in Taiwan and China " File import drug registra6on (IDR) for MARQIBO in Taiwan, Hong Kong and China " Ini6ate triple-‐nega6ve breast cancer trial in China " Receive marke6ng approval and ini6ate commercializa6on of MARQIBO in Hong Kong " Receive marke6ng approval and ini6ate commercializa6on of ZEVALIN in Taiwan " Expand management team, including adding on Chief Medical Officer " Provide update on proprietary ENMD-‐2076 " Provide update on clinical development plan for 2ME2 " File IDR for CE-‐MEPHALAN in Hong Kong, Taiwan, and China, pending partner’s FDA NDA approval " Con6nue to acquire clinical-‐stage drug candidate(s) to enrich pipeline Slide 29 Investment Highlights • Undervalued, with significant defined milestones in 2015 and beyond. Near-‐term inflec6on points include: – Ini6a6ng advanced clinical trial for ENMD-‐2076 in fibrolamellar hepatocellular carcinoma (FLC), with poten6al to be first drug to address FLC – Launching commercial ac6vi6es for ZEVALIN in Hong Kong • Strong cash posi6on, backed by successful VC’s and smart money • Strong product pipeline that includes in-‐licensed and proprietary products with significant, unprecedented market opportunity • Compelling business model, unique and differen6ated from compe6ng companies • An experienced, mo6vated management team and board with exper6se in naviga6ng the clinical and regulatory pathways in both North America and China • As a U.S.-‐based company with a wholly owned subsidiary and R&D opera6ons in China, CASI is a gateway for U.S. investors to tap into China’s fast growing pharmaceu6cal market, with assurance of NASDAQ public company governance and risk management Slide 30 NASDAQ: CASI www.casipharmaceu6cals.com Appendices ENMD-‐2076 An>tumor Ac>vity of ENMD-‐2076 Alone or in Combina>on with CDDP in an Orthotopic MDA-‐MB-‐231 Human Triple Nega>ve Breast Cancer Model Protocol-1 Protocol-2 Protocol-3 2000 Group (Mice) Protocol-1 Day 34- 49 Protocol-2 Day 50- 64 Protocol-3 Day 65-82 G1 No treatment ENMD-2076 200 mg/kg, po, qd Off study Mean tumor volume (mm3) 1750 6/8 regressions G2 1500 ENMD-2076 200 mg/kg, po, qd No treatment ENMD-2076 200 mg/kg, po, qd 7/9 regressions CDDP 6 mg/kg, ip, qw 9/9 progression s ENMD-2076 200 mg/kg, po, qd T/C = 0.54, p = 0.226 9/10 regressions ENMD-2076 + CDDP No treatment 1250 T/C=0.04, p = 0.011 1000 1/9 regressions Rx 750 G3 500 G4 250 T/C = -0.08, p = 0.006 0 30 40 50 60 Days post tumor implantation Slide 33 70 80 9/10 regressions 9/10 progressions Off study Off study ENMD-‐2076 Effects in HT-‐29 Colon Cancer XenograX Tumors PET CT showed significant decreases in 18FDC uptake aper treatment, associated with a marked reduc6on in prolifera6on as assessed by Ki-‐67 Slide 34 ENMD-‐2076 An>tumor Ac>vity of ENMD-‐2076 Along or in Combina>on with Paclitaxel in a TOV-‐21G Ectopic Human Ovarian Carcinoma Model Incidence Tumor Regression/Cohort (%) 100 90 80 • Combination is tolerable 70 60 50 4/9 4/9 40 3/9 30 2/9 20 1/9 1/9 100 50 10 0 Slide 35 8/9 • 9 mice/cohort • 46 treatment days • MTD regimen of Paclitaxel 0/9 Vehicle Paclitaxel 22 mg/kg q3dx4 ip 200 ENMD-2076 (mg/kg, qd po) 200 100 ENMD-2076 + Paclitaxel 50 ENMD-‐2076 An>tumor Ac>vity of ENMD-‐2076 in Three Different Human Hepatocellular Carcinoma (HCC) XenograX Model Slide 36 ENMD-‐2076 An>tumor Ac>vity of ENMD-‐2076 Against Breast Cancer Cell Lines In Vitro ENMD-‐2076 demonstrated more robust ac6vity against cell lines of the Triple-‐ Nega6ve Breast Cancer subtype compared to the luminal and HER2-‐ amplified subtypes Slide 37 ENMD-‐2076 Predic>ve Biomarkers of Triple-‐Nega>ve Breast Cancer (TNBC) Sensi>vity to ENMD-‐2076 TNBC cell lines with a p53 muta6on and/or p53 over expression showing more sensi6ve to the cytotoxic and pro-‐apopto6c effects of ENMD-‐2076 Slide 38 0% -10% colorectal colorectal ovarian pancreatic colorectal cervical ovarian rectal colorectal colorectal trachea colon colon ovarian melanoma renal cell ovarian cervical gastric colorectal ovarian rectal pancreatic breast colorectal colon ovarian ovarian carcinoid urachal ovarian ovarian colorectal bladder sarcoma breast colorectal colorectal colorectal colorectal renal cell renal cell ovarian renal cell ovarian ovarian colorectal ovarian ovarian neuroend colorectal melanoma neuroend ovarian ovarian ovarian hepatocellular ovarian Phase I Results Waterfall Plot of RECIST Measurements (n=58) 60% 50% Patients that continue on study 40% 30% 20% 10% -20% -30% -40% -50% Slide 39 ENMD-‐2076 CT Images from a SoX Tissue Sarcoma Pa>ent Baseline CT before treatment Slide 40 CT post 4 cycle of treatment 2ME2 (2-‐Methoxyestradiol) Effects of 2ME2 on Auto-‐immune Mouse Model of Mul>ple Sclerosis (MS) • Suppress development of autoimmune disorders in mouse experimental model of mul6ple sclerosis (MS) • Inhibit in vitro lymphocyte ac6va6on, cytokine produc6on, and prolifera6on in a dose-‐dependent fashion Slide 41 2ME2 (2-‐Methoxyestradiol) Significant In Vivo An>tumor Ac>vi>es Demonstrated, Especially in Combina>on with Standard of Care An6tumor Ac6vity of 2ME2 in Combina6on with XRT on PC3 Tumor Growth 1000 n = 5 mice/group Control 800 Tumor volume (mm3) 2ME2 75 mg/kg/d po x 5 Radia6on 2 Gy 600 T-‐C (days) to reach 200 mm3 0 2 Radia6on + 2ME2 (2 Gy, 4hr aper 2ME2 x 5) 23 400 200 * * * * *p < 0.05 compared to radia6on alone 0 0 Data: G. Amorino, UVa Slide 42 4 8 12 16 20 Days aper first treatment 24 28 32 2ME2 (2-‐Methoxyestradiol) Significant Single-‐agent In Vivo efficacy Demonstrated in Experimental Animal Models for Arthri>s Adop6ve Transferred Adjuvant Arthri6s Mean Arthri6c Scores 6 Arthri6s Score Vehicle 2ME2 3 mg/kg/d d0-‐21 2ME2 30 mg/kg/d d5-‐19 4 2 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Days post ADT Treatment with 2ME2 was for the dura6on of the 6mes shown, i.e., from 6me of arthritogenic lymphocyte injec6on (d0-‐21) or from 6me of first clinical limb inflamma6on/limp at day 5 for 14 days (d5-‐19) and observed un6l day 27. Slide 43 Ra6onale for CASI North America/China Development Strategy • North America and the West are genera6ng most of the innova6on and drug discoveries • The FDA’s guidance has great impact on the CFDA’s views and decisions • Drug development costs, par6cularly clinical development costs in the U.S., are prohibi6vely high and have been consistently increasing, while the success rate is dispropor6onately low • Advantages for new drug development in China include: – Lower costs, par6cularly in clinical development – Large pool of advanced educated scien6sts and physicians – Significantly larger pa6ent pool for trial enrollment – Improved quality in compliance with GLP, GCP and GMP • Incorporate China as an integral part of a global development program to reach proof of concept at lower costs -‐ dual development strategy • Clinical trials conducted in China under FDA IND, CFDA CTA and ICH GCP can be used for NDA submissions in both the U.S. and China • Data from drugs approved in the U.S. and other countries can be used to support Import Drug Applica6ons in China • More drugs can be developed in the pipeline for the same investment Slide 44 China Pharmaceu6cal Market A Significant, Unprecedented Opportunity • China is the fastest growing pharmaceu6cal market in the world • The percentage of healthcare spending in GDP is low among developed countries, while growing at fast pace in China • The pharmaceu6cal market will con6nue to grow with the growth of China’s economy and spending, with the oncology sector par6cularly strong due to rapid increase in oncology pa6ents • China is projected to be the 2nd largest pharmaceu6cal market by 2016 and the largest oncology market by 2019 to 2024 • There is currently no leading brand oncology company in China (most leading Chinese pharmaceu6cal companies achieved success through branded generics) • A company acquiring innova6ve oncology products from the West and commercializing in China with scale and efficiency will have a significant lead to become a major market par6cipant Slide 45 China Pharmaceu6cal Market Second Largest by 2016 China is projected to be the second largest pharmaceu6cal market in the world by 2016 Within the pharmaceu6cal market, oncology is the largest and fastest growing Slide 46 China Pharmaceu6cal Market Fastest Growing Slide 47 Appendix -‐ 4 China Cancer Growth Opportunity to Address Significant Unmet Medical Needs Tumor incidence and death are expected to grow rapidly worldwide • Cancer incidence is expected to reach 1.7 million in the U.S. and 3.4 million in China in 2015 • Cancer incidence is expected to increase to 2.1 million in the U.S. and to 4.4 million in China by 2025 • Five year prevalence is approximately 4.8 million in the U.S. and 5 million in China Source: Preven6on Strategy of Cancer in Eastern Asia Slide 48
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