Dedicated to Preventing and Treating Life-Threatening Viral Infections. W. Garrett Nichols, MD, MS Chief Medical Officer

Transcription

1 Dedicated to Preventing and Treating Life-Threatening Viral Infections W. Garrett Nichols, MD, MS Chief Medical Officer

2 Chimerix: Dedicated to Discovering, Developing and Commercializing Antivirals to Address Unmet Medical Needs Leveraging the potency and broad-spectrum activity of brincidofovir against multiple life-threatening viral infections First therapy for prevention of CMV in HCT recipients (fast-track designation) First and only treatment for Adenovirus infection (fast-track designation) Treatment for prevention of CMV in renal transplant First treatment for smallpox (fast-track designation) First treatment for Ebola Virus Active Discovery Platform Proprietary Lipid technology and Chimerix Chemical Library Novel candidate CMX16669 selected for development Successful follow-on offering in October 2014 Provided $121.7 million in gross proceeds Follow-on offering May 2014 generated $119 million in gross proceeds IPO (NASDAQ;CMRX) in April 2013, gross proceeds $118 million On 9/30/14, $188.4 million in cash, cash equivalents and short term investments 2

3 Chimerix Management Team Name / Title M. Michelle Berrey, M.D., M.P.H. President & Chief Executive Officer Timothy W. Trost SVP, CFO and Corporate Secretary W. Garrett Nichols, M.D., M.S. Chief Medical Officer Linda M. Richardson Chief Commercial Officer Michael D. Rogers, Ph.D. Chief Development Officer Experience Pharmasset Chief Medical Officer GlaxoSmithKline VP, Viral Diseases, Clinical Pharmacology & Discovery Medicine Argos Therapeutics VP and CFO InteCardia SVP and CFO PricewaterhouseCoopers Senior Manager ViiV Healthcare Head of Global Development GlaxoSmithKline VP, Medicines Discovery and Development Fred Hutchinson Research Center Principal Investigator Sanofi VP, Head of Global Lixisenatide Franchise Reliant Pharmaceuticals VP, Marketing GlaxoSmithKline Marketing, Sales & Market Research Pharmasset Chief Development Officer GlaxoSmithKline VP, Division of Viral Diseases, Discovery Medicine, HIV Clinical Research Michael Alrutz, J.D., Ph.D. Vice President, General Counsel Trimeris, Inc. General Counsel 3

4 Chimerix Product Pipeline Significant Opportunities for Expansion into Other Viruses and Patient Populations Brincidofovir (BCV) Prevention of CMV in HCT Treatment of AdV in HCT Smallpox BARDA Contract Ebola Virus Disease CMV Prevention in SOT Preclinical Phase 1 Phase 2 Phase 3 P2 Study Authorized by FDA SUPPRESS Enrollment ongoing AdVise Enrollment ongoing P3 (RPXV) Start 2014 In Planning CMX157 HIV, HBV Discovery Unit CMX16669 (CMV, BKV) Norovirus Influenza HBV IND-enabling studies underway Active Programs Ongoing 4

5 Dedicated to Preventing and Treating Life-Threatening Viral Infections Brincidofovir

6 Broad-Spectrum Activity Differentiates Brincidofovir Viral Family Virus Brincidofovir Cidofovir Ganciclovir* Foscarnet Acyclovir Maribavir Letermovir Cytomegalovirus (CMV, HHV-5) > Epstein-Barr Virus (EBV, HHV-4) < >10 Human Herpesvirus 6 (HHV-6A) Inactive >10 Herpes Human Herpesvirus 8 (HHV-8) >100 Inactive Herpes Simplex Virus 1 (HSV-1) Inactive >10 Herpes Simplex Virus 2 (HSV-2) Inactive >10 Varicella Zoster Virus (VZV, HHV-3) Inactive >10 Adenovirus Adenovirus (AdV-B7) Inactive >100 >10 Polyoma BK Virus (BKV) >200 Inactive >200 JC Virus (JCV) >0.1 Inactive Papilloma Human Papillomavirus 11 (HPV-11) Inactive Inactive Pox Variola Vaccinia >392 Inactive >144 Filovirus Ebola Virus 0.17 Potency expressed as EC 50 = concentration in µm required to reduce viral replication by 50% in vitro; indicates no data. Data are compiled from multiple sources and include multiple materials and methodologies. *Valganciclovir is rapidly converted to ganciclovir in vivo. Therefore, ganciclovir is the relevant compound for cell activity studies. 6

7 Immunosuppressed Patients are at Risk for Multiple Viral Infections: A Broad Spectrum Antiviral is Needed One third of patients who were enrolled in a BCV trial with an active DNA viral infection had two or more DNA viral infections Pediatric Patients Adult Patients Total Patients 15% 20% 4% 23% 9% 28% 57% 76% 68% 1 Virus 2 Viruses 3+ Viruses 1 Virus 2 Viruses 3+ Viruses 1 Virus 2 Viruses 3+ Viruses Clinician Reported Data From a subset of EIND, Study 350 and Study 202 database (n=386) 7

8 Clinical Development Plan: Potential Multiple-Indication NDA Study 301: CMV prev. in HCT Data 2H2015 Pilot Study 304: AdV Treatment Study 305: AdV Match Control EU Roadshow File NDA Multiple Indication NDA: 1) CMV in HCT 2) AdV in HCT/SOT 3) Smallpox Study 303: CMV Prevention in SOT Label US CMV in SOT Study 205: Ebola Treatment Smallpox Pivotal Animal Studies Market Expansion Studies 8

9 Robust Clinical Program for Brincidofovir Prevention of CMV in High Risk HCT Recipients: SUPPRESS - Currently enrolling in US, Canada & Europe Modeled after successful Phase 2 CMV prevention study in highest risk patients Hematologic safety allows peri-transplant dosing, important to avoid early reactivation Treatment of Life-Threatening Adenovirus Infections: AdVise - Pilot study enrolling, pivotal study design to be submitted to FDA in 2014 High historic mortality rates, similar to Study 350/EIND; two durations in pivotal trial Prevention of CMV in SOT Recipients - Design to be submitted to FDA in 2014 Kidney transplant population provides opportunity to demonstrate impact of brincidofovir on BK virus and overall graft function Treatment of Smallpox - Rabbit study design agreed with FDA in 2014 BARDA contract renewal announced August 2014 Treatment of Ebola Virus Disease - Phase 2 study authorized by FDA October 2014 Several patients treated with BCV for Ebola under EINDs 9

10 Dedicated to Preventing and Treating Life-Threatening Viral Infections SUPPRESS Clinical Trial

11 Phase 3 SUPPRESS Trial Enrolling Population: Allogeneic HCT recipients, CMV seropositive Primary endpoint: Prevention of CMV through Week 24 Design: Superiority vs. current standard of care (placebo) Power: >85% power to detect 50% reduction in CMV events vs placebo (assumed 30%) Dosing: Begins when patient can swallow tablet; twice-weekly through Week 14 Timeline: Data anticipated 2H2015 2:1 randomization n = 300 Increased risk for CMV infection Brincidofovir 100 mg BIW On-study follow up n = 150 Placebo BIW Week First Day of Dosing Last Dose Primary Endpoint: CMV Suppression 11

12 SUPPRESS Secondary Endpoints: Broad-Spectrum Antiviral Activity Enhances Value Proposition BK virus: brincidofovir demonstrated dose-related improvement in renal function and decrease in hematuria in Study 201 HHV-6: primary viral etiology for CNS events in HCT: delirium, memory loss, encephalitis Adenovirus: mortality of >80% in transplant patients, no available therapy. In Study 350/EIND, patients with AdV disease who received brincidofovir showed improved survival compared to historical data Non-relapse mortality: prevention of clinical events related to DNA viruses (CMV, HHV-6, AdV, HSV, VZV, EBV) may collectively yield a decrease in mortality Healthcare utilization: potential to demonstrate significant healthcare savings by preventing CMV disease and treatment costs 12

13 Highest Risk HCT Recipients Targeted in SUPPRESS Baseline Risk Factor BCV Study 201 N=230 n (%) Letermovir Phase 2 N=131 n (%) HLA mismatch 33 (14%) 0 Cord blood 15 (7%) 0 Ex vivo T-cell depletion 12 (5%) 0 Prior CMV infection 34 (15%) 0 GVHD grade 2 or higher 7 (3%) 0 Phase 3 study design for letermovir is identical to SUPPRESS and will therefore include higher-risk patients not previously studied, a primary endpoint at Week 24 to assess the potential for late CMV reactivation, and initiation early in the transplant period Brinci Study 201: NEJM 2013 Marty et al Letermovir: NEJM 2014 Chemaly et al 13

14 Dedicated to Preventing and Treating Life-Threatening Viral Infections AdVise Clinical Trial

15 Log10 copies/ml Observed Decrease In Plasma AdV Levels Of Patients In AdVise Phase 3 Pilot Study Is Promising Proportion with AdV DNA clearance from compartments other than plasma Respiratory secretions 5 / 12 (42%) Urine 5 / 15 (33%) Stool 4 / 15 (27%) Week (Relative to Dosing) 15

16 AdVise Pilot Data: Survival Improved in BCV-treated vs. Previous Reports Prospective, single center pediatric cohort (N=132) 1 Blood and compartment AdV PCR neg Blood neg, compartment PCR + Survival in AdVise Pilot Study: Any blood AdV PCR+ (N=36, 33 with disseminated disease, mortality 82%) All of Cohorts A/B/C: 17/48 (mortality 35%) All of Cohort B (Disseminated Disease): 11/29 (mortality 38%) 1 Lion T, et al. Blood 2003;102(3):

17 AdVise 304 Pilot Data: Conclusions BCV demonstrated potent virologic activity in patients with AdV disease 15 / 23 (65%) had 3 log 10 decline in AdV DNA by PCR (or were undetectable) Subjects treated with BCV appeared to have improved survival vs. historic controls Among allogeneic HCT subjects with disseminated disease, mortality was 38% (vs. ~ 60-80% reported in literature) No new safety signals were identified in this highly complicated patient population Data from the pilot portion of CMX support progression to pivotal Phase 3 study of BCV for AdV Young, IDSA

18 AdVise Phase 3 Randomized Study Design Populations: Cohort A - Allogeneic HCT recipients with localized or asymptomatic AdV infection Cohort B - Allogeneic HCT recipients with disseminated AdV disease Cohort C - Autologous HCT, Solid Organ Transplants, other immunocompromised Proposed Primary endpoint: AdV disease-free survival at Week 20 Design: 6 week vs. 12 week dosing duration Dosing: Twice-weekly (BIW) for 6 or 12 weeks Timeline: Final protocol 2H2014 Cohorts A & B 1:1 randomization Study Week: 0 BCV 100 mg BIW BCV 100 mg BIW Placebo BIW 6 On-study follow up On-study follow up

19 Dedicated to Preventing and Treating Life-Threatening Viral Infections Brincidofovir for SOT

20 BKV Continues to Impact Renal Transplant Survival Although graft survival has improved, 10-year graft survival is still <50% ~20% of renal transplant recipients have BK viremia in the first year posttransplant BKV-associated disease results in graft loss in 65% of affected patients US Renal Data System s Annual Data Report, 2010,

21 Phase 3 Solid Organ Transplant Study Trial Design Remains In Active Discussion With Regulators Population: Kidney transplant recipients at increased risk of CMV Primary endpoints: Non-inferior to Valcyte for prevention of CMV, opportunity to demonstrate superiority by prevention of BKV nephropathy Design: Non-inferiority vs. current standard of care (Valcyte) Dosing: Begins when patient can swallow tablet; twice-weekly through Week 14 Timeline: Study start anticipated 1H2015 Increased risk for CMV infection On-study follow up n = tbd BCV 100 mg BIW + Valcyte Placebo QD n = tbd Valcyte 900mg QD + BCV Placebo BIW Week 0 14 tbd First Day of Dosing Last Dose Primary Endpoint: CMV Suppression 21

22 SOT Phase 3 Secondary Endpoints: Differentiation from Valcyte Preservation of renal allograft function Impact on BK virus leading to improved renal function Comparison between cohorts as key pre-specified endpoint Impact on other DNA viruses EBV/PTLD (post-transplant lymphoproliferative disorder) AdV Health resource utilization Re-hospitalizations for GCV-associated neutropenia and 2 bacterial/fungal infections Concomitant medication use (GCSF) GCV intolerance 22

23 The Time is Right For A Broad Spectrum Antiviral Limitations of other antivirals remain and development programs for competitors lag brincidofovir High interest and growing awareness of brincidofovir Growing HCT population, particularly in the Americas and EU Allogeneic and autologous HCT populations are both at risk for re-activation of CMV Sizeable opportunity for use in HCT and SOT patients in US and EU Changing the dynamics in the diagnosis and treatment of adenovirus in immunocompromised patients will increase this opportunity There is significant overlap of DNA viruses in these patient populations Aim to create greater awareness of the overlap and drive screening behavior 23

24 Initial Brincidofovir Market: Opportunities in Transplant Transplants per year US EU HCT Allogeneic 7,000 14,000 Autologous 13,000 20,000 SOT Kidney 17,000 19,000 Liver 7,000 7,000 Other SOT 6,000 5,000 US HCT: 2012 figures from CIBMTR. US SOT: 2013 figures from Organ Procurement and Transplantation Network (OPTN). EU HCT: 2012 figures from EBMT. EU SOT: 2012 figures from WHO Global Observatory on Donation and Transplantation. 24

25 Initial Launch Strategy Brincidofovir Capitalize on the potential to launch brincidofovir in the US with three indications supporting the promise of a broad spectrum antiviral drug that protects fragile, at-risk patients from a variety of viral infections Potentially: First and only antiviral therapy indicated for the prevention of CMV infections in adult and pediatric allogeneic HSCT recipients First and only antiviral therapy for the treatment of lifethreatening adenovirus infections in immunocompromised patients, including allogeneic HSCT patients and other high risk populations First and only antiviral indicated for the treatment of smallpox 25

26 Brincidofovir Activity In Vitro Has Translated to Effects in Animals and Humans Virus Brincidofovir EC 50 (µm) BCV prevents mortality in lethal animal models Human Clinical Data Adenovirus Cytomegalovirus (CMV) Variola 0.11 ND ND Vaccinia Ebola virus 0.17* In progress In progress EC 50 = concentration in µm required to reduce viral replication by 50% in vitro. Data are compiled from multiple sources and include multiple materials and methodologies. *Value for wild type Mayinga; range of activity was over 3 assay types at CDC 26

27 BCV Has Multiple Potential Advantages Over Other Investigational Agents for EBOV Oral, BIW Dosing Large and relevant safety database Phase 3 clinical development progressing in CMV and AdV Tablets available for immediate use in clinical trials with stability at room temperature and under accelerated conditions Next Steps: 1. Animal efficacy studies Mouse and guinea pig models 2. Partner with global authorities to provide access through EINDs as appropriate 3. Implement Phase 2 study protocol for treatment of patients in US and EU 4. Recently announced study in West Africa with ISARIC/Oxford/MSF 27

28 BCV Treatment for Smallpox Development program with BARDA for BCV as a medical countermeasure to treat smallpox Contract extension signed August 28, 2014 for an additional 15 months Award of $17.0 million brings the total amount received to $53 million Phase 3 pivotal trial in RPXV (rabbitpox) model to begin late 2014 If positive, data from animal studies may support regulatory submission for BCV for the treatment of smallpox Could support BCV as the first medicine approved for smallpox Smallpox NDA submission timing would be dependent on FDA review of of the RPXV data and the need for additional data in the mouse ectromelia model 28

29 Dedicated to Preventing and Treating Life-Threatening Viral Infections Discovery Program

30 Chimerix Discovery Program Delivers Unique Antiviral Pipeline Chimerix Compound Library Focused library of unique structures designed to hit antiviral targets Proprietary Lipid Technology Enhanced drug delivery with a wide range of potential applications Novel Antiviral Pipeline Internal Research Program Team of virologists and chemists with extensive expertise in antiviral research 30

31 Dedicated to Preventing and Treating Life-Threatening Viral Infections CMX16669 Clinical Candidate

32 CMX16669: Potent Activity Against CMV and BKV with Encouraging Safety Profile Low oral dosage with daily or less frequent dosing No overt signs of toxicity in pilot studies in rats and dogs Potential for safety in pregnancy Patent protection through 2028 Potential to expand patient populations Potential for combination use with BCV 32

33 Selective and Potent In Vitro Activity of 669 EC50 (µm) CC50 (µm) SI Cell line CMV (n=12) 90.2 (n=3) 2941 MRC5 BKV 2.1 (n=4) 93 (n=2) 44 Vero - Inactive against AdV, CPXV, Dengue, EBV, FluA, HSV-1, HSV-2, MNV, RVFV, RSV, SARS, Tacaribe, VEEV, VZV, WNV, YFV; modest activity against HBV, HCV, HHV6 and polio 33

34 2015 is a Pivotal Year for Chimerix SUPPRESS Phase 3: CMV prevention in HCT AdVise Phase 3: AdV Treatment in HCT Agreement with EU Regulators AdV Match Control Study BCV NDA Preparation BCV Commercial Launch Planning Phase 3: CMV Prevention in SOT Smallpox Pivotal Animal Studies Study 205: Ebola Treatment Market Expansion Studies for BCV Initiate Clinical Study for CMX

35 Dedicated to Preventing and Treating Life-Threatening Viral Infections For further information please contact: Joe Schepers Executive Director, Investor Relations and Corporate Communications Corporate Overview 35