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Developing Well-Differentiated Antibiotics to Meet Medical Needs

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Developing Well-Differentiated Antibiotics to Meet Medical Needs Developing Well- Differentiated Antibiotics to Meet Medical Needs Cempra Corporate Presentation Prabhavathi Fernandes, Ph.D. President & CEO November 2014 Forward Looking Statement This presentation contains forward-looking statements regarding future events. These statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others: risks related to the costs, timing, regulatory review and results of our studies and clinical trial and those of our strategic partners; our need to obtain additional funding and our ability to obtain future funding on acceptable terms; our anticipated capital expenditures and our estimates regarding our capital requirements; our and our strategic partners’ ability to obtain FDA and foreign regulatory approval of our product candidates; our dependence on the success of solithromycin and TAKSTA; the possible impairment of, or inability to obtain, intellectual property rights and the costs of obtaining such rights from third parties; the unpredictability of the size of the markets for, and market acceptance of, any of our products, including solithromycin and TAKSTA; our ability to produce and sell any approved products and the price we are able to realize for those products; our ability to retain and hire necessary employees and to staff our operations appropriately; our ability to compete in our industry; innovation by our competitors; and our ability to stay abreast of and comply with new or modified laws and regulations that currently apply or become applicable to our business. Please refer to the documents that we file from time to time with the Securities and Exchange Commission. 2 Highlights . Cempra has two differentiated antibiotics with broad and large commercial potential ̶ Both in late stage of development Solithromycin – Potent 4th Generation Macrolide, First Fluoroketolide . First Oral and IV macrolide for monotherapy in CABP . Suspension for pediatrics – First in over 2 decades . Potential for broad adult and pediatric use TAKSTA – Long History of Use in EU for Prosthetic Joint Infections (PJI) . U.S. development for oral, chronic treatment of bone and joint infections replacing long-term IV and multiple surgeries 3 Cempra’s Portfolio Product Indication Formulation Preclinical Phase I Phase II Phase III Milestones Oral Community Acquired IV-to-Oral Bacterial Pneumonia Oral Suspension / Pediatric Solithromycin (CEM-101) Biodefense Animal Rule Oral / Suspension Urethritis Oral Anti-inflammatory / NASH Oral Oral-Chronic Prosthetic Joint Infections Taksta Acute and Chronic Oral-ABSSSI Fusidic Acid Treatment of MRSA Oral Suspension / Pediatric Non-Antibiotic Diabetic Gastroparesis and GERD Macrolide 4 Investing in Antibiotics Now Increasing antibiotic resistance to generic drugs Few products approved / in development Many are hospital intravenous use only CDC / FDA / WHO New laws to help antibiotic developers New regulatory guidance, increased development efforts, increased Pharma interest 5 Large Macrolide Market Opportunity 2013 US Retail Antibiotic Prescriptions Total 264 MM Annual Rxs Azithromycin, a macrolide, is the most Cephalosporins widely prescribed treatment for CABP 21.3 38.7 and other RTIs – >60% of market Beta-lactams 28.0 Fluoroquinolones . Broad spectrum of activity Macrolides 78.8 61.6 . Good safety Other antibacterials . Excellent tissue/intracellular distribution and 36.0 Tetracyclines/ aminoglycosides anti-inflammatory activity Source: IMS Health (Retail) AMR Hospital Data (Inpatient) . 51 Million prescriptions were written for azithromycin in the U.S. in 2013 2013 IMS New Prescription Audit Increasing resistance - 40% of U.S. pneumococci a; 96.4% in China b a Jones, RN. DMID. 2013;75:107-109; b Kim, SH. AAC. 2012;56:1418-1426.. Treatment failure of macrolide resistant pneumonia results in increased cost, and hospital admission Health Policy Institute, Univ. of California, Irvine. Reynolds et al, Antimicrobial Resistance and Infection Control 2014: 3:16 6 Need For a New Macrolide . In vitro activity of solithromycin and azithromycin against 927 Streptococcus pneumoniae from RTI samples collected in 2012-2013 MIC Percentage Antibiotic Region (µg/mL) S R 90% Europe (418) 100 0 0.06 Solithromycin NA (380) 100 0 0.25 Asia (129) 100 0 0.5 Europe (418) 71.3 28.0 > 1 Azithromycin NA (380) 56.3 42.6 > 1 Asia (129) 28.7 70.5 > 1 Morrissey, I. ECCMID 2014. Abstr. P1584. 7 Macrolides Have Broad Hospital & Primary Care indications . CABP and respiratory tract infections (RTIs) represent > 35MM hospital treatment days and > 115 MM prescriptions in the communitya 2013 AMR Hospital Days of Therapy 2013 IMS Retail Scripts 35 RTIs: ~115 MM scripts annually 40 ~34MM 30 ~29MM days 35 Millions ~28MM Millions ~28MM 25 30 20 25 15 20 ~13MM 15 Scripts ~10MM 10 ~6MM days 10 5 Days of Therapy Therapy of Days ~420k days ~400k days 5 0 CABP Bronchitis Sinusitis Gonorrhea 0 Sinusitis Otitis MediaBronchitis Pharyngitis CABP Hospital Days of Therapy Retail Scripts a Source: AMR Hospital Data, IMS NPA and NDTI . Outpatient treatment failures from resistance to generic antibiotics, resulting in more and more hospitalizations for IV therapy, risk of improperly treated infection, HAI b b Antimicrobial Resistance and Infection Control 2014: 3:16 . A new primary care antibiotic for RTIs that is safe and effective is an urgent need 8 What is Solithromycin? Currently Approved Macrolide Antibiotics Solithromycin - the first fluoroketolide Binds 23S RNA at 3 regions Llano-Sotelo B, Dunkle J, Kleoacki D, Zhang W, Fernandes P, Cate JH and Mankin AS. AAC 2010, 4961-4970 9 Solithromycin Highlights Clinical Trials . Phase 3 Oral, CABP completed enrollment Q3 2014, data expected Q1 2015 . Phase 3 intravenous-oral switch study; enrolling . Phase 3 in gonorrhea enrolling. Phase 2 completed with 100% cure in culture proven cases. Phase 1 in pediatrics, enrolling Strategic . BARDA HHS: $58MM contract – Development of Soli for pediatric use Partnerships and against bioterror pathogens . Toyama Chemical (FujiFilm): Global development program – exclusive license for Japan. $20MM upfront / milestones received; up to $50MM in additional milestones; tiered royalties based on sales Regulatory & IP . Qualified Infectious Disease Products (QIDP) granted by FDA designations; oral and IV formulations for CABP . Provides priority review – 8 months . QIDP for gonorrhea . NCE patent to 2025 plus PTEs; Polymorph patent to 2032, and additional patents 10 CABP – Most Frequent Infectious Disease in the U.S. Community Acquired Bacterial Pneumonia (CABP) – #1 cause of death from an infection . 5 to 10 million CABP cases annually, 1.1 million patients hospitalized per yeara ─ More common in older adults (>65 years) and young children Pneumococcal infections cause more deaths per year in U.S. than breast or prostate cancer. Xu, et al. Deaths: Final Data for 2007. Natl Vital Stat Rep. 2010;58:1-51. Respiratory disease incidence is increasing; growing numbers of COPD and asthma patients Drug Discovery News, May 2012. Appropriate empiric therapy is critical to positive outcomes . Multiple pathogens can be involved - Pneumococcus – the most frequent cause a Freeman, MK. CABP: A Primer for Pharmacists: US Pharmacist July 1, 2013 11 Rising Hospital Discharges for CABP . CABP remains the leading cause mortality in the US Source: 2011 HCUP, ARHQ.gov 12 Safety and Efficacy Deficiencies of Current CABP Therapies Current IDSA/ATS recommendation to give broad spectrum, empiric coverage: 1) A β-lactam plus . Requires intravenous cephalosporin Mortality rates a macrolide (e.g., ceftriaxone) in hospitalized and hospitalization CABP patients ─ No oral switch therapy is 23% replacement – 30-day ratea . Azithromycin for Legionella and a Freeman, MK. US Pharmacist. July 1, 2013 Mycoplasma Cost and hazards of HAI b Magill, SS. And CDC and Emory Authors. NEJM 2014. 1198-1208, 2014 Or 2) A fluoroquinolone . IV and Oral available – and have broad spectrum activity, (e.g., Levaquin, however, they are not in favor for treating CABP because: Avelox) ─ FQ treatment failure higher than ̶ Treatment failures from resistant strain selection ceftriaxone plus azi a C.difficile ─ Higher mortality when FQs used ̶ Kill bowel flora – associated with colitis without a macrolide b ̶ Adverse tendonitis, Achilles tendon rupture, hepatotoxicity and peripheral ─ FQs no longer used in CABP in neuritis, retinal detachment several countries ̶ Not approved for use in pediatrics a Fuller, DF, Low, EL.,CID 2005. 41: 118-121 b Martınez, JA., et al. CID. 2003, 36: 389-395 The only oral option is fluoroquinolone. but there is growing concern among physicians because of safety 13 Solithromycin – Spectrum of Activity that Addresses CABP Pathogens . Solithromycin has class-leading potency & spectrum in vitro against CABP pathogens Gram Organisms Solithromycin Azithromycin Cephalosporin Fluoroquinolone Positive Streptococcus pneumoniae Negative Haemophilus influenzae Staphylococcus Positive aureus Legionella Atypical pneumophila Atypical Mycoplasma pneumoniae / Chlamydophila Atypical pneumoniae . Interacts with bacterial ribosome at three sites – Resistance rare and it could only occur if mutations occur at three distinct sites 14 Solithromycin Has Distinct Advantages Over Azithromycin Solithromycin is being developed as oral capsules, pediatric oral suspension and intravenous formulations ACTIVITY PK . 4-16 fold more active in vitro . Best
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