Lonza Peptides “The trusted peptides partner, serving your life cycle needs” Updated 14 Apr 2011.

Slide 1 Lonza Peptides “The trusted peptides partner, serving your life cycle needs” Updated 14 Apr 2011 Slide 2 slide 216-Aug-15 Certain matters discussed in this presentation may constitute forward-looking statements. These statements are based on current expectations and estimates of Lonza Group Ltd, although Lonza Group Ltd can give no assurance that these expectations and estimates will be achieved. The actual results may differ materially in the future from the forward-looking statements included in this presentation due to various factors. Furthermore, Lonza Group Ltd has no obligation to update the statements contained in this presentation. Note: All slides are incomplete without verbal comments. Disclaimer Slide 3 slide 316-Aug-15 Nature: An unlimited source of inspiration! “Predatory marine cone snails use a diverse mixture of peptides known as Conopeptides in the capture of their prey … Each cone snail may contain up to 200 peptides and given there are over 700 cone snail species, … the library of bioactive peptides using animal venoms is huge.” Slide 4 slide 416-Aug-15 Nature: An unlimited source of inspiration! Several peptides extracted from venoms are on the market: Brand NameOwnerSource Captopril (Capoten) BMSviper venom Prialt ® (Ziconotide)Airmidcone snail venom Byetta ® (Exanatide)Amylin-Eli Lillylizard venom Eptifibatide (Integrilin)Millenium/ Schering Ploughsnake venom Images FPO, Sources: www. sandesh.com,www.fotopedia.com,www.bangkokpost.com. Slide 5 slide 516-Aug-15 Agenda n The Challenges of Custom cGMP Peptides Manufacturing n Customer Value Proposition n Lonza, The Right Peptides Partner Slide 6 slide 616-Aug-15 Increasing Molecular Weight (MW) Chemical Molecule Aspirin (180 Da) Peptide 6mer (804 Da) Antibody Immunoglobulin G (150,000 Da) Protein Lysozyme (14,700 Da) Complexity by Molecular Weight Cell / Tissue Surface of an Animal Cell Slide 7 slide 716-Aug-15 Process development know-how is the key to future success n Right route selection from the beginning based on large-scale experience n Robust process development n Process validation n Process optimization Slide 8 slide 816-Aug-15 On average, producing 1 kg (net) of peptide generates over 5 metric tons of solvent. Capabilities and infrastructure are critical to success Required Infrastructure n Strategic (worldwide) sourcing n Raw materials in rail-tank-cars n Tank-farms n No open handling n Adequate warehousing n Solvent recylcing systems n Exhaust gas treatment n Waste Disposal Slide 9 slide 916-Aug-15 Quality n Impurity Profile n Purity n Scalable Process n GMP Slide 10 slide 1016-Aug-15 HAPI Peptides Matt- please add challenges AHSK* OEL (Occupational Exposure Limit) ADI (Acceptable Daily Intake) 1 > 1mg/m 3 > 10mg/d 2 0.1-1 mg/m 3 1-10 mg/d 3 0.01-0.1 mg/m 3 0.1-1 mg/d 4 0.1-10 µg/m 3 1-100 μg/d 5 1-100 ng/m 3 0.1-1 μg/d 6 < 1 ng/m 3 < 10 ng/d * Lonza Occupational hygienic substance category n Generic peptides like LHRH family are HAPIs, AHSK 5 (gosereline, decapeptil, leuprolide, busereline, desloreline, triptorelin…) n Abarelix, degarelix are also AHSK 5 n Avoid cross contamination AND protect the people n Low cleaning limit Slide 11 slide 1116-Aug-15 Conjugate Peptides PEPTIDE LipidAntibodySugarCPPPEG Peptides are versatile platforms for product design Slide 12 slide 1216-Aug-15 Pre-clinical Toxicology Commercial Phase IPhase IIPhase III Purity 95% 96-97% >98.0% European Pharmacopeia 6.5 Purity challenges based on new regulation in 2010 Slide 13 slide 1316-Aug-15 FDA New regulation will challenge peptide process development n Stage 1: Process Design n Stage 2: Process Qualification n Stage 3: Continued Process Verification Phase 0+1Phase 2Phase 3 Launch / Production Generic Process Life-cycle Slide 14 slide 1416-Aug-15 Agenda n The Challenges of Custom cGMP Peptides Manufacturing n Customer Value Proposition n Lonza, The Right Peptides Partner Slide 15 slide 1516-Aug-15 Global, Integrated, Strategic Supply Chain n Broad network of suppliers n Negotiation power n Regular suppliers audit n Security of starting materials supply (Group synergies, back integration for raw materials) Slide 16 slide 1616-Aug-15 Large-Scale Manufacturing Expertise n Multi-100 kgs of peptide API production yearly n Large purification HPLC capacity (up to 60 cm) n 3 Technologies (SPPS, HPPS,Recombinant DNA) n 4 Sites (Belgium, Switzerland, Czech Republic, China) Slide 17 slide 1716-Aug-15 Benefit from Lonza synergies during your peptide API development n Peptides Conjugates n Large-scale peptides for non-pharma applications (cosmetic, nutrition, detergent, surfaces treatment …) n Highly potent peptides n 2 nd generation process for large-scale peptide manufacturing via recombinant technologies Slide 18 slide 1816-Aug-15 Quality by Design at Lonza The definition A true answer to FDA expectations A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products with less extensive regulatory oversight Build quality in the process  Based on sound science and knowledge  Proactive to problems  Control strategy based on risk assessment  Continuous improvement and process verification Slide 19 slide 1916-Aug-15 Quality by design A Tailored Approach in Process R&D Process Design Process Qualification Continued Process Verification Phase 0+1 The roadmap to process validation process selection critical attributes risk assessment design space control strategy continuous improvement Knowledge Phase 2Phase 3 Launch / Production Generic Process Life-cycle Slide 20 slide 2016-Aug-15 Full Regulatory Support n DMF n CMC section n Audit n Inspection track records n Corporate experience n Accreditation from Japanese authorities Slide 21 slide 2116-Aug-15 Modeling of Peptide Purifications Study of Peptide Aggregation Collaboration / thesis Centrifugal Partition Chromatography (CPC) Collaboration / Thesis Nanofiltration and Molecular Imprinting EU Program SPPS and Methodology Consulting and Route scouting Continuous process Thesis Technology Development through R&D Outsourcing Trade secret Automatic Peptide Synthesizer Collaboration Slide 22 slide 2216-Aug-15 Easy, Effective, Regular Communication Customer- dedicated Data SharePoint In-house Video Conference Tools Worldwide Sales Presence Steering Committee Peptide Specialists QA Operations PM Customer Legal We bring everyone to the table Slide 23 slide 2316-Aug-15 Time Savings We serve all your life cycle needs Full In-house Capabilities 30 Years of Peptide R&D expertise Large-Scale Manufacturing Know-How Slide 24 slide 2416-Aug-15 Costs Savings Route selection, scale- up capabilities and expertise (low-risk of tech. transfer) based on long-term customer forecasts Swiss Tax Structure: Lonza to collaborate to establish tax holiday opportunities for commercial deliveries Lonza Nansha platform for ISO needs Strong expertise in process scale- up and cost improvement Slide 25 slide 2516-Aug-15 Nansha, China Small scale (100mg - 10g non-GMP) 10 peptide chemists Braine, Belgium Large scale (solid and solution phase) 50+ chemists/technicians Visp, Switzerland Large scale (solid and solution phase) USP + dedicated DSP 20+ chemists/technicians Multi-Site Multi-Technologies Financially Sound Backward Integrated Peptides Security of Supply for Chemical Processes Slide 26 slide 2616-Aug-15 Flexibility Experienced Project Management Team Unique Awareness of Peptide Challenges Custom Synthesis Mindset Multi-Site Four Shift Systems Slide 27 slide 2716-Aug-15 You will benefit from IP protection n Product Life Cycle Management meeting, including Lonza patent support n Transparency on Lonza IP strategy with our key customers to better protect their products from their competitors n We aim to protect a customer’s product during its life cycle n Access to Lonza patents portfolio Slide 28 slide 2816-Aug-15 Agenda n The Challenges of Custom cGMP Peptides Manufacturing n Customer Value Proposition n Lonza, The Right Peptides Partner Slide 29 slide 2916-Aug-15 Choose Lonza for: R&D n Quality by Design n Specific R&D know-how to improve your processes n 30 years of experience and successful track record n R&D peptide teams in Visp, Braine, Nansha Slide 30 slide 3016-Aug-15 Your small-scale samples platform milligram-scale gram-scale n Early stage non-GMP services to serve every step of your product life cycle n Specific knowhow, fast and low-cost efficient development n Dedicated peptide staff n IP protection From mg to grams, Lonza has your small-scale platform Preferred Collaboration with California Peptide Lonza, China Slide 31 slide 3116-Aug-15 Fuzeon ® (T-20 Roche) Case Study: Successful Route Selection Source: 2004 Trimeris - NP2D event Zermatt, Switzerland Slide 32 slide 3216-Aug-15 Case Study: Quality by Design (QbD) Bremelanotides ® (PT-141, Palatin Tech.) Slide 33 slide 3316-Aug-15 Case Study: Quality by Design (QbD) Catalyst n Pd(Ph 3 ) 4 n Pd(OAc) 2 / P(oTol) 3 n PdCl 2 (Ph 3 ) 4 Scavengers / proton donor n HCOOH/DIEA n Dimedone n Morpholine n AcOH/NMM n Phenylsilane n Me 2 NH.BH 3 (DMAB) Design Space Factor Screening DoE Optimization DoE Solution to selective Allyl/Aloc cleavage Slide 34 slide 3416-Aug-15 Case Study: Synergies lead to Innovation Recombinant E. coli (carboxy terminal fragment) H-Arg-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp- Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH = Semisynthesis of Bivalirudin ® n Inhibition of Thrombin n Therapeutic value in angioplasty after acute myocardial infarction API (Bivalirudin®) + Chemical Synthesis (amino terminal fragment) BOC-D-Phe-Pro-OSu fragment condensation deprotection final purification Slide 35 slide 3516-Aug-15 Successful Regulatory Inspections History: Lonza Braine, Belgium WhoWhenWhatRemarks FDA2001Pre-approval inspectionUCB Bioproducts Braine-l‘Alleud FDA2003Follow up InspectionUCB Bioproducts Braine-l‘Alleud FDA2005Pre-approval inspectionApproval by 12 march 2006 FDAJune 2009Successful GMP systems and pre-approval inspection FDAFebruary 2011Pre-approval inspectionBI, Nansha Korean FDANovember 2007Pre-approval inspectionApproval, June 2008 EU RegulatoriesDecember 2008GMP inspectionSuccessful GMP inspection Slide 36 slide 3616-Aug-15 Lonza’s Visp & Nansha facilities have a long history of successful inspections Slide 37 slide 3716-Aug-15 Let’s Share Our Peptides Future Together! © Wolfgang Staudt Peptides Excellence Customer Service Road to Success Experienced Teams Slide 38 Thank You