Finding the right partner for preclinical into phase I. Facts, Threats & Opportunities

Transcription

1 Nuvisan Presentation Outsourcing and Clinical Trials DACH, 9th October 2018 Finding the right partner for preclinical into phase I Facts, Threats & Opportunities 9 October

2 PASSIONATE PEOPLE FOR YOUR SCIENCE Nuvisan your European CRO/CDMO with services from research to rapid clinical Proof of Concept 9 October

3 OUTSOURCING FACTS Metrics in R&D: R&D spending is constantly growing Respondents expected early development growth to accelerate from 4.5% to 5.8% in 2018 (2,2% to 3,1% late stage development ). In-house vs. outsourcing trends The past four years showed a steady decline in internal resources according to respondents (2017: 25% / 2016: 36%) Staff reduction is affecting all areas early-stage (53%), latestage (47%) and in discovery (47%) Anecdotes: large pharma companies looking to bring specific functions back in-house or looking for other partner models What is client looking for: Clients preferring to working with like sized CROs (75% of SMid indicated they prefer partnership with a small or mid-size CRO, 90% of large pharma have indicated they were likely to partner with large CROs or a balanced mix. Source: PAREXEL Biopharmaceutical R&D Statistical Sourcebook 2018/2019 $200 $150 $100 $50 $ Global Total R&D Spending 18% 13% 8% 3% -2% R&D Spend ($ billion) Growth (%) Uncategorized; 19,2% Phase IV; 11,4% R&D Spending by function Ethical Pharmaceuticals, PhRMA members 2016 Approval; 3,7% Phase III; 28,0% Worldwide Active R&D Projects in Development Stage Prehuman / preclinical; 17,2% Phase I; 9,2% Phase II; 11,3% Pre-Clinical P I P II P III 9 October

4 WORKING FOCUS OF BIG PHARMA & BIOTECH PAST VS. PRESENT Research Development Phase I/IIa Phase IIb/III Registration & Launch Marketing & Sales BIG PHARMA PAST PRESENT Fully integrated companies Risk mitigation focus to M&S In-house In-house In-house Little in-house Technology Scouting / Incubator programs Outsourcing of the trial management In-licensing of projects, indications and regions Acquisition of companies Focus home market Global Core Expertise Out-licensing outside the home market SMB* PRESENT Full outsourcing approach Full-outsourcing due to the limited resources Out-licensing & Exit *Small and Medium-Sized Business 9 October

5 THE MAJORITY OF SERVICES TODAY ARE OUTSOURCED TO CROS AND CDMOS! Outsourcing big pharma SMB* Activities in R&D Hit & lead identification In vitro / in vivo DMPK Radiosynthesis API synthesis Manufacturing IMP & GMP qualification DS/DP IMPD writing CTA preparation & submission CSP / CSR writing Clinical trial conducts phase-i Bioanalysis CDM / STAT / CSR Vendor management Pharmacovigilance Today Today Companies are at risk to lose operational and scientific expertise in an increasing number of areas due to personnel reductions and outsourcing. This loss of know-how is accelerated by further factors.: Early retirement of the most experienced staff Lack of qualified junior staff Missing operational experience due to full outsourcing strategy *Small and Medium-Sized Business 9 October

6 CRO DEVELOPMENT STRATEGY OF RECENT YEARS Research Development Phase I/IIa Phase IIb/III Registration & Launch Marketing & Sales How are the big CROs developing? Reduction of in-house phase-i capabilities & closer collaboration with external sites to reduce overhead costs and minimize risks Building relations with specialized partners (e.g. universities), to get access to niche expertise without adding fixed costs Reducing fragmentation through mergers and extension in post-clinical services (e.g. Quintiles + IMS = IQVIA) How are mid-sized CROs developing? Acquisition of further business to transform to big CROs (e.g. LabCorp + Covance + Chiltern/Theorem) How are local CROs developing? Acquisition of further businesses to Increase in capabilities and extension of geographic coverage e.g. central lab provider, CMO Specialization to niche provider e.g. GMP labs for large molecules Integration of further services to increase the value chain 9 October

7 WHAT OUTSOURCING STRATEGY FITS MY BUSINESS? Tactical PROS: No pre-qualification of vendor pools required CONS: Limited opportunities to gain efficiencies & setting up vendor relations Outsourcing Model Preferred Provider Functional PROS: Reduction of the number of vendors & less vendor management CONS: Requires a large pool for selection & requires repeated outsourcing of comparable content PROS: Improved operational function & efficiencies CONS: Requires repetitive outsourcing task Smart Development PROS: One vendor thinking out of the box CONS: The performance of the entire project depends on the quality of one vendor 9 October

8 NUVISAN ALL SERVICES FROM ONE SINGLE SOURCE API synthesis GMP method development & validation In vitro / in vivo DMPK Formulation development & manufacturing Drug exposition calculation FIH FIM Trial Design GLP / GCP bioanalysis A COMPLETE SERVICE PORTFOLIO ENABLES A PROCESS ORIENTED APPROACH EU-Import & Packaging & labeling Post-clinical Services Safety Lab Services Clinical Conduct I/IIa EU QP release Clinical Study Protocol writing & CTA preparation Regulatory advice 9 October

9 CASE EXAMPLES FOR ROADBLOCKS: WHAT CAN HAPPEN IN YOUR PROGRAM Case 1 - Tox Study: Small biotech company calls for gap analysis prior to go in humans. 28 days Tox studies are completed without toxicokinetic sampling. According to the tox CRO this was not needed. Remaining questions: Was the drug absorbed? What are the dose exposure relationships? Differences between male and female? NOAEL versus the exposure? Should the SAD get an exposure cap? Case 2 Preclinical IMPD Package: Small biotech company request a recommendation for a preclinical package required to go into FIH The study package proposed by a global CRO contained various parts that would not be relevant, neither from scientific nor from the regulatory perspective. Nuvisan recommended a optimized package to save time and costs Case 3 - Formulation: Company decided to go with a lipid formulation into FIM. CDMO was checking the preclinical data and discovered a sufficient but low bioavailability. The offer for screening to find a suitable enhancement technique was rejected due to time pressure and budget issues. The preclinical CRO was only producing the data for bioavailability without a scientific interpretation of the data. Biotech company had only limited experience in preclinical. Biotech selected Nuvisan as clinical CRO partner to go into FIM. Compound failed to reach the needed bioavailability in the FIM study. Next milestone could not reached Biotech were getting in financial trouble. Additional rounds of funding were needed. Company was losing at least 1 year of time and probably +1,0 Mio.. 9 October

10 CASE EXAMPLE: SUCCESS CASE Background: Full Development of a Modified Release Antibiotic Dosage Form for a Virtual Pharmaceutical Company API and Idea supplied by the sponsor (no internal development resources/facilities available at sponsor) Tasks of Nuvisan along the value chain: Formulate API into modified extended release tablet in five dose strengths Test release characteristics compared to immediate release tablets to verify performance & reformulate to meet desired release characteristics Develop full panel of pharmaceutical tests to adequately characterize the product Develop discriminating dissolution parameters for product evaluation prior to clinical evaluation Prepare various prototypes for initial Phase I clinical evaluation to be performed under a variety of conditions (Fasted, Food Effect, Single Dose, Multiple Dose, etc.) Select and manufacture optimum prototype for full clinical evaluation Perform Phase I-III clinical trials to demonstrate product performance, safety, and therapeutic efficacy Support the sponsor in regards to regulatory filing of the product and competent authority needs Support the sponsor post approval with contract commercial manufacturing and initial launch of product Continue batch release of commercial product post approval Outcome: Today the product is FDA approved 9 October

11 KEY LEARNING FOR EARLY PROVIDER SELECTION Experience and expertise: Due to the strongly interconnected work packages of diverse nature and tapping into multiple functions (quality/cmc, preclinical, DMPK, clinical ), specific expertise and experience (track record) is needed at the vendor Interfaces and handling of product knowledge: During the stages from candidate to end of POC, multiple handovers in terms of critical data and product knowledge is required, as well as strong cross-functional collaboration Utilizing several vendors creates additional interfaces and significant additional risks of missing alignment, data interpretations and ill-informed decisions. Concentrating early development to one of few vendors with broad functional expertise and offerings for long-term collaboration for Early Development is preferred. 9 October

12 QUESTIONS TO BE RAISED IN YOUR PROVIDER SELECTION TO BUILD A SUCCESSFUL RELATIONSHIP Time horizon: What is my next target and the end objective? Resources: What are my expectations in terms of capacity and more important in terms of competencies, knowledge, motivation and experience...? Relation model: What do I expect from a CRO, extended work bench or a sophisticated provider of science and expertise to add value? Should the CRO just fill a gap in the development pathway, or am I looking for a CRO with an integrated approach (value chain)? Interaction: What can I provide to the CRO (preclinical data, information, methods etc.)? What can the CRO provide? Does the CRO really understand my needs? Is my potential partner working on eye-level / equal footing with me? Is the location of the CRO important for me? How much flexibility do I need in my project? When is the next step due and when should the project finish? How much budget can I allocate to outsourced activities? 9 October

13 CONCLUSION the increasing complexity of early development is driving demand for sophisticated CRO/CDMO partners that have a broad range of advanced capabilities combined with drug development competence and expertise to support the client during the drug development process in an focused, cost and time effective manner Pharmaceutical Services Non-Clinical Studies Clinical Trials Analytical labs Thank you very much for your attention! If you have further questions please feel free to contact us! Dr. David Surjo Executive Vice President / Phone / david.surjo@nuvisan.com 9 October