Meeting Priorities of Biotech & Small Pharma Companies

Transcription

1 Meeting Priorities of Biotech & Small Pharma Companies Dr. Andreas Orfanos, MBBCH,FFPM,MBA Thrasos Therapeutics Inc. Vice President Clinical Research & Development 28 Oct 2015

2 Montreal Technoparc Private, clinical-stage biotherapeutics company Founded (2003) as a research co. by leading Boston based scientists Canadian development company since 2010 with over 20 employees Research & clinical operations in Montreal; office in Boston US and Canadian investors Addressing Compelling Unmet Needs Acute Kidney Injury (AKI) Chronic Kidney Disease First in Class Technology Proprietary peptide drugs Protect, repair and restore injured tissue Fast Track designation (FDA) for Cardiac Surgery Associated - AKI Leading Phase II Study Safety & Efficacy of THR-184 in preventing Cardiac Surgery Associated - AKI N = 450+ patients across over 40 sites in NA 2

3 Background Andreas Orfanos

4 Biotechnology Industry Need for efficiency follows tight funding environment (global financial crisis and economic downturn) Venture capital funding has rebounded; but 20% of US companies raising funds garnered 82.6% of capital in 2010 Increased use of milestone-based payments vs. upfront dollars: increased risk sharing Today s scientific challenges more complex than those involved in developing earlier generations of biotech technologies and products Biotech out-license their product after Phase I/II or acquisition, or retaining products and taking them closer to the market Trials continue to become increasingly complex and global, the competition for access to patients, new investigators &studies Beyond borders Global Biotechnology Report 2011, Ernst & Young

5 Virtual Biotech Model Minimal infrastructure Access to expertise on an as needed basis CRO Limiting expenditure to what's necessary Other vendors Pre-clinical research Ensure efficiencies Develop compound(s) to an early clinical data package which can be partnered with pharma Legal Biotech company CMC Executive team with significant experience & network Regulatory Consulting

6 Outsourcing Biotech Often focus on single product or platform Small team with executive involvement Need for accessing outside expertise Transfer of responsibility of many functions Timelines related to key milestone payments Pharma Multi-product: marketed drugs and strong pipeline Large team with broad and in-depth expertise: mirrors CRO Need to complement several functions that may be in house Seeing more streamlined business model with strategic CRO partnership Timelines key with regards to corporate objectives Optimise trial performance: delivery of services in efficiently & effectively whilst ensuring patient safety & quality of data

7 Outsourcing Difficulties in Clinical Development Nearly one-third of respondents mention that finding a CRO with strong expertise / capabilities is the most difficult part Managing timelines, Maintaining quality, and Selecting the best CRO for the project are also difficult. Clinical Development Outsourcing Models, ISR Report (2 nd edition) 2015

8 Small Medium Enterprise vs. Pharma CRO Needs Close association between size of sponsor company and the size of the clinical service provider State of Clinical Outsourcing Survey, Avoca, 2011

9 Company Perspective

10 THR Phase II Study - Proof of Concept Prevention of AKI in subjects scheduled for cardiac surgery at increased risk for AKI Determined likely event rate based on select risk factors e.g. underlying kidney disease, diabetes in a separate prospective observational study; access to hospital database in addition to literature review Objectives: evaluate safety of THR-184 evaluate potential for THR-184 to prevent AKI associated with cardiac surgery in patients with known risk factors for AKI

11 Mapping out the Needs & Expectations Overall expectations: study timelines, quality Needs influenced by study scope Planning Site start- up Conduct Close-Out Results Design Protocol ecrfs Feasibility Regulatory approvals Data Mx, stats, data entry system, IWRS Vendors (central labs, clinical supplies) Contracts (CROs; Vendors, sites) Study documentation (DMP, SAP, SMP) Site & Investigator identification Site & investigator selection Informed consent IRBs /ECs Training & Site initiation visits First site(s) Investigator Meetings FPFV Clinical Monitoring Safety & PV; medical monitoring Site management Enrolment Quality Assurance LPLV Finalize queries Data base lock Drug reconciliation Archiving Analysis Reporting Publications Project Management Study Oversight Commitment & responsibility

12 Making the CRO Choice

13 Request for Proposal (RFP) sets the stage Key Considerations Detailed & specific RFP tailored to trial CRO target group Share questions applicable to all Team to review & evaluate Face-to-face bid presentation with finalists Reference checks Budget discussions thereafter On site visits, audits Inform all CROs Contract Kick off meeting Company Clinical trial parameters: stage of study (first in patients) complexity clinical setting geographical area experience of investigators Other support e.g. advisors Therapeutic area knowledge & previous experience (similar practice setting) Product characteristics & specific needs Key decisions e.g. EDC, PVP Company expertise & infrastructure Evaluation in keeping with RFP Ability to meet expectations: key timelines, quality

14 Evaluation RFP Matrix A B C D E F G Strategic Experience Nephrology, Cardiac Surgery, ICU Medical Advisory; protocol, CRFs Clinical Project Lead / Manager Feasibility assessment Site contact & recruitment / Site startup & Regulatory Oversight : DSMB, EAC, SC Clinical monitoring Pharmacovigilance & Drug Safety Data management Biostatistics & analysis: ASD, SAP, Interim & final analysis Bio-analytical Labs / Central lab Medical/study report writing Supply Chain Management QA Canadian Presence Budget & budget Management

15 CRO Selection Initial selection criteria Further considerations CRO should meet the needs of the particular project May require further company expertise & support Therapeutic area expertise & knowledge Network of centers: access to the targeted patient population Ability to execute: experience, efficiency & personnel Relationship: ability to work together May require access to other consultants & vendors Budget key but not necessarily initial criterion for decision; need to be detailed & consistent with requirements Contract: Comprehensive & detailed requirements Expertise /resources to contract IP, document & data protection Subcontracts Remedies Non-compete Strategic Alignment

16 Contracting Understanding the DNA of the Contracting Parties Different focus Different deliverables Contracting Time vs. Risk Preferable to work out contract in advance of work initiated (under LOI) The Devil is in the Detail Sets basis for project Avoids Out of Scope charges Based on RFP (company needs; comparable) Delegation Responsibility with company even if fully outsourced CRO remedy for defaults Take Control and Contract Direction Contracts with subcontracts (3 rd parties) Protect Ownership IP, data & documents Insolvency Sponsor access to data, etc. Build a Way Out Financial consequences of termination Less is Not More Comprehensive & detailed Time & resources for contracting Thorough assessment Define requirements How to Survive Contracting With Contract Research Organizations, Confidential Acquisition International

17 Managing the Study

18 Trial Governance Collective Oversight Recent events have highlighted need for sponsor CRO oversight Trial Steering Committee One out of three FDA inspections linked to CROs & vendor oversight DSMB / DMC Sponsor (company) Responsibility across the board: Sponsor CRO roles & responsibilities and management key Clinical Project Management Team Although sponsors can transfer responsibilities for monitoring to a CRO(s), they retain responsibility for oversight of the work completed by the CRO(s) who assume this responsibility. FDA Statistics & Data Management Drug Supplies CRO(s) Safety & Pharmacovigilance group Participating Centers Central Lab & Pharmacokinetic Analysis

19 Risk Mitigation Strategy: Select Examples Risk Potential outcome Preventative action Contingency Plan Study design Site identification & selection Enrollment Challenges in implementation due to design (surgical/icu study in high risk population) Risk of meeting study target timelines Risk of meeting study target timelines Observational study to estimate AKI event rate in target population Access to expertise in renal disease, cardiac surgery, critical care Access to expertise in ASD Feasibility survey Patient flow chart (funnel) Sponsor assessment visits Site selection (past history) Referrals from other sites Competitive enrollment Flexibility built into design ( e.g. regarding dose selection in Stage 2) Study amendment Additional sites Replace non-contributors Site-by-site management plan Increase allocated enrollment at certain sites

20 Study Project Management Dedicated project team; broad membership Leadership throughout trial process Clearly define scope of project Project plan reflecting organization's goals Agreement on timelines & resource planning High intensity periods: start up, Interim Analysis (IA), data base lock/analysis, close out Regular reports (metrics) Site Initiation Reports Site & Patient Enrollment Site feedback & satisfaction Actual vs. Budget Safety reports Weekly calls, face-to-face, ad-hoc if necessary Issues management

21 Site Management Plan Site selection: advisors, company, CROs Enrollment projections & tracking Site Startup Investigators Meeting SIV Enrollment targets for sites Site-by-site plan Track enrollment of sites & patients Replace & increase number of sites if necessary Letters to Qualified Investigator & team Weekly Newsletter Webinars (target PI/site research coordinator) Company/ SRO / SC contact with site personnel ( , phone or face-to-face) In addition to regular CRA activities

22 Critical Success Factors Andreas Orfanos

23 Critical Success Factors Working with your vendor to establish your needs and priorities Clearly define scope of project Project plan reflecting organization's goal Collaborative approach on study design, timelines & resource planning whilst recognizing company needs Strategic & cultural fit Maximizing your investment by promoting innovative planning CRO market research on sites & enrollment Identify & agree on sites, selection & site management activities Requires expertise in therapeutic area & network Expertise in study design e.g. Adaptive Study Design Early consultation with regulatory authorities Carefully identify & allocate necessary resources; streamline costs; based on project scope & RFP Identifying approaches to support sponsors interests Oversight Dedicated project management team Presence throughout trial process Ensure strong relationship and allow for productive trial service Regular meetings, conflict resolution Clear designation of responsibilities Regular meetings with sites Site by site management plan Strategic Fit & Alignment

24 New CRO Models Evolving Andreas Orfanos

25 New Small Pharma CRO Models Evolving Strategic & cultural fit Close association between size of sponsor company and the size of the clinical service provider (State of Clinical Outsourcing Survey Avoca, 2011) Growth in CRO industry, many options; however seeing consolidation Furthermore new models evolving large CROs with dedicated entity targeting smaller companies e.g. Quintiles Emerging Biopharma Solutions Partnerships Niche providers The Future of Clinical Development Outsourcing, ISR Reports

26 Conclusion. Value-added approach Upfront effort key in making a good choice Early involvement Leadership & day-to-day management key; particularly if work with multiple CROs Culture of team: mutual trust & transparency Issues management - collaborative Seamless approach Andreas Orfanos

27 Acute Kidney Injury (AKI) 27 Thrasos Therapeutics: Confidential

28 Issues Management (Conflict Resolution) 28 Develop & agree on an issue management/escalation plan or part of Quality Mx Identify potential risks & red flags in clinical trial program (risk mitigation strategy) Define & utilise metrics Implement process: rapidly be brought to the attention of senior management at an early stage if not resolved in a timely manner Also identify issues at site level through site support team Ensure follow up until issues addressed & resolved (monitor & track) Site support team Sponsor (company) Clinical Project Mx (CPM) Team CRO Site personnel Trial Steering Committee Other vendors Metrics Thrasos Therapeutics: Confidential