A SMALL FISH IN A BIG POND MATCHING THE NEEDS OF SMALLER PHARMA SPONSORS

Transcription

1 A SMALL FISH IN A BIG POND MATCHING THE NEEDS OF SMALLER PHARMA SPONSORS WITH THE RIGHT CRO DR SALLY ADAMS DEVELOPMENT DIRECTOR SCANCELL LTD 1

2 SCANCELL LTD Founded in 1997 as a spin-out from the University of Nottingham In 2006, sold pipeline of monoclonal antibodies to Arana Therapeutics, Australia Deal allowed Scancell to focus on its two innovative cancer immunotherapy programmes, ImmunoBody and Moditope Lead ImmunoBody product is SCIB1, a DNA plasmid therapy for patients with metastatic melanoma administered using an electroporation device SCIB1 entered clinical trials in

3 SCIB1 IMMUNOBODY ImmunoBody T cell activators are recombinant DNA plasmids that encode engineered human IgG1 antibody molecules that target only the high affinity Fc receptor on activated dendritic cells In SCIB1, melanoma-specific T cell epitopes have been inserted into the Complementarity Determining Regions of the antibody framework to make a genetic antigen/antibody complex Gene c engineering introduces elements of tumour-associated an gens into the an body structure TUMOUR CELL Immunisation of patients results in the generation of a tumour-specific immune response to reduce tumour size and/or prevent recurrence 3

4 SCIB1 DELIVERY DNA treatment strategies are attractive because of the relative ease of manufacture and the excellent safety profile However, injection of DNA alone does not result in potent immune responses in humans Electroporation generates controlled electrical pulses to create temporary pores in cell membranes and facilitates a dramatic increase in DNA uptake; it also acts like an adjuvant and induces inflammation SCIB1 is therefore injected using the TriGrid electroporation device (Ichor Medical Systems) The TriGrid 1.0 delivery system is a compact hand-held device that contains a syringe needle and four recessed electrodes Figur e 2. Application Cartridge Electrodes Integrated Applicator Injection Needle Pulse Stimulator 4

5 TRIGRID DELIVERY OF SCIB1 Electrode and needle insertion Safety check Drug administration Electric field application Procedure complete 5

6 SCIB1 TRIAL CHALLENGES Recombinant DNA Ethics Committee was GTAC in 2010 for Advanced Therapies Delivered using a non-ce marked device Involvement of Devices Division as well as Clinical Trials Unit of MHRA Cold chain (-20 o C) requirements for drug product/expiry date relabelling Fresh blood samples to be shipped in defined time period at ambient temperature 6

7 INSOURCING VS OUTSOURCING Small companies often don t have the infrastructure or experience to run clinical trials themselves Speed is often critical to get new products to the clinic as soon as possible and keep investors happy Choosing a full-service CRO is an attractive option All the services covered Skills and experience Global operations, if required Common policies and SOPs 7

8 THE CRO SELECTION PROCESS Small companies often don t have the personnel to evaluate all aspects of potential CRO partners The Request for Proposals needs to be sufficiently detailed for comprehensive and comparable bids to be prepared Identify organisations with key strengths: Regulatory expertise in relevant countries Previous therapeutic area experience Personal recommendations Face-to-face meeting with all key personnel from both CROs and Sponsor Open discussion critical Specify likely areas of difficulty and predictable pitfalls 8

9 ESSENTIAL ASPECTS Selection of project manager(s) critical Clearly define roles, responsibilities and timelines Discuss/review all plans and procedures Provide therapeutic area/product training Frequent feedback F2F meetings at regular intervals WHAT COULD POSSIBLY GO WRONG? 9

10 POTENTIAL PITFALLS Scope of project may change, particularly for phase 1/2 studies as amendments to protocol required Floods of change orders arrive Costings for original project not clear Changes result in significant cost increases and possible delays Personnel changes to CRO team Internal promotions/movements New personnel less experienced, new staff Access to senior level expertise to guide decision-making disappears Distance, time zones and language difficulties 10

11 MERGERS & ACQUISITIONS Pros More resources available Wider spread of resources (different countries) Opportunities to build new relationships New and innovative practices introduced Cons Loss of flexibility New personnel existing relationships lost Lag period before new structure begins to work effectively Administrative burden new processes, merger of SOPs etc Bigger organisation, less interested in small companies 11

12 CONSEQUENCES Changes can result in expectations not being met Resulting in Project not being delivered on time Project over-budget Project not conducted to the highest possible standards 12

13 CHALLENGES AND EXPECTATIONS Small- to medium-sized companies are pressured to prudently manage their resources, particularly financial Same is also true for larger companies but they have more money to spend Expectation of the full service CRO is to deliver projects as if they were a true extension of the Sponsor partner In reality, there are unmet expectations and failures due to a variety of circumstances 13

14 RELATIONSHIP TRENDS The bulk of large CROs revenues come from larger pharma clients Many of the largest pharmaceutical companies use outsourcing extensively Given this dynamic, small- to medium-sized companies offer very little in terms of benefit to the CRO Often create even greater challenges because of the hand-holding required due to limited Sponsor resources and experience For the CRO, it is understandable that larger clients get more attention larger companies have pipelines, money and keep CRO staff employed THAT S JUST BUSINESS! 14

15 THE PROBLEM For small- to medium-sized clients with their projects at stake, time and money are of the essence How can they be more effective in using their selected partner(s) and ensure that performance, timeliness and quality are being maintained? Regulators increasingly focussed on sponsor companies and their use of external providers, their oversight and compliance The Sponsor is responsible and accountable for the conduct of their studies 15

16 ONE-STOP SHOP VS SMALL, SPECIALITY CROS Advantages of using multiple, niche CROs (or freelancers) Specialists in particular aspects required (TMF filing, regulatory, monitoring, SAE reporting, data analysis etc) Generally smaller organisations more interested in small clients Good rapport with customers Flexible and fresh approach, new ideas Quick to implement change Competitive pricing Spreads the risk Avoids dependency Disadvantages Requires close management of multiple operations different level of management Multiple contracts to negotiate 16

17 THE SCANCELL EXPERIENCE Used medium-sized CRO to set up and initiate phase 1/2 study UK study, 6 centres Small but complex study First-in-Man drug administered using non-ce marked medical device Fresh blood samples to be collected with same-day delivery to lab for analysis Several protocol amendments Add further cohorts Take additional samples 17

18 SCIB1-001 STUDY DESIGN PHASE 1/2 STUDY IN PATIENTS WITH STAGE III/IV MELANOMA Primary Objective safety and tolerability Secondary Objectives immune responses; tumour responses Part 1 dose escalation with safety assessment after 3 doses (0.4 mg, 2 mg, 4 mg) Part 2 resected patients at highest tolerated dose (4 mg) No Maximum Tolerated Dose identified in Part 1; formulation improvements enabled higher dose to be evaluated Part 1 additional dose escalation cohort added (8 mg) Part 3 additional patients recruited at 8 mg dose STUDY SCHEDULE Patients dosed at Weeks 0, 3 and 6 weeks with boosts at 3 and 6 months Immune samples taken pre- and post-dosing Optional continuation phase with dosing every 3-6 months for up to 5 years Injection with EP Weeks 0 3 weeks 6 weeks 3 months 6 months Continuation phase (optional) 3-6 months Immune analysis samples 18

19 ISSUES Several personnel changes some enforced, some requested First company merged Merged company acquired More personnel changes Change orders prohibitively expensive with new-co infrastructure 19

20 THE SOLUTION Clinical database and input, SAE reporting and back-up Medical Monitor retained at original CRO Scancell Clinical Project Manager Manages CRAs Oversees clinical trial supplies Oversees budget and payments to sites Freelance CRAs directly contracted by Scancell Clinical Trial Supplies (CTS) consultant contracted Statistical, SAS programming and medical writing services contracted out CTS contract transferred from CRO to Scancell TMF storage and maintenance contracted out Clinical trial oversight provided by Scancell Development Director and contracted Medical Monitor and Regulatory Affairs specialist 20

21 BEST PRACTICE Whether using a One Stop Shop or multiple, speciality niche CROs, keys to a successful partnership include Establishment of a solid blueprint with a well-written protocol Selection of the appropriate CRO Establishment of well-defined service and quality agreements Inclusion of minimum qualification requirements for key CRO contacts Establishment of an oversight team to ensure performance and quality Ensuring that your corporate standards are utilized and maintained 21

22 SUMMARY Evaluate your core team to consider the sort of companies and partners that will best compliment your internal staff Decide which CRO model best suits your organisation Use simple keys to ensure working with CRO partner(s) results in a successfully and effectively run clinical trial Outsourcing of development resources continues to increase - need to ensure your programme receives the attention it deserves and STAND OUT FROM THE CROWD 22