Innovative Convalescent Plasma Programme Objectives Unveiled

CONVALESCENT PLASMA (CP) PROGRAMME Joint NHSBT NBTC Webinars 27thand 29th April 2020 16 April 2020 V1.0 This document is a draft and the information contained herein is subject to change 1

Key objectives ~1000 ICU patients randomised to treatment Successful completion of REMAP-CAP Trial 1 2 units per patient = 2,000 units Trial starts w/c 27th April; staged roll out 2500+ hospitalised patients randomised to treatment Successful completion of RECOVERY Trial 2 2 units per patients = 5000 units Trial starts by mid-late May; randomised 60 patients/day As soon as we have positive trial results, working with NHSE and NICE to design a clinical protocol to deliver to patients who would benefit at scale Maximise availability for hospitalised patients 3 Target of collection up to 10,000 units per week across UK Store plasma for a second wave of infection This document is a draft and the information contained herein is subject to change 2

Our objectives Our proactive strategy initially aims to supply 7,000 units of plasma for two clinical trials, simultaneously scaling the distribution of CP to meet ICU and non-ICU CP demand across the UK. End-to-end process 1 2 3 4 5 Manufacturing & Logistics Manufacture, store and distribute useful CP Donor Outreach Collection Testing Patient Treatment Identify, engage, assess and schedule in potential CP donors Screen and collect plasma from eligible donors Test for the presence of required antibodies in the donor s blood Selection, treatment and follow-up of patients receiving CP Identify all the options for sourcing potential donors Increase CP collection capacity using existing collection facilities, focusing on apheresis, whilst still enabling whole-blood donation Identify the most effective screening and neutralizing tests, to test for the concentration and quality of antibodies in donor plasma Extend collection and distribution network for plasma donations Triage plasma requests in line with trial protocol or NHSE clinical guidelines Define and assess donors against the minimum eligibility requirements Expand storage facilities to store plasma donations with the correct quality monitoring procedures Deliver treatment Assess results and follow-up with the patient Identify and set-up new collection centres to support scaled CP collection Scale up screening and neutralising Ab tests in order to complete clinical trial and initiate full roll-out Implement engagement methods and communication messages that enables scaled donor recruitment This document is a draft and the information contained herein is subject to change 3

15th April Model Output, initial refresh Key assumptions 95% sufficient titre, latest Imperial infection rates, 28 days from recovery to donation, 2% of infections hospitalised, 14% of hospitalised require ICU, ongoing lockdown, regional supply/capacity aligned, sufficient testing / manufacturing capacity is available Subject to change as data is refreshed, additional actuals are included and assumptions amended 120,000 1 Demand The draft analysis indicates a period of peak demand (ICU and non-ICU patient admissions) during w/c 30th March. 2 110,000 100,000 2 Supply The draft analysis indicates that the available *potential supply (to the point of extraction) peaks at w/c 11th May. The number of available CP units we identified in that week was approximately 114,000. This is the potential supply from all eligible donors, to the point of collection, before any quarantine and lab testing etc Apheresis Machine Capacity The draft analysis identified that the potential available CP unit supply (to the point of extraction) starts to meet or exceed ICU demand w/c 27th April and non-ICU demand w/c 4th May. 90,000 80,000 3 Base machine capacity constraints enable ICU patient demand to be first met during w/c 4th May and non- ICU demand 22nd June. 70,000 CP Units 4 Stretch machine capacity constraints enable non-ICU patient demand to be first met w/c 18th May. Further development of this capacity will enable surplus CP unit capacity to be stockpiled for a potential second wave. 60,000 50,000 Total potential plasma unit supply (to point of extraction) is significantly impaired post this date due to limitations in the Imperial forecasting model. 1 Hospital demand forecast is significantly impaired post this date due to limitations in the Imperial forecasting model. 40,000 30,000 20,000 4 10,000 3 3 0 09-Mar 16-Mar 23-Mar 30-Mar 06-Apr 13-Apr 20-Apr 27-Apr 04-May 11-May 18-May 25-May 01-Jun 08-Jun 15-Jun 22-Jun 29-Jun 06-Jul Weekly ICU CP Unit Demand Weekly hosp: Non-ICU CP Unit Demand 13-Jul 27-Jul 03-Aug 10-Aug 17-Aug 24-Aug 31-Aug 07-Sep 14-Sep 21-Sep Planned Stretch Machine Capacity Planned Base Machine Capacity 20-Jul Total potential plasma unit supply (Point of Extraction) These outputs must be viewed in conjunction with the analysis assumptions and limitations. *Potential supply is the total number of CP units that may be extracted from eligible donors without any constraints in the collection, testing and manufacturing processes (i.e. the total number of available CP units). This document is a draft and the information contained herein is subject to change 4

NHSBT considerations Collection in static sites only 76 additional apheresis machines added to capacity Largely additional capacity will be in existing centres 2-3 additional London/SE sites being added Risks Consumables - 100,000 additional harnesses added Staff 150 need to be recruited and trained Donors need to attend and be geographically collocated with collection ability Donor deferral for those who have previously received blood components This document is a draft and the information contained herein is subject to change 5

Testing and Logistics On each unit before issue we will measure RNA (1000 donors), Ab ELISA Neutralising Antibody titre collaboration with PHE and University of Oxford Neutralising Ab titres are key planned cut off of 1:100 which is equivalent to top quartile donors Some evidence that 28d from recovery ensures maximal NAb titres in component, higher in those who were sicker and people >40 years Logistics Order via OBOS No Pathogen Inactivation ABO selection as for FFP, will be HT negative Shelf life - 24 hour after defrosting Trial sites will be given a small stock of O and A B will be held centrally SHOT HV will apply, in addition to trial data This document is a draft and the information contained herein is subject to change 6

Convalescent plasma Convalescent plasma UK trial UK trial Patients admitted to ITU within last 48 hours Confirmed COVID CP versus standard care (+/- other randomised treatments) CP on study day 1 and day 2 Primary outcome number of organ support-free days up to D21 REMAP-CAP outcomes plus other domain specific outcomes arterial or venous thrombosis, SAEs Planned recruitment 2000 participants, approx. 1000 receive CP Intensive blood and respiratory sampling for a subgroup (400 participants)

Convalescent plasma Convalescent plasma UK trial UK trial Hospitalised patients Confirmed COVID CP versus standard care (+/- other randomised treatments) CP on study day 1 and day 2 Primary outcome 28 day mortality Other outcomes need for ventilation, renal support, hospital stay Also thrombotic outcomes and Transfusion-related AEs usually reportable to SHOT Planned recruitment at least 5000 participants, 2500 receiving CP Substantial amendment submitted to include children

What can you do? Ensure that your Trust is registered for the Trials Consider if your hospital has a way of signposting recovered staff who would like to donate - Dedicated convalescent plasma call-back team for NHS staff calling 0300 123 2323 - Or register standard way via website; https://www.nhsbt.nhs.uk/how-you-can- help/convalescent-plasma-clinical-trial/ - Alastair.Hunter@nhsbt.nhs.uk is NHSBT link for any hospitals who have inquiries re staff Donation Criteria - standard blood donor criteria apply - COVID19 illness - 28d from recovery suggest phone us from about 5 weeks from beginning of illness This document is a draft and the information contained herein is subject to change 9

This document is a draft and the information contained herein is subject to change 10