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Agenda
3Page
Today’s announcement, vision and ambition
Topic
Carl Sterritt, CEO
Speakers
Feraccru® study details Dr Mark Sampson, CMO
Feraccru® US next steps Carl Sterritt, CEO
Q&A
Today’s announcement
Results of Shield’s Pre-NDA Submission Meeting with FDA: Confirms plans to submit New Drug Application for Feraccru® as soon as possible, provides a strategic review update and announces appointment of Non-Executive Director
Vision & ambition
5Page
We aim to transform patients’ lives by helping them become people again, by enabling them to enjoy the things that make the difference to them in their everyday lives, whilst delivering value to all of our stakeholders
One drug product in one indication
Today
Leverage Feraccru across adjacent indications & expand geographies
Near term
Build a sustainable, profitable specialty pharma company
Ambition
Feraccru® profile
1Iron deficiency anemia2Inflammatory bowel disease
Novel oral, twice a day, (tablet) ferric
iron therapy
Now approved in Europe for the
treatment of ID in adults
Non-salt
Simple oral administration
Efficient absorption
Rapid Hb rise
Placebo-like safety
More cost effective than IV
Taken without food
Important advantages and differentiated mechanism
of action compared to current standard-of-care
for IDA
Geographic and label expansions expected to increase Feraccru’starget patient population *
First-line therapy, salt-based oral irons
Current standard-of-care IDA
Second-line, intravenous irons
* Now approved in EU for Iron Deficiency
Overview of non-dialysis dependent chronic kidney disease and iron deficiency anemia
Chronic kidney disease (CKD)– Chronic progressive condition– “Renal” diet limits protein and can lead to low iron intake– Iron absorption poor with iron salts– Increases blood loss through kidneys
8Page
*Centers for Disease Control and Prevention. National Chronic Kidney Disease Fact Sheet, 2017
Overall prevalence of CKD in the United States is c.14%*
Anaemia is a major complication of CKD
Average of 15.4%of patients having anemia
Prevalence increases with the stage of CKD, rising from around 10% at stage 1 to approximately 55% at stage 5 and is associated with:
• Fatigue, lethargy, decreased quality of life and is also believed to be associated with cardiovascular complications, hospitalisations, and increased mortality.
• As with IDA, due to other diseases, currently available oral iron supplements are associated with limited efficacy and dose-limiting tolerability issues.
Kidney damage w/ normal GFR1 ≥90
Description eGFR (mL/min/1.73m2)Stage
Kidney damage w/ mildly reduced GFR2 60-89
Mild to moderately reduced GFR 3a 45-59
Moderately reduced GFR 3b 30-44
Severely reduced GFR4 15-29
Kidney failure5 <15 or dialysis
Normal Kidney Function
CKD background and staging
Sources: Mayo Clinic; National Kidney Foundation; National Kidney Disease Education Program
CKD Clinical staging
ST10-01-303 Study Schema
ScreeningUp to 14
DaysRandomisation
Ferric Maltol30mg bd
Placebo bd
36 week open label Ferric Maltol 30mg bd
End of studyWeek 52
Telephone Follow up
16 week double blind phase
A Phase 3, Randomized, Placebo Controlled, Prospective, Multicenter Study with Oral Ferric Maltol for the Treatment of Iron Deficiency Anemia in Subjects with Chronic Kidney Disease
Change in Hb from Baseline (g/dL) – ITT*
ITT: intention-to-treat *Based on SAP V1.0
0.19
0.51
0.45
-0.01
0.05
0.15
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
Week 4 Week 8 Week 16
Hb–
g/dl
Feraccru Placebo
p = 0.0009
p = 0.1686
N=56N=111
Concomitant Medications – Not permitted
• IV iron injections, intramuscular or depot iron administrations• Single agent oral iron supplementation, taken specifically to treat anemia (e.g. ferrous
sulfate, fumarate and gluconate) • Ferric citrate or sucroferric oxyhydroxide• ESAs• Blood transfusions or donations• Dimercaprol, chloramphenicol or methyldopa
Removal of subjects from study criteria (selected)
• Use of prohibited concomitant medications• Initiation of dialysis• Blood transfusions or donations for any cause• Any dose or frequency changes to myelosuppressants during the double-blind treatment
period• Requirement for major surgery. Minor surgeries not associated with significant blood loss,
in the Investigator’s judgement, are permitted (e.g. surgery related to fistulae or vascular access, minor dental extractions, incision and drainage of abscess or simple excisions)
Summary of Subjects with Data Removed from ITT Analysis as a result of Confounding Events
Event Ferric maltol subjects Placebo subjects
Haemorrhage1 2 0
Haemorrhagic anemia 0 1
ESA 4 0
RBC/RBC concentrate 3 0
Haematochezia 1 0
Blood/Blood related products 0 2
IV iron 0 3
Ferrous sulfate 3 2
Total (N) subjects 13 8
ESA: erythropoietin stimulating agent; RBC: red blood cell; IV: intravenous; 1. Gastrointestinal haemorrhage (1), haemorrhoid haemorrhage (1)
Change in Hb from Baseline (g/dL) – ITT (MI)*
0.16
0.49 0.5
0.03 0.03
-0.02
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
Week 4 week 8 week 16
g/dL
Feraccru
P=0.3259
P=0.0149P=0.0052
N=56N=111
ITT: intention-to-treat; MI: multiple imputations*Based on SAP v1.1
Change in Hb is more apparent by week 16 in subjects with serum ferritin <250ng/ml
Change in Hb: Ferritin <250ng.ml Change in Hb: Ferritin >250ng.ml
Summary of Ferritin (µg/L) (ITT - LOCF)
Visit Mean (SD)
Ferric Maltol (N=111) Placebo (N=56)
Baseline 97.03 (88.499) 104.21 (80.035)
Week 4 101.32 (86.768) 98.23 (78.813)
Week 8 108.20 (91.739) 96.77 (73.622)
Week 16 123.22 (109.003) 94.57 (78.982)
ITT: intention-to-treat; LOCF: last observation carried forward
Analysis of Change (ANCOVA) from Baseline in Ferritin (µg/L) at Week 16 (ITT – LOCF)
Assessment LS Means (SE) LSM Difference (SE)
95% CI p-value
Ferric Maltol
Placebo Ferric Maltol -Placebo
Week 4 4.23 (2.360) -5.87 (3.328)
10.10 (4.088) (2.029, 18.174)
0.0145
Week 8 10.93 (3.429)
-6.96 (4.836)
17.89 (5.940) (6.160, 29.620)
0.0030
Week 16 25.49 (5.400)
-8.25 (7.614)
33.73 (9.354) (15.264, 52.205)
0.0004
ITT: intention-to-treat; LOCF: last observation carried forwardLS = Least Squares; SE = Standard Error; LSM = Least Squares Means; CI = Confidence Interval
Adults in the US with IDA related to CKD
1US Rental Data Service 2017 Annual Report
31m CKD
16m CKD 3-5
15.5m CKD 3+
4m
661 K
468 K Dialysis
Renal Failure
193 K Transplanted
Non- Dialysis
14% of the Adult Population (244m)
7.7%Age 20+
26.4% Stage 3+4 Anemia (Stauffer et al)
Anaemia
Key messages and near term news flow
AEGIS-CKD study will be filed with US FDA as soon as possible• Timelines will be communicated in due course
AEGIS-CKD results highlights • Study meets primary endpoint (change in Hb from baseline at 16 weeks ) when
confounding measurements are excluded from ITT analysis• Change in Hb already statistically significant at Week 8• No additional pivotal clinical trials needed• Work will be funded within current cash resources
Strategic review update• EU licensing options• US market opportunity for Feraccru
Group’s 2017 preliminary results – 11 April 2018
21Page
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