Galleri Test

The Galleri® Test

A single blood test screening for a shared cancer signal across 50+ cancer types

UK First

Preologi is the first private organisation in the United Kingdom authorised to provide the Galleri® test.

Why it matters: the screening gap patients face today

• Screening is recommended for only a small number of cancer types in the UK — including breast, cervical, bowel and targeted lung cancer screening
• Around 6% of all cancers are currently diagnosed through screening programs
• The UK has some of the lowest cancer survival² and some of the highest rates of emergency cancer presentation³ among comparable high-income countries
• Many cancers are not found until symptoms appear, and nearly half of staged-cancers are diagnosed at later stages, when they can be harder to treat.

How the Galleri® test can address this

• Screen for 50+ Cancer Types — from a single blood sample
• 4x as many cancers were detected through screening when Galleri was added to usual NHS care, compared with usual NHS screening alone⁴
• <escape><</escape>1/200 False Positive Cases — 99.6% Specificity⁴
• 93% accuracy for cancer signal of origin⁵ — this guides an efficient diagnostic work-up

A bold new era

• The Galleri® test is a pioneering multi-cancer early detection (MCED) test
• It analyses cell-free DNA shed by cells — including cancer cells — into the bloodstream, detecting methylation patterns unique to cancer from a single blood sample, across more than 50 cancer types.
• Many of these cancers currently have no recommended detection or screening program in the UK.

The science: how it works

1. Blood sample — A single sample, no special prep
2. cfDNA extraction — DNA shed by cells is isolated
3. Methylation sequencing — Reads DNA methylation patterns
4. Methylation patterns classification — Determines if a cancer signal is present
5. Cancer Signal Origin — Predicts most likely tissue of origin

Galleri® is a screening aid, not a diagnostic test. A positive result needs diagnostic confirmation; a negative result does not rule out cancer.

What is the Galleri® test

Galleri is a multi-cancer early detection (MCED) test developed by GRAIL. Rather than looking for one cancer at a time, it analyses methylation patterns in cell-free DNA (cfDNA) in the bloodstream to identify a signal associated with cancer.

When a cancer signal is detected, the test correctly predicts the cancer signal origin in 93% of cases.⁵

Its particular value is that most of these cancers have no recommended screening program in the UK at all.

Galleri is designed to complement — not replace — established programmes such as breast, cervical and bowel screening.

What it cannot do

• A ‘No Signal Detected’ result does not mean you are cancer-free. Galleri looks for a signal associated with cancer in the bloodstream, but no test can detect every cancer. A ‘No Signal Detected’ result means that Galleri did not detect a cancer signal at the time of testing; it does not rule out cancer or guarantee that cancer is not present.
• It does not replace NHS screening. If you are due a mammogram, a bowel-screening kit, a smear or a lung scan, have those. Galleri sits alongside them, it does not stand in for them.
• It does not investigate symptoms. If something is worrying you, a doctor's appointment is the right front door, not this test.
• The impact of the test on cancer survival is not currently known. It has not yet been established whether using Galleri to detect cancer improves survival.

The Galleri® test screens for a signal across 50+ cancers

These include many cancers with no existing NHS screening programme.⁶

A selection of the cancer types:

• Chest & airway: lung, head & neck, oesophageal.
• Digestive: colon & rectum, pancreatic, stomach, liver, bile duct, gall, bladder and anus.
• Women’s health: breast, ovarian, cervix, uterus
• Blood & other: lymphoma, leukaemia, plasma cell myeloma, melanoma, bladder & upper urinary tract — and more than 50 in total.

Who it’s for

Galleri is intended as an addition to standard screening for adults at higher risk of cancer — typically those aged 50 and over.⁷

• Adults aged 50 and over, or adults aged 22
• Individuals with a personal history of cancer, smokers or former smokers
• Anyone wishing to take a proactive approach with their health

Sensitivity across cancer types

• 40.4% — 12-month episode sensitivity, all cancer types⁸
• 73.7% — 12-month episode sensitivity, group of 12 pre-specified cancers*⁸
• 69.3% of newly diagnosed cancers (n=114) were detected at stage I-III⁹

The 12 pre-specified deadly cancers - responsible for ~2/3 of US cancer deaths⁸:

Anus · Bladder · Colon/rectum · Oesophagus · Head & neck · Liver/bile duct · Lung · Lymphoma · Ovary · Pancreas · Plasma cell neoplasm · Stomach

From evidence to implementation

PATHFINDER 2

35,000 patients. One Galleri® test. 12-month follow-up.

• 53% of cancers detected were stage I or II¹⁰
• 6.5-fold increase in screen-detected cancers within a year, when added to recommended screening*¹⁰

NHS-Galleri Trial

142,000 patients. Three Galleri Tests. 3-year follow-up.

Adding annual Galleri screening to standard of care screening resulted in the following as compared to standard of care alone.

• Progressive year-on-year reduction in stage IV cancer with annual Galleri screening plus standard of care vs standard of care alone. 26% reduction in year 3 of annual screening for 12 pre-specified cancers⁴
• 4-fold increase in cancers detected through screening with Galleri alongside usual NHS screening, compared with usual NHS screening alone⁴
• 25% reduction in cancers diagnosed via emergency presentation⁴

What the studies show

Galleri is supported by a large evidence base for a screening test in the intended-use population : the PATHFINDER and PATHFINDER 2 studies (around 42,500 participants) and the NHS-Galleri trial — the world’s largest MCED study, with more than 142,000 participants.⁴

• 99.6% specificity — fewer than 1 in 200 people without cancer, will receive a false positive result⁸
• 40.4% overall sensitivity across all cancers (73.7% for the 12 deadliest cancers).⁸
• ~93% accuracy in predicting the cancer’s tissue of origin.¹⁷
• 61.6% positive predictive value — around 6 in 10 positive results are confirmed as cancer.¹¹

More aggressive cancers tend to release more cell-free DNA into the bloodstream at early stages, making them more likely to be detected by Galleri.

Includes screening for breast, cervical, colorectal, and lung

Detection sensitivity by cancer stage

Cancer stage Detection sensitivity (all cancers)¹⁶

Stage I 16.8%

Stage II 40.4%

Stage III 77.0%

Stage IV 90.1%

PATHFINDER 2

PATHFINDER 2 — more than 35,000 participants, one Galleri test, 12-month follow-up. 53% of cancers detected were stage I or II, and adding Galleri to recommended screening for breast, cervical, colorectal, and lung produced a almost seven-fold increase in screen-detected cancers within a year.⁴

NHS-Galleri trial

NHS-Galleri trial — more than 142,000 participants aged 50–77 on a randomised controlled trial where one arm received annual Galleri testing in addition to standard-of-care and other arm had standard-ofcare.

The trial showed findings consistent with a shift toward earlier-stage cancer diagnosis, approximately four times more cancers found when Galleri test is added to standard UK screening programmes. There was a 25% reduction in cancers detected through emergency presentation.

The study did not meet is primary end point of a statistically significant fall in combined stage III and IV cancer diagnosis. Although by year 3 there was a 26% reduction in stage IV cancer diagnoses for the 12 prespecified cancers.⁴

Sensitivity varies considerably by cancer type; it is highest for the higher-mortality cancers that shed more DNA earlier.

No MCED test has yet published evidence that screening reduces cancer mortality.

More about the Landmark NHS-Galleri trial results

The trial showed more cancers detected earlier and a substantial reduction in late-stage cancer diagnoses when the Galleri® test was added to standard-of-care cancer screening in England and used annually for 3 years.

The NHS-Galleri trial was conducted in partnership with the National Health Service (NHS) in England. The NHS helped enrol 142,000 participants.¹²

This first-and-only-of-its-kind trial showed important and encouraging results¹²

4x more cancers detected

After 3 years of annual screening with the Galleri test, when added to standard-of-care screening in England (breast, colorectal, cervical, and high-risk lung cancers), more than 4 times as many cancers were found compared with standard-of-care screening alone.¹²

More cancers found at earlier stages

The trial showed that adding the Galleri test to standard-of-care screening shifted detection toward earlier stages, with 16% increases in stage I and II cancer diagnoses across a group of 12 prespecified cancers.¹²

Group of 12 prespecified cancers

1. Anus
2. Bladder
3. Colorectal
4. Oesophagus
5. Head and neck
6. Liver/bile duct
7. Lung
8. Lymphoma
9. Myeloma/plasma cell neoplasm
10. Ovary
11. Pancreas
12. Stomach

Earlier-stage cancer is often associated with:

• More treatment options
• Potential for less intensive treatment
• Better outcomes
• Higher survival

Reduction of stage IV cancer diagnoses

The trial found at least a 20% reduction, (round 3 for all cancers was 20%), in stage IV cancers in the second and third years of screening with the Galleri test compared with standard-of-care screenings alone.¹²

This was observed across all cancers combined as well as the group of 12 deadly cancers.

Stage IV cancer is the most advanced stage — when cancer has spread to other parts of the body, is hardest to treat, and survival is lowest.

While the NHS-Galleri trial showed a positive trend toward reduction of stage III-IV diagnoses over the three screening rounds, it missed the primary endpoint of a statistically significant reduction in these diagnoses.

Why stage IV reduction is important

Reducing late-stage diagnoses is expected to improve outcomes and survival rates, as survival depends strongly on the stage at which cancer is found.¹⁵

The Galleri test has not been evaluated for survival benefit.

In England, five year survival across a majority of cancer types is around 84% for people diagnosed at an early stage (stage I or II). Survival drops to roughly 39% for people diagnosed at a late stage (stage III or IV).

The NHS-Galleri trial results support the test's safety and performance in a large, real-world population setting, and suggest that adding an annual Galleri test to recommended screenings through a simple blood test may have meaningful clinical benefits:

• Helps find more cancers
• Finds cancers earlier
• Reduces the number of stage IV cancers
• Reduces emergency room cancer diagnoses

Important information: Intended use & limitations of the Galleri® Test

• Intended for adults with an elevated risk of cancer, such as those aged 50 or older.
• Does not detect all cancers; must be used in addition to, not instead of, routine screening.
• A positive result requires diagnostic confirmation through further clinical investigation.
• A negative result does not rule out cancer or replace ongoing screening participation.
• Not recommended for those pregnant, aged 21 or under, or in active cancer treatment.
• No MCED test — including Galleri — has yet published evidence that screening reduces mortality; this is the subject of ongoing trials.

Source: GRAIL, Galleri Important Safety Information & Intended Use⁷