ANNUAL REPORT AND ACCOUNTS 2025

MAXIMISING

SHAREHOLDER

VALUE

YOUR BOARD

Sets Syncona’s purpose,

investment objective and policy,

strategic objectives and risk

appetite, ensuring effective

management of shareholder

and other stakeholder interests.

YOUR INVESTMENT

MANAGER

Responsible for execution of the

investment strategy and the day-to-day

management of the portfolio; focusing

on maximising value across the portfolio

and driving assets to late-stage

development, where SIML believes

significant value can be accessed.

“Volatile market conditions have

persisted in CY2025. There are

a number of factors which have

significantly impacted cost of

and access to capital. However,

fundamentals remain robust,

and we are positive about the

long-term value of innovation

and new product development,

around which Syncona’s strategy

has been centred.”

CHRIS HOLLOWOOD

CEO, SYNCONA INVESTMENT

MANAGEMENT LIMITED (SIML)

“Against a continuing difficult

market backdrop, the Board

remains confident in the SIML

team’s ability to maximise value

from the portfolio in line with

a proposed new investment

objective and policy to move

to an orderly realisation of

Syncona’s portfolio assets,

balancing returning further

cash to shareholders in a timely

manner and maximising value.”

MELANIE GEE

CHAIR, SYNCONA LIMITED

SYNCONA LIMITED

SYNCONA INVESTMENT

MANAGEMENT LIMITED

Effective stewardship

of stakeholder interests

Maximising value

across the portfolio

04

Chair’s statement

08

Value creation

10

Our strategy

12

Our business model

14

Our stakeholders

16

Our KPIs

18

Manager’s review

26

Market review

30

Portfolio review

42

ESG review

46

People and

culture review

Contents

STRATEGIC REPORT

At a glance

02

SYNCONA LIMITED

Chair’s statement

04

Value creation

08

— Our strategy

10

— Our business model

12

— Our stakeholders

14

— Our KPIs

16

SYNCONA INVESTMENT

MANAGEMENT LIMITED

Manager’s review

18

Market review

26

Portfolio review

30

ESG review

42

People and culture review

46

REPORTING DISCLOSURES

SECR disclosure

52

TCFD report

54

Risk management

58

Principal risks and uncertainties

62

Viability assessment and statement

69

GOVERNANCE

Corporate governance report

70

Board of Directors

76

Report of the Nomination

and Governance Committee

80

Report of the Audit Committee

84

Report of the Remuneration Committee

89

Directors’ report

95

Statement of Directors’ responsibilities

99

FINANCIAL STATEMENTS

Independent Auditor’s report

100

Unaudited Group portfolio statement

106

Consolidated statement of

comprehensive income

107

Consolidated statement of financial position

108

Consolidated statement of changes in net assets

attributable to holders of Ordinary Shares

109

Consolidated statement of cash flows

110

Notes to the consolidated financial statements

111

SHAREHOLDER INFORMATION

AIFMD Disclosures (unaudited)

134

Report of the Depositary to the shareholders

135

Company summary and e-communications

for shareholders

136

Glossary

137

Alternative performance measures

139

Advisers

IBC

SYNCONALTD.COM

SYNCONA LIMITED

1

2

3

4

COMMERCIAL

LATE-STAGE CLINICAL

CLINICAL

PRE-CLINICAL

INVESTMENTS

AND MILESTONES

4.5%

39.2%

29.7%

20.0%

6.6%

At a glance

OUR PURPOSE IS TO MAXIMISE VALUE

AND TRANSFORM PATIENT OUTCOMES

OUR STRATEGY AND

BUSINESS MODEL

DEFINE DIRECTION

Our Investment Manager, SIML, has created a portfolio

of leading life science companies that are seeking

to deliver transformational treatments to patients.

A PORTFOLIO WITH

SIGNIFICANT POTENTIAL

SIML is actively managing a strategic

portfolio of 14 companies which are

diversified across different stages of

the development cycle and a range

of therapeutic areas.

OUR MATURING

PORTFOLIO

POWERS PERFORMANCE

AN EXPERT TEAM FOCUSED

ON VALUE CREATION

Founded by the Wellcome Trust in 2012,

SIML is a leading life science investor

with a strong track record of significant

value creation from exits.

The team has a broad range of scientific,

operational, clinical, financial and

commercial expertise enabling them

to effectively manage an increasingly

mature portfolio.

OUR INVESTMENT

MANAGER

DRIVES DELIVERY

A FOCUS ON MAXIMISING

VALUE FROM THE PORTFOLIO

The Board intends, subject to FCA and

shareholder approval, to propose a change

to the Company’s investment objective

and policy to move to an orderly realisation

of its portfolio assets, with a view to

achieving a balance between returning

cash to shareholders in a timely manner

and maximising value.

SIML has created a portfolio of life science

companies. The SIML team is investing in

and managing these companies to deliver

key value inflection points, which have the

potential to deliver significant NAV growth

through M&A and liquidity events.

MAXIMISE VALUE

FOR SHAREHOLDERS

DELIVER KEY VALUE

INFLECTION POINTS

MAINTAIN DISCIPLINED

CAPITAL ALLOCATION

REALISE SIGNIFICANT

SHAREHOLDER RETURNS

PORTFOLIO BY CLINICAL STAGE

02

£1.05bn

Net Asset Value (NAV)

(170.9p per share

1,2

)

(2024: £1.24bn, 188.7p per share)

(9.5)%

NAV per share return

1

(2024: 1.2%)

1. Alternative performance measure, please refer to page 139.

2.

Fully diluted, please refer to note 14 to the financial statements on page 122.

3.

Please see Glossary on page 137 for definition.

SEEKING TO MAXIMISE VALUE FOR SHAREHOLDERS

AND MEET A DIVERSE RANGE OF REQUIREMENTS

–

The Board has, in consultation with SIML and advisers,

undertaken a comprehensive review of options to maximise

value for shareholders

–

This follows a period of underperformance for the biotech

sector and negative sentiment towards listed investment

companies which has impacted Syncona’s share price

–

The Board has engaged extensively with shareholders, who

expressed a range of perspectives, reflecting a diverse share register

FOCUS ON RETURNING CAPITAL FROM REALISATIONS

BALANCED WITH MAXIMISING VALUE

–

The Board intends, subject to FCA and shareholder approval,

to propose changes to the Company’s investment objective

and policy to move to an orderly realisation of portfolio assets

with a view to achieving a balance between returning cash

to shareholders in a timely manner and maximising value

–

Alongside the proposed new investment objective and policy,

the Board intends to adopt a new capital allocation policy to

support existing portfolio companies, which have the potential

to deliver liquidity via M&A or public markets, deliver key value

inflection points and preserve portfolio company value in

third-party financings

–

It is the Board’s intention that net proceeds from the disposal of

interests in private portfolio companies will be returned to shareholders,

subject to retaining a prudent reserve for operating costs

FINANCIAL PERFORMANCE

STRATEGY UPDATE

–

If approved, the Board intends that the new investment

objective and policy will be reviewed by the Board once

significant proceeds have been returned to shareholders

or at three years to ensure the continued return of net proceeds

from realisations is still maximising value for shareholders

or whether new investments should be re-instated

POTENTIAL ACCELERATION OF CASH RETURNS

–

The Board is also exploring options to accelerate realisations,

which may include a sale of a small portion of its interests in

certain of its portfolio companies at a modest implied premium

to the current share price and at a discount to NAV

SEEKING TO OFFER CERTAIN SHAREHOLDERS

OPPORTUNITY TO ROLL INTERESTS INTO A NEW

INDEPENDENT PRIVATE FUND MANAGED BY SIML

–

The Board recognises that certain shareholders may wish

to continue to have exposure to new and early-stage life

science companies

–

As such, the Board is exploring the possibility of providing

institutional shareholders with an opportunity to roll their

interests in the Company into a new investment vehicle

independent of the Company (“New Fund”)

–

The New Fund’s strategy would be to build world-class

companies from ground-breaking science or technology

£765.4m

Life science portfolio valuation

1

(2024: £786.1m)

(17.0)%

Life science portfolio return

1

(2024: 2.2%)

£287.7m

Capital pool

1,3

(2024: £452.8m)

£135.3m

Capital deployment

1

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

Chair’s statement

Maximising value

for shareholders

“Our intention to propose the change

of investment objective and policy,

and our ambitions, are the result

of extensive engagement with our

shareholders and the significant

work and partnership with the SIML

team. This process has underpinned

our confidence in the SIML team’s

ability to deliver strong risk-adjusted

returns from our existing assets over

time, as relevant markets stabilise

and volatility decreases.”

MELANIE GEE

CHAIR, SYNCONA LIMITED

04

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

STRATEGIC REPORT

PERFORMANCE AGAINST A VOLATILE MARKET BACKDROP

Against volatile global macroeconomic conditions, Syncona ended

the year with net assets of £1.05 billion (170.9p per share),

delivering a NAV per share return of (9.5%). This decline in NAV per

share was primarily driven by the significant fall in Autolus’ share

price. Public and private market conditions have been challenging

for Syncona and our portfolio companies with interest rates, trade

policies, regulatory uncertainty and pharma pricing significantly

impacting cost of and access to capital.

Syncona’s share price continues to be impacted by the significant

headwinds facing the markets its portfolio companies operate in.

It has also been impacted by the negative sentiment towards both

listed investment companies and biotech companies. During the

year the share price declined by 29.5%, with the shares moving

from a premium to a material discount to NAV over the last three

years, with the shares now trading at a 48.2% discount to NAV

1

.

CAPITAL ALLOCATED TO SHARE BUYBACKS

The Board allocated a further £35.0 million to share buybacks during

the year, taking total capital allocated to share repurchases since

September 2023 to £75.0 million. In total 40.1 million shares were

repurchased in the 12 months at an average discount of 37.4%,

resulting in an accretion of 4.96p per share over the year. A further

£6.5 million

1

of shares have been bought back since the period end,

at an average discount of 49.8%.

In light of the strategy update outlined and given the current share

buyback arrangements with Deutsche Numis came to an end

on 18 June 2025, the Board has been advised to pause the ongoing

share buyback until it is in a position to provide a further update on

the Company’s new strategy. As of 13 June, there is £5.4 million

of cash allocated to buybacks that remains to be deployed.

COMPREHENSIVE REVIEW OF STRATEGIC OPTIONS

WITH DISCUSSIONS ONGOING

The Board has, in consultation with SIML and advisers, undertaken a

comprehensive review of options to maximise value for shareholders.

As part of this review, the Board has engaged extensively with

shareholders, who expressed a range of perspectives, reflecting

Syncona’s diverse shareholder register. The results of this strategic

review have been shared in a separate announcement.

The review follows a period of underperformance for the biotech

sector with the S&P Biotechnology Index still 52.0%

1

below its

peak in February 2021. Market conditions have been particularly

challenging for early-stage life science companies, with cost of and

access to capital impacted for biotech companies across all stages

of the development cycle. The challenging market backdrop and

broader negative sentiment towards listed investment companies

have continued to impact the price of Syncona’s Ordinary Shares, with

the price moving from a premium to a material discount to NAV over

the last three years. Over this period, the SIML team has rebalanced

the portfolio, prioritising capital towards the most promising assets.

Having taken on board the variety of views, the Board has decided

that, subject to FCA approval, it intends to propose a new investment

objective and policy to shareholders to move to an orderly realisation

of its portfolio assets, with a view to achieving a balance between

returning cash to shareholders in a timely manner and maximising

value. Alongside this, the Board intends to amend Syncona’s capital

allocation policy.

1. As at 13 June 2025.

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

05

SYNCONA LIMITED

Chair’s statement

continued

“Global macroeconomic conditions have been challenging, with markets

for Syncona and our portfolio particularly difficult with increased

volatility in 2025. Our financial performance has been significantly

impacted by the decline of Autolus’ share price. Against this backdrop,

the SIML team has worked closely with the portfolio companies to

attract external investment across an increasingly late-stage portfolio

and the Board is pleased with the progress that has been made.”

06

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

STRATEGIC REPORT

The Board also recognises that certain shareholders may wish to

continue to have exposure to a similar strategy to Syncona’s existing

investment objective and policy, which incorporates creating early-

stage life science and technology companies. As such, the Board is

exploring the possibility of providing institutional shareholders with an

opportunity to roll their interests in the Company into a new private

investment vehicle (“New Fund”) independent of the Company, which

would be managed by SIML. Discussions are ongoing with a number

of sophisticated institutional and strategic investors and London-based

university and research partners around participating in the New Fund.

The Board is also exploring options to accelerate cash returns to

shareholders, which may include the sale of a small portion of its

interests in its portfolio companies at a modest implied premium to

the current share price and at a discount to NAV. If the New Fund is

successful in raising sufficient new capital, the Company would seek

to enter into such a sale to the New Fund and will keep the market

updated on progress as and when appropriate.

CHANGES TO THE BOARD

The Company also announces that Virginia Holmes will not be seeking

re-election to the Syncona Board at the upcoming Annual General

Meeting in August this year. Virginia has been an invaluable member

of the Board since joining in January 2021 and myself and the Board

thank her for her service as a Senior Independent Director over the

last four and a half years. In the event a new investment objective

and policy is approved by shareholders, it is the Board’s intention

to reduce the size of the Board to reflect the Company’s strategy.

ONGOING COMMITMENT TO SUSTAINABILITY

Syncona will maintain a strong commitment and high standard in its

approach to sustainability as the SIML team continues to manage

the portfolio to maximise value. The Board recognises the ongoing

importance of focusing on sustainability issues as a business and

social imperative, whilst also understanding that this is a key priority

for our stakeholders. Our portfolio companies and the patients they

seek to treat will continue to be at the heart of SIML’s investment

management process and Syncona will publish an updated

Sustainability Policy and Responsible Investment Policy in the event

a change to the investment objective and policy is proposed and

approved at a general meeting. Alongside this, the Company will also

provide an update on our commitment to the Syncona Foundation.

OUTLOOK AND CONCLUSION

Global macroeconomic conditions have been challenging throughout

the year with increased volatility in 2025. Interest rates and trade

policies have significantly impacted markets and in addition, the

biotech sector continues to face a number of regulatory and policy

headwinds, where there is ongoing uncertainty. Whilst Syncona’s

performance during the year has been significantly impacted by the

share price performance of Autolus, the SIML team has worked hard to

position the portfolio to maximise value over the medium term and the

Board is pleased with the progress on this front. The adverse market

backdrop and broader negative sentiment towards listed investment

companies have continued to impact Syncona’s share price, with the

shares moving from a premium to a material discount to NAV over

the last three years. The Board has been very focused on addressing

this and our strategy update announcement is the result of extensive

engagement with our shareholders, who hold a diverse set of views

for the future of their investment in Syncona. The Board has worked

closely with SIML, and our advisers and looks forward to keeping

shareholders updated as discussions continue to progress.

Syncona has a diverse shareholder base, and the Board has a resolute

focus on offering our shareholders the opportunity to participate in the

medium-term value available from the portfolio and access near-term

cash returns, or to retain exposure to early-stage companies by rolling

their interest in the Company into a new private vehicle independent

of the Company. The Board is confident in the SIML team’s ability to

deliver strong risk-adjusted returns from our existing assets over time,

as relevant markets stabilise and volatility decreases.

MELANIE GEE

CHAIR, SYNCONA LIMITED

18 June 2025

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

07

SYNCONA LIMITED

Value creation

Seeking to

generate returns

for shareholders

14

Strategic portfolio companies

10

Key value inflection points expected across

our maturing portfolio over the next three years

OUR STRATEGY

A focus on maximising

value for shareholders

The Board intends, subject to FCA and

shareholder approval, to propose a change to

the Company’s investment objective and policy

to move to an orderly realisation of its portfolio

assets, with a view to achieving a balance

between returning cash to shareholders

in a timely manner and maximising value.

OUR BUSINESS MODEL

Driving value across

the portfolio

SIML takes a disciplined approach to capital

allocation and actively manages its companies

to drive value in a maturing portfolio.

SIML has a resolute focus on working with

the portfolio companies to deliver key value

inflection points, which have the potential to

deliver significant NAV growth through M&A

and liquidity events.

READ MORE: P10

READ MORE: P12

OVERVIEW

08

We are seeking to maximise value for shareholders. Our Investment

Manager, SIML, actively manages our portfolio companies to deliver key

value inflection points, which have the potential to deliver significant

NAV growth through M&A and liquidity events.

7

Key stakeholder groups

£1.05bn

Net assets

OUR STAKEHOLDERS

Considering stakeholder

perspectives

In delivering our strategy and creating value,

we are always considering the perspectives of

key stakeholder groups in our decision-making.

OUR KPIs

Measuring our

performance

We measure our performance against a

number of financial and non-financial KPls

that are aligned to our strategic priorities.

READ MORE: P14

READ MORE: P16

OUR STAKEHOLDERS

OUR KPIs

OUR BUSINESS MODEL

OUR STRATEGY

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

09

SYNCONA LIMITED

Value creation

continued

A FOCUS ON MAXIMISING

VALUE FOR SHAREHOLDERS

The team at SIML have created an increasingly mature portfolio

of companies, that they are building and scaling to late-stage

development, where SIML believes the best value is achieved.

The SIML team actively manage the portfolio, progressing

its companies through the development cycle.

SIML has a resolute focus on the delivery of 10 key value inflection

points from across the portfolio over the next three years.

A key value inflection point is a material de-risking event for

a portfolio company that has the potential to drive significant

NAV growth, for example by increasing the possibility of a

realisation event, such as M&A. These milestones can also

enable companies to access significant capital including through

financings and IPOs, which may take place at valuation uplifts.

PERFORMANCE IN FY2024/5

–

78.5% of the strategic portfolio’s value is now at

the commercial, late-stage clinical or clinical-stage

–

69.0% of gross capital deployed towards late-stage

clinical or clinical-stage assets

–

Autolus received FDA approval for AUCATZYL

®

–

Beacon initiated its Phase II/III pivotal VISTA study

for laru-zova (AGTC-501) in XLRP

PERFORMANCE IN FY2024/5

–

SIML delivered 10 capital access milestones across

the portfolio, alongside three key value inflection points

from Spur and Beacon

–

Total of £310.6 million raised across seven financings

during the period with £175.5 million raised externally

from leading life science investors

OVERVIEW

OUR STRATEGY

OUR INVESTMENT MANAGER HAS A MULTI-DISCIPLINARY TEAM…

MAXIMISE VALUE

FOR SHAREHOLDERS

DELIVER KEY VALUE

INFLECTION POINTS

Our Investment Manager, SIML, is focused on investing in and managing our portfolio

companies to deliver key value inflection points. The team at SIML have created

an increasingly mature portfolio of companies that they are building and scaling.

The Board intends, subject to FCA and shareholder approval,

to propose a change to the Company’s investment objective

and policy to move to an orderly realisation of its portfolio assets,

with a view to achieving a balance between returning cash to

shareholders in a timely manner and maximising value.

Alongside the proposed new investment objective and policy,

the Board also intends to adopt a new capital allocation policy

which will seek to continue to financially support existing portfolio

companies, invest to deliver their identified key value inflection

points in those companies which have the potential to provide

liquidity via M&A or the public markets, and additionally to

preserve portfolio company value in third-party financings. It is the

Board’s intention that net proceeds from the disposal of interests

in private portfolio companies will be returned to shareholders,

subject to retaining a prudent reserve for operating costs.

A disciplined approach to capital allocation in line with the proposed

updates to the Company’s capital allocation policy:

–

Continuing to actively manage those existing portfolio companies

where SIML believes the best value can be achieved

–

Investing to deliver key value inflection points in those companies,

where there is the potential to provide liquidity via

M&A and the public markets

–

Protecting portfolio company value in third-party financings

–

Conserving the Company’s liquidity to achieve these aims

PERFORMANCE IN FY2024/5

–

The Board allocated £35 million to share buybacks in the

year, taking total commitments to share buybacks since

September 2023 to £75 million

–

The Board is also exploring options to provide shareholders

with the opportunity to access accelerated cash returns,

which may include a sale of a small portion of its interests

in its portfolio companies at a modest implied premium to

the current share price and at a discount to NAV

PERFORMANCE IN FY2024/5

–

£135.3 million deployed into the life science portfolio in the

year; below the Company’s guidance of £150-200 million,

reflecting a disciplined approach to capital allocation and

success in raising external financing

–

£43.0 million of shares repurchased through the share

buyback at an average 37.4% discount to NAV per share,

resulting in accretion of 4.96p to NAV per share

OUR KPIs

OUR BUSINESS MODEL

REALISE SIGNIFICANT

SHAREHOLDER RETURNS

MAINTAIN DISCIPLINED

CAPITAL ALLOCATION

3

4

…WITH THE SKILL SET AND TRACK RECORD TO DELIVER VALUE FROM A MATURING PORTFOLIO:

OUR STAKEHOLDERS

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

11

SYNCONA LIMITED

DRIVING VALUE ACROSS

THE PORTFOLIO

OVERVIEW

OUR BUSINESS MODEL

OUR STRATEGY

Value creation

continued

DRIVING OUR MATURING PORTFOLIO TO LATE-STAGE DEVELOPMENT

OUR STRATEGIC PRIORITIES

A PORTFOLIO OF LIFE SCIENCE COMPANIES BASED ON WORLD-CLASS SCIENCE, MANAGED BY AN EXPERT TEAM:

1

MAXIMISE VALUE

FOR SHAREHOLDERS

2

DELIVERY OF KEY VALUE

INFLECTION POINTS

3

DISCIPLINED CAPITAL

ALLOCATION

4

REALISE SIGNIFICANT

SHAREHOLDER RETURNS

SIML’S NAV GROWTH FRAMEWORK

KEY ENABLERS

OF VALUE

OUR KPIs

DELIVERING VALUE WITH

OUR BROADER STAKEHOLDERS

450+

Patients dosed in clinical trials

by Syncona companies since 2012

88%

Response rate in SIML’s 2

nd

employee engagement survey

1,200+

Employees across

the Syncona portfolio

78.5%

Value of the strategic

portfolio in clinical-stage

and commercial companies

£35.0m

Allocated to share buybacks

during the year

SHAREHOLDERS

PORTFOLIO

COMPANIES

£175.5m

Of external capital raised by Syncona

companies during the year

1

New company, Slingshot Therapeutics,

the Syncona Accelerator

CO-INVESTORS

SCIENTIFIC

RESEARCH

COMMUNITY

PATIENTS

INVESTMENT

MANAGER

LIFE SCIENCES

ECOSYSTEM

GENERATING SIGNIFICANT CASH PROCEEDS

As our companies mature, there is the potential for liquidity

through M&A and realisations of listed shares. In all cases

we are driven by the balance of risk and reward, and we sell

companies to crystallise significant risk-adjusted returns.

If our investment strategy is successful, we anticipate that

we will generate significant cash proceeds from exits or

other liquidity events. The Board intends, subject to FCA

and shareholder approval, to propose a change to the

investment objective and policy. If approved, it is the Board’s

intention that net proceeds from the disposal of interests in

private portfolio companies will be returned to shareholders,

subject to retaining a prudent reserve for operating costs.

EXITS

PROTECTING VALUE

Life science development is inherently risky and

some companies won’t succeed. When issues arise

in our portfolio we take quick and decisive action

to recover as much value as possible, reallocating

capital and resource.

REALISING SIGNIFICANT VALUE

FOR SHAREHOLDERS

To maximise value and aligned with our strategic priorities, our Investment Manager,

SIML, takes a hands-on, active approach to managing our maturing portfolio

of life science companies. SIML takes a disciplined approach to capital allocation,

seeking to drive the portfolio companies to late-stage, where SIML believes

significant value can be accessed for shareholders. This model and differentiated

approach to value creation also creates broader value for our stakeholders.

OUR STAKEHOLDERS

“The perspectives of the

Company’s stakeholders

are a key consideration in

Board decision-making

and are integrated into

all discussions held.”

VIRGINIA HOLMES

SENIOR INDEPENDENT DIRECTOR,

SYNCONA LIMITED

The perspectives of the Company’s stakeholders are a key

consideration in Board decision-making and are integrated into

discussions held at the Board, as well as within ongoing engagement

and oversight of the Investment Manager. The Board engages with

stakeholders both directly and indirectly through the Investment

Manager’s team, which is responsible for the day-to-day management

of many key stakeholder relationships.

OVERVIEW

OUR STAKEHOLDERS

OUR STRATEGY

OUR BUSINESS MODEL

CONSIDERING STAKEHOLDER

PERSPECTIVES

SHAREHOLDERS

PORTFOLIO

COMPANIES

CO-INVESTORS

SCIENTIFIC

RESEARCH

COMMUNITY

PATIENTS

INVESTMENT

MANAGER

LIFE SCIENCES

ECOSYSTEM

SECTION 172

OUR KEY STAKEHOLDERS

MAINTAINING A REPUTATION FOR HIGH STANDARDS

OF BUSINESS CONDUCT

Value creation

The Board has, in consultation with SIML and

advisers, undertaken a comprehensive review

of options to maximise value for shareholders.

As part of this review, the Board has engaged

extensively with shareholders, who expressed

a range of perspectives, reflecting Syncona’s

diverse shareholder register. As a result of this

process, the Board intends, subject to FCA and

shareholder approval, to propose a change to

the Company’s investment objective and policy

to move to an orderly realisation of its portfolio

assets, with a view to achieving a balance

between returning cash to shareholders in

a timely manner and maximising value.

PRIMARY STAKEHOLDERS IMPACTED

HOW THE BOARD CONSIDERED IMPACT ON

STAKEHOLDERS IN ITS DECISION-MAKING

The comprehensive review sought to enhance the Board’s

understanding of the diverse range of views held by

shareholders and enable these to be considered, as a whole,

when identifying possible options for maximising shareholder

value. It was clear from the review that shareholders held a

diverse range of views that would require different approaches

across varying time-frames.

As part of the review, the Board considered the possible impact

of the potential options on Syncona’s long-term objectives

and its ability to continue to meet its strategic goals. The views

of other stakeholders were also considered including: the

implications for portfolio companies and our co-investors of

pursuing options seeking to maximise value in the medium

term; and the potential impact to the SIML team of an orderly

realisation of the portfolio and changes to strategic goals.

In June and November 2024, the Board

approved further allocations to the share

buyback programme initiated in September

2023, taking the total allocation since the

programme’s inception to up to £75 million.

The decision to implement the share buyback

programme and to continue to allocate further

funds to it was informed by regular reviews

of capital allocation requirements across the

portfolio, and a view by the Board that the

shares continue to represent a compelling

investment opportunity and a way to enhance

shareholder value in challenging market

conditions for the sector.

PRIMARY STAKEHOLDERS IMPACTED

HOW THE BOARD CONSIDERED IMPACT ON

STAKEHOLDERS IN ITS DECISION-MAKING

In assessing whether to allocate further capital to the share

buyback programme, the Board sought the perspectives of

shareholders directly, and through its Investment Manager,

and took these into account in its decision-making. The Board

also considered the potential impact on portfolio companies

and, indirectly, co-investors of the decision to allocate capital

to the share buyback, and the long-term implications for

the Company’s ability to meet its strategic goals, noting that,

following the decision, the Company would remain funded

to deliver on its key value inflection points.

DECISION 1

DECISION 2

FURTHER ALLOCATIONS TO

SHARE BUYBACK PROGRAMME

MAXIMISING VALUE

FOR SHAREHOLDERS

OUR KPIs

– Shareholders

– Co-investors

–

Portfolio companies

– Shareholders

– Co-investors

–

Portfolio companies

–

Investment manager

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

15

SYNCONA LIMITED

COMMERCIAL

LATE-STAGE

CLINICAL

CLINICAL

PRE-CLINICAL

INVESTMENTS

AND MILESTONES

4.5%

39.2%

29.7%

20.0%

6.6%

CAPITAL POOL AS A % OF NAV

-20%

-15%

-10%

-5%

0%

1 YEAR

3 YEARS

5 YEARS

Life science return

NAV per share return

LIFE SCIENCE PORTFOLIO

72.7%

CAPITAL POOL

27.3%

MEASURING OUR PERFORMANCE

We measure our performance against a number of financial and non-financial

key performance indicators (KPIs).

Given the proposed change of investment objective and policy, we have removed

the KPI which relates to building a portfolio of 20-25 companies. We continue

to review and update our KPIs to ensure that they are in line with our strategy.

6

Clinical trials commenced in the year

NAV PER SHARE/PORTFOLIO RETURN (ANNUALISED)

£0m

£200m

£400m

£600m

£800m

FY23

FY24

FY25

FEMALE

MALE

45.5%

54.5%

£310.6m

Of capital raised across the portfolio,

including £175.5m from leading

external life science investors

£4.4m

Donated to The Syncona Foundation

OUR STRATEGIC PRIORITIES

OUR RISKS

PORTFOLIO COMPANIES

–

Scientific theses fail

–

Clinical development doesn’t deliver a commercially

viable product

–

Portfolio concentration risk to platform technology

–

Concentration risk and binary outcomes

ACCESS TO CAPITAL

–

Not having capital to invest

–

Private/public markets don’t value or fund

our companies when we wish to access them

–

Capital pool losses or illiquidity

PEOPLE

–

Reliance on small number of key individuals

at our Investment Manager

–

Systems and controls failures

–

Unable to build high-quality team/team culture

–

Unable to execute business plans

MACROECONOMIC ENVIRONMENT

–

Macroeconomic environment has a negative

impact on sentiment for portfolio companies

and Syncona business model

ACCESS TO CAPITAL

SUSTAINABILITY AND THE SIML TEAM

1

2

3

4

1

2

3

4

RATIONALE

Ensuring our portfolio companies have access to

capital underpins our Investment Manager’s ability

to drive our portfolio companies to late-stage

development where significant value can be

accessed through M&A or liquidity events.

HOW WE MEASURE PROGRESS

–

Available capital to deliver key value

inflection points

–

Aggregate capital raised across Syncona

and its portfolio companies

2025 HIGHLIGHTS

–

Syncona is funded to deliver on all portfolio

company key value inflection points over

the next three years

–

Seven portfolio company financings,

with disciplined capital allocation across

the portfolio to prioritise capital access

RATIONALE

A measurement of both the Board and SIML’s

strong commitment to sustainability and people.

HOW WE MEASURE PROGRESS

–

Performance against the four pillars

of Syncona’s Sustainability Policy

2025 HIGHLIGHTS

–

Establish and integrate patient impact framework

with outputs for current portfolio now developed

–

Launch of AUCATZYL

a significant milestone as

a CAR-T therapy which has been developed and

will be manufactured in the UK

–

0.35% donation to The Syncona Foundation,

with £4.4 million donated to its charities

–

Implemented improvements to reporting based

on outputs of UN PRI

questionnaire

–

Materials developed to support the

development of net zero targets and

shared with portfolio companies

–

New Chief People Officer

–

Established and launched new values

–

Strengthened our commitment to supporting

families with the introduction of new parental

leave and childcare policies

–

Created the Syncona Leadership Academy

–

Interim net zero target approved and published

–

Delivered refreshed training on ESG

to all employees

–

Delivered next stage of sustainability issues

matrix project

CAPITAL RAISED BY THE PORTFOLIO

LEADERSHIP AND SENIOR INVESTMENT TEAM

2. Syncona has signed up to PRI through the Company’s Investment Manager, SIML.

SYNCONA LIMITED

Manager’s review

Driving value

across the portfolio

“The portfolio is well positioned

over the medium term with 10

key value inflection points over

the next three years, including

two expected before the end of

CY2025, each with the potential

to drive significant NAV growth

through M&A and liquidity events.”

CHRIS HOLLOWOOD

CEO, SIML

14

Strategic portfolio companies

78.5%

Of the strategic portfolio in clinical,

late-stage clinical and commercial assets

3

Key value inflection points

delivered in the year

£135.3m

Deployed into the portfolio

£310.6m

Raised across seven financings,

with £175.5m raised from leading

external life science investors

18

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

STRATEGIC REPORT

Against ongoing challenging market conditions, we are pleased with

the significant work that has been undertaken in FY2024/5. There has

been positive clinical progress and substantive funding raised across

Syncona’s maturing portfolio, whilst our team has continued to take

a rigorous and disciplined approach to capital allocation.

LIFE SCIENCE PERFORMANCE AND VALUATION

AGAINST CHALLENGING MARKET BACKDROP

The considerable volatility in the market and broader investor sentiment

towards biotech assets has impacted the performance of Syncona’s

life science portfolio, which generated a negative return of 17.0%

in the year. Notably, the 75.7% decline in the Autolus share price,

despite U.S. Food and Drug Administration (FDA) approval for its lead

asset, AUCATZYL

®

and commercialisation in the US, impacted the

Company’s financial performance. Across Syncona’s private portfolio,

we were pleased to complete the Beacon, Purespring Therapeutics

(Purespring) and Forcefield Therapeutics (Forcefield) financings in the

year. Both the Beacon and Forcefield financings were completed at

uplifts of 17.6% and 37.6%, respectively, and Syncona’s overall interest

in Purespring remained unchanged. However, amidst ongoing market

challenges and following material third-party interest from potential

Series B syndicate investors, Resolution has been partially written

down by 23.6%. Syncona is pleased with the progress the company

has made with the first patient dosed in its lead programme post-

period end and has invested £19.0 million as part of a Series B

financing in September 2024 to deliver its next key value inflection

point. Elsewhere, Biomodal, which is a Syncona investment and

passively managed by the SIML team, has also been written down

by £15.0 million, reflecting the anticipated value of a future financing

round. Syncona last committed to Biomodal at its Series B in 2015.

MATURING PORTFOLIO CONTINUES TO DELIVER

STRONG CLINICAL PROGRESS AND ATTRACT

SIGNIFICANT INVESTMENT

The strategic portfolio of 14 companies is increasingly diversified

across therapeutic area and modality and weighted towards clinical,

late-stage clinical and commercial companies, where 78.5% of

strategic portfolio value is held. There has been strong clinical

execution across the portfolio, particularly amongst these later-stage

assets, with Beacon publishing positive data from its Phase II DAWN

and SKYLINE trials in XLRP, and Spur publishing data from its Phase

I/II trial in Gaucher disease. These significant clinical milestones

are key value inflection points for the companies, with Beacon

now enrolling patients in a Phase II/III pivotal trial and Spur aligning

with the FDA on the design of a single-arm Phase III trial to support

potential accelerated approval of FLT201. Overall, across the portfolio

there have been 10 capital access milestones, and three key value

inflection points delivered since 31 March 2024.

There has been a total of £310.6 million raised across seven

financings in the year, including £175.5 million from leading external

life science investors, broadening the financial scale of the portfolio

and demonstrating the quality and progress of the companies.

SIGNIFICANT OPPORTUNITY TO MAXIMISE VALUE

THROUGH DELIVERY OF A RICH SET OF KEY VALUE

INFLECTION POINTS ACROSS THE PORTFOLIO

The SIML team continues to focus on maximising value for

shareholders through driving the existing portfolio to late-stage

development, where it believes significant value can be accessed

through M&A and liquidity events. The portfolio has both proactively

and naturally matured, and we are expecting 10 companies to be

in the clinic in the next 12 months. There are 10 key value inflection

points expected in the next three years, including two expected before

the end of CY2025. These have the potential to drive significant NAV

growth through M&A and liquidity events, and the portfolio companies

are making good progress towards their delivery.

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

19

SYNCONA INVESTMENT MANAGEMENT LIMITED

Manager’s review

continued

CAPITAL ALLOCATION, DEPLOYMENT

INTO PORTFOLIO AND SIML COSTS

SIML has continued to maintain a rigorous and disciplined approach to

the allocation of capital to maximise risk-adjusted returns for shareholders.

In total, Syncona deployed £135.3 million of capital in the year into its life

science portfolio; below guidance for the year of £150-200 million. This

reflects both SIML’s disciplined approach and success in raising external

capital. In total, 77.2% of gross capital deployed was to fund companies

to key value inflection points.

At 31 March 2025, Syncona had a capital pool of £287.7 million and

remains funded to deliver on all portfolio company key value inflection

points over the next three years. Approximately 80% of the capital pool

is allocated to commitments and underwriting current key value inflection

points, with remaining capital allocated to driving broader portfolio

company milestones and protecting value in third-party financings.

We monitor the asset allocation and foreign exchange exposure within the

capital pool based on the capital allocations to the life science portfolio

and market conditions, with a focus on generating a real return above UK

inflation with a core strategy of capital preservation and liquidity access.

The capital pool is managed on a matrix basis of liquidity and volatility to

optimise risk-adjusted returns. A balance is maintained between liquidity

and volatility at an overall capital pool level. This gives flexibility in ensuring

that the pool is fully invested when the need for cash is low but as demand

for liquidity rises, the capital pool is able to provide it within a managed

volatility level. The capital pool is held in cash, treasury bills and a number

of low volatility, highly liquid, multi-asset and credit funds or mandates,

managed by Kempen and M&G with portfolio mandates to deliver a core

CPI (consumer price index) return over the mid-term. The overall weighted

return across the Company’s capital pool during the year was 4.0%.

BEST IDEAS

PRE-CLINICAL

CLINICAL

LATE-STAGE

CLINICAL

Autolus Therapeutics

Beacon Therapeutics

Spur Therapeutics

iOnctura

Resolution Therapeutics

Quell Therapeutics

Anaveon

Mosaic Therapeutics

Purespring Therapeutics

OMass Therapeutics

Forcefield Therapeutics

Yellowstone Biosciences

Kesmalea Therapeutics

Slingshot Therapeutics

COMPANIES ON THE MARKET

COMPANIES MOVING TOWARDS

BEING ON THE MARKET

COMPANIES MOVING TOWARDS

PUBLISHING DEFINITIVE DATA

COMPANIES WHO HAVE

COMPLETED OPERATIONAL

BUILD AND/OR ARE

MOVING TOWARDS

EMERGING EFFICACY DATA

COMPANIES MOVING

TOWARDS OPERATIONAL BUILD

Syncona investment point

Key value inflection point (KVIP)

BLA

2

COMMERCIAL

NEXT EXPECTED CAPITAL

ACCESS MILESTONES

OUR VIEW OF POTENTIAL KEY

VALUE INFLECTION POINTS

H2 CY2025 (new)

–

Full data from Phase I/II SLE programme

–

Phase II initiation of SLE programme

CY2025

–

Commercial traction following US launch of AUCATZYL

®

(obe-cel)

CY2026

–

Data readout from its Phase II/III pivotal VISTA trial in XLRP

H1 CY2026 (delayed from H2 CY2025)

–

Initiation of Phase III trial in Gaucher disease

CY2026

–

Initiation of Phase I/II trial in Parkinson’s disease

H1 2028

–

Completion of the pivotal stage of its Phase III trial

in Gaucher disease

CY2026

–

Data readout from its Phase II trial in uveal melanoma

CY2026

–

Interim data readout from its Phase I/II trial in end-stage

liver disease

Q1 CY2026 (new)

–

Completion of first stage of Phase I/II trial

in liver transplantation

CY2025

–

Interim data readout from its Phase I/II trial in liver transplantation

CY2026 (new)

–

Full data readout for the Phase I/II trial in liver transplantation

CY2026

–

Data readout from its Phase I/II trial of ANV600

H1 CY2026 (new)

–

Initiation of first clinical study for lead drug combination

H2 CY2026 (new)

–

Initiation of clinical study for second drug combination

H2 CY2025 (updated from CY2026)

–

Initiation of Phase I/II trial in complement-mediated

kidney disease

H1 CY2027 (new)

–

Complement biomarker clinical data

H2 CY2025

–

Initiation of Phase I trial of its MC2 programme

H1 CY2026 (new)

–

Data from Phase I trial of MC2 programme

1. Refer to Glossary for definitions of capital access milestones and key value inflection points.

2. Biologics License Application.

3. By value.

“We have continued to maintain a rigorous and disciplined

approach to the allocation of capital to each portfolio

company to maximise risk-adjusted returns for shareholders.”

KATE BUTLER

CFO, SIML

Specific portfolio company capital access milestones and key value inflection points

1

(which are set out below) are not without

risk and their impact will be affected by various factors including the market environment at the time of their delivery.

1.

Gross capital excludes other assets/liabilities and cash held within the Investment

Manager, SIML.

2. Using NAV at 31 March 2025.

Manager’s review

continued

The SIML team is focused on driving portfolio companies to

deliver a rich set of key value inflection points (KVIPs). When

delivering these milestones, portfolio companies demonstrate

positive clinical progress and the likelihood of therapies being

developed into approved products increases.

–

KVIPs are material de-risking events for a portfolio company

that have potential to drive significant NAV growth through

M&A and liquidity events

–

These milestones can also enable companies to access

significant capital, including through financings and IPOs,

which may take place at valuation uplifts

–

Primarily, KVIPs are the delivery of emerging clinical

efficacy or definitive clinical data, with the latter typically

being more valuable

–

The delivery of emerging efficacy data and subsequent

milestones increasingly builds intrinsic value in a company

–

Realisation events are typically required to fully unlock

the intrinsic value created through KVIP delivery

–

These events can take time to crystallise and any NAV

growth is unlikely to occur simultaneously with key value

inflection points

KEY

INTRINSIC VALUE*

NAV FROM FINANCING*

COST*

KVIP

FOUNDING

OPERATIONAL BUILD

ILLUSTRATIVE VALUE

APPRECIATION THROUGH

DELIVERY OF KVIPS

EXAMPLE OF A RECENT KVIP DELIVERY

Beacon has generated a strong set of data across its

clinical trials in X-linked retinitis pigmentosa (XLRP) and

continues to show strong momentum as it progresses

through the clinic.

During the year, Beacon delivered two KVIPs from its lead gene

therapy programme, laru-zova (AGTC-501) in XLRP. Firstly, Beacon

presented positive 24-month interim safety and efficacy data from

the Phase II SKYLINE trial. Data showed a 57% response rate in

the 24-month analysis of retinal sensitivity, showing the potential

of AGTC-501 as a one-time therapy for XLRP. Secondly, Beacon

presented positive three-month interim safety and efficacy data

from the Phase II DAWN trial. The data showed promising early

improvements in low luminance visual acuity, a critical measure of

visual function used as a primary endpoint in the pivotal VISTA trial,

reinforcing compelling efficacy data shown previously.

READ MORE: P34

1. Biologics License Application.

2.

Includes sales of Nightstar, Blue Earth, upfront proceeds from sale of

Gyroscope, upfront proceeds from Neogene and upfront consideration of

Clade. Reflects original Syncona Partners capital invested where applicable.

All IRR and multiple on cost figures are calculated on a gross basis.

* Illustrative only.

MOVING TOWARDS BEING ON THE MARKET

EVENTS THAT BUILD

INTRINSIC VALUE INTO

THE PORTFOLIO

3.9x

Aggregate multiple

of cost from Syncona’s

five exits

2

EMERGING EFFICACY

DEFINITIVE DATA

MARKET

BLA

1

ACCEPTANCE

Delivery of KVIPs post emerging efficacy increases the possibility of M&A,

which has the potential to build intrinsic value

EXAMPLE OF A RECENT KVIP DELIVERY

Spur continues to make strong clinical progress and the

SIML team has been particularly encouraged by data

published from its lead programme in Gaucher disease.

In October 2024, Spur delivered a KVIP with positive data from

lead gene therapy programme, FLT201, in Gaucher disease.

Data from the Phase I/II GALILEO-1 trial was presented at the

European Society of Gene and Cell Therapy Annual Congress

and underlined the efficacy and durability profile of FLT201, as

well as the long-lasting potential of this therapy beyond current

standard of care for the thousands of patients with the disease.

Furthermore, the data de-risked Spur’s technology and supported

the advancement of the company’s pre-clinical pipeline into more

prevalent disorders, including Parkinson’s disease.

Manager’s review

continued

WORKING IN PARTNERSHIP WITH THE BOARD

TO MAXIMISE VALUE FOR SHAREHOLDERS

We have worked closely with the Board as they have reviewed options

to maximise value for shareholders. We recognise that the share price

performance over the last three years has been disappointing and

there is a diverse range of views across Syncona’s shareholder

register. We believe there is a significant opportunity to maximise value

from the portfolio over the medium term by focusing on the delivery of

the key value inflection points we have outlined. We are also confident

in the long-term opportunity to continue the strategy of creating and

building companies leveraging world-class research and are working to

explore the possibility of a New Fund for interested current institutional

Syncona shareholders and prospective new investors.

OUTLOOK

Challenging market conditions have persisted in CY2025. There

are a number of factors, including interest rates, trade policies,

regulatory uncertainty and pharma pricing, which continue to

weigh on sector sentiment.

Nevertheless, once trade policies embed and predictability returns

to the market, then we believe there are reasons for optimism.

Long-term structural trends remain positive in life sciences with

innovation still critical to developing the best products for patients.

We believe we have a strong team, robust operating model and

we manage a well-positioned portfolio to maximise value over the

medium term. There is a long-term opportunity to scale our platform

to support the continued evolution of the life science sector in the

UK and critically to enable shareholders to access the significant

value from investing in companies to late-stage development.

We look forward to keeping the market updated on the portfolio’s

continued progress and engaging with stakeholders on the

continued path forward.

CHRIS HOLLOWOOD

CEO, SIML

18 June 2025

24

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

STRATEGIC REPORT

31 MARCH

2024

(£M)

NET

INVESTMENT

IN THE

PERIOD

(£M)

VALUATION

ON CHANGE

(£M)

FX

MOVEMENT

(£M)

31 MARCH

2025

(£M)

% OF

GROUP NAV

VALUATION

BASIS

2,3,4

FULL

DILUTED

OWNERSHIP

STAKE

5

(£M)

FOCUS

AREA

STRATEGIC PORTFOLIO COMPANIES

ON THE MARKET

AUTOLUS

169.5

(16.3)

(116.2)

(2.4)

34.6

3.3

Quoted

9.9

Cell therapy

LATE-STAGE CLINICAL

SPUR

135.6

43.8

2.8

–

182.2

17.3

Cost

79.2

Gene therapy

BEACON

94.7

9.6

15.4

(2.2)

117.5

11.2

PRI

41.0

Gene therapy

CLINICAL

QUELL

84.7

2.8

–

(2.1)

85.4

8.1

PRI

33.7

Cell therapy

RESOLUTION

50.0

19.0

(13.5)

–

55.5

5.3

Adjusted Cost

82.6

Cell therapy

ANAVEON

35.7

–

–

(0.1)

35.6

3.4

PRI

36.9

Biologics

MOSAIC

7.3

18.2

–

–

25.5

2.4

Cost

54.3

Small

molecules

IONCTURA

25.6

–

–

(0.5)

25.1

2.4

PRI

21.9

Small

molecules

PRE-CLINICAL

PURESPRING

45.3

5.0

0.9

–

51.2

4.9

PRI

41.7

Gene therapy

OMASS

43.7

6.0

–

–

49.7

4.7

PRI

29.0

Small

molecules

KESMALEA

12.0

8.0

–

–

20.0

1.9

Cost

59.7

Small

molecules

YELLOWSTONE

1.0

15.5

–

–

16.5

1.6

Cost

60.9

Biologics

FORCEFIELD

6.5

1.7

2.4

–

10.6

1.0

PRI

49.6

Biologics

SLINGSHOT

0.0

5.6

–

–

5.6

0.5

Cost

100.0

Accelerator

INVESTMENTS AND MILESTONE PAYMENTS

NEOGENE

MILESTONE

PAYMENT

2.2

–

4.0

(0.1)

6.1

0.6

DCF

–

Cell therapy

CLADE

MILESTONE

PAYMENT

0.0

0.7

0.1

–

0.8

0.1

DCF

–

Cell therapy

CRT PIONEER

FUND

33.9

(1.3)

(5.3)

–

27.3

2.5

Adjusted

Third Party

64.1

Oncology

BIOMODAL

18.0

–

(15.0)

(0.3)

2.7

0.3

Adjusted PRI

5.5

Epigenetics

ACHILLES

11.0

–

2.4

(0.3)

13.1

1.2

Expected

proceeds

22.7

Cell therapy

CENTURY

0.0

4.3

(3.8)

(0.1)

0.4

0.0

Quoted

1.3

Cell therapy

CLADE

9.4

(9.4)

–

–

0.0

0.0

–

–

Cell therapy

TOTAL LIFE

SCIENCE

PORTFOLIO

786.1

113.2

(125.8)

(8.1)

765.4

72.7

CAPITAL POOL

452.8

(177.8)

12.4

0.3

287.7

27.3

TOTAL

1,238.9

1,053.1

100

1. Portfolio valuations reflect Syncona’s total interest in a company or investment.

2. Primary input to fair value of equity holding.

3. The basis of valuation is stated to be “Cost”, this means the primary input to fair value is capital invested (cost) which is then calibrated in accordance with the Valuation Policy.

4. The basis of valuation is stated to be “PRI”, this means the primary input to fair value is price of recent investment which is then calibrated in accordance with the Valuation Policy.

5. Percentage holding reflects Syncona’s ownership stake at the point full current commitments are invested.

Life science portfolio valuations

1

SYNCONA INVESTMENT MANAGEMENT LIMITED

Market review

“The fundamentals for

investing in healthcare

remain strong and

wherever there is

innovation, there

is opportunity for

investors.”

CHRIS HOLLOWOOD

CEO, SIML

Fundamentals are

robust, despite

uncertainty

26

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

STRATEGIC REPORT

A healthier biotech sector

–

Coming to the end of a significant period of restructuring and

consolidation, which has led to a biotech market with healthier

fundamentals and higher-quality companies

–

The best science and businesses have survived and valuations

have been corrected

–

Late-stage assets have led public and private market recoveries,

with many being acquired

Positive macro trends challenged by renewed uncertainty

–

Inflation and interest rates have been trending in the right direction

and this should provide tailwinds for the cost of capital to come

down, which is an essential element for a return to growth

–

However, uncertainty lingers due to political and economic volatility

and this is delaying biotech’s road to recovery

An upcoming patent cliff for pharma

–

Pharma is facing a patent cliff of over $350 billion by 2030

1

and has >$1.5 trillion in deal capacity

2

–

Pharma has been focused on later-stage assets, but the pool

of sizeable targets is shrinking after an uptick in M&A

–

Nevertheless, pharma needs to replenish its pipeline and this

will drive M&A activity and recycle capital into the biotech sector

The biotech sector is emerging from a significant period of restructuring and

consolidation, resulting in a market with stronger fundamentals and higher-quality

companies. However, renewed economic and political uncertainty have added

to the issues weighing on the sector and delaying the recovery.

1. Evaluate Pharma / Stifel Healthcare: Biopharmaceutical Outlook for 2025.

2. Source: iqvia.com/locations/emea/blogs/2025/01/biopharma-m-and-a-outlook-for-2025.

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

27

SYNCONA INVESTMENT MANAGEMENT LIMITED

Market review

continued

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2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

2019

2020

2021

2022

2023

2024

2025

BETTER FUNDAMENTALS BUT UNCERTAINTY RUMBLES ON

The challenges experienced by biotech in 2024 have persisted so far in

2025, with economic and political uncertainty now adding to structural

issues that have weighed on the sector, such as the cost of capital.

Nevertheless, once those policies embed and predictability returns to

the market, then we believe there are greater reasons for optimism.

We are progressing through the tail of the longest biotech bear market

I’ve experienced in my career. Thankfully, innovation has not wavered

in the face of market adversity. We have more ways to treat disease

than ever before and new breakthroughs continue to deliver

transformational benefits for patients and society.

Ultimately, the fundamentals for investing in healthcare remain strong

and wherever there is innovation, there is opportunity for investors.

Whilst the rewards on offer haven’t been quite so clear over the last

few years, a combination of factors are now converging to give us

more confidence that brighter days are ready to return, once a more

stable policy environment comes into view.

A MUCH-NEEDED RESET

It’s important to note that, whilst biotech has been profoundly

challenged in recent years, the sector has come a long way. You can

track this by following the XBI, which provides a good barometer of

performance across the sector.

In the summer of 2008, the XBI peaked at $23, before the financial

crisis sent it crashing back down. It didn’t get above this again

for three years, until mid-2011. Wind the clock forward 10 years

to February 2021 and the XBI peaked at over $170, as biotech

emerged as the white knight of the global pandemic and cheap

capital propelled a boom of interest and activity.

However, the boom was followed by a bust. By January 2022 the

XBI dropped below $100, where it remains today. As the bear market

bedded in, the cost of capital soared, companies struggled to execute

financings and competition for cash intensified.

Biotech is a cash intensive business and capital access is the primary

driver of the sector’s health. The sheer volume of capital available

during the bull market meant that biotechs entered this period with

the strongest balance sheets they’d ever had. Companies were able

to defer difficult decisions in the hope that the sun would come out –

but it didn’t.

As the gloom persisted, the sector was forced into a wave of

restructuring, consolidation and rationalisation. This is now largely

complete. Although it has been tough, the correction has been

necessary for a recovery. Valuations have come down from unrealistic

highs and only the best businesses have survived. This leaves the

sector in better shape and primed for growth.

AN IMPROVED PLATFORM

At SIML, we quickly recognised the scale of the challenge and have

been very proactive in our portfolio management. We implemented

a clear strategy to ensure that the best clinical programmes in our

portfolio were financed, that our category leaders had secure paths

forward, and that we maximised value elsewhere through sales or

consolidation. Additionally, we set out to take advantage of market

conditions, selectively adding clinical-stage opportunities, such as

with Beacon and iOnctura.

The result? We’ve built a better-quality portfolio, that is more diverse

across modality and now is 78.5% in clinical stage and commercial

companies with two new companies expected to be in the clinic before

year end. The portfolio is now well-financed and in a strong position to

deliver a lot of clinical data – which is the oxygen of growth in our sector.

This proactivity and not shying away from difficult decisions have

kept us ahead of the curve and have positioned the portfolio for strong

risk-adjusted returns as markets improve.

At the turn of the year, we were cautiously optimistic for biotech

markets in the latter half of 2025. However, after a year of elections,

renewed political and economic volatility is dampening our outlook,

which is also compounded by recent upheaval at the US FDA. We

hope to see more predictable macroeconomic conditions before

XBI index

Source: Bloomberg.

Peaked at

$23

Back above

$23

Peaked at

$174

Back below

$100

$0

$20

$40

$60

$80

$100

$120

2028

2027

2026

2025

2024

2023

2022

0.0%

1.5%

3.0%

4.5%

6.0%

7.5%

9.0%

Total sales at risk ($bn)

% sales at risk

the year is out. But, for now, it seems to be delaying biotech’s path

to recovery, despite improving fundamentals elsewhere in the sector

and cost of capital on a downward trajectory.

MARKET DYNAMICS

The challenges outlined above dramatically impacted valuations in

the public markets, which was well documented. Thankfully, however,

there was some recovery here. Strong clinical data is once again

driving value and later-stage assets have been leading the charge

in terms of financings and M&A.

Dynamics in the private markets are sometimes harder to spot.

In the initial throes of the bear market, venture capitalists (VCs) stopped

doing new deals and reserved capital for their existing portfolio. When

this happens, there is very little pricing adjustment and investments get

marked flat.

In the second phase of the bear market, when VCs are confident

their portfolio is secure, they can initiate new deals. This can lead

to pricing adjustments, which can be difficult. While the range of

valuations remains wide, this dynamic is being worked through,

rebasing the sector so it can access the capital required to position

it for future growth.

A LOOMING PATENT CLIFF

A further dynamic in valuation is biotech’s big brother – the pharma

sector. Pharma is fast approaching a patent cliff of over $350 billion in

worldwide sales by 2030. Faced with this loss of exclusivity problem,

companies are either recognising the need to plan for declining

revenues or turning to M&A.

Pharma is looking to biotech to restock its pipeline. The trend has

been for pharma to focus on late-stage assets that will really move

the needle. These later-stage assets are further de-risked and more

likely to bring nearer-term rewards. We have seen an uptick in M&A

in the first quarter of 2025, including an increase in acquisitions of

commercial-stage public companies.

We are heading towards a standoff where pharma still needs to acquire

innovation, but the pool of ‘ideal’ profile acquisitions is significantly

smaller. This means that pharma may need to go for earlier-stage

assets to access big market opportunities or look at smaller market

opportunities to stay at later stages.

It’s going to be interesting to see how it shakes out, but my guess is that

they’ll do both. Either way, potential M&A activity is another reason for

optimism, as it will drive valuations and recycle capital into the sector.

RETURNING TO GROWTH

In summary, it’s a tale of convergent forces paving a slow path out

of the bear market, but with these positive drivers being suppressed

by political and economic uncertainty.

Firstly, biotech has now largely restructured, leaving us with better

companies and better fundamentals. Secondly, pharma needs to

spend money to address a looming patent cliff, and this will catalyse

a recovery.

The final piece of the puzzle is the macroeconomic environment.

Headwinds that the sector has experienced in the last few years are

abating as interest rates decline, but policy uncertainty has stepped

in to delay the recovery.

When this uncertainty finally clears the convergence will be able to

complete. When that happens, Syncona will be ready to make the

most of it.

CHRIS HOLLOWOOD

CEO, SIML

18 June 2025

£310.6m

Raised across seven financings, with £175.5m

raised externally from leading life science investors

Portfolio review

“The portfolio has

naturally matured,

and we are expecting

10 companies to be

in the clinic in the

next 12 months.”

ROEL BULTHUIS

MANAGING PARTNER AND

HEAD OF INVESTMENTS, SIML

Actively managing

our maturing

portfolio

30

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

STRATEGIC REPORT

Syncona’s maturing life science portfolio is diversified across different stages

of the development cycle and a range of therapeutic areas.

1. Life science portfolio is valued at £765.4m at 31 March 2025.

2. Strategic portfolio companies valued at £715.0m at 31 March 2025.

3. Excludes Slingshot Accelerator.

Commercial (one company)

4.5%

Late-stage clinical (two companies)

39.2%

Clinical (five companies)

29.7%

Pre-clinical (six companies)

20.0%

Investments and milestones (N/A)

6.6%

On the market (one company)

4.8%

Moving towards the market (two companies)

41.9%

Moving towards definitive data (two companies)

11.3%

Moving towards emerging efficacy data (seven companies)

36.1%

Moving towards operational build (two companies)

5.9%

Cell therapy (three companies)

24.5%

Gene therapy (three companies)

49.1%

Small molecules (four companies)

17.6%

Biologics (three companies)

8.8%

LIFE SCIENCE PORTFOLIO

1

STRATEGIC PORTFOLIO

2

STRATEGIC PORTFOLIO

2,3

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

31

SYNCONA INVESTMENT MANAGEMENT LIMITED

Portfolio review

continued

1. By value.

A DIVERSIFIED PORTFOLIO

Syncona’s life science portfolio was valued at £765.4 million at 31 March 2025

(31 March 2024: £786.1 million), delivering a (17.0)% return in the period. It comprises

the strategic portfolio companies, potential milestone payments, and investments,

which are non-core and provide optionality to deliver returns for shareholders.

Syncona’s strategic portfolio consists of the 14 core strategic life science portfolio companies where Syncona has significant

shareholdings and plays an active role in the company’s development. These companies are diversified across modality

and therapeutic area, with eight companies at the commercial or clinical stage (two late-stage clinical) and the remainder

at pre-clinical stage.

OUR NAV GROWTH FRAMEWORK

Syncona is continuing to report against SIML’s NAV Growth Framework, to give shareholders more clarity on which milestones

and what stage of the development cycle we anticipate the Company’s portfolio companies will be able to access capital and drive

significant NAV growth, through M&A and liquidity events. Syncona’s portfolio companies are mapped against the categories below:

5.9%

Of strategic portfolio

1

36.1%

Of strategic portfolio

1

–

Mosaic Therapeutics

–

Quell Therapeutics

– Anaveon

–

Purespring Therapeutics

–

Forcefield Therapeutics

–

OMass Therapeutics

–

Autolus Therapeutics

–

Spur Therapeutics

–

Beacon Therapeutics

41.9%

Of strategic portfolio

1

4.8%

Of strategic portfolio

1

–

Resolution Therapeutics

– iOnctura

11.3%

Of strategic portfolio

1

–

Kesmalea Therapeutics

–

Yellowstone Biosciences

–

Slingshot Therapeutics

1. Companies where delivery against milestones

has the potential to enable access to capital

–

Clearly defined strategy and business plan

–

Leading management team established

–

Clinical strategy defined

–

Initial efficacy data from Phase I/II in patients

2. Companies where delivery against milestones

has the potential to deliver NAV uplifts

–

Significant clinical data shows path to marketed product

–

Moving to pivotal trial and building out commercial

infrastructure

–

Commercialising product

–

Revenue streams

3.3%

Of NAV

9.9%

Shareholding

In November 2024, Autolus received FDA approval for

its lead CAR-T cell therapy, AUCATZYL

®

(obe-cel), and

has since commenced commercial launch in the US.

As Autolus transitioned to a commercial stage company,

Syncona rebalanced its exposure to the business and,

as such, sold 14.0% of its holding at an average price

of $4.50, generating proceeds of $21.2 million (£16.3

million). As announced previously, AUCATZYL

®

has

the potential to be a best-in-class therapy for patients

with relapsed or refractory B-cell precursor acute

lymphoblastic leukaemia (r/r B-ALL), supported by its

very positive tolerability profile compared to current

CD19 CAR T-cell therapies. It is encouraging to see

that 39 treatment centres are now fully activated (as

of 7 May 2025) and that first quarter sales were ahead

of expectations at $9.0 million. We look forward to seeing

further progress with their commercial launch, which

we view as a key value inflection point for the company.

COMPANY FOCUS

Autolus is developing, commercialising and delivering next

generation programmed T-cell therapies for the treatment of cancer

and autoimmunity with a clinical pipeline targeting haematological

malignancies, solid tumours and autoimmune diseases.

FINANCING STAGE

Cash and cash equivalents at 31 March 2025 totalled $516.6 million.

Autolus estimates that, with its current cash, cash equivalents and

marketable securities, it is well capitalised to drive the launch and

commercialisation of obe-cel in r/r adult ALL, as well as to obtain data

in the lupus nephritis pivotal trial and multiple sclerosis Phase I trial.

LEAD PROGRAMME

Autolus received marketing approval from the FDA for AUCATZYL

®

and subsequently commenced commercial launch in the US. In

December 2024, the National Comprehensive Cancer Network

®

added

AUCATZYL

®

to its Clinical Practice Guidelines in Oncology for the

treatment of adult patients with r/r B-ALL. Post-period end, Autolus

received conditional marketing authorisation from the MHRA and the

European Medicines Agency’s (EMA) Committee for Medicinal Products

for Human Use (CHMP) has recommended European Commission (EC)

approval, with an EC decision on a conditional marketing authorisation

application expected in H2 2025. Autolus is working with the UK

National Institute for Health and Care Excellence (NICE) and the NHS

to potentially achieve access for eligible patients in England.

Autolus has presented updated data on obe-cel in adult ALL at various

conferences during the year, further building on previously published

data highlighting its tolerability and long-term response.

COMMERCIALISATION PROGRESS

In preparation for the broader commercialisation of AUCATZYL

®

,

Autolus delivered significant operational milestones to enable the

company to launch the product at a scale that can serve the expected

global demand. Global production capacity will be served by Autolus’

specialist 70,000 sq. foot advanced manufacturing facility (the

Nucleus), the UK’s first purpose-built CAR T-cell manufacturing unit.

The first commercial launch in the US is progressing on track, with

39 centres fully activated as of 7 May 2025 and coverage secured

for approximately 90% of total US medical lives. Autolus continues to

expect to complete authorisation of 60 treatment centres by the end

of 2025, covering approximately 90% of the target patient population.

PIPELINE PROGRAMMES

Post-period end, Autolus reported preliminary data from the Phase I

CARLYSLE dose confirmation study of obe-cel in refractory Systemic

Lupus Erythematosus (SLE) patients, which supported the progression

of obe-cel into a planned Phase II trial in lupus nephritis, a kidney

disease caused by SLE. The first patient in this trial is expected to

be dosed by end of CY2025. Full data with longer-term follow-up from

CARLYSLE is expected by the end of CY2025. Autolus also plans

to advance obe-cel into clinical development in progressive multiple

sclerosis. The company expects to dose its first patient in a Phase I

dose escalation study by the end of CY2025. BioNTech’s product

option for AUTO1/22 was not exercised as a result of BioNTech’s

pipeline prioritisation.

PEOPLE UPDATE

Autolus announced the appointment of Matthias Will, M.D., as Chief

Development Officer. He joined Autolus from Dren Bio, Inc., a privately

held biotech company, where he served as Chief Medical Officer

(CMO), and has previously held roles at CytomX Therapeutics, Gilead,

and Novartis. The company also appointed Mike Bonney as Chair of

the Board of Directors, and Ravi Rao M.D. as Non-Executive Director.

KEY VALUE INFLECTION POINT

Commercial traction following US launch of AUCATZYL

®

(obe-cel)

in r/r adult ALL expected in CY2025.

Board seats

–

Date of founding

2014

Date of Syncona investment

2014

Syncona capital invested

£147.0m

Number of employees

c.650

Uncalled commitment

–

Total capital raised

£1,312.9m

Syncona valuation

£34.6m

Key competitors

Gilead, Cabaletta, Kyverna

BEST

IDEAS

CLINICAL

CLINICAL

CLINICAL

BLA

AUCATZYL (obe-cel) –

Adult ALL

Obe-cel – LN

Obe-cel – MS

Obe-cel – Paediatric ALL

Obe-cel – B-NHL & CLL

Obe-cel – PCNSL

AUTO8 – MM

AUTO8 – LC amyloidosis

AUTO1/22 – Paediatric ALL

AUTO6NG – Neuroblastoma

AUTO4/5 – Peripheral TCL

AUTO9 – AML

Portfolio review

continued

11.2%

Of NAV

41%

Shareholding

Beacon has generated a strong set of data from

its Phase I/II HORIZON and Phase II SKYLINE trials

supporting the therapeutic benefit and safety profile

of laru-zova (formerly AGTC-501) in the treatment

of the blinding condition X-linked retinitis pigmentosa

(XLRP). This includes positive data from SKYLINE

which underlines the durability profile of the therapy

and supports our thesis that laru-zova could be a

potentially life-changing treatment for patients

suffering from XLRP. The company continues to show

strong momentum as it progresses through the clinic,

reinforced by the initiation of its Phase II/III VISTA

trial, which was announced in the period and is

currently enrolling.

COMPANY FOCUS

Beacon is an ophthalmic AAV-based gene therapy company founded

to save and restore the vision of patients with a range of prevalent

and rare retinal diseases that result in blindness.

FINANCING STAGE

Beacon raised $170 million (£134 million) in a Series B funding in July

2024. Forbion led the round and, alongside Syncona, the financing

was supported by existing investors Oxford Science Enterprises and

the University of Oxford, and new investors TCGX and Advent Life

Sciences. The financing took place at a 17.6% uplift to Syncona’s

31 March 2024 valuation of the company.

LEAD PROGRAMME

During the period, Beacon announced the initiation of its Phase II/III

pivotal VISTA study for laru-zova in XLRP. Beacon plans to use the data

generated from the VISTA trial, in combination with data from the Phase

I/II HORIZON, Phase II SKYLINE, and Phase II expansion DAWN trials,

to support its regulatory strategies in the EU and US. During the period,

Beacon also released positive data from these three clinical trials:

–

Interim data from the Phase II SKYLINE trial showed a 57%

response rate in the 24-month analysis of retinal sensitivity,

the primary endpoint for the trial. This was a key value inflection

point for the company and showed the potential of laru-zova

as a one-time therapy for XLRP.

–

Three-month data in the Phase II expansion DAWN trial showed

promising early improvements in low luminance visual acuity (LLVA),

a critical measure of visual function used as a primary endpoint in

the pivotal VISTA trial. This was also key value inflection point for

the company.

–

Data from the Phase I/II HORIZON trial demonstrated that a

difference in visual function between the treated and untreated

eyes was still observed at month 36.

–

Post-period end, positive six-month data in the Phase II expansion

DAWN trial was presented at Association for Research in Vision

and Ophthalmology (ARVO) 2025 Annual Meeting.

OPERATIONAL UPDATE

In April 2024 Beacon announced the sale of its GMP manufacturing

facility in Alachua, Florida to Ascend Advanced Therapies (Ascend).

The transaction includes a long-term partnership with Ascend to

secure GMP product supply for laru-zova, enabling the company

to focus on clinical development.

PIPELINE PROGRAMMES

Beacon’s second retinal disease programme is targeting dry

age-related macular degeneration, a leading cause of irreversible

vision loss in people over 60.

PEOPLE UPDATE

Beacon announced the appointment of Lance Baldo, M.D. as CEO,

and Thomas Biancardi as Chief Financial Officer (CFO). Lance brings

more than 20 years of experience in biopharmaceuticals including the

successful launch of two new indications and a new formulation for

Lucentis while at Genentech. Most recently, he served as CMO at

Freenome, an early cancer detection company, where he led the design

and execution of the company’s medical strategy to support its pipeline,

from clinical trials through registration and commercialisation. Thomas is

a biopharmaceutical industry veteran with over 25 years of financial and

operational leadership experience, predominantly within ophthalmology.

During his career, he has assisted numerous companies in raising

capital and establishing clinical and commercial operations.

KEY VALUE INFLECTION POINTS

Data readout from its Phase II/III pivotal VISTA trial in XLRP

expected in CY2026.

Board seats

2

Date of founding

2023

Date of Syncona investment

2022

Syncona capital invested

£89.9.m

Number of employees

70

Uncalled commitment

£18.6m

Total capital raised

£229.7m

Syncona valuation

£117.5m

Key competitors

Janssen (MeiraGTx) in XLRP, Apellis,

IvericBio (Astellas) and 4DMT in dAMD

BEST

IDEAS

PRE-

CLINICAL

CLINICAL

LATE-STAGE

CLINICAL

BLA

Laru-zova (AGTC-501)

– XLRP

17.3%

Of NAV

79.2%

Shareholding

Spur continues to make strong clinical progress and

Syncona has been encouraged by the data published

from its lead Gaucher disease programme (FLT201).

This includes the data published at the European

Society of Gene and Cell Therapy (ESGCT) 31

st

Annual

Congress, demonstrating a favourable efficacy and

safety profile for FLT201, and further data published

at WORLDSymposium in February 2025. This data

de-risks Spur’s technology and supports the

advancement of the company’s pre-clinical pipeline

into more prevalent disorders, including Parkinson’s

disease. We believe FLT201 can be a first- and

best-in-class gene therapy for Gaucher disease

patients with the potential of delivering value for

Syncona shareholders. Spur is now preparing to

advance FLT201 into a Phase III trial.

COMPANY FOCUS

Developing transformative gene therapies for patients suffering from

chronic debilitating diseases.

FINANCING STAGE

During the year, Syncona provided £43.8 million of financing to support

the development of the company’s pipeline.

LEAD PROGRAMME

The company presented positive data from its lead Gaucher disease

programme at the American Society of Gene & Cell Therapy in May

2024, reinforcing the safety, tolerability and efficacy profile of FLT201,

as well as its potential to improve quality of life for patients. Importantly,

the data showed levels of lyso-Gb1

1

were substantially reduced in

patients with persistently high lyso-Gb1 levels, despite years of prior

treatment with enzyme replacement therapy (ERT), the current standard

of care for Gaucher disease patients, or substrate reduction therapy

(SRT). This was reinforced with further data readouts during the period,

including at the ESGCT 31

st

Annual Congress in October 2024. The

data presented at ESGCT was a key value inflection point for Spur,

underlining the efficacy, safety and long-lasting potential of FLT201.

Further data presented at WORLDSymposium in February 2025

demonstrated durable reductions in lyso-Gb1 of between 33-96%

in patients who entered the trial with high levels.

The company is on track to initiate its Phase III trial in Gaucher disease

during H1 CY2026, with Spur gaining FDA alignment on the design of

a single-arm study to support potential accelerated approval of FLT201.

The accelerated pathway would be based on reductions in lyso-Gb1

after six months, with full approval based on improvement or

maintenance of haemoglobin levels after 12 months.

PIPELINE PROGRAMMES

The company presented new pre-clinical data at the inaugural GBA1

meeting from its GBA1 Parkinson’s disease research programme,

demonstrating that its engineered enzyme reduces the accumulation of

-Synuclein, a protein that plays an important role in the development

and progression of Parkinson’s disease, more effectively than the

naturally occurring protein. The company also selected a candidate,

SPR301, for development in Parkinson’s disease. Spur has decided

to discontinue the development of SBT101 in adrenomyeloneuropathy

(AMN). Spur recently published a safety update from the Phase I/II

clinical trial of SBT101, and the company’s view is an efficacy signal

will take a longer period of time to generate, and the company’s capital

is better prioritised to Gaucher and Parkinson’s disease.

KEY VALUE INFLECTION POINT

Completion of the pivotal stage of its Phase III trial in Gaucher

disease expected in H1 CY2028.

Board seats

2 (including Chair)

Date of founding

2015

Date of Syncona investment

2015

Syncona capital invested

£395.5m

Number of employees

65

Uncalled commitment

–

Total capital raised

£590.1m

Syncona valuation

£182.2m

Key competitors

Eli Lilly

BEST

IDEAS

CLINICAL

CLINICAL

CLINICAL

BLA

FLT201 – Gaucher disease

Portfolio review

continued

8.1%

Of NAV

33.7%

Shareholding

Quell Therapeutics (Quell) continues to make clinical

and operational progress, announcing positive safety

and translational data from the initial safety cohort

of three patients from its lead QEL-001 programme

in liver transplantation in the year.

This data supported Quell’s subsequent decision to advance QEL-001

into the efficacy cohort of its Phase I/II trial which is now underway,

with initial translational data demonstrating enhanced QEL-001

engraftment in the first three patients of the efficacy cohort.

COMPANY FOCUS

Developing engineered T-regulatory (Treg) cell therapies to treat a range

of conditions such as solid organ transplant rejection, autoimmune and

inflammatory diseases.

FINANCING STAGE

Raised $156 million in a syndicated Series B financing in November 2021.

CLINICAL UPDATE

Quell presented safety data from its lead programme at the American Transplant

Congress in June 2024, demonstrating that QEL-001 was safe and well

tolerated by liver transplant patients. Further translational data was presented

at the ESGCT Annual Congress in October, demonstrating durable enrichment

of the QEL-001 CAR-Tregs in liver grafts, and at the EASL Congress in

May 2025, demonstrating enhanced engraftment of QEL-001 CAR-Tregs

after ATG conditioning. The company has advanced QEL-001 to the efficacy

cohort of the LIBERATE Phase I/II trial, with three patients dosed to date.

PARTNER PROGRAMMES

In November 2024, AstraZeneca selected a candidate to progress

from the type 1 diabetes Treg cell therapy collaboration programme,

triggering a $10 million milestone payment to Quell. Post-period end

in June 2025, AstraZeneca selected a candidate to progress from the

inflammatory bowel disease Treg cell therapy collaboration programme,

triggering a second $10 million milestone payment to Quell.

PEOPLE UPDATE

Luke Beshar was appointed as Chair of Quell’s Board of Directors.

Luke has more than 35 years of strategic development, financial and

transactional experience from his Board and C-suite executive roles

at several innovative, high-growth public and private companies.

KEY VALUE INFLECTION POINT

–

Interim data readout from its Phase I/II trial in liver

transplantation expected in CY2025

–

Full data readout for the Phase I/II trial in liver transplantation

expected in CY2026

Board seats

1

Date of founding

2019

Date of Syncona investment

2019

Syncona capital invested

£64.2m

Number of employees

c.150

Uncalled commitment

–

Total capital raised

£232.4m

Syncona valuation

£85.4m

Key competitors

Sangamo, Sonoma, GentiBio, Abata, Tr1x,

PolTreg, Tract Therapeutics, RegCell

BEST

IDEAS

PRE-

CLINICAL

CLINICAL

LATE-STAGE

CLINICAL

BLA

QEL-001 – Liver transplant

Anaveon has previously published positive

pre-clinical data for ANV600 and Syncona believes

this pre-clinical data, combined with the clinical data

from the previous-generation compound, supports

ANV600’s anticipated clinical safety and efficacy.

Anaveon will be reporting data from its Phase I dose

escalation and expansion cohorts clinical trial of

ANV600 in CY2026, which will provide further insight

into the value potential of this programme. The

company is on track to declare the recommended

Phase II dose as monotherapy and in combination

with anti-PD1 checkpoint inhibition in H2 CY2025.

COMPANY FOCUS

Clinical development of a PD-1 targeted IL-2 receptor agonist, a type

of protein that could enhance a patient’s immune system to respond

therapeutically to cancer. The company has also announced a PD-1

targeted IL-21 bispecific compound and an anti-PD-1 depleting

antibody, both currently in pre-clinical stages.

FINANCING STAGE

Raised CHF 110 million (£90 million) in a syndicated Series B financing

in 2021.

LEAD PROGRAMME

During the period Anaveon entered the clinic with its Phase I/II trial

of ANV600.

PEOPLE UPDATE

Dieter Weinand has been appointed Chair of the Board of Directors.

Dieter is an experienced business leader in the pharmaceutical industry

and is the former Chair and CEO of Bayer Pharmaceuticals. New CMO

Richard Sachse joined in February 2025. Richard has 25 years of drug

development leadership in oncology, immunology and neurology,

across both early and late-stage development.

KEY VALUE INFLECTION POINT

Data readout from its Phase I/II trial of ANV600 expected in CY2026.

Board seats

2

Date of founding

2017

Date of Syncona investment

2019

Syncona capital invested

£52.4m

Number of employees

24

Uncalled commitment

–

Total capital raised

£114.7m

Syncona valuation

£35.6m

Key competitors

Bright Peak Therapeutics

BEST

IDEAS

PRE-

CLINICAL

CLINICAL

LATE-STAGE

CLINICAL

BLA

ANV600 –

Range of solid tumours

3.4%

Of NAV

36.9%

Shareholding

2.4%

Of NAV

21.9%

Shareholding

iOnctura is driving its lead candidate roginolisib towards

late-stage development and we believe it can deliver

high patient impact across a broad range of indications.

Since adding this clinical-stage opportunity to Syncona’s portfolio last

year, the SIML team worked closely alongside iOnctura’s management

team to review its pipeline and explore the breadth of roginolisib’s utility,

whilst prioritising indications that can deliver the most value over the

nearest timeframe. We are pleased with the progress made in uveal

melanoma and to see the expansion of the roginolisib opportunity,

with Phase II trials initiated in non-small cell lung cancer (NSCLC) and

myelofibrosis in addition to uveal melanoma. SIML believes roginolisib

has the potential to modulate an important biological pathway in cancer

with a side-effect profile that will allow it to benefit many patients.

COMPANY FOCUS

Developing selective cancer therapeutics against targets that play

critical roles in multiple tumour survival pathways.

FINANCING STAGE

Syncona led a €86 million (£68.4 million) Series B financing of iOnctura

in March 2024 as part of a leading syndicate including existing investors

Merck Ventures, Inkef Capital, Schroders Capital, VI Partners and

the 3B Future Health Fund, as well as new investors the European

Innovation Council and XGEN Venture.

LEAD PROGRAMME

iOnctura’s lead programme, roginolisib, is a first-in-class allosteric

modulator of PI3K delta (PI3K

), which has potential application across

a variety of solid tumour and haematological cancers. The company

expanded its clinical trial programme for roginolisib to non-small cell lung

cancer via a supply agreement with GSK. The company has commenced

its randomised Phase II trial in uveal melanoma, with dosing of patients

underway, and post-period end it dosed the first patient in its Phase II trial

in NSCLC. Sites are screening patients for a Phase II trial in myelofibrosis.

PIPELINE PROGRAMMES

The company has a number of clinical and pre-clinical pipeline

programmes in broader oncology indications.

KEY VALUE INFLECTION POINT

Data readout from its Phase II trial in uveal melanoma expected

in CY2026.

Board seats

2

Date of founding

2017

Date of Syncona investment

2024

Syncona capital invested

£25.7m

Number of employees

20

Uncalled commitment

–

Total capital raised

£73.0m

Syncona valuation

£25.1m

Key competitors

Ideaya Biosciences (in uveal melanoma)

BEST

IDEAS

PRE-

CLINICAL

CLINICAL

LATE-STAGE

CLINICAL

BLA

Roginolisib –

Uveal melanoma

Roginolisib – NSCLC

and myelofibrosis

IOA-289 –

Pancreatic cancer

Resolution remains the global leader in macrophage

cell therapy, having established the value of this

modality through publication of the MATCH II academic

clinical data showing efficacy in patients with end-stage

liver disease. Resolution has entered the clinic and

is focused on trial execution and demonstrating the

impact that its engineered macrophage cell therapy

RTX001 can have on a severely ill patient group with

end-stage liver disease.

COMPANY FOCUS

Resolution is pioneering regenerative macrophage therapy

in inflammatory and fibrotic diseases.

FINANCING STAGE

During the year Syncona committed £63.5 million in Series B financing

to Resolution. Since the year end, SIML has been exploring the

possibility of syndicating some of its Series B commitment. Amidst

ongoing market challenges and following material third-party interest

from potential Series B syndicate investors, Resolution has been

partially written down by 23.6%. However, Resolution is funded to

support the early clinical development of lead programme RTX001,

and deliver data from the programme.

CLINICAL UPDATE

The complete three-year MATCH II data presented at the American

Association of the Study of Liver Disease (AASLD) in November

2024, demonstrated excellent safety and efficacy of non-engineered

macrophage cell therapy in patients with advanced cirrhosis. In

parallel, pre-clinical data presented at the Keystone Symposia on

Fibrosis suggests superior anti-inflammatory and anti-fibrotic effects

of engineered macrophages RTX001 compared to non-engineered

macrophages. Resolution is now actively recruiting patients in its

EMERALD study, a Phase I/II clinical trial of RTX001 in end-stage

liver disease, in the UK and Spain.

KEY VALUE INFLECTION POINT

Interim data readout from its Phase I/II trial in end-stage liver

disease expected in CY2026.

Board seats

2

Date of founding

2020

Date of Syncona investment

2018

Syncona capital invested

£68.9m

Number of employees

57

Uncalled commitment

£32.5m

Total capital raised

£101.4m

Syncona valuation

£55.5m

Key competitors

Carisma

BEST

IDEAS

PRE-

CLINICAL

CLINICAL

LATE-STAGE

CLINICAL

BLA

RTX001

–

End-stage liver

disease

5.3%

Of NAV

82.6%

Shareholding

Portfolio review

continued

2.4%

Of NAV

54.3%

Shareholding

Using proprietary computational methods and

models, Mosaic discovers and develops novel

therapeutic combinations for the targeted treatment

of cancer. Mosaic’s deal with Astex to in-license assets

having extensive clinical exposure as monotherapies

has significantly de-risked and accelerated the

company’s development path. Mosaic now expects

to start the first clinical study of its lead drug

combination in H1 CY2026.

COMPANY FOCUS

Oncology therapeutics company using advanced computational

methods and next-generation cancer models to discover and

develop novel targeted combination medicines.

FINANCING STAGE

£22.5 million Series A announced in April 2023, led by Syncona

alongside Cambridge Innovation Capital. During the period the

financing was extended by a further £5.7 million.

1

PLATFORM CAPABILITIES

Mosaic’s technology platform uses proprietary disease models and

machine learning to enable identification of novel biological intervention

to drive responses in cancer. The company will then leverage these

insights to build a pipeline of programmes.

PEOPLE UPDATE

The company appointed Dr Barry Davies as Chief Scientific Officer

(CSO). Barry brings over 25 years of experience in drug discovery,

including 19 years at AstraZeneca where he was most recently

Senior Director, Global Project Leader.

PIPELINE UPDATE

Post-period end, the company in-licensed two clinically experienced

targeted small molecules to enable a pipeline of biomarker defined

combination programmes identified through its platform.

Board seats

2 (including CEO and Chair)

Date of founding

2020

Date of Syncona investment

2022

Syncona capital invested

£25.5m

Number of employees

30

Uncalled commitment

–

Total capital raised

£28.2m

Syncona valuation

£25.5m

Key competitors

IDEAYA Biosciences, Isomorphic Labs,

Recursion, Repare Therapeutics,

Tango Therapeutics

BEST

IDEAS

CLINICAL

CLINICAL

CLINICAL

BLA

COMPANY FOCUS

Precision nephrology company, developing multiple locally delivered

gene therapies for the treatment of chronic renal diseases which are

currently inadequately addressed by existing treatments.

FINANCING STAGE

Purespring raised £80 million in an oversubscribed Series B financing

in September 2024, with Syncona committing £19.9 million alongside

a leading syndicate led by Sofinnova Partners, in collaboration with

Gilde Healthcare, Forbion, and British Patient Capital. Proceeds will

be used to advance Purespring’s pipeline of disease modifying gene

therapies into the clinic and support the expected initiation of a Phase

I/II clinical trial in H2 CY2025 for its lead programme PS-002 targeting

IgA nephropathy (IgAN), a chronic kidney disease principally affecting

young adults.

DEVELOPMENT UPDATE

Purespring presented pre-clinical data at the American Society of

Nephrology (ASN) Kidney Week 2024, demonstrating that targeting

podocytes to modulate complement activation reduces signs of

kidney disease in animal models and is an effective therapeutic

strategy. Post-period end, Purespring was granted orphan drug

designation for its lead programme PS-002 for the treatment of

patients with primary IgAN.

PEOPLE UPDATE

Purespring has appointed Haseeb Ahmad as CEO who has over 25 years

of experience in the life science industry and a strong commercial track

record in both high-prevalence and rare diseases. Previously, Haseeb led

Novartis Europe and Novartis Gene Therapies and had numerous global

and in country leadership roles at Novartis and Merck & Co.

KEY VALUE INFLECTION POINT

Complement biomarker clinical data expected in H1 CY2027.

Board seats

2 (including Chair)

Date of founding

2020

Date of Syncona investment

2020

Syncona capital invested

£50.0m

Number of employees

47

Uncalled commitment

£5.0m

Total capital raised

£115.0m

Syncona valuation

£51.2m

Key competitors

Novartis, Calliditas Therapeutics, Vertex

Pharmaceuticals, Vera Therapeutics, Otsuka,

Sanofi, Travere Therapeutics and Apellis

4.9%

Of NAV

41.7%

Shareholding

1.9%

Of NAV

59.7%

Shareholding

COMPANY FOCUS

An opportunity to create a new generation of small molecule oral

drugs addressing diseases through modulating protein homeostasis.

FINANCING STAGE

Kesmalea Therapeutics (Kesmalea) raised £20.0 million in a Series

A financing led by Syncona in 2022 alongside Oxford Science

Enterprises. An additional £5.0 million was raised in 2023 with

Syncona committing £4.0 million.

DEVELOPMENT UPDATE

The company progressed development of its platform SELFTAC

technology and discovery programmes, focusing on oncology and

the central nervous system.

PEOPLE UPDATE

Kesmalea has appointed Robert Johnson as CEO. Robert was

previously CEO of Adrestia Therapeutics until its acquisition by

Insmed. Prior to that, he was co-founder and Chief Business

Officer at Affinia Therapeutics.

Board seats

2

Date of founding

2020

Date of Syncona investment

2022

Syncona capital invested

£20.0m

Number of employees

10

Uncalled commitment

–

Total capital raised

£25.0m

Syncona valuation

£20.0m

Key competitors

Arvinas, Nurix, Amphista, Origami, TRIMTech

COMPANY FOCUS

Pioneering soluble bispecific T-cell receptor (TCR)-based therapies to

unlock a new class of cancer therapeutics, with a focus on frequently

expressed peptide antigens presented by HLA class II.

FINANCING STAGE

Syncona committed £16.5 million to Yellowstone Biosciences

(Yellowstone) in a Series A financing in 2024.

PEOPLE UPDATE

The company has built out its team and is making progress on

its research plan with the next milestone being target nomination.

Board seats

2

Date of founding

2024

Date of Syncona investment

2024

Syncona capital invested

£16.5m

Number of employees

20+

Uncalled commitment

–

Total capital raised

£16.5m

Syncona valuation

£16.5m

Key competitors

Novartis, Calliditas, Reata, Sanofi, Travere,

Omeros, Alexion, Apellis

1.6%

Of NAV

60.9%

Shareholding

COMPANY FOCUS

Developing small molecule drugs to treat endocrine and

immunological conditions.

FINANCING STAGE

OMass Therapeutics (OMass) raised £75.5 million in a Series B

financing in April 2022, with an additional £10 million investment

from British Patient Capital announced in May 2023.

DEVELOPMENT UPDATE

OMass selected the candidate molecule for its lead MC2 programme,

a G protein-coupled receptor (GPCR) for the adrenocorticotrophic

hormone (ACTH). This will support the development of the

programme in diseases of adrenocorticotropic hormone (ACTH)

excess, including Congenital Adrenal Hyperplasia (CAH) and

ACTH-dependent Cushing’s Syndrome.

KEY VALUE INFLECTION POINT

Data from Phase I trial of MC2 programme expected in H1 CY2026.

Board seats

2

Date of founding

2016

Date of Syncona investment

2018

Syncona capital invested

£41.4m

Number of employees

62

Uncalled commitment

–

Total capital raised

£128.5m

Syncona valuation

£49.7m

Key competitors

Crinetics, Neurocrine

4.7%

Of NAV

29%

Shareholding

MOVING TOWARDS EMERGING EFFICACY DATA

MOVING TOWARDS OPERATIONAL BUILD

MOVING TOWARDS EMERGING EFFICACY DATA

SYNCONA LIMITED ANNUAL REPORT AND ACCOUNTS 2025

39

SYNCONA INVESTMENT MANAGEMENT LIMITED