®

Pioneering

innovative

lifesaving

treatments

Annual Report 2022

1

Contents

The Swedish version of the 2022 Annual Report represents the legally binding version and prevails

7.

Shareholder information

8.

Directors’ report

9.

Financials

10. Governance

11. Remuneration

12. Glossary

1.

Overview

2.

Strategy

3.

Market

4.

Technology

5.

Growth

6.

New opportunities

Overview

Strategy

Market

Technology

Growth

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Our vision

We envision a world

where all patients with

rare immunologic

diseases can lead long

and healthy lives

Hansa Biopharma (“Hansa”, “the Company”, “we”) is a

commercial-stage biopharmaceutical company pioneering the

development and commercialization of innovative, lifesaving

and life altering treatments for patients with rare

immunological conditions.

Hansa has developed a first-in-class immunoglobulin G (IgG)

antibody cleaving enzyme therapy, which has been shown to

enable kidney transplantation in highly sensitized patients.

Hansa has a rich and expanding research and development

program, based on the Company’s proprietary IgG-cleaving

enzyme technology platform, to address serious unmet

medical needs in transplantation, autoimmune diseases,

gene therapy and cancer.

Hansa Biopharma is based in Lund, Sweden,

and has operations in Europe and the U.S.

Hansa

Biopharma

in brief

Strategy

Market

Technology

Growth

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Overview

2

3

Strategy

Market

Technology

Growth

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Overview

4

Chairman’s letter

5

2022 highlights

6

CEO statement

8

Anticipated future milestones

Overview

1

Dear Shareholders,

2022 was another exciting and successful year

for Hansa Biopharma, with continued progress

and achievement of several key milestones in

both R&D and commercial operations. Despite

an unpredictable and challenging geopolitical

environment, we were able to pivot quickly to

meet unexpected operational demands, while

continuing to advance our key priorities.

I began my role as the Chairman of the Board of Directors at

Hansa Biopharma in June of 2022 and have been impressed

with the progress to date. Additionally, the entire organization

has demonstrated strong dedication and perseverance.

I remain impressed by the Company’s strong purpose-driven

culture and how colleagues across the organization work

together to deliver on our mission to develop innovative,

lifesaving and life altering therapies to patients with rare

conditions. It is a pleasure to now be part of this journey and

I look forward to continuing to work with the Board and the

leadership team while setting a strategic direction for Hansa

to advance its IgG-antibody cleaving technology platform

and products to the patients who need them.

During 2022, the Company set a strong foundation for the

commercialization of Idefirix

®

including successful market

reimbursement in four of the five largest markets in Europe.

This further validates the important role Idefirix

®

can play in

kidney transplantation. Additionally, several countries

consider Idefirix

®

a lifesaving and cost effective treatment

option. With the emergence of imlifidase, new international

consensus guidelines for a management pathway for kidney

transplant patients with high unmet need has been created.

The Company progressed several important phase 2 and 3

trials increasing the total number of programs in the clinic to

seven – a significant accomplishment for a company of this

size and a testament to our fierce commitment to advancing

our science and exploring the potential of our leading

technology platform.

Two new phase 3 programs were advanced including the

Post Approval Efficacy Study (PAES) of Idefirix in highly

sensitized kidney transplant patients and a global study in

anti-GBM disease. A phase 2 trial in antibody mediated

rejection (AMR) also moved ahead and the positive top line

data demonstrating statistically significant superiority

compared to current standard of care was communicated in

Q4 2022. Additionally, two pre-clinical projects progressed

– the NiceR program including our second-generation

antibody-cleaving enzyme candidate HNSA-5487 targeting

repeat dosing and a program in Duchenne Muscular

Dystrophy (DMD) in partnership with Sarepta. Both of these

programs will advance to clinical stage later this year.

2022 remained challenging for the technology and biotech

industries as a whole. The direct and indirect impact to

companies caused by rising interest rates, sector rotation and

geopolitical uncertainties, remain and have resulted in weak

valuations of many biotech companies. Despite this, the Board

was pleased with the successful execution of two financing

events last year. This enabled the Company to extend its cash

runway into 2025. With financing secured, a validated

technology platform with an exciting late-stage pipeline and a

highly engaged and committed organization, Hansa is

well-positioned to deliver on its strategic priorities in 2023 and

become a leading player in rare immunologic diseases.

On behalf of the Board of Directors,

Peter Nicklin

Chairman, Hansa Biopharma AB

Lund, Sweden, March 2023

Chairman’s letter

One immediately senses a strong

purpose driven culture among

the Hansa colleagues

2022 highlights

Agreement with AskBio to

evaluate feasibility of

imlifidase ahead of gene

therapy in Pompe disease

First patient enrolled in

the EU post approval

efficacy study (PAES)

Results of the Phase 2 study of

imlifidase in patients with anti-GBM

disease published in Journal of the

American Society of Nephrology

USD 70m non-dilutive

financing transaction,

extending Hansa’s cash

runway through 2024

Great Place to

Work

®

for third

consecutive year

Successful execution

of a directed share

issue of SEK 416m

(USD ~40m)

Completion of

preclinical work with

lead NiceR candidate

for repeat dosing

(HNSA 5487)

Announcement of

positive topline data from

the imlifidase phase 2

study in AMR

Market access granted in

France through a reimbursed

Early Access Program

Pricing and reimbursement

achieved for Idefirix

®

in Germany

Temporary marketing

authorization granted

in Switzerland

Poland Positive

reimbursement

decision for Idefirix

®

Pricing and

reimbursement granted

for Idefirix for use in Italy

ESOT guidelines

published in Transplant

International

Scotland Positive

reimbursement

decision for Idefirix

®

Pricing and reimbursement

granted for Idefirix for use in

Czech Republic

Announcement of plans to

initiate a clinical study with

imlifidase as a pre-treatment to

Sarepta’s SRP-9001 gene

therapy in DMD in 2023

NICE

recommends use

of Idefirix

®

Marketing authorization

in Israel for Idefirix

®

(imlifidase)

2022

2023

January

February

March

April

May

June

July

August

September

October

November

December

5

While the global geopolitical and financial environment made

2022 a very challenging year for the biotech sector overall, I

am very pleased with the solid performance and strong

progress across our R&D and commercial operations.

Commercial launch activities and market access efforts

for Idefirix

®

in Europe continued to progress as planned.

Importantly, by year-end 2022, commercial access had been

obtained in eleven European countries, including four of the

five largest markets: Germany, UK, Italy and France.

Additional market access procedures are ongoing in nine

countries, including Spain.

In August, the first medical guidelines for desensitization

treatment of highly sensitized kidney transplant patients were

published by the European Society for Organ Transplantation,

ESOT. These guidelines are the first to include Idefirix

®

and

represent the first international consensus on a management

pathway for kidney transplant patients with high unmet need.

The early publication of these guidelines underscores the

important role that Idefirix

®

can play as a new, transformative

therapy to enable kidney transplantation, and is an important

step in ensuring its use as a potential new “Gold Standard” in

desensitization protocols.

On the clinical development side, we continued to make

progress across our pipeline. In November, we presented

topline data from our phase 2 program in kidney transplant

AMR (post transplantation episodes or organ rejection),

demonstrating significantly superior capacity of imlifidase to

rapidly reduce donor specific antibodies (DSA) levels in

comparison to plasma exchange in the five days following the

start of the treatment.

During the year, we initiated two new phase 3 studies:

- the European Post Approval Efficacy Study in kidney

transplantation and the pivotal, global phase 3 study in

anti-GBM disease. Both studies will target 50 patients and

involve a significant number of clinics as we broaden our

experience with imlifidase to become a potential new

standard of care in both transplantation and acute

autoimmune diseases.

In the U.S., patient enrollment continues in our third ongoing

phase 3 study, the pivotal ConfIdeS trial in kidney

transplantation. The ConfIdeS study is evaluating imlifidase

as a potential desensitization therapy to enable kidney

transplants in highly sensitized patients waiting for a

deceased donor kidney through the U.S. kidney allocation

system. We expect to complete enrollment in the first half of

2023, while completion of randomization is expected in the

second half of this year. There has been strong interest from

leading transplantation centers to participate in this trial,

and we expect to initiate around 20 leading centers across

the U.S.

The enrollment in the phase 2 program in Guillain-Barré

Syndrome (GBS) was impacted by the COVID-19 pandemic

due to staff constraints in trial centers and a shortage of IVIg at

a subset of participating hospitals. We have worked to mitigate

these hurdles and saw an increase in patient enrollment at the

CEO statement

I am very pleased with the

solid performance and strong

progress across our R&D and

commercial operations

2022 was a successful year at Hansa,

with solid performance and strong

progress across the organization.

Søren Tulstrup

President and CEO,

Hansa Biopharma AB

end of 2022. A completion of enrollment in the GBS trial is

expected in the first half of 2023, with a top line data expected

in the second half 2023, as previously guided.

I am pleased with the achievements made in our preclinical

development programs, in particular in the Duchenne

Muscular Dystrophy (DMD) project with Sarepta Therapeutics

in gene therapy and the NiceR program, which is exploring

utilization of second-generation enzymes for repeat dosing.

In DMD, imlifidase is being investigated as a potential

pre-treatment in patients with pre-existing IgG antibodies to

Sarepta’s SRP-9001. To date, the data appears promising,

and plans have been announced to initiate a clinical study in

2023. In the NiceR program, we completed IND enabling

toxicology studies at the end of the year for our lead

candidate, HNSA-5487. A CTA approval has since been

obtained and we expect to begin a clinical trial in the first

half of 2023.

In addition, while the capital markets for biotech companies

remained challenging throughout 2022, I am pleased that we

were able to successfully secure additional financing through

two transactions last year, enabling us to extend our cash

runway into 2025. In July, we raised USD 70m through a

non-dilutive financing transaction with NovaQuest, and in

December we raised USD 40m in a directed share issue

targeting U.S. and other international healthcare specialist

investors. The funds raised will help finance preparations for

a potential U.S. launch of imlifidase in kidney transplantation

and further advance our exciting pipeline of drug candidates.

I am particularly grateful to our employees for their

commitment, passion, and hard work over the past year. We

are dedicated to building and maintaining a high-

performance team, while also creating a rewarding and

stimulating workplace for our employees. A clear reflection of

our successful efforts in this regard was the certification as a

Great Place to Work

®

for the third consecutive year.

At Hansa, sustainability is at the core of all we do, and during

2022 we continued to build on the formalized ESG framework

which was created in 2021. Embarking on this journey, we

have identified key objectives for our environmental, social

and governance priorities, which will be addressed separately

in our CSR Report.

We now have an exciting year ahead with several key

milestones across our platform and therapeutic areas as we

continue to pursue the development and launch of new,

transformative medicines that will enable patients with rare

immunologic diseases to lead long and healthy lives.

Søren Tulstrup

President and CEO,

Hansa Biopharma AB

Lund, Sweden, March 2023

CEO statement

continued

A clear reflection of our

successful efforts in this

regard was the

certification as a Great

Place to Work

for the

third consecutive year

Anticipated future milestones

Anti-GBM Phase 3:

First patient enrolled

(H1 2023)

HNSA 5487 (Lead NiceR candidate)

Initiate Phase 1 study

(H1 2023)

Long-term follow-up study

in kidney transplantation

5-year data readout

(H2 2023)

GBS Phase 2:

First data readout

(H2 2023)

U.S. Kidney transplantation

BLA submission

(2024)

GBS Phase 2:

Complete enrollment

(H1 2023)

U.S. Kidney transplantation:

Complete randomization

(H2 2023)

AMR Phase 2:

Full data readout (H2 2023)

U.S. Kidney transplantation:

Complete enrollment

(H1 2023)

Sarepta DMD pre-treatment:

Commence Clinical study

(2023)

2023

2024

8

Strategy

Market

Technology

Growth

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Overview

9

10

Potential indication universe

12

Business model

13

Our strategic priorities

Overview

Market

Technology

Growth

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Strategy

2

Strategy

10

Overview

Market

Technology

Growth

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Strategy

Potential indication universe

1

The EU Commission has granted conditional approval for imlifidase in highly sensitized kidney transplant patients

2

In the U.S. a new study has commenced targeting a BLA filing by 2024

First generation antibody

cleaving enzyme technology

Obtained EU conditional approval

1,2

Planned clinical program

Clinical program

Research program

Opportunities currently not pursued

Partnership Preclinical program

(Sarepta Therapeutics Inc. and AskBio)

Hansa’s first-generation antibody-cleaving

enzyme, imlifidase, is a protein with

properties that enable it to quickly and

effectively inactivate IgG antibodies.

Imlifidase is derived from the human

pathogen,

Streptococcus

pyogenes.

Imlifidase is being developed for the treatment and

prevention of diseases and conditions caused by IgG

antibodies in the acute phase, including desensitization

prior to kidney transplantation. The Company has

received conditional approval for marketing in Europe

for this indication.

We are also investigating the potential use of imlifidase

as a treatment of active antibody mediated rejection

(AMR) episodes in kidney transplantation and in solid

organ transplants, both pre- and post-transplantation

(e.g., heart and lung).

Looking beyond transplantation, there are several other

growth vectors and areas where imlifidase may play a role,

including acute autoimmune diseases, gene therapy and

oncology. More specifically, we are investigating rare

life-threatening conditions such as anti-GBM antibody

disease and Guillain-Barré Syndrome (GBS), which are both

ongoing clinical programs in phase 3 and 2 respectively.

In addition, Hansa, with its partners, is investigating

imlifidase as a pre-treatment to potentially enable gene

therapy in patients with pre-existing neutralizing antibodies

(NAbs) against the viral vectors used by the gene therapy.

Through the partnership with Sarepta Therapeutics,

imlifidase is being investigated in Duchenne Muscular

Dystrophy (DMD) and Limb-Girdle Muscular Dystrophy

(LGMD) and through the partnership with AskBio, a

subsidiary of Bayer AG, in Pompe disease.

Further, we are exploring potential indications within

oncology such as allogeneic HSCT. Stem cell

transplantation is a significant indication where, there is a

high unmet medical need for patients with high levels of

donor specific antibodies due to the current absence of

adequate desensitization methods.

Beyond imlifidase for the acute treatment in IgG mediated

conditions and diseases, we are also developing new

IgG-cleaving enzymes under the program “NiceR” (Novel

Immunoglobulin Cleaving Enzymes for Repeat Dosing).

These “next-generation” enzymes from the NiceR program

will be designed to have a lower propensity to induce

immunity in order to increase the therapeutic window. The

new enzymes are being developed to be potentially utilized

in several IgG-driven autoimmune diseases where patients

experience flares, or in transplantation where repeat dosing

would be beneficial and add further value. Following

completion of IND enabling toxicology studies late 2022 and

the subsequent approval of a Clinical Trial Application early

2023, Hansa expects to initiate a clinical trial during the first

half 2023 with HNSA-5487, its lead IgG-cleaving enzyme

candidate for repeat dosing.

Lastly, Hansa and argenx BV have been evaluating the

therapeutic potential of combining imlifidase and

efgartigimod, argenx’s FcRn antagonist. A combination of

imlifidase and efgartigimod or other FcRn antagonists

could potentially be used in both the acute and the

chronic setting of autoimmune diseases and

transplantation. Any potential next steps will be evaluated.

Potential indication universe

continued

Looking beyond transplantation, there

are several other growth vectors and

areas where imlifidase may play a role,

including acute autoimmune diseases,

gene therapy and oncology

Business model

Leveraging a unique and proprietary technology platform to develop new

therapies in areas of high unmet medical need in rare disease

Revenue / sales

Upfront payments

Milestone payments

Royalties

Transplantation

Autoimmune diseases

Gene therapy

New therapies and oncology

Growth engine

Leveraging proprietary

antibody cleaving

enzyme technology

Value chain

Commercialization

Evolution into a fully integrated biopharmaceutical company

Own commercial

infrastructure

Partnership

strategy

Drug

discovery

Drug

development

Supply

operations

Distribution

Controlling the full value chain

Build-up of franchises

Indications and therapies

Multiple income streams

F(ab’)2

Fc

*

Idefirix approved in EEA under conditional approval for kidney transplantation

Our strategic priorities

Hansa’s mission is to become a global leader in rare diseases through

the development of innovative, lifesaving and life altering treatments

for patients with rare immunological conditions

The Company’s strategy is anchored on the proprietary

enzyme technology platform and with a goal of developing

and commercializing immunomodulatory first-in-class or

best-in-class treatments for organ transplants, rare

IgG-mediated autoimmune conditions, and gene therapy, as

well as exploring the potential application of the technology

platform in oncology. To deliver on the ambition we have

three key priorities:

1. Commercialize

Idefirix

®

in first

indication and markets

2. Advance ongoing

imlifidase clinical

programs in

transplantation and

autoimmune diseases

3.

Expand IgG-cleaving

enzyme technology

platform into new

disease areas and

indications

Build focused, integrated, agile and empowered international organization

and seek partnerships to accelerate growth and reduce risk

Strategy

1. Commercialize Idefirix

®

in first indication

and markets

In August 2020, Hansa received conditional approval from the

European Commission for Idefirix

®

(imlifidase) for the

desensitization treatment of highly sensitized adult kidney

transplant patients with positive crossmatch against an available

deceased donor.

We have launched Idefirix

®

in several major European countries

driving reimbursement and partnering closely with leading clinical

experts. In 2022, commercial access was obtained in eleven

European countries, including Germany, UK, France (through a

reimbursed Early Access Program) and Italy. We continue to

advance access and reimbursement in nine other countries

including Spain, Portugal, and Switzerland. Following completion of

our post-approval commitments, we will seek full approval from the

European Commission.

In the U.S. we have initiated ConfIdeS, a pivotal phase 3 study to

support the submission of a Biologics License Application (BLA).

The ConfIdeS trial is currently enrolling patients and the Company

expects to submit a BLA for accelerated approval in 2024. Given

that 10-15% of patients waiting for a kidney transplant in the U.S.

are considered highly sensitized, the approval and availability of

Idefirix

®

would be an important option for these patients.

Beyond Europe and the U.S., the Company is exploring commercial

opportunities for Idefirix in markets where the EMA approval can be

leveraged to gain approval and market access.

2.

Advance ongoing imlifidase clinical programs in

transplantation and autoimmune diseases

We have an ongoing clinical program in phase 2 in AMR and GBS as

well as we end of December 2022 initiated a pivotal phase 3 program

in

anti-GBM.

In active AMR, we are investigating imlifidase in acute and chronic acute

AMR episodes post kidney transplantation. Today there is no approved

drug in this indication. AMR episodes occur in 5-7%

1

of patients and is

a significant challenge to long-term graft survival.

In November, 2022, Hansa announced top-line data from the imlifidase

phase 2 study in AMR post kidney transplantation, demonstrating a

statistically significantly difference of imlifidase versus plasma

exchange to reduce levels of donor-specific antibodies (DSAs) in the

five days following treatment. The full data set is expected to be

announced in the second half of 2023.

We also have two ongoing clinical-stage programs in rare acute

autoimmune diseases – anti-GBM antibody disease and GBS. In

anti-GBM, we initiated a pivotal global phase 3 study at the first sites in

the U.S. end of December 2022 with the first patient expected to be

treated in the first half of 2023. Anti-GBM is an acute autoimmune

disease where antibodies are directed against an antigen intrinsic to the

glomerular basement membrane (GBM), causing acute injury of kidney

and/or lung function. Anti-GBM is an ultra-rare and very serious disease

that annually affects approximately 1.6 people per million worldwide.

In 2022 key data from the investigator-initiated phase 2 trial were

published in the Journal of American Society of Nephrology (JASN)

showing that two-thirds of patients achieved dialysis independence six

months after treatment with imlifidase, compared to typically two-thirds

of patients losing their kidney function and ending up on dialysis after

six months. The positive data from the phase 2 trial supported a new

pivotal study targeting 50 patients with anti-GBM disease across 30-40

sites in the U.S., U.K., and Europe.

We are also developing imlifidase for the treatment of GBS for which

we have an ongoing clinical program in phase 2 targeting 30 patients at

ten centers across the U.K., Netherlands and France. GBS is an acute

autoimmune attack on the peripheral nervous system, which affects

approximately 1 in 100,000 people

2

.

Completion of enrollment in the GBS trial is anticipated in the first half

of 2023 with a first high level data read-out expected in the second half

of 2023.

3.

Expand IgG-cleaving enzyme technology

platform into new disease areas and indications

As part of Hansa Biopharma’s platform strategy and objective to

broaden the application of imlifidase as a potential therapy to

change the course of IgG-mediated immunological diseases, the

Company has in recent years started to explore new therapeutic

areas, where our IgG antibody-cleaving enzyme technology platform

would have relevance to address indications with a high unmet

medical need indications both through Investigator-Sponsored Trials

(IST) programs and Hansa-Sponsored Trials.

In gene therapy, Hansa is working with two partners, Sarepta

Therapeutics and AskBio (Bayer AG) in three programs, namely

DMD, LGMD and Pompe disease, where imlifidase is being

evaluated as a potential pre-treatment to gene therapy in patients

with pre-existing neutralizing antibodies (NAbs) against adeno-

associated virus (AAV). Nabs against the AAV-based vector

commonly used in gene therapies remain a major challenge and

make these patients ineligible to receive gene therapy treatment.

We see significant potential for our antibody-cleaving enzyme

technology to help overcome this barrier.

Another major therapeutic area Hansa is looking into, is oncology,

where one of the key indications Hansa intends to explore further is

allogeneic hematopoietic stem cell transplantation (HSCT), also

known as “bone-marrow transplantation”. Anti-HLA antibodies

against the donor may prevent the successful engraftment of donor

cells in a patient requiring allogenic HSCT. Desensitization treatment

of patients with high levels of donor specific antibodies (DSA) prior

to allogeneic HSCT transplant is a challenge where imlifidase may

have the potential to transform the standard of care by enabling

clinicians to inactivate DSAs prior to transplantation, thus having the

potential to enable successful transplantation.

Lastly, we are aiming at developing next generation IgG-cleaving

enzymes with the objective of enabling repeat dosing across our four

franchises and where patients may benefit from more than one dose

of an IgG-modulating enzyme (e.g., dealing with flares). HNSA-5487

has been selected as our lead IgG-eliminating enzyme candidate

from the NiceR program. Following the completion of IND enabling

toxicology studies and a CTA, which subsequently was approved, it

is our intention to initiate a clinical trial for HNSA-5487 during the

first half 2023.

Our strategic priorities

continued

1

Puttarajappa et al., Journal of Transplantation, 2012, Article ID 193724

2

McGrogan et al., ”The Epidemiology of Guillain-Barré Syndrome Worldwide“, Neuroepidemiology;2009, 32(2):150-63

15

16

Helping highly sensitized patients

who cannot access a kidney

18

Highly focused and sequenced launch strategy

20

Ongoing market access processes

21

Interview: Providing a new opportunity to a

growing number of highly sensitized patients on

kidney transplants lists

23

Interview: Building experience with imlifidase-

enabled kidney transplantations

Overview

Strategy

Technology

Growth

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Market

Market

3

Helping highly sensitized patients

who cannot access a kidney

The kidney transplantation landscape

According to the Global Observatory on Donation and

Transplantation there are approximately 170,000 patients in

the U.S. and Europe, alone, waiting for a new kidney.

However, given that organ availability continues to be a

limiting factor, only approximately 50,000 kidney transplants

are performed in these markets, of which, roughly 73% are

from deceased donors

1

.

During the last few years, transplantation and organ

donation rates in Europe experienced a significant decline,

mainly due to the pandemic, as the Covid-19 outbreak posed

unique challenges for both organ procurement and

transplantation, and the fact that a large number of

transplant centers would not allow the use of deceased

donor organs with evidence of previous infection or

exposure. The U.S. experienced less of a decline compared

to Europe due to a series of new initiatives implemented

including the acceptance of organs from a higher age group

than previously included, and from individuals who died of

cardiorespiratory failure.

A subgroup of kidney transplant patients, representing

between 10-15% of those waiting for kidney transplantation

1

,

are so-called highly sensitized. This means that these

patients are highly sensitized against potential donor tissues

due to prior exposure to foreign antigens during pregnancy,

after blood transfusions, from previous organ

transplantations, or, in rare cases, infections. The presence

of donor specific antibodies is either an absolute or relative

contraindication, depending on the breadth and strength of

the antibody response. For this group of patients with a wide

range of anti-HLA antibodies, it is extremely difficult to find a

compatible donor.

In 2020, the European Commission granted a conditional

approval in the European Union for Idefirix

®

(imlifidase),

representing the first conditionally approved treatment for

adult patients waiting for a kidney transplant who are highly

sensitized against tissue from the donor and who have a

positive crossmatch test against an available kidney from

deceased donor. The basis for this conditional approval was

based on two completed phase 1 studies in healthy subjects

and four completed phase 2 studies in highly sensitized

kidney patients. In total, 53 healthy subjects have been

exposed to imlifidase and 46 patients were transplanted

after imlifidase treatment. Post-hoc analyses of the data,

pooled from all studies, showed that 43 out of a total of 46

patients had a functioning kidney six months after

transplantation. A post approval efficacy study (PAES) in 50

highly sensitized patients in Europe was initiated in 2022 and

will run in parallel with the commercial launch until 2025 at

the latest. The PAES will support integrating the commercial

and scientific approach and help broadening the clinical

experience with imlifidase.

~50,000

Transplants performed across U.S.

and Europe in 2021

73% of kidneys from deceased donors

10-15%

Highly sensitized patients

awaiting kidney transplant

~170,000

Total number of patients

waitlisted in 2021

across U.S./EU

2021

2020

2019

2018

5,234

18,410

6,867

17,406

6,442

15,561

5,811

14,827

5,971

19,519

2017

8%

3%

*

10%

7%

4%

23,644

24,273

22,003

20,638

25,490

Up to 15% of the patients waiting for a new

kidney are highly sensitized

~50,000 transplants are done annually across

the U.S. and Europe

Breakdown of the kidney transplant waitlist in U.S. and EU

1

U.S. annual kidney transplants

13%

22%

*

1%

3%

2%

5,824

7,766

7,820

7,565

2020

7,400

2021

2019

2018

2017

21,826

24,700

28,053

27,917

27,075

Highly focused and sequenced

launch strategy

Our European launch strategy

Idefirix

®

is the first and only treatment approved in Europe for

desensitization treatment of highly sensitized patients. The

introduction of this potential transformative drug is viewed by

many leading experts, clinicians and payers as enabling a

paradigm shift towards equity of access for highly sensitized

patients to potentially lifesaving and life altering kidney

transplants. To reach this goal we work closely with the

transplant community to reshape the area of desensitization

and integrate Idefirix

®

into clinical practice as a new standard

of care.

As part of our launch strategy, we are initially focused on

targeting leading centers with the potential to become

centers of excellence. At Hansa, we believe that the long-

term market uptake of this innovative therapy is highly

dependent on successful early experiences in key early

adopter centers. It is critical for a successful launch of

Idefirix

®

, that positive outcomes are generated in the first

patients and for clinical centers to build the foundation

necessary for expanded use of Idefirix

®

as a potential new

“Gold Standard” in desensitization protocols.

Our anticipated “S”-shaped launch curve reflects this careful

approach in the initial years of commercialization until more

accelerated growth occurs, which is anticipated mid-term, as

the Company expands beyond the first wave of early-launch

countries and leading clinics, leverages the full potential in the

five largest European markets and prepare for a U.S. launch,

following FDA approval. Longer term, Hansa may consider

expanding the label to include other solid organs such as heart

and lung and living donor transplantation.

During 2022, Hansa secured positive pricing and

reimbursement decisions in four of the five largest markets

- the U.K., Germany, Italy and France, through a reimbursed

early access program. In total, market access has now been

secured in eleven countries, while market access procedures

are ongoing in nine countries including Spain,

1

which

represents the last of the five major European markets.

1

A positive recommendation for pricing and reimbursement of Idefirix

®

published on February 6, 2023 https://www.sanidad.gob.es/profesionales/

farmacia/pdf/20230202_ACUERDOS_CIPM_230.pdf

Initial years of commercialization

Illustrative

Mid term

Longer term

1.

Build the foundation for Idefirix

®

in EU to

become a new Standard of Care

>

Commercialize in early-launch countries focusing on

leading clinics and early adopters

>

Secure Pricing and Reimbursement agreements

>

>

>

engagement, patient organizations and medical

conferences

>

approval and establish long-term outcomes

Expanding internationally will lead to more

accelerated growth mid term

early-launch centers and in the five largest markets

after completing market access

ConfIdeS study and FDA approval

Support patient and organ access for highly

sensitized patients

Potential label expansion may enable

new growth pockets longer term

Commercialize in AMR in kidney upon potential approval

transplantations such as heart and

Sales initially remain “low and volatile” between

quarters during the initial launch years until early

to

become a new SoC

Market access has now been secured in

eleven European countries and procedures

are ongoing in nine countries including

Spain

2

, which represents the last of the

five major European markets

Unit

ed Kingdom

2,917

Transplants

1

Germany

1,992

Transplants

1

France

3,252

Transplants

1

Spain

2,950

Transplants

1

Italy

2,043

Transplants

1

1

Annual kidney transplantations 2019 (pre COVID-19)

and Transplantation, 2019

A positive recommendation for pricing and reimbursement of Idefirix

Spain was published on February 6, 2023 https://www.sanidad.gob.es/

profesionales/farmacia/pdf/20230202_ACUERDOS_CIPM_230.pdf

Israel

Providing a new opportunity to a growing number of

highly sensitized patients on kidney transplants lists

In 2022 Hansa secured pricing and reimbursement

for Idefirix

®

in several key European countries – how

did you do it?

A

. Pierre-Henri:

We made significant progress

commercialising Idefirix

®

in Europe last year. We have a

product, we were able to expand our footprint in key

markets in Europe. Inclusive of all national authorizations,

reimbursement in eleven European countries including four

of the five largest markets. Additionally, we secured

progress outside of Europe. Currently, we have access and

Idefirix

®

Why is achieving access in the five largest markets in

Europe important to the success of Idefirix

®

?

A

.

Pierre-Henri:

Achieving reimbursement in the five most

populated countries in Europe is an important objective

and a priority in our European launch strategy, as it secures

access to Idefirix

®

for a significant portion of European

highly sensitized patients. Germany, UK, France, Italy, and

performed in Europe.

2

specialised centres with the capability to include Idefirix

®

Beyond these five markets, how are you

progressing commercialisation efforts in Central

and Eastern Europe?

Pierre-Henri:

Pierre-Henri Patin, VP Commercial Europe, and Gina Ewy, VP Global Market Access

Q

.

Gina, as the VP of Global Market Access you and your

team are involved in every step of the pricing and

reimbursement negotiations. What are you hearing

from regulators and health decision makers?

A.

Gina:

We believe the progress we’ve made in several

countries in Europe is largely due to our ability to

demonstrate the high unmet need of highly sensitized

transplant patients and the clear value that Idefirix

®

can

bring to this patient population. Regulators and decisions

makers recognise the important role Idefirix

®

can play in

enabling patients to receive a life altering kidney

transplant and eliminate the need for timely and costly

dialysis treatments. I think the recommendation by NICE

in the UK is a great example where the unmet needs of

highly sensitized kidney transplant patients drove the

conversation resulting in reimbursement and access of

Idefirix

®

for patients and clinicians

Q

.

You mentioned the value of Idefirix

®

in providing the

opportunity for lifesaving kidney transplantation.

Can you elaborate on this?

A

.

Gina:

Transplantation is the preferred treatment for all

chronic kidney disease patients. This includes many

highly sensitized patients, who currently have very few

chances to receive an organ offer due to the presence of

donor specific antibodies. By rapidly inactivating

Immunoglobulin G, Idefirix

®

enables an otherwise

incompatible kidney transplant to occur. Clinical evidence

confirms that successful kidney transplants are

associated with a better survival and quality of life

outcomes compared to remaining on dialysis

3,4

. Idefirix

®

works alongside allocation systems to increase equity in

access to transplant for highly sensitized patients, who

otherwise have little to no hope for a transplant due to

sensitization status.

Q

. Considering the countries Pierre-Henri mentioned,

how many highly sensitized patients could potentially

be eligible for Idefirix

®

?

A

.

Gina:

In Europe, the classification of highly sensitized

patients and eligibility vary from country to country and is

dependent on the allocation system. Highly sensitized

patients account for approximately 10% to 15% of

patients waiting for kidney transplants.

5

This number is

even higher in some countries including Spain where one

patient in five, so 20% is classified as highly sensitized

against potential donor tissues.

These are patients in

urgent need of innovative treatments as they have so far

been unable to find a suitable donor and have been left

on transplant waiting lists. With these authorizations in

place, a growing number of highly sensitized patients can

be considered for transplantation from a deceased donor

with the use of Idefirix

®

.

Dr Lucrezia Furian, Associate Professor of Surgery, Department of Surgical Oncological and Gastroenterological Sciences,

University of Padova, Italy, shares her experience in performing the first imlifidase-enabled kidney transplantation in Italy.

1

Q

.Dr Furian, you and your team at the University Hospital

of Padova recently performed a successful kidney

transplantation following desensitization with

imlifidase in a highly sensitized patient. Can you tell

us more about this?

A

.

On November 1st, 2022, following desensitization with

imlifidase we were able to successfully perform a kidney

transplantation in a very highly sensitized patient who had

been on dialysis for almost 14 years and had previously

rejected another donor kidney. The patient is doing well and

at home with their family. This is a great example of how

new innovative treatments can help patients who may

previously had little to no other treatment options.

Q

.How important was it to appropriately and

effectively desensitize the patient before

attempting transplantation?

A

.

Achieving an effective desensitization through a rapid

inactivation of IgG, and specifically of pre-formed donor-

specific antibodies, was crucial to enable transplantation.

The patient had been listed in the national kidney allocation

system for many years, and still it took 14 years to be able to

perform a transplant due to their significantly high level of

sensitization. We were able to successfully perform the

transplant because of the almost complete inactivation of

pathogenic antibodies using imlifidase. Without imlifidase

we would not have been in the position to offer this patient a

kidney transplant.

Q

.Why was this patient so immunologically complex and

why was it decided to treat this candidate?

A

.

For some kidney patients, identified as highly sensitized,

finding a compatible donor is particularly challenging.

These patients present antibodies against potential donors,

usually developed following a previous transplant, blood

transfusion or pregnancies. Therefore, those patients are

often waiting a long time for a suitable organ. The patient we

decided to treat with imlifidase presented all these

complexities. We knew it was going to be challenging, but

we also knew that this patient had high unmet need and

was left with no other treatment option.

Q

.You are also one of the authors of the European Society

for Organ Transplantation’s (ESOT) guidelines for

desensitization. How important is it to have a

comprehensive desensitization strategy in place that

physicians can use to predict and address potential

problems in the treatment of highly sensitized patients?

A

.

Imlifidase, although crucial, is not sufficient without a

thorough desensitization and post-transplant strategy.

After years of research, we believe we have refined this

approach for the best patient outcomes. Together with

other leaders in the field, we have worked with ESOT to

develop the first international consensus protocol,

published in 2022. It took us four years of research to be

able to define a deimmunization protocol suited for

treating highly sensitized patients such as this one. Now

we have a potent tool at our disposal, and a protocol

defined by experts to maximise our chances of success.

Q

.The picture you’re depicting is that of an advancement

in renal transplantation, do you see this as a pathway

to new opportunities for highly sensitized patients?

A

.

Highly sensitized kidney transplant patients have so far lived

with limited to no hope of receiving a kidney transplant. With

the introduction of new treatment options and approaches,

we can address the unmet need in of these patients. It is

also critically important to ensure we identify appropriate

candidates who can benefit the most from this

desensitization treatment, and that clinicians are familiar

with the desensitization guidelines to ensure that

appropriate protocols are put in place to manage these

patients during and after transplantation.

In medicine, there are no silver bullets. There is hard work,

innovation, and forward progress that create new options

for better patient outcomes particularly in those cases

where there remains high unmet need. I think the success

we had with the highly sensitized patient at the University

Hospital of Padova is a good example of where innovation

has given hope.

.

24

25

The role of immunoglobulin antibodies

26

Imlifidase – a novel approach to eliminating pathogenic IgG

27

Progress of IgG-modulating technologies

28

Our unique antibody cleaving enzyme technology may have

relevance across a range of indications

30

Intellectual property rights and orphan drug designations

Overview

Strategy

Market

Growth

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Technology

4

Technology

An immune response begins with the recognition of a pathogen

or foreign molecule, followed by a reaction to eliminate it

The role of immunoglobulin antibodies

IgM

IgG

IgA

IgE

IgD

0.002%

Antibody of allergy

and anti-parasitic

activity

1%

B Cell Receptor

13%

Secreted into mucus,

tears, saliva

80%

Main blood

antibody,

neutralizes toxins,

opsonization

6%

% of total

antibody

in serum

Function

Primary response,

fixes complement.

Monomer serves as

B-cell receptor

A wide variety of immune cells and molecules

are involved in the development of immune

responses. Antibodies, also known as

and used by the immune system to recognize

and eliminate pathogens or other foreign

material. Each antibody binds to one of many

molecules on the microorganism’s surface,

antibodies for a given pathogen.

Imlifidase – a novel approach to eliminating pathogenic IgG

Imlifidase’s

Mode of Action

is that it very

rapidly and effectively cleaves

Immunoglobulin G (IgG) within 2-6 hours from

a 15-minute infusion. The IgG is cleaved

below the so-called ‘hinge region’, creating

an F(ab’)2 and an Fc component.

After treatment, intact IgG levels will drop below detectable

levels and stay supressed for approximately 5-7 days, creating

a window for a kidney transplantation before it gradually returns

back to normal levels during the weeks following treatment. The

imlifidase enzyme is highly specific to IgG and all subclasses of

IgG and has been demonstrated to not affect other Ig-isotypes.

Imlifidase is an enzyme originating from a human pathogen, a bacterium called

Streptococcus pyogenes

which is a species of Gram-positive, spherical bacteria in

the genus

Streptococcus

and is usually known for causing a strep throat infection

Rapid onset of action that inactivates IgG below

detectable level in 2-6 hours from a 15-minute infusion

IgG antibody-free window for approximately one week

Progress of IgG-modulating technologies

PLEX, plasmapheresis,

immunoadsorption

Mechanically removes antibodies

from circulation

B-cell depleting mAbs

Lowering antibody levels

through B-cell elimination

Proteasome inhibitors

Depletes antibody producing

long-lived plasma cells and lowers

overall immunoglobulin levels

IV/SC immunoglobulins

IVIg/SCIg contains healthy

antibodies that replaces

pathogenic antibodies

Complement inhibitors

Prevents binding of

complement protein to

antibodies

FcRn-inhibitors

Lowering IgG through

blocking of antibody

recycling

1950s

1980s

1990s

2000s

2010s

2020s

Mechanisms can be both complementary and competing

Imlifidase – IgG-cleaving enzyme

Deactivates IgG within 2-6

hours through enzymatic

cleavage. IgG-free window

for approximately one week

Unique mechanism-of-action

is the basis for competitive

advantage vs other IgG-

modulating therapies

FC

F(ab’)

2

Imlifidase

Complement

binding to IgG

Complement

inhibition

Cell lysis

Our proprietary antibody-cleaving enzyme

technology platform targeting pathogenic

antibodies is at the core of our business. To

sharpen our focus and commitment toward

advancing Hansa’s platform beyond kidney

transplantation, we have established four

distinct franchises in transplantation,

autoimmune diseases, gene therapy and

oncology/new therapies.

Imlifidase is designed to inactivate IgG antibodies in both

plasma and tissue, with a single intravenous treatment in

monophasic autoimmune diseases, transplantation, and gene

therapy. We are also developing a second generation of

IgG-cleaving enzymes under the umbrella “NiceR”. The new

enzymes are designed to have lower immunogenicity, thereby

potentially enabling multiple administration for inactivation of

flares in relapsing diseases. Specifically, we completed IND

enabling toxicology studies at the end of 2022 for the lead

NiceR candidate HNSA-5487. A CTA approval has since been

obtained and we expect to start a clinical trial in the first half

2023. These new enzymes could potentially open a new

treatment paradigm in a broad range of indications.

In addition to identifying the most relevant indications for our

enzymes, we are also exploring how our unique antibody-

cleaving enzyme technology potentially can be used in

combination with other technologies targeting IgG antibodies.

For example, FcRn inhibitors, which do not give the same rapid

and effective response as imlifidase but can be useful for

long-term management in indications known to be driven by

disease-causing IgGs.

Our unique antibody cleaving enzyme

technology may have relevance across

a range of indications

28

Overview

Strategy

Market

Growth

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Technology

GBS

Anti-

GBM

Kidney

Trans-

plantation

EU

AMR

Kidney

Trans-

plantation

U.S.

Duchenne

Limb-

Girdle

Pompe

EnzE

HCST

(Bone

Marrow)

OUR VISION

TODAY

Targeting rare IgG mediated diseases

Expanding our

commercial franchises

Regulatory approval (conditional)

Partnership (preclinical development)

Potential indications (currently not pursued)

Intellectual property rights and

orphan drug designations

Hansa aims at securing broad patent and

related IP protection for our current and

future products and treatments developed

within our technology platform.

The Company’s patent and related IP position is global, and

covers markets deemed to be of critical clinical, manufacturing

and commercial relevance for the product pipeline. As our

technology platform further develops, we will pursue new

patent and related IP filings.

Our IP portfolio currently includes patent families related to

imlifidase and its use, with coverage up to 2035, in key

markets. Geographically, these patent families cover a large

number of jurisdictions, including the U.S., Europe and Japan.

Our lead product, imlifidase, is protected by six patent families

including both granted patents and pending applications and

cover the use of isolated imlifidase. The most significant patent

families protecting imlifidase and its use provides basis for

extended patent term extensions (PTEs), which are available in

certain major markets, including the U.S. and the EU (as

supplementary protection certificate, SPC). The term of the

PTE/SPC can vary from zero to maximum five years,

depending on the time taken to obtain marketing approval.

Patents with expirations up to 2035 can be extended up to five

years via available patent term extensions.

In addition to patent and IP related protection, the Company

continuously evaluates the opportunities for market exclusivity

for drug candidates through orphan drug designations and

data exclusivity.

Orphan drug designation is granted to therapies aimed at

treating life-threatening or chronically debilitating rare diseases

where no therapeutic options are either authorized, or where

the drugs will be of significant benefit to those affected by the

condition. Rare diseases are those defined as having a

prevalence of no more than five in 10,000 persons in Europe or

affecting less than 200,000 patients in the U.S. The designation

provides development and commercial incentives, including

ten years of market exclusivity in the EU and seven years in the

U.S., protocol assistance on the development of the drug,

including clinical studies and certain exemptions from or

reductions in regulatory fees.

Since 2017, Hansa has been granted five orphans drug

designations by EMA/EC and the FDA across transplantation,

anti-GBM antibody disease and GBS (only FDA).

EMA/AC orphan drug designation

>

Imlifidase for the prevention of graft rejection

following solid organ transplantation (2017)

>

Imlifidase for the treatment of the rare and acute

disease anti-GBM (2018)

Since 2017, Hansa has been granted

five orphans drug designations by

EMA/EC and the FDA across

transplantation, anti-GBM antibody

disease and GBS (only FDA)

FDA orphan drug designation

>

imlifidase for the prevention of antibody-mediated

organ rejection in solid organ transplantation (2015)

>

imlifidase for the treatment of Guillain-Barre

Syndrome (2018)

>

imlifidase for the treatment of the rare and acute

disease anti-GBM (2018)

31

Overview

Strategy

Market

Technology

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

Growth

Growth

32

Our development programs

33

Continuous progress in our ongoing clinical programs

34

U.S. randomized control trial “ConfIdeS”

36

Interview: Hansa’s Post Authorization Efficacy Study (PAES)

in highly sensitized kidney transplant patients

37

Opportunities beyond kidney transplantation

38

Hansa’s antibody cleaving enzyme technology

40

Active antibody mediated rejection (AMR)

41

Guillain-Barré Syndrome (GBS)

42

Exploration of Hematopoietic Stem

Cell Transplantation (HSCT)

5

Our development programs

Broad clinical pipeline in transplantation and autoimmune diseases

Research/

preclinical

Phase 1

Potentially pivotal/

Phase 2

Phase 3

Marketing

authorization

Marketed

Next anticipated

milestone

Imlifidase

EU: Kidney transplantation in highly

sensitized patients

1.2

EU: Additional agreements around

reimbursement / Post approval study

to be completed by 2025

U.S.: Kidney transplantation in highly

sensitized patients

1.2

Completion of enrollment (64 patients)

H1 2023

Anti-GBM antibody disease

3

First patient enrolled (50 patients)

Antibody mediated kidney transplant

rejection (AMR)

Full data read-out H2 2023

Gullain-Barre Syndrome (GBS)

Completion of enrollment

(30 patients) H1 2023

Pre-treatment ahead of gene therapy in

Duchenne (Partnered with Sarepta)

Preclinical research

Pre-treatment ahead of gene therapy in

Limb-Girdle (Partnered with Sarepta)

Initiate clinical study of imlifidase as

pre-treatment in DMD 2023

Pre-treatment ahead of gene therapy in

Pompe disease (Partnered with AskBio)

Preclinical research

NiceR

Recurring treatment in autoimmune diseases,

transplantation and oncology

Initiate Phase I study of HNSA-5487

(Lead NiceR candidate) H1 2023

EnzE

Cancer immunotherapy

Research

>

30/30 patients enrolled in the AMR

phase 2 study

>

Data read out demonstrates a statistically

significantly superior capacity of

imlifidase to rapidly reduce levels of

DSAs compared to plasma exchange

(SoC) in the five days following the start

of the treatment

>

Full data read out expected H2 2023,

which will determine the path forward for

imlifidase in patients with active AMR

Antibody Mediated Rejection

phase 2

>

New pivotal Phase 3 study initiated in first

sites in the U.S and U.K. end of 2022

>

Open label, randomised controled study

targeting 50 patients to be treated with

imlifidase and SoC or SoC alone

>

Kidney function (eGFR) will be evaluated

as the primary endpoint

>

The first patient is expected to be enrolled

in H1 2023

Anti-GBM

phase 3

>

25/30 patients enrolled in the GBS

phase 2 study

>

10 centers are active and open for

recruitment

>

Aim to complete enrolment of GBS

patients H1 2023

>

Aim to communicate first high-level data

read out in H2 2023

Guillain-Barré Syndrome

phase 2

>

51/64 patients enrolled for randomization

>

13 centers active and open for

recruitment; continously adding new

clinics, with a goal of at least 20, to

further increase entollment capacity

>

Expect to complete enrollment H1 2023

and complete randomization in H2 2023

>

BLA submission is expected in 2024

under the accelerated approval path

U.S. ConfIdeS trial in kidney

transplantation phase 3

Enrollment status February 1, 2023

Completed

5

25

13

51

Patients enrolled

Patients remaining

Initiated

Continuous progress in our

ongoing clinical programs

U.S. randomized control trial “ConfIdeS”

The ConfIdeS trial is evaluating imlifidase

as a potential desensitization therapy to

enable kidney transplants in highly

sensitized patients waiting for a

deceased donor kidney through the

U.S. kidney allocation system.

The trial is expected to randomize 64 highly sensitized

kidney transplant patients with a cPRA of ≥99.9%,

representing a subset of very highly sensitized patients that

continue to be disadvantaged despite prioritization under

the U.S. kidney allocation system. When a donor organ

becomes available and a positive crossmatch with the

intended recipient indicates that the organ is not

compatible, the patient will be randomized to either

imlifidase desensitization treatment or to a control arm

that will receive standard of care (i.e. waiting for a more

compatible kidney offer or receiving an experimental

desensitization treatment). The study’s primary endpoint

for imlifidase to evaluate benefit in transplanting highly

sensitized patients is kidney graft function at 12 months,

measured by eGFR (estimated Glomerular Filtration Rate).

Robert A. Montgomery, M.D., Professor of Surgery and

Director, NYU Langone Transplant Institute in New York

City, has been appointed National Coordinating Investigator

for the ConfIdeS trial. The trial will enroll patients at up to

20 leading transplantation centers in the U.S (13 leading

centers were active on December 31, 2022).

Completion of enrollment in the study is expected in the

first half of 2023, while randomization is aimed for

completion by the second half of 2023. Following a

12-month follow-up period, results are expected to support

a BLA under the accelerated approval pathway in 2024, as

previously guided.

In addition to the ongoing ConfIdeS trial in kidney

transplantation, Hansa is also carrying out a post approval

efficacy study (PAES) in parallel with the commercial launch

in Europe. The PAES was initiated in July 2022 and is an

obligation under the European conditional marketing

authorization and will be used to further investigate the

long-term graft survival in 50 highly sensitized kidney

transplant patients treated with Idefirix

®

. The PAES is

expected to be completed by end of 2025, at the latest.

In addition to this, a long-term follow-up study is also done

in patients who have undergone kidney transplantation after

imlifidase administration as part of the four phase two

studies. In 2021 the three-year follow-up data was published

demonstrating graft survival of 84% after imlifidase

treatment and transplantation and a mean eGFR of 55 mL/

min/1.73 m2, which is in line with expectations in imlifidase

treated transplant patients compared to outcomes in

patients undergoing HLA-incompatible transplantation.

The next read-out on the long-term follow-up trial is

expected in the second half 2023, when the five-year data

is expected to be published.

Lastly, Hansa is conducting a rebound study in patients

treated with imlifidase prior to kidney transplantation. The

study aims at including twelve patients to assess whether

imlifidase, in combination with bortezomib, belatacept,

rituximab and IVIg, can suppress DSA and the occurrence

of AMR in highly sensitized crossmatch positive patients

undergoing living or deceased donor transplantation.

34

Overview

Strategy

Market

Technology

New

opportunities

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

159

1,204

0

43

2,619

726

268

372

0

57

41

166

179

86

218

172

615

218

506

397

580

910

316

1,041

168

577

124

371

296

674

285

764

736

86

1,684

1,579

5

243

540

20

26

41

3

463

296

0

41

371

Cedars Sinai

Keck Hospital of USC

Houston Methodist Hospital

Saint Barnabas Medical Center

Washington University

School of Medicine

UAB Hospital

Methodist Specialty &

Transplant Hospital

MedStar Georgetown

Hospital of the University

of Pennsylvania

John Hopkins

Columbia University

Hospital

NYU Langone

Northwestern Memorial Hospital

41

1

2019 data from Organ Procurement & Transplantation Network

2

United Network for Organ Sharing

3

EDQM. (2020). International figures on donation and

Transplantation 2019 and SRTR Database and individual

assessments of allocation systems

U.S. randomized control trial “ConfIdeS”

continued

Q

.Why is Hansa conducting a post-authorization efficacy

and safety trial?

A

.

Jan:

In 2020, Hansa received a conditional authorization

by the European Commission for Idefirix

®

. With that

authorization came the obligation to run a post-

authorization efficacy study, a confirmatory trial. The

PAES we are now running is a truly international European

study, involving patients and transplant centers across

many different European countries. Its completion will

allow us to collect the necessary evidence to turn the

conditional authorization in the European Union into a full

marketing authorization by the end 2025 at the latest.

Q

.Can you describe the trial design? What’s its

advancement status?

A

.

Lina:

The study is set to include a total of 50 patients

across 20 centers in Europe. The patients will receive

imlifidase and subsequently undergo a kidney

transplantation. As of February 2023, thirteen sites are

open for recruitment with several imlifidase-ready patients

having been identified. End of 2022 seven patients have

been transplanted following desensitization with imlifidase.

Q

.What challenges does this trial pose?

A.

Jan:

Imlifidase represents a paradigm shift in the

management of highly sensitized kidney patients. With

imlifidase, we enable incompatible kidney transplantation

by turning a positive crossmatch to negative. That is done

by inactivating the donor-specific antibodies with a broad

reactivity against human leukocyte antigens, which can

cause an immune response against non-self tissues such

as a donor’s organ. Historically, incompatible

transplantation has not been considered a viable option

and as a result, we must ensure desensitization is smoothly

integrated into the treatment process. This demands that a

high degree of coordination is ensured at transplant centers

early on in the initiation process with multi-disciplinary

teams being established.

Furthermore, since this is a cross-European trial, we work

with different regions and allocation systems and criteris for

sensitization. Importantly, we strive to accommodate

imlifidase at a country-by-country basis to complement the

allocation systems and local practices.

Another challenge comes with the complex immunological

status of the patients identified. With imlifidase we want to

provide an opportunity to those highly sensitized kidney

patients that so far have had very few or no chances to

receive a transplant due to their immunological status. Even

in the face of these complexities, we are seeing very

positive results, and this is thanks to the preparedness of

the treating physicians and the medical support we provide

to them.

Q

.From your description it seems that the collaboration

and communication with the transplant centres are

key to ensure the functioning of this trial. Can you

elaborate on that?

A

.

Lina:

Not only communication and collaboration, but also

proper preparation and support. We have established a

very good interaction with healthcare professionals from a

safety and initiation perspective, aimed at ensuring that they

are prepared when their transplant center starts enrolling

and possess the knowledge needed to start using imlifidase

in the an effective and controlled manner, in accordance

with the clinical trial protocol. This starts with the

collaboration with HLA laboratories, which assist in

identifying the best possible donor organ for a certain

patient, continues with the desensitization procedure, and

extends into the follow up during the post-operative phase.

Q

.Do you feel this approach is working? What is the

response you are seeing by healthcare professionals?

A

.

Lina:

Yes, we can definitively say that this approach has so

far been successful, and a good part of its success is

thanks to the unique commitment we see from physicians

themselves. Most of the professionals we are in contact

with through the trial have known imlifidase for long time

and are eager to use it, because ultimately, they are driven

by the desire to treat these highly sensitized patients who

have been left waiting for long time. They are aware of the

complexities that come with treating these patients, but this

doesn’t discourage them. On the contrary, they find being

able to assist these patients and accompany them through

the process very rewarding. They want to study, learn, and

perfect the procedure, they are truly involved and

committed, and we can see this in every meeting and

scientific exchange we have with them.

Jan:

Putting all these aspects together, we are confident

that this PAES trial will be beneficial for Hansa, the

transplant community, and, most importantly, for patients,

because we believe it will help build the knowledge

on imlifidase-enabled transplantations in Europe and further

strengthen the confidence on the role imlifidase can play in

enabling kidney transplant for those highly sensitized

patients with the highest unmet medical need.

Jan Tollermar, Senior Medical Director, Lina Nilsson Senior Clinical Resource Manager

Hansa’s Post Authorization Efficacy Study (PAES)

Opportunities beyond kidney transplantation

Hansa’s unique antibody-cleaving platform

may have relevance in numerous autoimmune

diseases, where IgG autoantibodies play

an important role

What is an Autoimmune disease?

>

Humoral or cell-mediated immune responses to self-antigens

(breaking of tolerance)

>

Requires genetic predisposition, and often triggered by viral,

bacterial and/or other environmental factors

>

3-5%

1

of populations affected; mainly women (75%)

2

Over 100

Multiple sclerosis, Neuromyelitis optica

Hashimoto’s disease, Graves’ disease

Rheumatoid arthritis, Dermatomyositis

Anti-GBM disease

Psoriasis, Pemphigus

Wegner’s granulomatosis

Guillain-Barré Syndrome, Myasthenia gravis

Crohn’s disease

Autoimmune hemolytic anemia, Immune thrombocytopenia

1

DeVrieze, B.W. and Hurley, J.A. Goodpasture Syndrome.

StatPearls Publishing, Jan 2021. https://www.ncbi.nlm.

nih.gov/books/NBK459291/ [accessed 2021-03-29]

2

Patel, M et al. The Prevalence and Incidence of

Biopsy-Proven Lupus Nephritis in the UK. Arthritis &

Rheumatism, 2006

3

Berti A, Cornec D, Crowson CS, Specks U, Matteson EL.

The Epidemiology of ANCA Associated Vasculitis in the

U.S.: A 20 Year Population Based Study. Arthritis

Rheumatol. 2017;69

4

Myasthenia Gravis. National Organization for Rare

Disorders, https://rarediseases.org/rare-diseases/

myasthenia-gravis/ [accessed 2021-03-29]

5

Guillain-Barré Syndrome. Orpha.net, https://www.orpha.

net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2103

[accessed 2021-03-29]

6

Chronic Inflammatory Demyelinating Polyneuropathy:

Considerations for Diagnosis, Management, and

Population Health. The American Journal of Managed

Care, https://www.ajmc.com/view/chronic-infammatory-

demyelinating-polyneuropathy-considerations-for-

diagnosis-management-and-population-health

[accessed 2021-03-29]

7

Marrie, R.A. The Incidence and Prevalence of

Neuromyelitis Optica. International Journal of MS Care,

2013 Fall: 113-118

8

Mehren, C.R. and Gniadecki, R. Epidermolysis bullosa

acquisita: current diagnosis and therapy. Dermatol

Reports, 2011-10-05

9

Wertenteil, S. et al. Prevalence Estimates for Pemphigus

in the United States. JAMA Dermatol, May 2019: 627-629

10

Immune Thrombocytopenia. National Organization for

Rare Disorders, https://rarediseases.org/rare-diseases/

immune-thrombocytopenia// [accessed 2021-03-29]

11

Warm Autoimmune Hemolytic Anemia. National

Organization for Rare Disorders, https://rarediseases.

org/rare-diseases/warm-autoimmune-hemolytic-

anemia/ [accessed 2021-03-29]

12

Litvinova, E. et al. Prevalence and Significance of

Non-conventional Antiphospholipid Antibodies in

Patients With Clinical APS Criteria. Frontiers in

Immunology, 2018-12-14.

Rapidly progressive

glomerulonephritis

Neurological

disorders

Skin

disorders

Blood

disorders

EBA

<1,000 patients*

8

Pemphigus

vulgaris

~40,000*

9

~10,000 patients*

5

Myasthenia

gravis

~210,000*

4

NMO

~20,000*

7

CIDP

~55,000*

6

~1,000 patients*

Lupus

nephritis

~35,000*

2

ANCA-

associated

vasculitis

~325,000

*3

AHA

<1,000 patients*

8

ITP

~75,000*

10

WAHA

~95,000*

11

APS

~350,000*

12

Clinical programs

Potential indications (currently not pursued)

Total disease populations in EU & US, based

on prevalence and population data

Chronic inflammatory demyelinating

polyradiculoneuropathy

Neuromyelitis optica

Epidermolysis bullosa acquisita

Immune thrombocytopenia

Warm antibody hemolytic anemia

Antiphospholipid syndrome

Acquired hemophilia A

Heparin‐induced thrombocytopenia

Acute Anti-GBM antibody disease

(Goodpasture’s disease)

Anti-GBM, a rare acute autoimmune disease affecting kidneys and lungs

GN is a leading cause for kidney disease

GNN

Glomerulonephritis (GNN)

Diabetic neuropath

Adult polycytic kidney

disease

Hypertonicity

Pyelonephritis

Uremia

Others

Anti-GBM (anti-glomerular basement membrane disease),

also known as “Goodpasture´s disease”, is an acute and very

severe inflammatory disease impacting the kidneys. For

largely unknown reasons, the immune system develops

IgG-antibodies that recognize a membrane associated

antigen in the kidney and sometimes, in the lungs. Anti-GBM

is one form of glomerulonephritis (GNN), which comprises a

number of inflammatory diseases in the kidney and is a

leading cause of kidney disease. In glomerulonephritis, the

inflammation starts in the glomeruli (filtering unit of the

kidneys) and the small blood vessels. The result is an acute

immune attack on these organs. In most cases, anti-GBM

antibody disease leads to significant loss of kidney function,

requiring chronic dialysis or results in death.

Anti-GBM is an ultra-rare disease that affects approximately

1.6 per million people globally, every year

(e.g. 1,000 cases

across EU and the U.S. annually). For one out of six

patients, anti-GBM can become fatal during the acute

phase of the disease, while the majority of patients will end

up on chronic dialysis

. Only one in three anti-GBM patients

will have a preserved renal function after six months with

current treatment

.

In March 2022, Hansa announced that key data from an

investigator-initiated phase 2 trial (GoodIdeS) of imlifidase to

treat anti-GBM disease were published in Journal of

American Society of Nephrology (JASN)

. The study, led by

Principal Investigator, Mårten Segelmark, Professor of

Nephrology at Lund University, previously Linköping

University, showed that two-thirds of patients achieved

dialysis independence six months after treatment as

compared to typically two-thirds of patients losing their

kidney function and ending up on dialysis after six months.

The publication recognizes the study’s significance in

autoimmune diseases as it suggests that deactivation of

autoantibodies could alter the course of an autoimmune

disease, allowing restoration of kidney function. These

positive results mark an important milestone for the

expansion of imlifidase outside transplantation and into

autoimmune diseases.

Following the successful data in the phase 2 trial we have

commenced a pivotal phase 3 with the first sites initiated in

December of last year. The new global study is an open-

label, 1:1 randomized, controlled study targeting 50 patients

to be treated with either imlifidase and Standard-of-Care or

Standard-of-Care alone at up to 50 sites in the U.S. and

Europe. Today’s Standard-of-Care consists of a combination

of plasma exchange, cyclophosphamide and steroids. For

patients randomized to the imlifidase arm, the first round of

plasma exchange after randomization will be replaced by the

administration of imlifidase.

As a primary endpoint, kidney function will be evaluated by

eGFR at 6 months from randomization, while anti-GBM

antibody levels, pulmonary symptoms, safety,

pharmacokinetic/pharmacodynamic (PK/PD) and health

related quality of life measures, among others, will be

assessed as secondary endpoints.

More information about the trial is available at:

ClinicalTrials.gov under NCT05679401 (2022).

Kluth et al. J Am Soc Nephrol. 1999 Nov;10(11):2446-53

Hellmark et al. J Autoimmun. 2014 Feb-Mar;48-49:108-12

Cohort of 13 studies (661 patients in anti-GBM 1993-2017) Treating anti-GBM disease with imlifidase Mårten Segelmark, Professor OF Nephrology

Kluth et al. J Am Soc Nephrol. 1999 Nov;10(11):2446-53 and Hellmark et al. J Autoimmun. 2014 Feb-Mar;48-49:108-12

Uhlin F. et al. JASN. 2022; https://jasn.asnjournals.org/content/early/2022/03/08/ASN.2021111460

the glomeruli

Early symptoms

Todays treatments

are inadequate

Growth

Active antibody mediated rejection (AMR)

Long term graft survival is challenged by AMR episodes post transplantation

Active antibody mediated rejection, or AMR, is a serious

condition after transplantation that occurs in roughly 5-7

1

%

of kidney transplants and is a significant challenge to

long-term graft survival. AMR is the main cause for graft

dysfunction and loss after kidney transplantation. Today’s

standard of care for AMR treatment includes plasma

exchange and treatment with steroids and IVIg. AMR

patients not treated successfully risk graft failure, dialysis

and return to the waitlist.

2

Hansa has run a randomized, open-label, multi-center,

controlled phase 2 study in AMR. 30 patients with acute or

chronic acute AMR were enrolled across centers in France,

Germany, Austria, Australia and the U.S. The study is

designed to evaluate the safety and efficacy of imlifidase in

eliminating donor specific antibodies (DSAs) in acute AMR

patients, post transplantation. Twenty patients were

randomized to receive imlifidase treatment comprised of one

intravenous dose of 0.25mg/kg, while 10 patients in the

active control arm received 5-10 sessions of plasma

exchange. Efficacy and safety are monitored over a 6-month

period, post treatment. More information about the trial is

available at ClinicalTrials.gov under NCT03897205 (2019).

In November 2022, Hansa announced positive topline data

from the AMR study demonstrating a statistically

significantly superior capacity of imlifidase to rapidly reduce

levels of donor-specific antibodies (DSAs) compared to

plasma exchange in the five days following the start of the

treatment. These first results are another important

milestone in executing on Hansa’s strategy to expand the

reach of our IgG antibody cleaving technology platform to

address significant unmet medical needs in a wide spectrum

of disease areas and indications. We plan to publish the full

dataset from the AMR study in the second half of 2023.

1

Puttarajappa et al., Journal of Transplantation, 2012, Article ID 193724

2

Puttarajappa et al., 2012; Jordan et al., 2015

PLEX (Multiple rounds)

Imlifidase

Illustrative

Guillain-Barré Syndrome (GBS)

Guillain-Barré Syndrome is an acute autoimmune attack

on the peripheral nervous system

GBS is an aggressive neurological disease of the peripheral

nervous system that affects 1-2 in 100,000 people, annually,

representing an addressable population of ~11,000 per year

in the seven major markets.

1

GBS is the most frequent cause

of acute neuromuscular weakness in the western world and

can affect anyone at any age and many patients deteriorate,

despite standard of care treatment.

Two thirds of GBS patients have severe symptoms, resulting

in an inability to walk unaided, and 20-30% require

mechanical ventilation for weeks or months

2

. While patients

are typically treated with either IVIg or plasmapheresis, a

significant unmet medical need remains, as not all patients

fully recover from GBS. Up to 40% of patients will lose

strength and have ongoing pain. Mortality is estimated at

between 3-5%.

3,4

Hansa is investigating imlifidase in an open-label, single arm,

multicenter phase 2 study evaluating the safety, tolerability

and efficacy of imlifidase in GBS patients, in combination

with standard of care intravenous immunoglobulin (IVIg). We

are targeting 30 GBS patients to be enrolled across clinics in

France, the UK and the Netherlands. GBS patients enrolled

in the study will receive a single dose of 0.25 mg/kg of

imlifidase and will be compared with a matched control

group of GBS patients treated with IVIg, from the

International GBS Outcome Study (IGOS) database.

Completion of enrollment in the GBS trial is anticipated H1

2023 with a first, high level data read out in the second half

of 2023.

1

Seven Major Markets Seven major markets include US, Germany, UK, France,

Spain, Italy, and Japan

Fletcher DD, Lawn ND, Wolter TD, et al. Long-term outcome in patients with

GuillainBarré syndrome requiring mechanical ventilation. Neurology

2000;54:2311–5

McGrogan et al.,” The Epidemiology of Guillain-Barré Syndrome Worldwide“,

Neuroepidemiology;2009, 32(2):150-63

van den Berg et al., 2014

Illustrative

Illustrative

Time from onset of weakness (weeks)

Infection

Course of GBS

Antibodies

Time from onset of weakness (weeks)

Infection

Course of GBS

Antibodies

Exploration of Hematopoietic Stem

Cell Transplantation (HSCT)

1

https://ashpublications.org/blood/article/134/Supplement_1/2035/427903/

One-and-Half-Million-Hematopoietic-Stem-Cell

2

Ciurea et al. The European Society for Blood and Marrow Transplantation

(EBMT) Consensus Guidelines for the Detection and Treatment of

Donor-specific Anti-HLA Antibodies (DSA) in Haploidentical Hematopoietic

Cell Transplantation. Bone Marrow Transplant. 2018;53(5):521-534. Available

at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232774/

Bone marrow cells from patients’ own body (no issues)

HLA-identical

sibling

HLA-matched

unrelated donor

Autologous HSCT

Haploidentical

donor

Allogenic HSCT

Pre-existing DSAs may result in primary graft failure and poor survival

after allogenic hematopoietic stem cell transplantation

43

Overview

Strategy

Market

Technology

Growth

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

New

opportunities

6

44

Imlifidase in gene therapy – an emerging opportunity

45

Systemic gene therapy is an emerging opportunity

46

Neutralizing antibodies are a barrier that precludes gene therapies

47

Collaborations in gene therapy with Sarepta and AskBio

48

Research and preclinical development projects

New

opportunities

Imlifidase in gene therapy – an emerging opportunity

Genetic disorders are caused by defective genes which fail

to produce a functioning protein. Gene therapy treatments

are designed to introduce genetic material into cells to

compensate for these non-functioning genes. Thus, if a

mutated gene causes an essential protein to be faulty or

missing, gene therapy may be able to introduce a normal

copy of the gene to restore the gene function to produce the

desired protein.

In order to transfer a healthy and functioning gene into a

cell, non-replicating and non-disease causing viruses,

usually adeno-associated virus vectors (AAVs), are utilized.

The transfer and insertion of the healthy gene and its vector

into a cell is called transduction.

There are vectors that can be administered locally to

selected target tissues including specific cells in the eye

and the brain. There are also vectors that can be distributed

systemically, targeting liver or muscle cells. Since most

people have been exposed to adenoviruses at some point in

their lives, there is a relatively high prevalence of preformed

antibodies against AAVs. The prevalence of those

antibodies varies significantly between the different type of

vectors and can be as high as up to 70% in the general

population (e.g. AAV 1)

1

. The presence of antibodies against

AAV blocks the transduction, thus preventing successful

gene therapy treatment in those patients. This means that a

substantial proportion of patients are excluded from the

possibility of having a potentially disease-curing gene

therapy treatment.

We believe that imlifidase has the potential to eliminate

antibodies which can bind and inhibit gene therapy, thereby

enabling effective transfer of a healthy gene sequence into

these patients. The concept of using imlifidase as a

potential pre-treatment to overcome pre-existing antibodies

to AAV-based gene therapy was highlighted in “Nature

Medicine,” in 2020

2

. In particular, highly encouraging results

from preclinical studies were published, demonstrating that

imlifidase could eliminate the blocking effect of NAbs

towards AAVs in a mouse model, in non-human primates, as

well as in human plasma samples from patients with

antibodies against AAVs.

1

Boutin et al (2010), Griffin et al (2019), Wang et al (2018), Calcedo & Wilson

(2013), Falese et al (2017), Haiyan et al (2017), Ellsworth et al (2018), Greig et

al (2017)

2

Leborgne, C., Barbon, E., Alexander, J.M. et al. IgG-cleaving endopeptidase

enables in vivo gene therapy in the presence of anti-AAV neutralizing

antibodies. Nat Med 26, 1096–1101 (2020). https://doi.org/10.1038/

s41591-020-0911-7

Antibodies prevent effective transfer of

Imlifidase is a unique IgG antibody-cleaving

with extremely high specificity

Nabs/IgG

IgG

F(ab’)2

Fc

Systemic gene therapy is an emerging opportunity

Rare monogenic diseases

From hundreds of patients to thousands of patients

DM-1

100,000

Astellas

Hemophilla

+55,000

Spark, BioMarin, uniQure,

Takeda, Pfizer, Freeline

Duchenne

20,000

Sarepta, Pfizer,

Astellas

OTC-

deficiency

20,000

Ultragenyx

SMA

+30,000

Novartis

Wilson

40,000

Viviet, Ultragenyx

Limb-

Girdle

20,000

Sarepta, Genethon,

AskBio

Fabry-

9,000

Freeline,

UniQure Sangamo

Pompe

10,000

Spark, AskBio,

Astellas

HAE

8,000

BioMarin,

Regenxbio

PKU

25,000

BioMarin

Late Preclinical

Clinical

Market

Preclinical programs with Sarepta and AskBio

Planned clinical study with Sarepta

Prevelance of Nabs in AAVs

AAV 1

AAV 2

AAV 8

AAV 6

AAV 7

AAV 9

AAV 5

Up to 10%

Up to 20%

Up to 30%

Up to 30%

AAV-rh74

AAV 4

CNS, Eye,Skeletal muscle

CNS, Eye,Kidney

Liver, CNS, Heart, Eye, Pancreas, Skeletal muscle

Liver, Skeletal muscle

Liver, Skeletal muscle

Heart, Liver, Lung, Skeletal muscle

CNS, Liver,

Lung Eye

CNS, Eye, Skeletal muscle

Up to 2%

CNS,

Lung, Eye

1

Source: Boutin et al (2010), Griffin et al (2019), Wang et al (2018), Calcedo & Wilson (2013), Falese et al (2017), Haiyan et al (2017), Ellsworth et al (2018), Greig et al (2017)

Neutralizing antibodies are a barrier

that precludes gene therapies

Up to 45%

Up to 60%

Up to 60%

Up to 70%

Collaboration with Sarepta Therapeutics

Since 2020 we have collaborated exclusively with Sarepta

Therapeutics to develop and promote imlifidase as a

potential pre-treatment prior to the administration of gene

therapy in Duchenne Muscular Dystrophy (DMD) and

Limb-Girdle Muscular Dystrophy (LGMD) in patients with

pre-existing NAbs to adeno-associated virus.

Under the terms of the agreement, Hansa received USD 10

million as an upfront payment and is eligible for up to USD

397.5 million in development, regulatory and sales

milestones, as well as royalties on any Sarepta gene therapy

sales enabled through pre-treatment with imlifidase in

NAb-positive patients. In addition, Hansa will book all future

sales of imlifidase when used as a pre-treatment.

The partnership is progressing as planned, with preclinical

investigations completed during 2022. In November 2022,

the two companies announced plans to initiate a clinical

study with imlifidase as a pre-treatment to Sarepta’s

SRP-9001 gene therapy in DMD in 2023. The announcement

followed an earlier release from Sarepta Therapeutics in

September 2022, in which Sarepta Therapeutics announced

that it had submitted a BLA to the U.S. FDA for the

accelerated approval of SRP-9001 to treat ambulant patients

with DMD.

In LGMD the collaboration is progressing as planned,

currently at a preclinical stage.

About Duchenne Muscular Dystrophy (DMD)

Duchenne muscular dystrophy is a rare genetic disease. It

predominantly affects males, but, in rare cases, can also

affect females. Duchenne causes the muscles in the body to

become weak and damaged over time and is eventually fatal.

The genetic change that causes Duchenne—a mutation in

the DMD gene—happens before birth and can be inherited,

or new mutations in the gene can occur spontaneously.

Muscle weakness becomes increasingly noticeable between

the ages of 3 and 5, and most patients use a wheelchair by

the time they are 12. During adolescence, heart and

breathing muscles weaken, leading to serious, life-threatening

complications. Duchenne affects approximately 1 in 3,500

to 5,000 males born worldwide. Approximately 15% of

patients have pre-existing IgG antibodies to AAVrh74.

About Limb-girdle muscular dystrophy (LGMD)

Limb-Girdle muscular dystrophy is a group of distinct

diseases that cause weakness and wasting of the muscles,

generally starting with the muscles around the hips and

shoulders and eventually progressing to the arms and legs.

However, some subtypes start distally at the leg or arm

muscles and then progress to the hip and shoulder muscles.

LGMD can be caused by a single gene defect that affects

specific proteins within the muscle cell, including those

responsible for keeping the muscle membrane intact. Taking

into account the various subtypes, limb-girdle muscular

dystrophy has a global prevalence of approximately 1.63 per

100,000 individuals worldwide. Over 30 subtypes exist, and

both genders are affected equally.

Collaboration with AskBio

Since January 2022 we have collaborated with AskBio

(subsidiary of Bayer AG), a fully integrated AAV gene therapy

Company dedicated to developing medicines that improve

the quality of life for patients with genetic diseases.

Collaborations in gene therapy with Sarepta and AskBio

To evaluate the feasibility of imlifidase as pre-treatment ahead of gene therapy for patients

with pre-existing neutralizing antibodies (NAbs) to adeno-associated virus (AAV)

The collaboration is designed to evaluate the potential use of

imlifidase as a pre-treatment prior to the administration of

AskBio’s gene therapy in Pompe disease in a preclinical and

clinical feasibility program for patients with pre-existing NAbs

to the adeno-associated viral vector used in AskBio’s gene

therapy. Under terms of the agreement, Hansa received a USD

5 million payment upon execution of the agreement and AskBio

has the exclusive option to negotiate a full development and

commercialization agreement following evaluation of the results

from an initial phase 1/2 study.

AskBio’s gene therapy candidate, AAV2/8-LSPhGAA, is being

investigated for the treatment of Pompe disease. This gene

therapy candidate combines AAV2 and AAV8 capsids, to

deliver a liver-specific promoter to express the GAA enzyme. It

is currently being investigated by AskBio in an open-label,

phase 1/2 study (ClinicalTrials.gov: NCT03533673), in which 8

patients with Late-Onset Pompe disease will be enrolled. For

further information regarding AskBio’s gene therapy program in

Pompe disease, please refer to www.askbio.com.

About Pompe disease

Pompe disease is a rare genetic, often fatal, disorder caused by

a defect in a gene making an enzyme called acid alpha-

glucosidase (GAA). GAA is used to break down glycogen (a

sugar used to store energy in cells) and a defect GAA enzyme

leads to accumulation of glycogen in the body’s cells. The

glycogen accumulation in certain organs and tissues,

especially muscles, liver and heart, severely impact normal

organ function. While enzyme replacement therapy (ERT) has

shown promise in patients with Pompe disease, no curative

therapy is available.

Pompe disease is estimated to affect 1 in 40,000 births in the

U.S.

1

, and equates to an incidence of ~200 per year in the U.S

and Europe. Additionally, data indicates that the prevalence of

Pompe disease in the U.S. and Europe, combined, is

approximately 10,000

2

. The percentage of patients that are

expected to have NAbs against the AAV8-vector components

used in AskBio’s gene therapy is 40-60%

3

.

Research and preclinical

development projects

“NiceR” program and lead candidate “HNSA5487”

– new set of enzymes for repeat dosing; potentially enabling

treatment of relapsing diseases.

Hansa is developing novel IgG-degrading enzymes under

the program name, “NiceR” (Novel Immunoglobulin Cleaving

Enzymes for Repeat dosing). The objective of the enzymes

developed from the NiceR program is to enable repeat

dosing in a broad array of indications with significant unmet

medical need including reoccurring transplantation,

relapsing autoimmune diseases and oncology, where

patients may benefit from more than one dose of an

IgG-modulating enzyme.

A broad repertoire of novel immunoglobulin cysteine

endopeptidases has been developed and patented within

the program and a lead candidate was selected in 2019 for

clinical development. At the end of 2022 Hansa announced

completion of IND-enabling toxicology studies and that a

CTA approval had been obtained for the lead candidate

“HNSA-5487” to start a first clinical trial in the first half 2023.

EnzE – Enzyme-based antibody Enhancement

Hansa is exploring EnzE as a potential therapeutic intervention

in oncology, in which imlifidase administration prior to

therapeutic antibody treatment may lead to a more efficient

anti-tumor therapy through cleaving the abundance of normal

IgG in blood. The project is currently in a research stage.

NiceR can potentially inactivate flares

Illustrative

flare 1

flare 2

flare 3

flare (n)

Time

48

Overview

Strategy

Market

Technology

Growth

Shareholder

information

Directors’ report

Financials

Governance

Remuneration

49

Overview

Strategy

Market

Technology

Growth

New

opportunities

Directors’ report

Financials

Governance

Remuneration

Shareholder

information

50

Shareholder information

51

Ownership and analyst coverage

Shareholder

information

7

Shareholder information

Hansa share price development versus peer group

1

during 2022

1/22

2/22

3/22

4/22

5/22

6/22

7/22

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XBI

Peer group

HANSA

1

Peer group consist of Scandinavian biotech/pharma companies with negative EBIT and 1-year average

market capitalisation of above 2 000m SEK (2022-02-14)

Hansa Biopharma’s shares are listed on Nasdaq OMX

Stockholm, under the ticker HNSA and are included in

several indexes including, but not limited to:

OMX Nordic Mid Cap

OMX Stockholm Health Care

OMX Stockholm Mid Cap

OMX Stockholm Pharmaceuticals & Biotechnology

STOXX Europe Total Market Small Index

According to the shareholder register maintained by

Euroclear Sweden AB, as of 31 December 2022, Hansa

Biopharma had approximately 19,000 shareholders,

compared to approximately 18,000 shareholders as of

31 December 2021. Information regarding shareholders

and shareholdings is updated each quarter on the

Company’s website, www. hansabiopharma.com.

Total shares issued as of 31 December 2022 amounted to

52,443,962 ordinary shares outstanding and 2,590,279

C-shares. At year end 2022, the share capital amounted to

SEK 55,034,241. At the general meeting, each ordinary share

entitles the holder to one vote and each shareholder may

vote the full number of shares held by him or her. All

outstanding shares are fully paid up. The Company’s share

capital is denominated in Swedish kronor (SEK) and divided

among the Company’s shares with a quotient value of SEK 1

per share.

Price development for the HNSA share in 2021 and 2022

Ownership and analyst coverage

Top 10 largest shareholders, 31 December 2022

Owners

Number of shares

HNSA

Capital (%)

Redmile Group, LLC

10 896 553

20.8

Försäkrings AB Avanza Pension

2 209 783

4.2

Fjärde AP-Fonden (AP 4)

2 207 397

4.2

Nexttobe AB

2 155 379

4.1

Olausson, Thomas

1 917 000

3.7

Tredje AP-Fonden (AP 3)

1 389 650

2.6

Braidwell, L.P.

974 528

1.9

Handelsbanken Asset Management

908 266

1.7

C WorldWide Asset Management

799 749

1.5

Heights Capital Management, Inc.

667 169

1.3

Other

28 318 488

54.0

Total

52 443 962

100.0

Source: IHS Markit/IPREO compiled and processed data

from various sources, including Euroclear, Morningstar,

Factset and the Swedish Financial Supervisory Authority

(Finansinspektionen)

Analyst coverage 2022 and 2023

Analyst

Bank / Research institution

(year of initiation)

Location

Email

Phone

Christopher Uhde

SEB (2016)

Stockholm

christopher.uhde@seb.se

+46 (0) 876-385 53

Gonzalo Artiach

Castañón

ABG Sundal Collier (2018)

Stockholm

Gonzalo.Artiach@abgsc.se

+46 (0) 8 566 286 91

Zoe Karamanoli

RBC (2017)

London

zoe.karamanoli@rbccm.com

+44 7834 765119

Naresh Chouhan

Intron Health Research (2020)

London

naresh@intronhealthresearch.com

+44 7939 224 322

Douglas Tsao

H.C. Wainwright (2021)

New York City

dtsao@hcwresearch.com

+1 212-916-3968

Erik Hultgård

Carnegie (2019)

Stockholm

erik.hultgard@carnegie.com

+46 (0) 858-869 237

Johan Unnerus

Redeye (2008)

Stockholm

johan.unnerus@redeye.se

+46 (0) 724 023 385

Ludvig Svensson

Erik Penser Bank (2021)

Stockholm

ludvig.svensson@penser.com

+46 (0) 704 962 535

Lars Hatholt

Ökonomisk Ugebrev (2020)

Copenhagen

hatholt@outlook.com

+45 22 23 78 15

Ingrid Gafanhão

Bryan Garnier (2022)

Paris

ingrid.Gafanhao@kempen.com

+31 689 937 525

Suzanne van Voorthuizen

Kempen (2019)

Amsterdam

s.vanvoorthuizen@vanlanschotkempen.com

+31 6 29 71 3490

Ownership by type and location, 31 December 2022

Ownership by type

Ownership by country

Institutions

VC

High net-worth

Retail

Sweden

United States

Europe

Hansa Biopharma shareholders

As of 31 December 2022

51

52

Overview

Strategy

Market

Technology

Growth

New

opportunities

Shareholder

information

Financials

Governance

Remuneration

Directors’ report

53

2022 Directors’ report

Directors’

report

8