* Total deal values including potential milestone payments
** BMS decided not to exercise its option
Source: Corporate webpages
Deals in IPF, fibrosis and DTx
11 | Annual Report 2022 Vicore Pharma Holding AB (publ)
T
he renin-angiotensin system
(RAS) is a hormone system that
regulates several important phys-
iological processes. In this system the
AT1 receptor is a well-established drug
target with ARB’s (Angiotensin receptor
blockers) as a block-buster drug class,
while the AT2 receptor has been more
elusive and difficult to study. With C21
as the first-in-class highly selective small
molecule AT2 receptor agonist (ATRAG)
taken into clinical trials, the therapeutic
benefit of targeting the AT2 receptor is
becoming increasingly apparent.
The renin-angiotensin
system (RAS) and the AT2
receptor
The RAS is regulated by the hormone
Angiotensin II and the peptide fragments
Ang 1-9 and Ang 1-7 which act on the AT1
and AT2 receptors.
The AT1 receptor is mainly involved
in blood pressure regulation through
several different mechanisms related to
constriction of blood vessels and fluid
retention, but also contributes to innate
immunity through proinflammatory
actions. When this system “over-
shoots”, it can also contribute to the
pathogenesis of diseases such as hyper-
tension, myocardial infarction and different
fibrotic conditions including pulmonary
fibrosis and chronic kidney disease.
The expression of the AT2 receptor, on
the other hand, is normally low in adult
tissues but can be upregulated during
repair and regeneration situations,
following immune and vascular reac-
tions to injury. There is strong scientific
evidence for an important protective
role of AT2 receptor activation in several
serious diseases related to cellular
senescence, fibrosis and microvascular
dysfunction. In addition to IPF, these
include e.g. pulmonary hypertension,
chronic kidney disease, atherosclerosis,
heart failure and several cognitive
disorders such as Alzheimer’s disease.
The benefit of AT2 receptor stim-
ulation has been demonstrated in
more than 100 preclinical studies, and
clinical evidence is now accumulating,
validating the preclinical results. In lung
disease, C21 can restore lung function
both in IPF and wildtype COVID-19
infection. In COVID-infection involving
the lower airways (alveoli) C21 treated
patients had a significantly lower risk
of needing oxygen supplementation
and at the 3-month follow-up, treated
patients had fewer pathological signs
on chest computer tomography.
ATRAGs - Unlocking
the potential of a
new class of drugs
ACE inhibitors
AT2R
Angiotensin 1-9
Angiotensin 1-7
AT1R
Cytoplasm
Renin
ACE
ACE2
ATRAGs
Angiotensin ll
Angiotensin l
Angiotensinogen
ARBs
•Hypertension
•Fibrosis
•Inflammation
•Small vessel dilation
•Resolution
•Repair
ACE: Angiotensin Converting Enzyme. ARB: Angiotensin ReceptorBlocker. ATRAG: Angiotensin II Type 2 ReceptorAgonist. AT1R: Angiotensin II Type 1 Receptor. AT2R: Angiotensin II Type 2 Receptor
Interim data from the ongoing AIR trial
in IPF indicates that patients on C21
can regain lung function, seen as an
increase in forced vital capacity.
Vascular effects of C21, seen as
increase in blood flow, was demon-
strated in systemic sclerosis patients
with severe vasculopathy and fibrosis.
The effects on endothelial cells have
now also been demonstrated in
healthy volunteers, where a robust
dilation of peripheral vessels was seen.
Since endothelial dysfunction is a key
component in many severe diseases
this finding is clinically relevant.
Vicore’s candidate drug C21 and the
new compounds C106, C103, C112
and C111 are AT2 receptor agonists
(ATRAGs). With a strong position in
ATRAG chemistry and an evolving
platform of promising new ATRAGs
with patent protection to at least
2040, Vicore holds a unique and large
potential in this area.
The renin-angiotensin system
12 | Annual Report 2022 Vicore Pharma Holding AB (publ)
Normal alveolusLung fibrosis developmentAlveolar repair
AEC1
AEC - Alveolar Epithelial Cell
Fibroblasts
AEC2
Extracellular
matrix
Myofibroblasts
CO
2
O
2
AEC1 – gas exchange. AEC2 – repair functionDysfunctional AEC2 – trigger for fibrosis
C21 stimulates AEC2 and alveolar repair
Gas exchange
TGFβ-1
ATRAG
Normal alveolus
AEC1 cells – gas exchange. AEC2 cells – repair function
Normal alveolusLung fibrosis developmentAlveolar repair
AEC1
AEC - Alveolar Epithelial Cell
Fibroblasts
AEC2
Extracellular
matrix
Myofibroblasts
CO
2
O
2
AEC1 – gas exchange. AEC2 – repair functionDysfunctional AEC2 – trigger for fibrosis
C21 stimulates AEC2 and alveolar repair
Gas exchange
TGFβ-1
ATRAG
Lung fibrosis development
Dysfunctional AEC2 cells – trigger for fibrosis
Normal alveolusLung fibrosis developmentAlveolar repair
AEC1
AEC - Alveolar Epithelial Cell
Fibroblasts
AEC2
Extracellular
matrix
Myofibroblasts
CO
2
O
2
AEC1 – gas exchange. AEC2 – repair function
Dysfunctional AEC2 – trigger for fibrosis
C21 stimulates AEC2 and alveolar repair
Gas exchange
TGFβ-1
ATRAG
Alveolar repair
ATRAG stimulates AEC2 cells and alveolar repair
Mechanism of action in IPF
IPF develops in lung alveoli – tiny air-filled sacks where the
exchange of oxygen and carbon dioxide takes place. Type 2
alveolar epithelial cells (AEC2) maintain alveolar integrity to keep
the lungs healthy and functioning properly. In IPF, the AEC2 cells
become dysfunctional and lose their ability to repair and maintain
alveolar integrity which is a starting point for fibrosis.
AT2 receptors are highly expressed on the AEC2 in the alveoli.
ATRAGs bind to and activate the AT2 receptor, triggering
protective signaling pathways, promoting alveolar repair and
maintenance of alveolar integrity.
13 | Annual Report 2022 Vicore Pharma Holding AB (publ)
At December 31, 2022, the registered share capital comprised 81,847,979 ordinary shares. All shares are
fully paid and no shares are reserved for transfer. Each share carries one vote. The quota value amounts to
0.5 SEK (0.5 SEK). No shares are held by the company itself or its subsidiaries.
The share premium reserve refers to capital from new share issues that have been issued at a price that
exceeds the quotient value and includes deductions of expenditures for new share issues.
Note 17 Other provisions
Social security contributions related to share-based incentive
programs
2022
Dec 31
2021
Dec 31
Opening amount5075,312
Provisions for the year237-4,805
Total744507
For more information about incentive programs, see Note 8 "Share-based payments" for the group.
Note 18 Liabilities to group companies
Current liabilities
2022
Dec 31
2021
Dec 31
Opening cost75,0000
Reclassifications-75,0000
Additions075,000
Closing carrying amount075,000
Note 19 Accrued expenses and deferred income
2022
Dec 31
2021
Dec 31
Accrued personnel-related expenses1,8671,799
Accrued consulting fees425150
Other199135
Total2,4912,084
Note 20 Supplementary information to the cash flow statement
Adjustment for items not included in the cash flow
2022
Dec 31
2021
Dec 31
Incentive programs, salary costs8532,526
Incentive programs, social security contributions*237-4,805
Provision payroll tax, pension premium8064
Total1,170-2,215
Note 21 Pledged assets and contingent liabilities
For information about pledged assets and contingent liabilities in the parent company, see Note 29
"Pledged assets and contingent liabilities" for the group.
Note 22 Related-party transactions
Sales of
goods or
services
Purchase
of goods or
servicesOther
Receivables
on closing
day
Payables
on closing
day
Transactions with subsidiaries
202230,4020013,0000
202137,866085932 38675,000
Sales of goods or services relate to reinvoiced costs and management fee.
For information about salaries and remuneration to employees and senior executives, see Note 7
"Employees and personnel costs" for the group.
For further information on related-party transactions, see Note 28 "Related-party transactions"
for the group.
57 | Annual Report 2022 Vicore Pharma Holding AB (publ)
Signatures
Sara Malcus
Board member
Carl-Johan Dalsgaard
CEO
Hans Schikan
Board member
Jacob Gunterberg
Chairman
Maarten Kraan
Board member
The undersigned give their assurance that the annual accounts have been prepared in accordance with generally accepted accounting standards in Sweden and that
the consolidated financial statements have been prepared in accordance with international accounting standards, IFRS, as adopted by the EU. The annual accounts
and the consolidated financial statements each provide a fair and accurate impression of the parent company’s and the group’s position and earnings. The Administra-
tion Report for the parent company and the group provides a fair and accurate overview of the parent company’s and the group’s operations, position and earnings, and
describes material risks and uncertainties faced by the parent company and the companies included in the group.
Gothenburg April 4, 2023
Our audit report was submitted on April 4, 2023
Ernst & Young AB
Linda Sallander
Authorized Public Accountant
Heidi Hunter
Board member
58 | Annual Report 2022 Vicore Pharma Holding AB (publ)
Auditors-
Report
To the general meeting of the shareholders of
Vicore Pharma Holding AB (publ), corporate
identity number 556680-3804.
Report on the annual accounts and
consolidated accounts
Opinions
We have audited the annual accounts and
consolidated accounts of Vicore Pharma Holding
AB (publ) for the year 2022. The annual accounts
and consolidated accounts of the company are
included on pages 23-57 in this document.
In our opinion, the annual accounts have been
prepared in accordance with the Annual Accounts Act
and present fairly, in all material respects, the financial
position of the parent company as of 31 December
2022 and its financial performance and cash flow for
the year then ended in accordance with the Annual
Accounts Act. The consolidated accounts have been
prepared in accordance with the Annual Accounts Act
and present fairly, in all material respects, the financial
position of the group as of 31 December 2022 and
their financial performance and cash flow for the year
then ended in accordance with International Financial
Reporting Standards (IFRS), as adopted by the EU,
and the Annual Accounts Act. The statutory adminis-
tration report is consistent with the other parts of the
annual accounts and consolidated accounts.
We therefore recommend that the general meeting
of shareholders adopts the income statement and
balance sheet for the parent company and the group.
Our opinions in this report on the annual accounts
and consolidated accounts are consistent with
the content of the additional report that has been
submitted to the parent company's audit committee
in accordance with the Audit Regulation (537/2014)
Article 11
Basis for Opinions
We conducted our audit in accordance with Inter-
national Standards on Auditing (ISA) and generally
accepted auditing standards in Sweden. Our
responsibilities under those standards are further
described in the Auditor’s Responsibilities section.
We are independent of the parent company and the
group in accordance with professional ethics for
accountants in Sweden and have otherwise fulfilled
our ethical responsibilities in accordance with
these requirements. This includes that, based on
the best of our knowledge and belief, no prohibited
services referred to in the Audit Regulation
(537/2014) Article 5.1 have been provided to the
audited company or, where applicable, its parent
company or its controlled companies within the EU.
We believe that the audit evidence we have
obtained is sufficient and appropriate to provide a
basis for our opinions.
Key Audit Matters
Key audit matters of the audit are those matters
that, in our professional judgment, were of most
significance in our audit of the annual accounts
and consolidated accounts of the current period.
These matters were addressed in the context of
our audit of, and in forming our opinion thereon, the
annual accounts and consolidated accounts as a
whole, but we do not provide a separate opinion
on these matters. For each matter below, our
description of how our audit addressed the matter
is provided in that context.
We have fulfilled the responsibilities described
in the Auditor’s responsibilities for the audit of
the financial statements section of our report,
including in relation to these matters. Accordingly,
our audit included the performance of procedures
designed to respond to our assessment of the
risks of material misstatement of the financial
statements. The results of our audit procedures,
including the procedures performed to address
the matters below, provide the basis for our audit
opinion on the accompanying financial statements.
Key Audit Matter 1
DescriptionHow our audit addressed this key audit matter
As of December 31, 2022, a substantial part (20.1% or SEK
68.1 million) of the Group's total assets consists of patents,
licenses and similar rights (hereinafter referred to as the
assets). The Company tests the assets for impairment
annually and when events or changes in conditions indi-
cate that the carrying value of the assets may be below the
recoverable amount. Impairment testing involves a number
of material estimates and judgments, including estimating
value in use by assessing the likelihood of future product