Indicate by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
On June 25, 2026, ProQR
Therapeutics N.V. (“ProQR”) issued a press release entitled “ProQR Announces Positive Phase 1 Target Engagement Data
for AX-0810, Establishing First Clinical Validation of the Axiomer RNA Editing Platform.” A copy of the press release is attached
hereto as Exhibit 99.1 and is incorporated herein by reference.
ProQR hereby incorporates
by reference the information contained herein into ProQR’s registration statements on Form F-3 (File No. 333-282419,
File No. 333-270943, File No. 333-263166 and File No. 333-285767).
Pursuant to the requirements
of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto
duly authorized.
Exhibit 99.1
ProQR Announces Positive Phase 1 Target Engagement
Data for AX-0810, Establishing First Clinical Validation of the Axiomer RNA Editing Platform
| · | Data
from ongoing Phase 1 study of AX-0810 in healthy volunteers demonstrated dose-dependent target
engagement on all key biomarkers in the evaluable 3 mg/kg and 6 mg/kg cohorts |
| · | AX-0810
demonstrated up to 8-fold change (6 mg/kg) in total bile acids in serum, exceeding the 2-fold
threshold identified by the Company as a meaningful indicator of NTCP modulation, along with
concordant readouts of bile acid profile and TUDCA markers |
| · | Favorable
safety and tolerability profile observed with AX-0810 to date, with no serious adverse events
or pruritus reported; pharmacokinetic findings to date support sustained target engagement,
including a half-life of eight weeks |
| · | The
NTCP biomarker findings support advancement of next-generation candidate AX-0811 and future
clinical studies in biliary atresia |
LEIDEN, Netherlands & CAMBRIDGE, Mass., June 25,
2026 – ProQR Therapeutics N.V. (Nasdaq: PRQR) (ProQR or the Company), a clinical-stage biotechnology company dedicated to changing
lives through transformative RNA therapies based on its proprietary Axiomer™ RNA editing technology platform, today announced positive
target engagement data from its ongoing Phase 1 clinical study evaluating AX-0810, the Company’s first investigational Axiomer
RNA editing oligonucleotide (EON), in healthy volunteers.
AX-0810 is a GalNAc-conjugated, subcutaneously administered Axiomer
RNA EON designed to selectively modulate NTCP, a key transporter responsible for bile acid uptake from the bloodstream into the liver.
Through this novel mechanism, AX-0810 aims to reduce toxic bile acid accumulation in the liver, the underlying driver of cholestatic
liver diseases including biliary atresia, and has the potential to be disease modifying.
AX-0810 Phase 1 Study Overview
The ongoing multiple ascending dose (MAD) Phase 1 study enrolled 33
healthy volunteers, including 24 participants receiving AX-0810 and nine participants receiving placebo across the 3 mg/kg, 6 mg/kg,
and 9 mg/kg cohorts. The data reported today include findings from 22 participants in cohorts 1 and 2, receiving 3 mg/kg and 6 mg/kg
doses, respectively. Data from the 9 mg/kg cohort are not yet available.
NTCP Target Engagement Confirmed Across All Three
Predefined Biomarker Measures
The data demonstrated clear evidence of NTCP target engagement consistent
with the biological rationale and preclinical findings. Across the evaluable 3 mg/kg and 6 mg/kg cohorts, administration of AX-0810 resulted
in dose-dependent increases in total bile acids in serum of up to 8-fold, exceeding the Company’s predefined target engagement
threshold of 2-fold as a meaningful indication of NTCP modulation. Concordant dose-dependent changes in conjugated bile acids and circulating
TUDCA levels further support specificity of NTCP modulation.
Administration of AX-0810 resulted in increased hepatotoxic conjugated
bile acids in circulation, keeping them from accumulating in the liver, supporting the specificity of NTCP modulation and the expected
pharmacologic profile. Increased circulating TUDCA (i.e., decreased clearance through NTCP) following challenge further confirms NTCP
target engagement. Together, the Company believes the consistent dose-response observed across these independent biomarker measures provides
convergent evidence of NTCP modulation in humans following administration of AX-0810.
Increased levels of conjugated bile acids in serum circulation led
to dose-dependent and statistically significantly increased urinary excretion of conjugated bile acids, indicating that NTCP modulation
may allow the body to lower concentration of toxic bile acids.
AX-0810 is designed to specifically edit the bile acid binding pocket
of the NTCP protein, while preserving the other functions of the protein such as hormonal transport. The Phase 1 data to date confirmed
there were no changes in hormone levels in circulation, supporting the intended mechanism of action of AX-0810. The Company anticipates
that preservation of the other NTCP functions and the expected infrequent dosing frequency could be key differentiators of ProQR’s
RNA editing approach in modulating NTCP for cholestatic disease.
Favorable Safety and Pharmacokinetic Profile
AX-0810 demonstrated a favorable safety and tolerability profile in
cohorts 1 and 2, with no serious adverse events or pruritus reported across the evaluated cohorts to date. Pharmacokinetic findings were
consistent with the expected profile, including half-life of eight weeks based on available data, supportive of sustained target engagement.
“The concordant responses across all three predefined
biomarkers provide compelling clinical target engagement evidence that AX-0810 is modulating NTCP biology in humans as intended,”
said Cristina Lopez Lopez, MD, PhD, Chief Medical Officer of ProQR. “We observed dose-dependent increases in total bile acids of
up to 8-fold, together with a selective shift toward protecting the liver from toxic conjugated bile acid uptake, and increased circulating
TUDCA levels following a challenge in which TUDCA was orally administered. These findings support the expected pharmacology of NTCP modulation
and were accompanied by a favorable safety and tolerability profile and pharmacokinetics consistent with sustained target engagement.
The biomarker responses observed in healthy volunteers were consistent with the biology predicted from our preclinical studies, supporting
our confidence in the translational potential of NTCP modulation for patients with biliary atresia, a disease with significant unmet
medical need.”
Participants in the Phase 1 study of AX-0810 continue
to be followed through the planned 12-week follow-up period across all cohorts. ProQR plans to present full data from the Phase 1 study
at a medical or scientific conference later this year.
AX-0811 Next Generation NTCP EON Demonstrates
Cholestasis Reduction in Animal Model
The biomarker findings established in the AX-0810
Phase 1 study support continued advancement of ProQR’s NTCP franchise, including AX-0811, a next-generation NTCP-targeting RNA
editing oligonucleotide generated using the Company’s AI-enabled discovery engine. AX-0811 demonstrated robust cholestasis reduction
in a preclinical cholestasis animal model and in humans is projected based on modeling to support at least 4-fold higher editing at lower
dose levels, with a projected half-life greater than three months. ProQR expects to submit a Clinical Trial Application (CTA) in mid-2026
for AX-0811 and anticipates initial human clinical data in healthy volunteers by year-end 2026.
Next Development Steps for NTCP Franchise and
Beyond
The Company has selected biliary atresia (BA) as the
initial indication for Phase 2 development of AX-0810 or AX-0811, based on strong biological rationale and high unmet medical need. To
inform the design of the Phase 2 program, ProQR plans to conduct an investigator-initiated trial (IIT) in pediatric participants with
BA in China. The Company expects to report initial clinical data from the IIT in the first half of 2027.
“The AX-0810 data represent an important milestone
both for the NTCP program and for the Axiomer RNA editing platform,” said Daniel A. de Boer, Founder and Chief Executive Officer
of ProQR. “The human target engagement data generated with AX-0810, together with the promising preclinical profile of AX-0811,
strengthen our confidence in the potential of the NTCP franchise to address significant unmet need in biliary atresia and further reinforce
the broad potential of our Axiomer RNA editing platform.”
Upcoming anticipated milestones:
NTCP franchise
| · | AX-0810
data from the 9 mg/kg cohort and 12-week follow up from the ongoing Phase 1 study expected
by year-end 2026 |
| · | AX-0811
CTA filing in mid-2026, with initial data in healthy volunteers expected by year-end 2026 |
| · | IIT
in pediatric biliary atresia in China, with initial data targeted for first half of 2027 |
| · | Potentially
registration-enabling Phase 2 program, subject to regulatory interactions, expected to start
in mid-2027 with first interim analysis data expected by mid-2028 |
Other pipeline candidates
| · | AX-0422
for MPS1 / Hurler Syndrome (IDUA) CTA filing for a first-in-patient study anticipated in
early 2027 and initial data expected in the first half of 2027 |
| · | AX-2911(PNPLA3)
FIH IIT in China expected in the first half of 2027 |
About Axiomer™
ProQR is pioneering a next-generation RNA base editing technology
called Axiomer™, which could potentially yield a new class of medicines for diverse types of diseases. Axiomer™
“Editing Oligonucleotides”, or EONs, mediate single nucleotide changes to RNA in a highly specific and targeted way using
molecular machinery that is present in human cells called ADAR (Adenosine Deaminase Acting on RNA). Axiomer™ EONs are
designed to recruit and direct endogenously expressed ADARs to change an Adenosine (A) to an Inosine (I) in the RNA – an Inosine
is translated as a Guanosine (G) – correcting an RNA with a disease-causing mutation back to a normal (wild type) RNA, modulating
protein expression, or altering a protein so that it will have a new function that helps prevent or treat disease.
About ProQR
ProQR Therapeutics is dedicated to changing lives through the creation
of transformative RNA therapies. ProQR is pioneering a next-generation RNA technology called Axiomer™, which uses a
cell’s own editing machinery called ADAR to make specific single nucleotide edits in RNA to reverse a mutation or modulate protein
expression and could potentially yield a new class of medicines for both rare and prevalent diseases with unmet need. Based on our unique
proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind.
Learn more about ProQR at www.proqr.com.
Forward Looking Statements
This press release
contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are
often indicated by terms such as “continue,” "anticipate," "believe," "could," "estimate,"
"expect," "goal," "intend," "look forward to", "may," "plan," "potential,"
"predict," "project," "should," "will," "would" and similar expressions. Such forward-looking
statements include, but are not limited to, statements regarding our business, technology, strategy, preclinical and clinical model data;
our initial pipeline targets and the upcoming strategic priorities and milestones related thereto; the continued advancement of our lead
development pipeline programs, including ongoing and planned clinical trials; expectations regarding the ongoing Phase 1 clinical study
of AX-0810 in NTCP for cholestatic diseases, including our ability to complete the Phase 1 clinical study for AX-0810, biliary atresia
as our primary indication for AX-0810 or AX-0811, and the anticipated timing of additional Phase 1 target engagement data from the 9
mg/kg cohort and the 12-week follow-up period by year-end 2026; the potential of AX-0810 to be disease modifying; our expectations regarding
the safety and therapeutic benefits of AX-0810 and AX-0811, including the planned dosing levels and their efficacy; our ability to collaborate
with investigators to execute and recruit for an investigator-initiated trial in pediatric participants with biliary atresia in China
and to generate meaningful data therefrom, including the anticipated timing of initial data readout in the first half of 2027; the anticipated
potentially registration-enabling Phase 2 program for AX-0810 or AX-0811, subject to regulatory interactions, including the expected
initiation in mid-2027 with first interim analysis data expected by mid-2028; risks and uncertainties
associated with conducting clinical trials in China, including evolving regulatory requirements; our pipeline targets, including the
planned Phase 1 clinical trial of AX-0811 in NTCP for cholestatic diseases; our ability to recruit for and complete a Phase 1 clinical
trial for AX-0811, including the anticipated timing of a CTA filing in mid-2026 and initial data readout by year-end 2026; the anticipated
first-in-human study of AX-0422 targeting IDUA for Hurler syndrome, with a CTA filing expected in early 2027 and anticipated initial
clinical data readout in the first half of 2027; the anticipated investigator-initiated study in China of AX-2911 targeting PNPLA3 for
MASH in the first half of 2027; our expectations regarding clinical updates across multiple programs in 2026 and 2027; the therapeutic
potential and development timeline regarding AX-0810, AX-0811, AX-0422, and AX-2911; our participation at upcoming scientific conferences;
the continued development and advancement of our Axiomer platform; the therapeutic potential of our Axiomer RNA editing oligonucleotides
and product candidates; the timing, progress and results of our preclinical studies and other development and pipeline activities, including
the release of data related thereto; our patent estate, including our anticipated strength and our continued investment in it, as well
as the timing of our clinical development; our AI strategy and expectations regarding AI’s ability to accelerate Axiomer discovery;
and the potential of our technologies and product candidates. Forward-looking statements are based on management's beliefs and assumptions
and on information available to management only as of the date of this press release. Our actual results could differ materially from
those expressed or implied by these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties
and other factors in our filings made with the Securities and Exchange Commission, including certain sections of our most recent annual
report filed on Form 20-F. These risks and uncertainties include, among others, the cost, timing and results of preclinical studies and
clinical trials and other development activities by us and our collaborative partners whose operations and activities may be slowed or
halted due to shortage and pressure on supply chains and logistics in the global market, economic sanctions and international tariffs;
the likelihood of our preclinical and clinical programs being initiated and executed on timelines provided and our reliance on our contract
research organizations and predictability of timely enrollment of subjects and patients to advance our clinical trials and maintain their
own operations; risks related to the development and optimization of new technologies, the results of preclinical studies, or clinical
studies not being predictive of future results in connection with future studies; our reliance on contract manufacturers to supply materials
for research and development and the risk of supply interruption from a contract manufacturer; the potential for future data to alter
initial and preliminary results of early-stage clinical trials; the unpredictability of the duration and results of the regulatory review
of applications or clearances that are necessary to initiate and continue to advance and progress our clinical programs; the ability
to secure, maintain and realize the intended benefits of collaborations with partners, including the collaboration with Lilly and partnership
with Ginkgo; the possible impairment of, inability to obtain, and costs to obtain intellectual property rights; possible safety or efficacy
concerns that could emerge as new data are generated in research and development; general business, operational, financial and accounting
risks, and risks related to litigation and disputes with third parties; and risks related to macroeconomic conditions and market volatility
resulting from global economic developments, geopolitical events and conflicts, inflationary pressures, fluctuating interest rates, tariffs
and potential for significant changes in U.S. policies and regulatory environment. Given these risks, uncertainties and other factors,
you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking
statements, even if new information becomes available in the future, except as required by law.
ProQR Therapeutics N.V.
Investor
and media contact:
Sarah Kiely
ProQR Therapeutics N.V.
T: +1 617 599 6228
skiely@proqr.com
or
Investor contact:
Peter Kelleher
LifeSci Advisors
T: +1 617 430 7579
pkelleher@lifesciadvisors.com
