ProQR Therapeutics NV (Nasdaq: PRQR) has reported significant progress in its RNA editing pipeline, positioning the company for multiple clinical milestones over the next two years. The Netherlands and Cambridge-based biotech firm announced its year-end 2024 operating and financial results on March 13, highlighting advancements across its proprietary Axiomer™ RNA editing technology platform.
The company's lead program, AX-0810, which targets NTCP for cholestatic diseases, is on track for Clinical Trial Application (CTA) filing in Q2 2025, with first clinical data expected in Q4 2025. This represents a critical step forward in ProQR's mission to develop transformative RNA therapies using its innovative ADAR-mediated RNA editing approach.
"As we continue to advance our Axiomer ADAR-mediated RNA editing platform and pipeline, ProQR is entering a pivotal phase of growth and innovation," said Daniel A. de Boer, Founder and Chief Executive Officer of ProQR. "With up to four clinical trial data readouts anticipated in 2025 and 2026, including topline data for our NTCP program later this year, we believe we are poised to demonstrate the broad therapeutic potential of RNA editing."
Pipeline Expansion and Strategic Partnerships
ProQR's pipeline now spans both liver and central nervous system (CNS) applications. In addition to AX-0810, the company is advancing several other promising candidates:
- AX-2402, targeting the R270X mutation in the MECP2 gene for Rett Syndrome, with clinical candidate selection expected in 2025 and clinical trial initiation in 2026
- AX-2911, targeting PNPLA3 for Metabolic dysfunction-associated steatohepatitis (MASH), also with clinical candidate selection in 2025 and trial initiation in 2026
- AX-1412, targeting B4GALT1 for cardiovascular diseases, with an update on GalNAc delivery optimization expected by mid-2025
The company has strengthened its position in the RNA editing field through strategic partnerships. In December 2024, ProQR expanded its collaboration with the Rett Syndrome Research Trust, securing additional funding for a total of up to $9.2 million to support the advancement of AX-2402 into clinical trials.
ProQR's most significant partnership remains its $3.9 billion collaboration with Eli Lilly. This relationship includes potential milestone payments and an option for Lilly to expand targets for an additional $50 million payment to ProQR.
Financial Position and R&D Investment
ProQR reported a strong financial foundation with €149.4 million in cash and cash equivalents as of December 31, 2024, compared to €118.9 million at the end of 2023. This financial position provides runway into mid-2027, according to company projections.
In October 2024, the company significantly bolstered its finances through an underwritten public offering of 18,000,000 ordinary shares and a concurrent private placement of 3,523,538 ordinary shares with Eli Lilly, plus the exercise of underwriters' options for additional shares. These transactions generated gross proceeds of approximately $82.1 million.
Research and development costs increased to €36.4 million for 2024, compared to €25.1 million in 2023, reflecting the company's increased investments in platform development and advancing pipeline programs. Despite this increased R&D spending, general and administrative costs decreased to €13.7 million from €16.2 million in the previous year.
Net loss for 2024 was €27.8 million or €0.32 per diluted share, comparable to the €27.7 million loss (€0.35 per diluted share) reported for 2023.
Axiomer™ Technology Platform
ProQR's Axiomer™ platform represents a novel approach to RNA editing. The technology uses "Editing Oligonucleotides" (EONs) to mediate single nucleotide changes to RNA by leveraging ADAR (Adenosine Deaminase Acting on RNA), a molecular machinery naturally present in human cells.
The platform is designed to recruit and direct endogenously expressed ADARs to change an Adenosine (A) to an Inosine (I) in RNA—with Inosine being translated as Guanosine (G). This approach enables correction of disease-causing mutations, modulation of protein expression, or alteration of protein function to prevent or treat disease.
In December 2024, ProQR appointed Dr. Peter A. Beal as Chief ADAR Scientist to drive the development and optimization of the Axiomer platform. Dr. Beal, a leading expert in ADAR and RNA biology from the University of California, Davis, brings valuable expertise to advance the company's RNA editing capabilities.
Looking Forward
De Boer emphasized the company's readiness to capitalize on upcoming opportunities: "Our successful financing in October 2024 further strengthens our financial foundation, providing cash runway into mid-2027. With this strong position, we believe we are well equipped to advance key upcoming milestones, including submission of the CTA for our first RNA editing pipeline program, AX-0810, on track for Q2 2025 and there following our first clinical data readout in Q4 of this year."
As ProQR continues to advance its pipeline and platform, the company is positioning itself as a leader in the emerging field of RNA editing therapeutics, with potential applications across both rare and prevalent diseases with unmet medical needs.
