CMN Weekly (28 March 2025) - Your Weekly CRISPR Medicine News

Top picks

• At meeting on guardrails for gene editing of human embryos, some call for a dead end. This write up in STAT discusses a recent meeting in Washington where experts, including CRISPR pioneer Keith Joung, emphasised that science remains far from safely implementing human embryo gene editing. Industry representatives showed little interest in pursuing the technology commercially, while the article highlights tensions between rare disease advocates and those calling for permanent restrictions on heritable gene editing.

Research

• In an article published yesterday in Frontiers in Immunology, researchers in Denmark and the United States share their findings from a study to characterise different cell subsets from in vitro differentiated plasmacytoid dendritic cells (pDCs). pDCs are multifunctional immune cells with roles in innate and adaptive immunity, and this study identified a distinct population that is a major producer of IFNα in response to TLR9 stimulation and which displays a transcriptomic profile similar to what is seen for circulating pDCs. The team also explored the possibility of rerouting subset specification during the differentiation of haematopoietic stem and progenitor cells (HSPCs) to pDCs by controlling gene expression of key master transcription factors (TFs) using CRISPR-Cas9 gene editing. They identified TFs associated with the pDC differentiation trajectory that are essential for the development of TLR9-responsive HSPC-pDCs, as well as TFs that increase their frequency. The authors propose that their findings improve our understanding of in vitro-differentiated pDC cultures that may spur further developments in their use as an immunomodulatory cell therapy.
• Scientists in China have engineered circular guide RNA (cgRNA) for Cas12f that significantly improve gene activation efficiency in vitro and in mouse liver. When combined with phase separation, gene activation efficiency was further increased. They also found that cgRNA enhances the editing efficiency and narrows the editing window of adenine base editing by approx. 1.2–2.5-fold. Their findings were published today in Nature Communications.

Clinical

• At the 2025 ACMG Annual Clinical Genetics Meeting held recently in in Los Angeles, iEUCURE announced full data for the first infant dosed with ECUR-506 in the ongoing OTC-HOPE Phase 1/2 clinical trial. ECUR-506, co-developed with Precision BioSciences, is a meganuclease-based, in vivo liver-targeting therapeutic candidate designed to treat ornithine transcarbamylase deficiency (OTCD) in infants. OTCD is a rare X-linked inherited metabolic disorder that causes ammonia to accumulate in the blood. The company reports that this patient achieved complete clinical response per study protocol and data suggests partial restoration of functional OTC enzyme activity in the liver. See the official press release for further details and read more about ECUR-506 in a previous clinical update.
• Epicrispr Biotechnologies has secured $68 Million in Series B financing from multiple investors, as well as regulatory clearance from New Zealand’s Medsafe to initiate a clinical trial for its first-in-class disease-modifying epigenetic neuromuscular therapy, EPI-321. EPI-321 is being developed as a treatment for facioscapulohumeral muscular dystrophy (FSHD). It works by silencing aberrant expression of DUX4, a gene that is incorrectly activated in FSHD and leads to progressive muscle degeneration. Delivered systemically via a clinically-validated AAV vector, EPI-321 has demonstrated robust suppression of DUX4 expression and protection of muscle tissue in pre-clinical models. EPI-321 has already received FDA Fast Track, Rare Pediatric Disease, and Orphan Drug designations. See the press release for further details.
• Verve Therapeutics announced this week that the FDA has cleared its IND application for VERVE-102, which is being developed as a treatment for heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD). VERVE-102 is a novel, investigational in vivo base-editing therapy designed to be a single-course treatment that inactivates the PCSK9 gene in the liver to durably lower blood low-density lipoprotein cholesterol. For the IND submission, Verve provided the FDA with interim clinical data from the dose-escalation portion of the ongoing (in Canada and the UK) Heart-2 Phase 1b clinical trial of VERVE-102, which has so far been well-tolerated, with no treatment-related serious adverse events and no clinically significant laboratory abnormalities observed. See the official press release for further details.
• Beam Therapeutics announced in a press release published yesterday that the FDA has cleared its IND application to begin a clinical trial of BEAM-302 in the United States. BEAM-302 is an in vivo base-editing therapeutic candidate in development for the treatment of alpha-1 antitrypsin deficiency, and is currently being evaluated in a Phase 1/2 clinical trial in the UK. Earlier this month, the company announced positive initial data from that trial, demonstrating the first-ever clinical genetic correction of a disease-causing mutation through base-editing technology. You can read more about that update here.
• Earlier this week, YolTech Therapeutics announced promising interim clinical data from an investigator-initiated trial of YOLT-101. YOLT-101 is an in vivo base-editing therapeutic candidate in development for the treatment of heterozygous familial hypercholesterolemia (HeFH). Patients with HeFH have elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. YOLT-101 is designed to reduce the LDL-C levels in those patients through editing of PCSK9 gene, which enhances low-density lipoprotein receptor (LDLR)-mediated uptake of LDL particles. Read the official press release for further details.

Full-year 2024 financial results

• Precision BioSciences reports fourth quarter and fiscal year 2024 financial results and provides a business update. The company's meganuclease-based pipeline includes two clinical-stage in vivo liver-directed programmes for chronic hepatitis B and ornithine transcarbamylase deficiency (in partnership with iEUCURE). In the press release, Precision reported that its anticipated cash runway into the second half of 2026 is expected to enable achievement of key Phase 1 clinical inflection points across its wholly owned in vivo gene-editing programmes.
• 2seventy bio reports fourth quarter and full year 2024 financial results. The company recently entered a definitive merger agreement to be acquired by Bristol Myers Squibb at a price of $5.00 per share in an all-cash transaction that is expected to close in the second quarter of 2025. The company ended 2024 with approximately $184 million in cash, cash equivalents, and marketable securities. See the press release for further details.
• Vor Bio reports fourth quarter and full year 2024 financial results and provides a company update. The company reported that a clinical data update for VCAR33 is planned for the first half of 2025 and a trem-cel + Mylotarg clinical data update is planned for the second half of 2025. According to the press release, Vor Bio anticipates the initiation of the first trem-cel+VCAR33 treatment system clinical trial in the second half of 2025. Trem-cel is Vor Bio’s lead engineered haematopoietic stem cell product candidate and is developed from healthy donor haematopoietic stem and progenitor cells. These cells are CRISPR-Cas9-edited to delete the CD33 gene. CD33 is a cell surface antigen that is abundantly expressed in the vast majority of acute myeloid leukaemia (AML) cases, and it is one of the main validated target antigens in AML to date. VCAR33^ALLO is a CD33-targeting CAR-T cell therapy generated from healthy cells isolated from the same donor from which the patient was previously transplanted with trem-cell. The company reports that $55.6 million in private placement was completed in December 2024.
• Korro Bio reports full year 2024 financial results and provides business updates. The press release includes a summary of recent updates on Korro's RNA-editing therapeutic candidate for alpha-1 antitrypsin deficiency, KRRO-110, which is currently being evaluated in the Phase 1/2a REWRITE clinical trial with an interim readout expected in the second half of 2025. You can read more about KRRO-110 in a recent clinical trial update here. Financially, the company ended 2024 with $163.1 million in cash, cash equivalents and marketable securities. Cash runway into the second half of 2026 is expected to fund KRRO-110 through completion of the REWRITE trial and progress additional product candidates. See the official press release for further details.

Other industry news

• AccurEdit Therapeutics announced this week that the FDA has granted Orphan Drug Designation to its in vivo gene-editing candidate ART001. ART001 is a CRISPR-based therapy delivered via lipid nanoparticles (LNPs) that is designed to treat transthyretin amyloidosis (ATTR). It is currently the first and only LNP-based in vivo gene-editing product worldwide that has cleared an IND in China and the United States. Clinical data released to date shows that a single dose of ART001 can achieve a >90% reduction of transthyretin (TTR) in the serum, and that reduction has remained stable for more than 15 months, thus exceeding the natural renewal cycle of the human liver. Read the official press release here.
• Intellia Therapeutics announced this week that the FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to nexiguran ziclumeran (nex-z, also known as NTLA-2001) for the treatment of transthyretin (ATTR) amyloidosis with cardiomyopathy (ATTR-CM). The candidate, which is being evaluated in the Phase 3 MAGNITUTE trial, is designed to be a single-dose cure for ATTR by selectively reducing the levels of mutated TTR protein in the blood, through CRISPR-Cas9-based inactivation of the TTR gene in liver cells. Nex-z has been granted Regenerative Medicine Advanced Therapy designations by the FDA for both cardiomyopathy and polyneuropathy as well as Orphan Drug Designation by the FDA and European Commission. See the press release here.
• ERS Genomics Limited and Jumpcode Genomics announced a non-exclusive CRISPR/Cas9 license agreement yesterday. The agreement grants Jumpcode access to ERS’ CRISPR/Cas9 patent portfolio, empowering the company to advance the sensitivity and efficiency of next-generation sequencing and expand applications across multiple research and clinical areas.

Reviews and editorials

• Genome Editing Headwinds: Can CRISPR Stay on Target? In this editorial, Rodolphe Barrangou at North Carolina State University discusses how genome-editing companies face significant challenges amid decreased trust in scientific expertise and investor disappointment with clinical progress. Despite financial pressures forcing cutbacks across biotech, food, and agricultural genome-editing sectors, the article points to encouraging developments in clinical trials, crop advances, and regulatory progress as reasons for cautious optimism about the field's future potential.
• An Overview and Comparative Analysis of CRISPR-SpCas9 gRNA Activity Prediction Tools. Authors in China, Denmark, Spain and Ireland, provide a brief overview of in silico tools for CRISPR design, and assess the CRISPR datasets and statistical metrics used to evaluate model performance. They benchmark seven machine learning (ML) and deep learning (DL)-based CRISPR-Cas9 editing efficiency prediction tools across nine CRISPR datasets covering six cell types and three species. They found that the DL models CRISPRon and DeepHF outperform the other models exhibiting greater accuracy and higher Spearman correlation coefficient across multiple datasets. They have now compiled those CRISPR datasets and in silico prediction tools into a GuideNet resource web portal, aiming to facilitate and streamline the sharing of CRISPR datasets. They also summarise features affecting CRISPR gene-editing activity, providing important insights into model performance and the further development of more accurate CRISPR prediction models.
• Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence. This article highlights the critical discussion points from a workshop held in September 2024 by the Reagan-Udall Foundation for the FDA in collaboration with the FDA and the Gates Foundation. The workshop focused on exploring strategies for global regulatory convergence, the role of international collaborations and the potential pathways to making gene therapies affordable and accessible to all.
• CAR-T therapy dilemma and innovative design strategies for next generation. This review introduces and summarises the role of CRISPR and other innovative technologies in next-generation CAR-T-cell design and delivery to overcome the key barriers of current CAR-T cells.

News from CRISPR Medicine News

• The GenE-HumDi webinar '(Epi)genome editing in CAR T cells' featuring Dr. M. Silvia Roman Azcona from the University of Freiburg is now available on-demand. Watch it right here.
• On Wednesday, our sister publication CARBON published its monthly newsletter bringing you all the latest news on how gene editing can shape agriculture for the future to guarantee food security in times of population growth and climate change. Read it here.