Abstract
Two gene editing therapy developers have reduced their workforces, saying they needed to focus their limited resources on development of their most advanced programs.
Scribe Therapeutics said it was shrinking its staff by 20% and pivoting toward advancing genome editing and epigenetic modifying technologies that generated positive preclinical data last year.
Scribe’s lead pipeline program, which targets proprotein convertase subtilisin/kexin type 9 (PCSK9) in order to treat elevated low-density lipoprotein cholesterol (LDL-C), applies the company’s two platforms through separate candidates. One is STX1100, which uses the X-Editor (XE), a double-strand break genome editing approach that according to the company shows no detectable off-target editing.
The other platform is STX1150, a CasX-based epigenetic silencer, which uses Scribe’s Epigenetic Long-Term X-Repressor (ELXR) modifiers, designed to turn off gene expression of multiple genetic targets without cutting DNA.
“Building on the strong validation of our genome editing and epigenetic modifying technologies in non-human primates in 2024 we are now shifting our internal focus to clinical development,” Scribe co-founder, President, and CEO Benjamin Oakes, PhD, said in a statement to news outlets. “This evolution necessitates business adjustments to allocate resources to where they are most impactful.” 1
Intellia Therapeutics, which has used its gene editing technologies to develop CRISPR-based therapies, said it is slicing 27% of its staff over the course of 2025, and halting development of NTLA-3001, a treatment of alpha-1 antitrypsin deficiency-associated lung disease, and several research-stage programs.
The company said it will focus its development resources on two CRISPR therapeutic candidates. One is NTLA-2002, designed to reduce kallikrein activity and prevent attacks in people living with hereditary angioedema (HAE). The other is nexiguran ziclumeran (nex-z, formerly called NTLA-2001), which if approved would be the first one-time treatment for transthyretin (ATTR) amyloidosis. NTLA-2001 is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein and is the first CRISPR therapy candidate to be administered systemically to edit genes inside the human body.
Intellia said it expects to incur charges of approximately $8 million associated with the reorganization, which are anticipated to be incurred in the first quarter of 2025.
“We have made significant progress and built strong momentum in 2024 with three actively enrolling, Phase 3, pivotal studies. Our early clinical data for both NTLA-2002 and nex-z support novel, highly differentiated product profiles that directly address the significant unmet needs of patients and prescribers in HAE and ATTR,” said John Leonard, MD, Intellia’s President and CEO. “We understand the significant potential of our late-stage programs, and within a challenging market environment, have made a difficult decision to focus our resources predominantly on NTLA-2002 and nex-z where we have the greatest opportunity to create significant, near-term value.” 2
PFIZER ENDS HEMOPHILIA A GENE THERAPY COLLABORATION WITH SANGAMO THERAPEUTICS
Pfizer has ended its nearly 8-year, up to $545 million collaboration with Sangamo Therapeutics to develop Sangamo’s gene therapy candidate for adults with moderately to severe hemophilia A, giroctocogene fitelparvovec, less than a year after the companies announced positive topline data from a Phase III trial.
As a result, Sangamo will regain global development and commercialization rights to giroctocogene fitelparvovec as of April 21. As control of the program shifts from Pfizer back to Sangamo, all trial participants will continue to be monitored as planned during the transition period, Sangamo said.
In July 2024, Pfizer announced positive topline results from the Phase III AFFINE trial (NCT04370054) showing that the study met its primary objective of non-inferiority, as well as superiority, of total annualized bleeding rate (ABR) from week 12 through at least 15 months of follow-up post-infusion compared with routine Factor VIII (FVIII) replacement prophylaxis treatment. Following a single 3e13 vg/kg dose, giroctocogene fitelparvovec showed a statistically significant reduction in mean total ABR compared with the pre-infusion period (1.24 vs. 4.73).
Pfizer had been expected to lead submissions seeking regulatory approvals for giroctocogene fitelparvovec, including a Biologics Licensing Application (BLA) to the U.S. Food and Drug Administration (FDA), and a Marketing Authorization Application (MAA) to the European Medicines Agency.
“While we were surprised and extremely disappointed by Pfizer’s decision to end our collaboration so close to the anticipated BLA and MAA submissions respectively, especially given the compelling pivotal clinical trial data, we appreciate their collaboration in leading a robust and successful clinical development program and for advancing the asset to this important stage,” Sangamo CEO Sandy Macrae, MBChB, PhD, said. “We believe it is well positioned for regulatory submissions and potential commercialization.” 3
Macrae said Sangamo was committed to exploring a path forward for giroctocogene fitelparvovec, including seeking a new partner with the focus and understanding of the commercial environment for genomic medicines.
The company is also committed, he added, advancing its wholly owned neurology genomic medicine pipeline and progressing its Fabry gene therapy program isaralgagene civaparvovec (formerly ST-920) toward a potential BLA submission in the second half of 2025.
In neurology, Sangamo said it is preparing to begin enrolling patients for a Phase I/II study of ST-503 for idiopathic small fiber neuropathy in mid-2025. The company also expects to file a Clinical Trial Authorization (CTA) submission for the prion disease program in the fourth quarter of 2025. Both are subject to securing adequate additional funding.
AFFINE is open-label, multicenter, single-arm trial designed to assess the efficacy and safety of a single infusion of giroctocogene fitelparvovec in 75 adult men with moderately severe to severe hemophilia A. Before being included in assessments of the key endpoints of AFFINE’s primary efficacy analysis, 50 trial participants completed a minimum 6 months of routine Factor VIII replacement prophylaxis therapy during a lead-in study (NCT03587116) that provided data for comparison with post-giroctocogene fitelparvovec treatment.
ROCHE EXERCISES OPTION TO DEVELOP DYNO’S AAV VECTOR FOR NEUROLOGICAL GENE THERAPY
Roche has exercised its option to license from Dyno Therapeutics a novel capsid for use in a gene therapy program for an undisclosed neurological disease indication.
Roche’s option exercise triggered a $7 million payment to Dyno, with company also having the potential to earn more than $220 million in payments ties to achieving development, regulatory, and commercial milestone payments, plus royalties, all in connection with Roche’s use of Dyno’s capsid to develop and commercialize a neurological disease-targeting gene therapy.
The exercise of this license option concluded an initial collaboration by Dyno and Roche that began in 2020. In October 2024, the companies announced a second collaboration agreement providing Roche with further access to Dyno’s platform and sequence design methods for the treatment of neurological diseases, including Dyno’s Low-shot Efficient Accelerated Performance (LEAPSM) technology, designed to accelerate gene therapy vector engineering by generating high-performance out-of-distribution capsid proteins.
Dyno received $50 million upfront from Roche to launch the second collaboration, under which Dyno could receive more than $1 billion in potential preclinical, clinical, and sales milestone payments, plus royalties on net sales of commercial products. 4
“Granting the license of a Dyno capsid to a leading drug development company like Roche is a significant achievement for AI in gene therapy,” said Eric Kelsic, PhD, Dyno’s founder and CEO. “This latest advancement in one of our partnerships is further validation of the proven effectiveness of our gene delivery platform and continued and rapid advancement of our sequence design capabilities.” 4
REGENERON ACQUIRES OXULAR, ADDING TO EYE DISEASE PORTFOLIO
Regeneron Pharmaceuticals has acquired Oxular, an Oxford, U.K.-based developer of gene therapies for retinal diseases, for an undisclosed price.
The acquisition adds to a Regeneron eye disease portfolio anchored by the multi-indication vascular endothelial growth factor (VEGF) inhibitors Eylea® and Eylea HD (aflibercept), co-marketed with Bayer. The Eylea/Eylea HD franchise generated $12.875 billion in 2023.
Oxular develops gene therapies that apply two of the company’s technologies. One is Oxuspheres™, a drug-containing, biodegradable polymer system designed to deliver clinically therapeutic drug levels over prescribed treatment periods to targeted tissues involved in retinal disorders, while maintaining low drug levels elsewhere in the eye, all with the aim of minimizing off-target side effects.
Oxular’s other technology is Oxulumis®, a minimally invasive, semi-automated administration device for routine delivery of therapeutics via an illuminated microcatheter to the posterior suprachoroidal space of the eye, adjacent to specific tissues involved in retinal disease. Oxulumis are designed to enable safe, routine drug administration without penetrating the eye’s intraocular space.
The single disclosed clinical candidate in Oxular’s pipeline, OXU-001, is a formulation of dexamethasone using biodegradable Oxuspheres that are designed to be delivered via Oxulumis.
OXU-001 is a treatment for diabetic macular edema that has advanced to the Phase II OXEYE trial (NCT05697809), a two-part, randomized 52-week study launched in 2023. Patients were set to be monitored monthly for 52 weeks, with the primary endpoints at week 24 consisting of safety and efficacy.
Founded in 2014 as Precision Ocular, Oxular completed a $37 million financing led by Forbion in 2021. Proceeds from the financing were intended to fund Phase II human clinical trials evaluating OXU-001, as well as accelerate the development of the company’s early-product pipeline.
News of the acquisition was disclosed on January 2 in a LinkedIn post by Mark Gaffney, a strategic advisor and board member of Oxular who had served as its CEO until October 2024. Gaffney is now CEO of Calluna Pharma, a developer of first-in-class antibodies intended to treat inflammatory and fibrotic diseases.
“The ophthalmology team at Regeneron is uniquely positioned to maximize the use of Oxular’s proprietary technologies,” Gaffney wrote. “A special thank you to all of the employees, advisors, Board members and shareholders who made this transaction possible. I wish each of you all the best in your next ventures. Upward and onward!” 5
NOVARTIS REPORTS POSITIVE TOPLINE PHASE III DATA IN CHILDREN AND ADULTS WITH SMA
Novartis has reported positive topline data from its Phase III STEER trial (NCT05089656) evaluating the efficacy and safety of intrathecal onasemnogene abeparvovec (OAV101 IT), a one-time gene therapy candidate designed to treat spinal muscular atrophy (SMA) type 2 in treatment-naïve patients ages 2 to under 18 years who are able to sit but have never walked independently.
STEER met its primary endpoint by showing an increase from baseline across the study population in total Hammersmith Functional Motor Scale—Expanded (HFMSE) scores. The increase was seen in patients treated with OAV101 IT compared with sham controls indicating better motor function in patients with SMA.
The randomized, double-blind STEER trial’s efficacy and safety results for OAV101 IT were compared against sham controls in order to mimic the administration of an investigational drug, without delivering any active treatment, Novartis said.
The safety profile of OAV101 IT was favorable, with similar overall adverse events and serious adverse events between arms of the study. The most common adverse events were upper respiratory tract infection, pyrexia, and vomiting, Novartis said.
Novartis said it plans to share results from STEER with the U.S. Food and Drug Administration (FDA) and other regulatory agencies. Data will be presented at an upcoming medical meeting in 2025.
“The totality of evidence clearly supports a positive risk benefit profile of OAV101 which is expected to support registration covering a broad range of SMA patients,” said Shreeram Aradhye, MD, President, Development and Chief Medical Officer, Novartis. “We remain committed to leading innovation in SMA treatment through our one-time gene therapies, uniquely designed to replace the function of the missing or defective SMN1 gene.” 6
PRECIGEN SUBMITS BLA FOR RRP GENE THERAPY
Precigen has completed its rolling submission for a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for zopapogene imadenovec (also called PRGN-2012) for the treatment of adults with recurrent respiratory papillomatosis (RRP).
At deadline, Precigen said the submission was in the initial 60-day review period, during which time the FDA will decide whether to accept the BLA for further review and set a target action date under the Prescription Drug User Fee Act (PDUFA). The BLA included a request for priority review, which, if granted, would reduce the FDA’s review timeline from the standard 10-month to a priority 6-month review from the date the submission is accepted by the FDA.
PRGN-2012 is an investigational AdenoVerse® gene therapy designed to elicit immune responses directed against cells infected with human papillomavirus (HPV) 6 or HPV 11. PRGN-2012 has received the FDA’s Breakthrough Therapy Designation, Orphan Drug Designation, and accelerated approval pathway, as well as the European Commission’s Orphan Drug Designation.
If approved, PRGN-2012 would be the first FDA-authorized therapeutic for the treatment of adults with RRP.
Precigen’s BLA submission is supported by data from a pivotal Phase I/II clinical trial evaluating the safety and efficacy of PRGN-2012 in adult patients with RRP. Of the 38 total patients enrolled in the study, three received four administrations of PRGN-2012 at 1 × 1011 particle units (PU)/dose while 35 patients received four administrations of PRGN-2012 at the recommended phase 2 dose (RP2D) of 5 × 1011 PU/dose over a 12-week treatment period via subcutaneous injection.
The study met its primary endpoints, which included safety and Complete Response rate defined as the percentage of patients who required no RRP surgeries in the 12-month period following completion of treatment with PRGN-2012. Key secondary endpoints of the trial included HPV-specific immune responses, extent of papilloma growth as measured by Derkay scoring, and quality of life as measured by Vocal Handicap Index-10 (VHI-10).
“The submission of our BLA is an extremely important step in bringing the first therapy to fight this devastating disease,” said Helen Sabzevari, PhD, President and CEO of Precigen. “We look forward to working closely with the FDA on next steps now that we have completed the BLA submission and we are excited by the potential to bring PRGN-2012 to patients with RRP as quickly as possible.” 7
JAMES WILSON-FOUNDED GEMMABIO COMPLETES $34M SEED FINANCING
GEMMA Biotherapeutics (GEMMABio) has completed a $34 million seed financing round whose proceeds are intended to help it expand operations and fund programs to accelerate the development and delivery of gene therapies to patients worldwide.
Founded by gene therapy pioneer James M. Wilson, MD, PhD, GEMMABIO focuses on expanding research and global access to advanced therapies for patients living with rare diseases.
Double Point Ventures, Bioluminescence Ventures, and Earlybird Venture Capital co-led the seed round, with additional funding from Savanne Life Sciences.
“We are delighted by the enthusiastic support from our engaged and high-quality partners, who share our vision for the future of gene therapy,” said Dr. Wilson, the President and CEO of GEMMABio. “Their involvement comes at a pivotal moment in the industry, and together, we are committed to expanding and speeding access to affordable gene therapies for the patients who need them most.” 8
GEMMABio was launched on October 1 when Dr. Wilson stepped down as director of the Gene Therapy Program at the Perelman School of Medicine at the University of Pennsylvania. The company’s active programs include a collaboration with the Oswaldo Cruz Foundation (Fiocruz), the main supplier of immunobiologics, biopharmaceuticals, and diagnostics to the Brazilian Ministry of Health.
GEMMABio said it is actively seeking strategic partners with whom to collaborate on its mission of bringing innovative therapies to market.
In addition to his position at GEMMABio, Dr. Wilson is also Chairperson of Franklin Biolabs, a contract research organization that provides a full range of services to the global genetic medicines industry, from discovery to clinical vector manufacturing. Dr. Wilson is a former editor-in-chief and clinical development editor of Human Gene Therapy.