Industry Insights: From rare disease to chronic indications, cell and gene therapies broaden their impact

Summary

Wrapping up 2025 and commencing 2026, this edition highlights the continued expansion of cell and gene therapies beyond ultra-rare indications into chronic, degenerative, and inflammatory diseases, underpinned by advances in clinical and manufacturing maturity. Momentum continued across autologous and allogeneic cell therapies, including Parkinson’s and Duchenne muscular dystrophy programs, alongside efforts to extend engineered cell modalities beyond oncology, with CAR-Tregs explored in cardiovascular inflammation and CAR-NKT positioned as an off-the-shelf approach for solid tumors. US FDA actions reflected both expansion and caution, with approvals broadening access to gene replacement therapies alongside ongoing efforts to address AAV-associated safety risks. Ophthalmology emerged as a key focus, spanning first-in-human bioprinted corneal implantation, stem cell-derived retinal therapies in dry age-related macular degeneration (AMD), and a partnership targeting intravitreal AAV delivery for intermediate AMD. Business activity remains agile, with some promising financings, newco launches, and an acquisition centered on lipid nanoparticle delivery platforms.

COMPANY START-UPS

Link Cell Therapies launched from stealth with a $60 million Series A to advance logic-gated CAR-T programs [1]

Link Cell Therapies launched from stealth and reported a $60 million Series A financing led by Johnson & Johnson Innovation – JJDC, Inc., with participation from Samsara BioCapital, Sheatree Capital, Wing Venture Capital, and strategic investors including Bristol Myers Squibb and Kyowa Kirin. Link said it had raised $92 million across seed and Series A rounds. The company stated its lead program, LNK001 in renal cell carcinoma, was on track for an investigational drug application and Phase 1 dosing in 2026, with a colorectal cancer program targeting development candidate selection in 2026 and human studies in 2027 [1].

Addition Therapeutics emerged from stealth with $100 million to develop LNP-delivered RNA-to-DNA genetic medicines [2]

Addition Therapeutics emerged from stealth with $100 million to develop gene therapies intended to address limitations of viral vector delivery and durability. The company described a lipid nanoparticle (LNP) platform delivering RNA-to-DNA cargo targeted to specific genomic regions, and cited applicability across rare and chronic diseases, including an HIV program in collaboration with the Gates Foundation designed to drive long-term expression of protective antibodies.

REGULATORY UPDATES

Novartis received US FDA approval for Itvisma, an intrathecal gene replacement therapy for SMA in older patients [3]

Novartis reported US FDA approval of Itvisma, described as an intrathecal version of onasemnogene abeparvovec (Zolgensma), expanding gene replacement therapy access to patients with spinal muscular atrophy (SMA) beyond infants. The company stated it planned an imminent launch and listed a $2.59 million price. Novartis said the approval was supported by Phase 3 data showing improved and stabilized motor function. The intrathecal route was positioned to enable dosing in children aged 2 years and older, as well as teens and adults.

Sarepta received US FDA clearance to start ENDEAVOR Cohort 8 to evaluate a sirolimus-based immunosuppression regimen with ELEVIDYS [4]

Sarepta announced US FDA clearance to initiate Cohort 8 of the ENDEAVOR study to evaluate an enhanced sirolimus-based immunosuppression regimen intended to reduce acute liver injury and acute liver failure associated with AAV gene therapy in non-ambulatory Duchenne muscular dystrophy patients receiving ELEVIDYS. The company said ~25 non-ambulatory participants were expected to receive sirolimus as part of the regimen, and that Cohort 8 was expected to begin before year-end. Sarepta added that decisions on resuming commercial dosing for this population would be made in collaboration with the FDA after reviewing Cohort 8 data.

The US FDA approved Waskyra, an ex vivo lentiviral HSC gene therapy for Wiskott–Aldrich syndrome developed by a nonprofit [5]

A report described FDA approval of Fondazione Telethon ETS’s etuvetidigene autotemcel (Waskyra) for Wiskott–Aldrich syndrome (WAS), characterizing it as the first US gene therapy approval led by a nonprofit organization and the first gene therapy approved for WAS. The ex vivo therapy involved harvesting patient hematopoietic stem cells (HSCs), engineering them with lentiviral vectors to add a functional WAS gene sequence, and reinfusing the modified cells following conditioning with rituximab, busulfan, and fludarabine. The approval was based on two open-label, single-arm trials in 27 patients, with reported reductions in severe infection rates (from 2.0 to 0.2 infections per patient-year) and moderate/severe bleeding events (from 2.0 to 0.8 events per patient-year) after treatment, with follow-up reported up to 13.3 years.

MARKET TRENDS

Aspen Neuroscience raised $115 million to advance its autologous Parkinson’s cell therapy program [6]

Aspen Neuroscience reported the close of a $115 million Series C financing to support clinical development of ANPD001, an autologous induced pluripotent stem cell (iPSC)-derived dopaminergic neuronal precursor cell therapy for moderate to advanced Parkinson’s disease. The round was co-led by OrbiMed, ARCH Venture Partners, Frazier Life Sciences, and Revelation Partners, with new participation including Kite, a Gilead company). Aspen said proceeds would support ongoing ANPD001 trials, manufacturing scale-up for clinical and commercial supply, and pipeline expansion into additional neurological indications. The company highlighted dosing in the Phase 1/2a ASPIRO trial Cohort 3 using a cryopreserved, ready-to-dose commercial formulation and noted FDA Fast Track designation for ANPD001.

XOMA Royalty agreed to acquire Generation Bio and add its cell-targeted LNP delivery platform to its portfolio [7]

XOMA Royalty announced an agreement to acquire Generation Bio for $4.2913 per share in cash, with Generation Bio stockholders also receiving a non-transferable contingent value right (CVR). The CVR was structured to provide potential payments tied to net cash at closing above $29 million, potential savings related to Generation Bio’s Cambridge lease obligations, and proceeds from existing and future licensing of Generation Bio assets. XOMA said Generation Bio’s cell-targeted LNP delivery platform for small interfering RNA and other nucleic acid therapies would be included in XOMA’s portfolio. The CVR also provided for a share of proceeds from Generation Bio’s collaboration with Moderna, including potential development and commercial milestones and royalties on sales, delivered on a sliding scale up to 90% to CVR holders.

RESEARCH AND DEVELOPMENT HIGHLIGHTS

Penn researchers engineered anti-oxLDL CAR-Tregs that reduced atherosclerotic plaque in mice [8]

Researchers at the University of Pennsylvania reported a preclinical approach using CAR-T cells built from regulatory T cells (Tregs) to suppress inflammation in atherosclerosis. The team engineered CAR-Tregs targeting oxidized LDL (OxLDL) and showed, in initial in vitro experiments with human cells, that the engineered cells suppressed inflammatory responses to OxLDL and reduced plaque-associated cell buildup. In a mouse model predisposed to hypercholesterolemia and atherosclerosis, treatment with a mouse anti-OxLDL CAR-Treg reduced atherosclerotic plaque burden by ~70% after ~12 weeks versus controls, without reported disruption of general immune function. The investigators and Penn formed a spinout, Cartio Therapeutics, to advance the program toward clinical testing.

UCLA researchers developed an off-the-shelf CAR-NKT approach targeting mesothelin in pancreatic cancer models [9]

UCLA researchers described a preclinical engineered cell therapy platform using invariant natural killer T (NKT) cells modified with CAR targeting mesothelin (CAR-NKT) for pancreatic cancer. The team reported that the cell product could be mass-produced from donated blood stem cells and stored as an off-the-shelf therapy, and cited an estimated cost of ~$5,000 per dose. In orthotopic and metastatic mouse models (including liver metastasis models), the CAR-NKT cells were reported to home to tumor sites, infiltrate tumors, slow tumor growth, and extend survival, with minimal exhaustion signals in the tested settings. The investigators stated they were preparing submissions to the FDA to initiate clinical trials.

CLINICAL TRIALS AND RESEARCH

Hope Biosciences reported Phase 2 data for an allogeneic adipose-derived MSC therapy in early to moderate Parkinson’s disease [10]

Hope Biosciences Research Foundation reported positive topline results from a Phase 2 randomized, double-blind, placebo-controlled, single-center trial (NCT04995081) evaluating allogeneic adipose-derived mesenchymal stem cells (HB-adMSCs) in early to moderate Parkinson’s disease. Sixty participants were enrolled (30 treatment; 30 placebo) and received six intravenous infusions of 200 million cells over 32 weeks, with end of study at 52 weeks. The trial met its primary endpoint, with statistically significant motor function improvements versus placebo based on clinician-rated MDS-UPDRS Part III. By the sixth infusion, the treatment group achieved a mean change from baseline of −9.82 points versus −0.50 in placebo (adjusted mean difference −9.32; 95% CI [−15.11, −3.54]; p=0.0023). The organization reported the regimen was safe and tolerable.

Kyverna with positive registrational Phase 2 KYSA-8 data for miv-cel in stiff person syndrome [11]

Kyverna Therapeutics reported positive topline data from KYSA-8, a single-arm registrational Phase 2 study of mivocabtagene autoleucel (miv-cel; KYV-101), an autologous CD19-targeting CAR-T with CD28 co-stimulation, in stiff person syndrome. Twenty-six patients received a single dose and were followed through the week 16 primary analysis timepoint. The company reported statistically significant improvement in timed 25-foot walk (p=0.0002) with a median 46% improvement at week 16; 81% exceeded a 20% improvement threshold. Secondary endpoints (including modified Rankin Scale and stiffness and ambulation indices) were reported as highly significant (all p<0.0001), and 100% remained free of immunotherapies at last follow-up. Kyverna reported no high-grade cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome and said it planned a BLA submission in 1H 2026.

Precise Bio dosed the first patient with a 3D-bioprinted corneal implant in a Phase 1 study [12]

Precise Bio announced the first successful human implantation of PB-001, a cell-based, 3D-bioprinted corneal implant manufactured from cultured human corneal cells. The procedure was performed on October 29, 2025, at Rambam Medical Center in an ongoing Phase 1, single-arm trial in patients with corneal edema due to endothelial dysfunction. The company said PB-001 was produced using a robotic 3D-bio-fabrication system at a GMP facility at Sheba Medical Center, and was designed for cryopreservation and use with standard delivery devices. The study planned to enroll 10–15 patients and evaluate safety and tolerability, with exploratory 6-month efficacy outcomes; topline results were expected in 2H 2026.

Michigan Medicine reported early Phase 1/2a data for adult stem cell-derived RPE transplants in advanced dry AMD [13]

Michigan Medicine researchers reported early findings from a Phase 1/2a study evaluating retinal pigment epithelial (RPE) stem cell transplants for advanced dry age-related macular degeneration (AMD). The RPE stem cells were derived from adult postmortem donor eye tissue and were described as lineage-restricted to mature into RPE cells. In the lowest-dose cohort, six participants received 50,000 cells during ocular surgery; the investigators reported no serious inflammation or tumor growth. The treated eyes showed vision improvements compared with untreated eyes, with the low-dose cohort reading 21 additional letters on a standard eye chart 1 year after treatment. The team was monitoring additional cohorts dosed at 150,000 and 250,000 cells and stated that later-stage clinical development would be considered if safety remained acceptable.

Capricor reported positive topline Phase 3 HOPE-3 results for deramiocel in Duchenne muscular dystrophy [14]

Capricor Therapeutics reported positive topline results from HOPE-3, a pivotal Phase 3 randomized, double-blind, placebo-controlled trial (n=106) evaluating deramiocel, an investigational cell therapy, in Duchenne muscular dystrophy. The company said the study met the primary endpoint (PUL v2.0; p=0.03), and a key secondary cardiac endpoint (LVEF; p=0.04), with statistical significance achieved across all type 1 error-controlled secondary endpoints. Participants received intravenous deramiocel (150 million cells per infusion) or placebo every 3 months for 12 months. Capricor reported a safety and tolerability profile consistent with prior experience and said it planned to submit a response to a previously received Complete Response Letter incorporating HOPE-3 data.

First-in-human stem cell gene therapy shows early promise for Hunter syndrome [15]

Researchers at the University of Man­chester have reported early clinical progress from a first-in-human stem cell gene therapy for Hunter syndrome, or mucopolysaccharidosis type II, following treatment of a 3-year-old patient at Royal Manchester Children’s Hospital. The one-off autologous therapy involves ex vivo genetic modification of HSCs to restore production of the deficient enzyme, with the aim of achieving systemic and central nervous system delivery. Several months post-transplant, the patient has discontinued weekly enzyme replacement therapy and is showing sustained high circulating enzyme levels. The investigator-led study, sponsored by the University of Manchester, will enroll five children and builds on a decade of translational development. The approach could offer a safer, more effective alternative to donor bone marrow transplantation and has potential applicability across other inherited metabolic disorders.

COLLABORATIONS AND PARTNERSHIPS

Ikarovec optioned VectorBuilder’s intravitreal AAV capsid technology for IKAR-003 in intermediate AMD [16]

Ikarovec and VectorBuilder announced an exclusive worldwide option agreement for VectorBuilder’s AAV capsid technology to support Ikarovec’s gene therapy candidate IKAR-003 for intermediate AMD. Ikarovec said that, following further evaluation, the parties would enter a strategic partnership in which Ikarovec would lead clinical development and commercialization, with the proposed deal expected to be worth over $1 billion. The companies stated the capsid was intended to enable intravitreal delivery of IKAR-003, a one-time dual-pathway gene therapy combining neuroprotection and complement modulation to prevent progression to geographic atrophy or wet AMD. VectorBuilder cited non-human primate data indicating broad retinal transduction via intravitreal administration, including macular cell targeting.

References

1. Link cell therapies launches with vision of advancing CAR-T therapies in solid and liquid tumors. PR Newswire. Dec 15, 2025.

2. Wu G. Addition emerges with $100M to make gene therapies for chronic and rare diseases. BioPharma Dive. Dec 17, 2025.

3. Novartis. Novartis receives FDA approval for Itvisma^®, the only gene replacement therapy for children two years and older, teens, and adults with spinal muscular atrophy (SMA). Nov 24, 2025.

4. Sarepta. Sarepta announces approval to begin ENDEAVOR cohort 8 to evaluate enhanced immunosuppression regimen as part of ELEVIDYS gene therapy for non-ambulant individuals with Duchenne. Nov 25, 2025.

5. Mullard A. FDA approves first gene therapy from a non-profit organization, but pricing and access questions remain. Nat. Rev. Dec 17, 2025.

6. Incorvaia D. Aspen enriches Parkinson’s cell therapy trial with Kite-backed $115M series C. Fierce Biotech Nov 20, 2025.

7. XOMA Royalty. XOMA Royalty enters into agreement to acquire Generation Bio. Dec 15, 2025.

8. Penn Medicine. New CAR T strategy targets most common form of heart disease. Nov 21, 2025.

9. Wang L. UCLA scientists develop one-product-fits-all immunotherapy for pancreatic cancer. UCLA Health Nov 24, 2025.

10. Hope Biosciences Research Foundation. Hope Biosciences Research Foundation Reports Promising Phase II Trial Results for Stem Cell Therapy in Parkinson’s Disease. Business Wire Dec 22, 2025.

11. Kyverna Therapeutics. Kyverna Therapeutics announces positive topline data from registrational KYSA-8 trial of miv-cel (KYV-101) in stiff person syndrome. Dec 15, 2025.

12. Precise Bio. Precise Bio Achieves World’s First 3D-Bio-Printed Corneal Implant. BioSpace Nov 20, 2025.

13. Michigan Medicine – University of Michigan. Stem cell therapy helps AMD patients see again. ScienceDaily Nov 22, 2025.

14. Capricor Therapeutics. Capricor Therapeutics announces positive topline results from pivotal Phase 3 HOPE-3 study of deramiocel in Duchenne muscular dystrophy. Dec 3, 2025.

15. University of Manchester. New hope for children with devastating rare genetic disorder, thanks to world-first research in Manchester. Nov 24, 2025.

16. Ikarovec. Ikarovec to advance pipeline with exclusive worldwide option to VectorBuilder’s intravitreal capsid technology. Jan 6, 2026.