Industry Insights: Unpacking the FDA’s plausible mechanism pathway, regulatory turbulence, and progress in autoimmune cell therapy

Summary

Cell & Gene Therapy Insights presents a comprehensive overview of the latest developments shaping the cell and gene therapy landscape in October/November. This Industry Insights update reviews significant regulatory actions, including the US FDA’s recent stance on key investigational products, alongside major financing rounds, strategic acquisitions, and emerging clinical data across oncology, rare disease, and autoimmune indications.

COMPANY START-UPS

Azalea Therapeutics launches with US $82 million to pioneer in vivo gene editing [1]

Azalea Therapeutics has launched with Jennifer Doudna as a scientific co-founder, backed by an initial financing round of US $82 million, to push forward its vision of engineering therapeutic cells in vivo. For the advanced-therapies field, this launch underscores the growing pivot from manufacturing cells ex vivo toward in vivo interventions, but also heightens scrutiny around delivery specificity, off-target risk, and regulatory readiness.

REGULATORY UPDATES

FDA outlines regulatory pathway to support bespoke treatments for ultra-rare disease [2]

The FDA has introduced a new ‘plausible mechanism’ regulatory pathway to accelerate bespoke therapies for ultra-rare and single-patient conditions. Detailed in a New England Journal of Medicine article by Makary and Prasad, the framework enables approval without traditional trials when a scientifically credible mechanism of action is demonstrated.

US FDA roadblock for uniQure’s promising AMT-130 gene therapy for Huntington’s [3] 

The FDA has advised that existing Phase 1/2 data for uniQure’s AMT-130 gene therapy in Huntington’s disease are insufficient to support a marketing submission. Despite this regulatory pause, long-term data continue to show encouraging durability, and the company is engaging with US, UK, and EU regulators to define next steps.

FDA places clinical hold on Intellia’s CRISPR trials following liver event [4] [5]

The US FDA has issued a clinical hold on Intellia Therapeutics’ two Phase 3 MAGNITUDE trials of its in vivo CRISPR candidate, nexiguran ziclumeran (nex-z), following a serious liver-related adverse event. The company had paused dosing and screening days earlier after a patient experienced Grade 4 liver transaminases and increased total bilirubin. Intellia is working with regulators and investigators to identify the cause and implement safety measures.

FDA guidance update for drug development [6]

The US FDA has issued the final guidance report entitled Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments, the third in its PFDD series. The document provides a structured framework for ensuring that clinical outcome assessments capture aspects of health that are meaningful to patients and are scientifically robust for regulatory decision-making.

FINANCING AND MARKET TRENDS

AAVantgarde Bio secures US $141 million Series B for retinal gene therapy trials [7]

AAVantgarde Bio has raised US $141 million in Series B financing to advance its dual-AAV gene therapy programs for inherited retinal diseases. Funds will progress two lead candidates into planned clinical proof-of-concept trials: AAVB-039 for Stargardt disease (CELESTE trial) and AAVB-081 for Usher 1B syndrome (LUCE trial).

MERGERS AND ACQUISITIONS

Bristol Myers Squibb acquires Orbital Therapeutics for US $1.5 billion [8]

Bristol Myers Squibb has agreed to acquire Orbital Therapeutics for US $1.5 billion, expanding its cell therapy portfolio into in vivo CAR-T and RNA-based platforms. Orbital’s lead program, OTX-201, a next-generation CAR-T cell therapy approach, uses circular RNA to drive CD19 CAR expression in vivo. The deal underscores major pharma interest in RNA delivery technologies.

Lilly to acquire Adverum Biotechnologies [9]

Eli Lilly & Co. has agreed to acquire Adverum Biotechnologies, developer of the intravitreal gene therapy Ixoberogene soroparvovec (Ixo-vec) for wet age-related macular degeneration (AMD), in a transaction valued at up to US $1.5 billion.

The acquisition, expected to close in Q4 2025, underscores pharma’s growing interest in one-time AAV treatments that could replace frequent anti-VEGF injections.

CLINICAL TRIALS AND RESEARCH

Caribou Biosciences reports positive Phase 1 CaMMouflage trial data for CB-011 [9]

Caribou Biosciences reported compelling early data from its Phase 1 CaMMouflage trial of the allogeneic anti-BCMA CAR-T therapy CB-011 in relapsed/refractory multiple myeloma. Among 12 patients treated at the recommended dose, the overall response rate was 92%, with 75% achieving complete response and 91% minimal residual disease negativity.

Lyell Immunopharma secures global rights to next-generation CAR-T for metastatic colorectal cancer [10]

Lyell Immunopharma has acquired exclusive global rights to a next-gen CAR-T candidate targeting metastatic colorectal cancer, LYL273. The product, currently in clinical development, strengthens Lyell’s expansion into solid tumor cell therapies. LYL273 has demonstrated a 67% overall response rate, an 83% disease control rate, and a manageable safety profile in patients with refractory metastatic colorectal cancer enrolled in an ongoing US Phase 1 clinical trial.

Cell therapy momentum builds in autoimmune disease [12] [13] [14] [15] [16]

Multiple developers reported encouraging clinical progress for cell-based autoimmune therapies. Sonoma Biotherapeutics’ Phase 1 REGULATE-RA trial of SBT-77-7101 showed early efficacy in rheumatoid arthritis. Kyverna Therapeutics’ KYSA-6 Phase 2 data demonstrated 100% clinical response in myasthenia gravis. Bristol Myers Squibb’s Breakfree-1 study of CD19 NEX-T™ CAR-T therapy showed signs of early clinical activity across lupus and systemic sclerosis. Cabaletta Bio presented first rese-cel data without preconditioning in pemphigus vulgaris, while Cartesian Therapeutics advanced mRNA-engineered CAR-T programs toward late-stage development.

Regeneron reports encouraging gene therapy outcomes in pediatric hearing loss [17]

Regeneron Pharmaceuticals reported that its investigational gene therapy DB-OTO achieved meaningful and sustained improvements in hearing and speech perception in children with otoferlin-related profound genetic hearing loss.

Multiple sclerosis: Tr1X IND clearance [18] 

The FDA has cleared an Investigational New Drug (IND) application for Tr1X’s first-in-class allogeneic CAR-engineered Treg cell therapy TRX319 for progressive multiple sclerosis (MS) [18].

Hear how Tr1X navigated IND-enabling studies under FDA scrutiny and avoided a projected 6-month setback—gaining IND clearance in only 30 days in this on-demand Cell and Gene Therapy Insights webinar.

COLLABORATIONS AND PARTNERSHIPS

Nona Biosciences expands collaboration with Umoja Biopharma to advance in vivo CAR-T therapies [19]

Nona Biosciences has expanded its partnership with Umoja Biopharma, building on a multi-target antibody-discovery collaboration to develop novel in vivo CAR-T cell therapies. The agreement highlights the trend toward off-the-shelf and direct in vivo engineering approaches in CAR-T.

MeiraGTx in ophthalmology gene therapy collaboration with Eli Lilly

MeiraGTx Holdings plc has entered into a strategic partnership with Eli Lilly and Company, granting exclusive global rights to its AAV-AIPL1 program and other ophthalmology gene therapy technologies. The deal includes a US $75 million upfront payment and potential milestone payments exceeding US $400 million, with tiered royalties on future sales.

References

1. Azalea Therapeutics. Azalea Therapeutics launches with US $82 million financing to redefine precision genomic medicines by engineering cells directly inside each patient. Nov 4, 2025. 

2. Makary M, Prasad V. A plausible-mechanism pathway for bespoke therapeutics. N. Engl. J. Med. 2025; 393. Crossref

3. uniQure N.V. uniQure provides regulatory update on AMT-130 for Huntington’s disease. Nov 3, 2025. 

4. US Food and Drug Administration. Form 8-K filing: Intellia Therapeutics Inc. Oct 29, 2025.

5. Intellia Therapeutics. Intellia Therapeutics provides update on MAGNITUDE clinical trials of nexiguran ziclumeran (nex-z). Oct 27, 2025.

6. US Food and Drug Administration. Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments. Jun 2022.

7. AAVantgarde Bio. AAVantgarde closes $141 million Series B financing to advance its clinical programs in Stargardt disease and Usher 1B syndrome. Nov 3, 2025. 

8. Bristol Myers Squibb. Bristol Myers Squibb strengthens and diversifies cell-therapy portfolio with acquisition of Orbital Therapeutics. Oct 10, 2025.

9. Eli Lilly & Co. Lilly to acquire Adverum Biotechnologies. Oct 24, 2025.

10. Caribou Biosciences. Caribou Biosciences announces positive data from CaMMouflage Phase 1 trial of CB-011 in multiple myeloma. Nov 3, 2025.

11. Lyell Immunopharma. Lyell Immunopharma acquires exclusive global rights to a next-generation CAR-T-cell product candidate in clinical development for metastatic colorectal cancer. Nov 10, 2025.

12. Sonoma Biotherapeutics. Sonoma Biotherapeutics announces positive interim safety and efficacy data from Phase 1 REGULATE-RA study of SBT-77-7101 in refractory rheumatoid arthritis. Oct 29, 2025.

13. Kyverna Therapeutics. Kyverna Therapeutics announces positive interim Phase 2 data from KYSA-6 study of KYV-101 in generalized myasthenia gravis. Oct 29, 2025.

14. Bristol Myers Squibb. Bristol Myers Squibb presents encouraging data from Phase 1 Breakfree-1 study of CD19 NEX-T CAR-T cell therapy in three chronic autoimmune diseases at ACR Convergence 2025. Oct 25, 2025.

15. Cabaletta Bio. Cabaletta Bio presents first rese-cel data with no preconditioning demonstrating biologic activity and early clinical responses at the 2025 ESGCT Annual Congress. Oct 9, 2025.

16. Cartesian Therapeutics. Cartesian Therapeutics reports third-quarter 2025 financial results and highlights clinical progress across mRNA cell-therapy pipeline for autoimmune diseases. Nov 2025.

17. Regeneron Pharmaceuticals. DB-OTO results in the New England Journal of Medicine showcase dramatic and sustained improvements in hearing and speech perception in children with profound genetic hearing loss. Oct 12, 2025.

18. Tr1X. Tr1X announces FDA clearance of IND application for TRX319, a first-in-class allogeneic CAR-Tr1 Treg cell therapy for progressive multiple sclerosis, and $50 million in additional financing. Oct 14, 2025.

19. Nona Biosciences. Nona Biosciences announces expansion of collaboration with Umoja Biopharma to advance in vivo CAR-T cell therapies. Nov 4, 2025. 

20. MeiraGTx Holdings plc. MeiraGTx enters into strategic collaboration with Eli Lilly and Company to develop and commercialize genetic medicines in ophthalmology. Nov 10, 2025.