The fourth quarter of 2025 represented a definitive period of bifurcation in the advanced therapies sector. Between October and December, the cell therapy field simultaneously demonstrated its greatest clinical maturity to date- with functional cures becoming a realistic endpoint in multiple myeloma and lymphoma- while enduring a severe commercial and operational contraction among mid-sized and large pharmaceutical players. This dichotomy between clinical ascendancy and commercial consolidation defined the “exciting” and “non-exciting” developments of the quarter.
On the clinical front, the American Society of Hematology (ASH) Annual Meeting in December and the Society for Immunotherapy of Cancer (SITC) Annual Meeting in November provided unequivocal validation of next-generation modalities. The dominance of B-cell maturation antigen (BCMA) targeting agents in multiple myeloma was solidified by long-term survival data from Legend Biotech and Johnson & Johnson’s Carvykti, while Kite Pharma and Arcellx unveiled potentially best-in-class safety data for anito-cel, challenging the current standard of care.
Conversely, the “non-exciting” developments were characterized by a brutal correction in business strategy. The wholesale exit of Takeda and Galapagos from the cell therapy space in October marked a significant retreat of generalist pharma companies from internal cell therapy research, driven by the punishing economics of autologous manufacturing and the saturation of key targets. This consolidation was accompanied by a wave of layoffs and pipeline prunings that underscored a shifting investment thesis: capital is moving away from “me-too” autologous assets toward scalable, off-the-shelf, or in vivo platforms, and increasingly toward autoimmune indications.
1. The Hematologic Arena: Refining Efficacy and Redefining Safety
The hematologic malignancy space, particularly multiple myeloma (MM) and large B-cell lymphoma (LBCL), remains the primary theater of operation for cell therapy. Q4 2025 saw the narrative shift from “establishing efficacy” to “optimizing survivorship” and “democratizing access” through improved safety profiles and reduced manufacturing timelines.
1.1. The Battle for BCMA Supremacy: Anito-cel vs. Carvykti
The most fiercely contested segment of the cell therapy market in Q4 2025 was the BCMA-targeted landscape for relapsed/refractory multiple myeloma (r/r MM). While Legend Biotech and Johnson & Johnson’s Carvykti (ciltacabtagene autoleucel) has established itself as the efficacy benchmark, data presented at ASH 2025 by Kite Pharma (a Gilead company) and Arcellx regarding anitocabtagene autoleucel (anito-cel) suggests a formidable challenger has arrived.
1.1.1 Anito-cel: The Safety Differentiator
The Phase 2 iMMagine-1 trial results presented in December were a centerpiece of the ASH meeting. Anito-cel, which utilizes a novel D-Domain binder rather than a traditional single-chain variable fragment (scFv), achieved a 96% overall response rate (ORR) and a 74% complete response/stringent complete response (CR/sCR) rate in heavily pretreated patients.
However, the critical insight from this dataset lies not in the efficacy- which is comparable to Carvykti- but in the safety profile. The iMMagine-1 trial reported no cases of delayed neurotoxicity, such as Parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome, and no immune effector cell-associated enterocolitis. These delayed neurotoxicities have been a distinct liability for Carvykti, often requiring prolonged monitoring and hesitancy among community oncologists.
| Metric | Anito-cel (iMMagine-1) | Clinical Implications |
| Overall Response Rate (ORR) | 96% | Comparable to best-in-class, establishing high efficacy floor. |
| Complete Response (CR/sCR) | 74% | High depth of response in triple-class exposed patients. |
| Median Time to Response | 1 month (MRD neg) | Rapid kinetics crucial for aggressive disease control. |
| Delayed Neurotoxicity | 0% | Major differentiator allowing for potential outpatient use. |
| Parkinsonism | 0% | Eliminates a key safety concern associated with cilta-cel. |
| Grade 3+ ICANS | ~8% | Manageable toxicity profile for community adoption. |
By demonstrating a cleaner neurotoxicity profile, anito-cel effectively positions itself as the “community-ready” BCMA CAR-T. In the broader commercial context, this safety advantage addresses the primary bottleneck in CAR-T expansion: the capacity of academic medical centers. If anito-cel can be safely administered in outpatient settings or community hospitals due to its predictable toxicity profile, it could rapidly capture market share upon its anticipated 2026 launch.
1.1.2 Carvykti: Establishing the Cure Fraction
In response to the safety challenge from anito-cel, Legend Biotech and J&J focused on demonstrating unparalleled long-term durability. Updated data from the Phase 3 CARTITUDE-4 study presented at ASH demonstrated that in patients with standard-risk cytogenetics, the 30-month progression-free survival (PFS) rate was 80.5%.
This data is statistically profound. In the context of r/r MM, a disease historically characterized by inevitable relapse, a flattening of the PFS curve at 2.5 years suggests the existence of a “cure fraction”- a subset of patients who may never relapse. Legend Biotech reinforced this narrative by highlighting that patients treated in earlier lines (1-3 prior lines) exhibit better immune fitness (higher CD4+ naïve T cells), which correlates with these durable outcomes.
Commercially, Legend reported Q3 net trade sales of approximately $524 million, an 84% year-over-year increase, signaling that despite manufacturing constraints, demand remains voracious. The company’s move to double manufacturing capacity in 2025, including at its Tech Lane facility in Belgium, indicates an aggressive defense of its first-mover advantage in the high-efficacy BCMA segment.
1.2 Long-Term Curative Intent in Lymphoma
While myeloma therapies push for longevity, lymphoma therapies are now confirming cures. Kite Pharma presented a pooled analysis of 4-year follow-up data from the ZUMA-7 trial and 2-year data from the ALYCANTE trial at ASH 2025.
The data revealed a 4-year overall survival (OS) rate of roughly 44% in patients treated with Yescarta (axicabtagene ciloleucel) for second-line LBCL. This confirms that for nearly half of patients, a single infusion is curative. The consistency of efficacy across the randomized ZUMA-7 and the real-world ALYCANTE cohorts validates the therapy’s utility regardless of transplant eligibility, effectively expanding the addressable patient population to older or frailer individuals who were previously restricted to palliative care or less effective chemotherapies.
Furthermore, comparative real-world analyses presented at ASH 2025 highlighted significant differences in toxicity profiles among approved CD19 CAR-T therapies. A study comparing Yescarta, Kymriah (tisagenlecleucel), and Breyanzi (lisocabtagene maraleucel) found that Kymriah showed significantly lower rates of cytokine release syndrome (CRS) (44.4%) compared to Yescarta (68.6%), while Breyanzi demonstrated the lowest rates of neurotoxicity (ICANS) at 16%. This stratification allows clinicians to tailor therapy choice based on patient frailty and comorbidity profiles, a hallmark of a maturing therapeutic class.
1.3 The Next Generation: Rapid Manufacturing and Dual Targeting
A critical theme in Q4 was the industry’s attempt to reduce the “vein-to-vein” time- the interval between cell collection and infusion- which remains a significant cause of patient dropout within autologous cell therapy sector.
1.3.1 Novartis T-Charge Platform
Data presented on rapcabtagene autoleucel (rapca-cel) in B-cell acute lymphoblastic leukemia (ALL) utilized the T-Charge platform, which reduces ex vivo culture time to less than two days. This process preserves T-cell stemness (Tscm), theoretically leading to better persistence in the body. The Phase 1 data showed a 70% complete remission rate at the lowest dose level, with a manageable safety profile, validating the rapid manufacturing hypothesis. By reducing culture time, Novartis aims to address one of the primary logistical failures of Kymriah- manufacturing out-of-spec (OOS) rates and long turnaround times.
1.3.2 Kite’s Bicistronic CARs
Kite presented data on KITE-753 and KITE-363, dual-targeting (CD19/CD20) CAR-Ts manufactured in significantly reduced timeframes. KITE-753 demonstrated a 79% complete response rate in LBCL with a safety profile comparable to anito-cel. The strategic implication here is clear: the next battleground for CD19 therapies will not be efficacy (which is already high) but operational speed and the prevention of antigen-escape relapse via dual targeting. The ability to manufacture cells that are “younger” and less exhausted correlates directly with clinical durability, a scientific principle now driving the manufacturing upgrades across the sector.
1.3.3. Lyell’s CD19/CD20 CAR Asset
Lyell ended the year with positive clinical data presentations at the ASH Annual Meeting in December 2025. They presented data showing high rates of durable complete responses in patients with relapsed/refractory large B-cell lymphoma (LBCL). In the second-line setting, the therapy demonstrated an 83% overall response rate and 76% complete response rates in 3L+ setting, positioning it as a competitor to existing CAR-Ts like Yescarta.
2. The In Vivo Cell Therapy Updates
The clinical validation in vivo CAR-T therapies represented another significant development of Q4 2025.
2.1 Kelonia Therapeutics: Multiple Myeloma In Vivo CAR Therapy
At ASH 2025, Kelonia Therapeutics presented late-breaking data from its Phase 1 inMMyCAR study of KLN-1010, an in vivo lentiviral vector designed to transduce T cells directly within the patient’s body to express an anti-BCMA CAR.
The results were startlingly positive for a first-in-human trial: the first four patients achieved a 100% minimal residual disease (MRD) negative response rate. Crucially, this was achieved without lymphodepleting chemotherapy (fludarabine/cyclophosphamide), which is a prerequisite for current autologous CAR-T therapies and a major source of toxicity.
The implications of this are vast. By eliminating the need for apheresis, ex vivo manufacturing, and lymphodepletion, KLN-1010 transforms CAR-T from a complex procedure into a biologic product that can be stored in hospital pharmacies and administered simply. The observation of CAR-T cells up to three months post-infusion addresses the primary skepticism regarding in vivo approaches: durability. If these responses hold, the cost of goods sold (COGS) for cell therapy could drop by an order of magnitude, disrupting the business models of current market leaders like BMS and Gilead.
2.2 CREATE Medicines: Solid Tumor In Vivo CAR Therapy
Simultaneously, at SITC 2025, CREATE Medicines (formerly Myeloid Therapeutics) presented late-breaking data on MT-302, an in vivo CAR delivered via mRNA-lipid nanoparticles (LNP) targeting TROP2 in solid tumors.
Unlike viral vectors, mRNA-LNPs allow for transient expression and repeat dosing. The Phase 1 data showed a dose- and tumor burden-dependent low grade cytokine release syndrome observed in 51.9% of participants with no events of grade 3 or higher CRS and one Grade 4 ICANS event at the highest dose tested. Therapeutically, CAR⁺ myeloid cells observed within tumors with T-cell infiltration and cytokine induction (IFNγ, CXCL9/10), with just 1 patient showing response (partial) after 20 doses, out of 27 patients with advanced TROP2-positive solid tumors. While this efficacy may be less than what in vivo cell therapy may have achieved against hematological malignancies, it still provides a starting point for the sector targeting the innate immune system (myeloid cells) against solid tumors. Furthermore, CREATE Medicines initiated a frontline trial for MT-303 (GPC3-targeted) in hepatocellular carcinoma in December, combining their in vivo CAR with standard of care atezolizumab and bevacizumab.
3. Solid Tumors et al.
While hematologic successes continued, Q4 2025 saw renewed optimism for cell therapies in solid tumors, historically a graveyard for the modality.
3.1 MiNK Therapeutics and iNKT Cells
MiNK Therapeutics presented updated Phase 1 data at SITC 2025 for AgenT-797, an allogeneic invariant natural killer T (iNKT) cell therapy. In combination with anti-PD-1 agents, AgenT-797 demonstrated median overall survival of 23+ months in heavily pre-treated patients.
The mechanistic insight here is that iNKT cells act as “master regulators,” bridging innate and adaptive immunity to turn cold tumors hot via dendritic cell activation, thereby re-sensitizing them to checkpoint inhibition. The identification of durable remissions in testicular and gastric cancers- with one metastatic testicular cancer patient experiencing a complete remission for more than two years- suggests that allogeneic, off-the-shelf iNKT cells could serve as a universal adjuvant to existing immunotherapies. The favorable safety profile- no Grade ≥ 3 CRS and no neurotoxicity- further supports its potential as a combination partner.
3.2 Novel Targets: DARKFOX
Enara Bio presented preclinical data on “Dark Antigens”—novel targets derived from normally silenced regions of the genome (Dark Genome) that are re-expressed in cancer. Their presentation on a bispecific T-cell engager targeting a “DARKFOX” antigen (derived from an alternative open reading frame of FOXM1) highlighted a new class of tumor-specific antigens that could solve the on-target/off-tumor toxicity issues plaguing solid tumor cell therapies.
3.3 Novel Mechanisms: Macular Telangiectasia
In a rare non-oncology approval that technically falls under cell therapy, the FDA approved Encelto (revakinagene taroretcel) by Neurotech Pharmaceuticals in Q4 2025 (pushed from mid-year expectations). Encelto is an encapsulated cell therapy implant that secretes ciliary neurotrophic factor (CNTF) for Macular Telangiectasia Type 2. This approval validates the concept of “bio-factories”- implanting cells to secrete therapeutic proteins over long periods—opening a new avenue for chronic degenerative diseases.
4. The “Non-Exciting” Reality: Commercial Contraction
While the science accelerated, the business of cell therapy faced a harsh reality check in Q4 2025. The high capital expenditures (CAPEX), logistical complexities, and intensifying competition forced a significant consolidation of the market.
4.1 The Biotech Graveyard and Layoffs
The quarter was marred by a series of closures and reductions. Companies like Carisma Therapeutics (macrophage CARs) and Appia Bio effectively ceased operations or wound down after partnerships (e.g., with Moderna or Gilead) failed to yield sustainable progress or were terminated.
Layoffs continued to plague the sector:
- Pfizer: Cut 100 positions in Bothell, WA, as part of post-Seagen restructuring. These layoffs (a site heavily focused on Antibody-Drug Conjugates, or ADCs, and manufacturing) likely targeted legacy Seagen teams whose roles overlapped with existing Pfizer functions or projects that didn’t make the cut during the pipeline integration. It was a classic post-merger efficiency exercise.
- Galapagos: ~365 roles eliminated. This was attributed to Galapagos’ inability to sell its “decentralized” CAR-T manufacturing platform (cocoon technology), which produces cells at the hospital bedside rather than in a factory. While scientifically innovative, big pharma buyers deemed the decentralized business model too logistically complex and commercially unproven compared to the established centralized model. When no buyer emerged, Galapagos cut its losses to focus on small molecules.
- Carisma Therapeutics & Appia Bio: Ceased operations in 2025.
- Carisma: Relied on a partnership with Moderna to develop in vivo CAR-macrophages. When Moderna pulled out- likely to conserve its own cash or due to lack of preclinical progress- Carisma lost its primary funding source and credibility signal, forcing a wind-down.
- Appia Bio: Relied on a deal with Kite Pharma (Gilead) to develop invariant natural killer T (iNKT) cells. Kite let the deal expire/terminate, likely prioritizing its own internal “fast” CAR-T manufacturing (like the iMMagine-1 assets) over Appia’s earlier-stage tech. Without that big pharma backing, Appia could not raise fresh capital in a risk-averse market.
- Vor Bio: Underwent restructuring despite raising ~$265 million, with layoffs linked to pipeline prioritization. Vor Bio’s layoffs were not a sign of bankruptcy, but a strategic condition of their new funding. Investors likely demanded the company cut spending on early-stage, risky research projects to ensure the new cash would last all the way through the critical Phase 3 trials of their lead assets (like the shielding transplant platform). The layoffs were a “discipline” measure to focus 100% of resources on the assets most likely to get approved.
4.2 Commercial Headwinds: Gilead and BMS
Earnings reports in Q3/Q4 2025 revealed the strain on established players.
- Gilead/Kite: Reported an 11% year-over-year decline in cell therapy sales to $432 million in Q3 2025. This decline is attributable to “competitive headwinds,” a euphemism for the market share erosion caused by Carvykti in multiple myeloma (impacting the broader cell therapy sentiment) and the saturation of the LBCL market. Yescarta sales fell 10% and Tecartus fell 15%.
- BMS: While reporting a 60% surge in Breyanzi sales to $359 million, BMS saw Abecma revenues struggle to compete with Carvykti, growing only 9% to $137 million. The bifurcation is clear even within portfolios: best-in-class assets (Breyanzi in LBCL/CLL) grow, while inferior assets (Abecma) rapidly lose ground to superior competitors like Carvykti.
| Product | Company | Q3 2025 Sales (USD) | YoY Change | Narrative |
| Carvykti | Legend/J&J | $524M (Trade Sales) | +84% | Supply constrained but demand dominant in MM. |
| Yescarta | Gilead/Kite | $349M | -10% | Saturation in academic centers; facing bispecific competition. |
| Breyanzi | BMS | $359M | +60% | Gaining share in LBCL/CLL due to better safety profile. |
| Abecma | BMS/2seventy | $137M | +9% | Losing share to Carvykti; functionally a second-tier option. |
| Tecartus | Gilead/Kite | $83M | -15% | Declining demand in MCL/ALL. |
5. Regulatory Landscape: Vigilance and Progress
Regulatory agencies maintained a rigorous stance on safety while facilitating pathways for high-unmet-need therapies.
5.1 Clinical Holds and CRLs
5.1.1. Intellia Therapeutics
In November, the FDA placed a clinical hold on Intellia’s Phase 3 gene editing trials for ATTR amyloidosis following a patient hospitalization due to liver enzyme elevation. While this is a gene editing (CRISPR) trial rather than cell therapy, it casts a pall over in vivo therapy field, reminding investors that in vivo delivery vectors (LNPs/AAVs) carry systemic risks.
5.1.1. Atara Biotherapeutics
Despite receiving a Complete Response Letter (CRL) earlier in the year due to manufacturing inspection issues, Atara ended Q4 on a hopeful note. The FDA accepted its BLA resubmission for tab-cel (EBV-targeted T cells) with a Priority Review PDUFA date set for January 10, 2026. This highlights the persistent struggle with Chemistry, Manufacturing, and Controls (CMC), which typically accounts for majority of cell therapy CRLs.
5.2 Approvals and Designations
5.2.1. Mustang Bio
In July, Mustang Bio received Orphan Drug Designation for MB-101 in malignant gliomas, which they are advancing in combination with oncolytic viruses.
5.2.2. Senti Bio
Received Regenerative Medicine Advanced Therapy (RMAT) designation for SENTI-202, a logic-gated CAR-NK cell therapy for AML, in December 2025. SENTI-202 showed 50% Overall Response Rate (ORR) and 42% Complete Remission (CR)/CRh at the Recommended Phase 2 Dose (RP2D).
6. Emerging Frontiers: Autoimmune Diseases
A critical trend solidifying in Q4 2025 was the pivot of oncology-focused cell therapy companies toward autoimmune diseases. This strategic migration is a response to the overcrowding in oncology and the biological rationale that deep B-cell depletion can “reset” the immune system in patients with auto-immune disorders.
6.1 Fate Therapeutics: iPSC-CAR-T in Lupus
Fate Therapeutics presented updated Phase 1 data for FT819 (iPSC-derived CD19 CAR-T) in Systemic Lupus Erythematosus (SLE) at the ACR Convergence and later in December. Patients achieved rapid B-cell depletion and durable clinical remission (DORIS) without the need for intense lymphodepletion; showing that even with reduced conditioning, the iPSC-derived cells could effectively reset the immune system, leading to steroid-free remission in lupus nephritis patients.
6.2. Allogene and Century: Scaling for Autoimmunity
6.2.1. Allogene
Highlighted its ALLO-329 program for autoimmune disease, utilizing its “Dagger” technology to eliminate the need for standard lymphodepletion. They position this as a scalable solution for non-oncology indications where safety (avoiding chemo toxicity) is paramount. Furthermore, their ALLO-316- an allogeneic PBMC-derived CD70-specific CAR T product- targeting advanced clear cell renal cell carcinoma (RCC) confirmed an ORR of 33% (3/9) for patients after a median follow-up of 6.8 months.
6.2.2. Century Therapeutics
Announced a major pivot in November 2025, prioritizing its iPSC-derived beta islet cell program for Type 1 Diabetes (T1D) and its iPSC-derived CNTY-308 targeting autoimmune diseases. This move included initiating IND-enabling studies for the T1D program, aiming for a 2026 submission. This strategic realignment reflects the broader industry trend of applying cell therapy tech to chronic autoimmune conditions.
7. Financial Health and 2026 Outlook
The financial health of the sector remains precarious for pure-play biotechs, while big pharma consolidates.
7.1 Cash Runways and Capital Raises
- Allogene: Ended Q3 2025 with $277.1 million, projecting runway into H2 2027. This strong position allows them to weather the current downturn while advancing their ALPHA3 pivotal trial.
- Vor Bio: Raised $115 million in a public offering in November and another $150 million via private placement in December, bolstering its balance sheet to support its clinical trials in AML and gene-edited transplants.
- Mustang Bio: Continued to face delisting threats but regained compliance in early 2025.
7.2 Conclusion: The Industry in 2026
Q4 2025 was a quarter of stark contrast. Scientifically, the field achieved new heights: in vivo delivery works in humans, BCMA CAR-T can cure myeloma, and solid tumors are showing cracks in their armor. The exit of generalist pharma companies and the consolidation of assets indicate that cell therapy is maturing into a specialized, capital-intensive industry where only the most differentiated assets- those offering curative efficacy or radical ease of use- will survive.
As we move into 2026, the industry is bifurcating into two distinct futures:
- A highly specialized, high-efficacy autologous sector dominated by a few large players (Gilead, J&J, BMS) treating curative-intent oncology with assets like Anito-cel and Carvykti.
- A disruptive, democratized frontier led by iPSC-derived off-the-shelf innovators (Fate, Century) and in vivo players (Kelonia, CREATE) aiming to bring cell therapy to the masses and to new disease areas like autoimmunity.
The “excitement” is now found not just in survival curves, but in the disruptive technologies that promise to tear down the manufacturing barriers that have defined the field for a decade. The “non-exciting” reality is that for companies unable to bridge the gap between scientific promise and commercial scalability, the window for survival has closed.