Data Roundup: February 2025 Features Updates from WORLDSymposium, Tandem Meetings, and More

Last month, February 2025, the CGTLive® team was diligently tracking the latest data readouts and published literature on cell and gene therapies within oncology, neurology, rare diseases, and more.

As more and more innovative therapies enter the clinical trial field, more data is accrued every month, buoying excitement in the field and sometimes making or breaking the fates of small biotech companies. Last month delivered data updates from conferences including the 21st Annual WORLDSymposium, held February 3 to 7, 2025, in San Diego, California, and the 2025 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Honolulu, Hawaii, February 12 to 15, 2025, as well as some general data updates that came outside of medical meetings. Our team has highlighted these below.

Click the read more buttons for more details and information about each update.

Ultragenyx’s Gene Therapy UX111 Improves Clinical Function in MPSIII

February 6, 2025 - Ultragenyx’s UX111 (ABO-102), an adeno-associated virus (AAV) vector-based gene therapy intended to treat mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome), has improved clinical function in patients treated in the phase 1/2/3 Transpher A clinical trial (NCT02716246). Updated data from the study were presented at WORLDSymposium.

Transpher A treated 28 patients with UX111 in total across 3 different dose levels, with 22 patients having received the highest dose of UX111 (3x10¹³ vg/kg). Among the 17 patients in Transpher A’s modified intention to treat (mITT) group, which includes patients who received the high dose and at the time of enrollment were either no more than 2 years of age or older than 2 years with a cognitive developmental quotient of 60 or above, an improvement of +16 points was recorded for the model-based mean Bayley-III cognitive raw score from 24 to 60 months of age. By contrast, a natural history group used for comparison showed a decline of –6.8 points for the model-based mean Bayley-III cognitive raw score from 24 to 60 months of age, thus resulting in a +22.7 point treatment effect (P < .0001). Furthermore, raw scores for model-based mean receptive and expressive communication (P < .05) and fine motor function (P = .05) also showed significant improvement for the mITT group in comparison to the natural history group. Numerical improvements for the mITT group were also seen in gross motor scores, but these were not statistically significant. Ultragenyx stated that gross motor function losses are generally seen later in disease progression and thus longer-term follow-up may be necessary to establish statistical significance in this area. The company also pointed out that for all 5 subdomains of Bayley-III, a statistically significant correlation was observed between levels of heparan sulfate in cerebrospinal fluid (CSF-HS) exposure and estimated yearly rate of change.

Creative Medical Technology’s Cell Therapy AlloStem Reduces Insulin Dependency in Late-Stage Type 2 Diabetes

February 11, 2025 - Creative Medical Technology’s AlloStem (also known as CELZ-201), an investigational universal and proprietary allogenic cell line, has demonstrated the ability to reduce insulin dependency among patients with type 2 diabetes (T2D) treated in a pilot study.

The study enrolled 20 participants with late-stage T2D in total, with 10 being assigned for treatment with AlloStem and the other patients receiving optimized medical therapy. Creative Medical Technology stated that at 1 year posttreatment AlloStem showed an 80% overall efficacy rate in decreasing insulin dependency and stabilizing levels of hemoglobin A1c. In addition, the company pointed out that there were no serious safety events observed. In light of these findings, Creative Medical Technology noted that it intends to continue moving forward with development of AlloStem in T2D and to explore its potential use in other indications.

"The positive 1-year data from the study represents a significant milestone in our mission to revolutionize diabetes treatment and help a wide variety of patients who potentially may not benefit from autologous therapies," Timothy Warbington, the president and CEO of Creative Medical Technology, said in a statement. "With a diversified portfolio that includes CELZ-201 for early-stage T1D, CELZ-101 for brittle type 1 diabetes (T1D), and CELZ-201 for late-stage T2D, we are committed to delivering innovative solutions that transform patient care."

Phase 2 Trial for BMS's Liso-Cel Meets Primary End Point in R/R Marginal Zone Lymphoma Cohort

February 12, 2025 - Bristol Myers Squibb (BMS)’s phase 2 TRANSCEND FL clinical trial (NCT04245839) evaluating lisocabtagene maraleucel (liso-cel, marketed as Breyanzi), an autologous CD19-directed CAR T-cell therapy, has met its primary end point in its cohort for adult patients with relapsed/refractory (r/r) marginal zone lymphoma (MZL).

Liso-cel showed a statistically significant and clinically meaningful overall response rate in this cohort, which constituted the criteria for the primary end point. In addition, the cohort also met a key secondary end point for complete response rate. With regard to safety, BMS noted that no new safety signals were observed in the cohort. According to BMS, r/r MZL is the fifth indication for which liso-cel has shown clinically meaningful benefit, making it the CD19-directed CAR-T product that has shown efficacy and manageable safety in the highest number of B-cell malignancies.

“MZL is a slow-growing cancer that, for many, has a favorable prognosis,” Rosanna Ricafort, the vice president and head of Late Development Program Leadership, Hematology and Cell Therapy, at BMS, said in a statement. “But for those patients who relapse or become refractory, the disease can be quite aggressive, and there is a need for new effective and tolerable treatment options to address this unmet critical need. We are pleased that the TRANSCEND FL study supports the potential of Breyanzi in marginal zone lymphoma and look forward to presenting detailed results from the study at an upcoming medical meeting.”

CareDx’s AlloHeme Shows Accuracy in Detecting Relapse Following AlloHSCT in AML and MDS

February 13, 2025 - CareDx’s AlloHeme, a next-generation sequencing (NGS)-based assay, has demonstrated the ability to detect early relapse following allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to interim data from the prospective ACROBAT study (NCT04635384).¹ The results were presented at the 2025 Tandem Meetings by Monzr M. Al Malki, MD, an associate professor and the director of the Unrelated Donor Bone Marrow Transplant Program at City of Hope National Medical Center.

AlloHeme utilizes detection of increased mixed chimerism (iMC) at a threshold of 0.2% or greater in the recipient’s chimerism between 2 consecutive readings to predict relapse. The analytical cohort for the study included 141 patients with AML and 55 patients with MDS.

An interim analysis was conducted at 12 months postHSCT in order to determine the estimated diagnostic performance of AlloHeme. It was found to have a sensitivity of 0.93, a specificity of 0.88, a positive predictive value (PPV) of 0.58, and a negative predictive value (NPV) of 0.99, resulting in an area under the curve (AUC) of 0.90. Furthermore, Al Malki reported that for the patients who were iMC-positive, 25 relapsed during the 12 months postHCT period and after the second CD33 measurement, and 18 did not relapse during the 12 months postHCT period. On the other hand, for patients who were iMC-negative, 2 relapsed during the 12 months postHCT period and after the second CD33 measurement, and 128 did not relapse during the 12 months postHCT period.

Solid Biosciences’ Gene Therapy SGT-003 Produces Microdystrophin Expression in Patients With DMD

February 18, 2025 - Solid Biosciences SGT-003, an investigational next-generation AAV vector-based gene therapy, has produced expression of microdystrophin in patients being treated for Duchenne muscular dystrophy (DMD) in the phase 1/2 INSPIRE DUCHENNE clinical trial (NCT06138639).

The efficacy set for the interim data announced by the company includes 2 boys who were 5 years of age at the time of dosing and 1 boy who was 7 years of age at the time of dosing. As of 90 days posttreatment, the 3 boys showed microdystrophin expression at mean levels 110% of normal according to Western blot and at mean levels 108% of normal according to mass spectrometry. In addition, a mean 78% dystrophin-positive fibers were seen via immunofluorescence and the mean number of vector copies per nucleus was 18.7. A mean 42% neuronal nitric oxide synthase (nNOS)-positive fibers and a mean 70% beta sarcoglycan-positive fibers were also reported.

Solid also reported data on biomarkers of muscle injury and stress for the 3 patients at 90 days posttreatment, noting a mean 57% reduction in serum creatine kinase (CK) (IU/L), a 45% mean reduction in serum aspartate aminotransferase (AST) (IU/L), a 54% mean reduction in Serum alanine transaminase (ALT) (IU/L), and a 60% mean reduction in serum lactate dehydrogenase (LDH) (IU/L). A 42% mean reduction in serum titin (pmol/L) and a 59% mean reduction in embryonic myosin heavy chain (eMHC) positive fibers were also reported.