T-Cell Engager Cizutamig Shows Early Efficacy Signal in Generalized Myasthenia Gravis

Cizutamig (UCB), an investigational BCMA×CD3 T-cell engager, produced sustained disease improvement in patients with generalized myasthenia gravis (gMG) in interim results from a phase 1b dose-escalation trial. All 12 patients dosed across the first two cohorts met the trial's responder criteria, with no cases of cytokine release syndrome (CRS) reported.¹

Manuela Maronati, global asset head of neuroimmunology and rare diseases at UCB, which acquired cizutamig in 2026 through its up to $2.2 billion purchase of Candid Therapeutics, told NeurologyLive that the bispecific antibody is designed to harness T cells to deplete the immune cells responsible for producing pathogenic autoantibodies in gMG.² “It is really formatted and engineered to achieve a favorable safety profile and minimize cytokine release syndrome,” Maronati said. “But of course, it's still an investigational drug, so we are at phase one. We have encouraging data, but it's really, really early to say.”

The data, from an open-label, dose-escalation and dose-expansion phase 1b trial (NCT07215650) in seropositive (anti-AChR or anti-MuSK antibody) gMG, were presented at the 2026 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting and Myasthenia Gravis Foundation of America (MGFA) Scientific Session, held September 29 to October 2, 2026, in Orlando, Florida.^1,3

Twelve patients have been dosed across the first 2 of 4 planned cohorts (3 patients per cohort reported), with a mean age of 41 years and 67% female. At baseline, mean Quantitative Myasthenia Gravis (QMG) score was 22.3 and mean MG Activities of Daily Living (MG-ADL) score was 9.0. Overall, all patients achieved a sustained improvement of at least 3 points on the QMG and at least 2 points on the MG-ADL for at least 12 weeks, along with minimal symptom expression (MG-ADL score of 1 or less).¹

At week 12, mean change from baseline was negative 19.3 on the QMG and negative 7.7 on the MG-ADL in cohort 1, and negative 13.0 and negative 8.7, respectively, in cohort 2. Peripheral B cells, serum free light chains, and acetylcholine receptor autoantibodies each fell by a median of more than 90% from baseline across all patients.¹

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“The data are really encouraging. We see quite strong activity very early, and the patients responded very quickly to the drug, and the safety profile was very positive,” Maronati said. “But it's very early, and we need to study it in more countries, so having a multi-country study makes sure that what we are seeing as a hypothesis can really be confirmed.”

No treatment-emergent CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), adverse events of special interest, or dose-limiting adverse events occurred, and all treatment-emergent adverse events were grade 2 or lower. One grade 3 pneumonia serious adverse event, considered unrelated to treatment, occurred in cohort 1 and resolved.

“The safety of T-cell engagers in autoimmune disease is pivotal, and we will not move forward with something that doesn't have that as the first priority,” Maronati added. “So far, what we have seen is that it's very well tolerated. We have not seen CRS. We have not seen any ICANS.”

A crowded, heterogeneous gMG landscape

UCB already markets 2 approved gMG therapies: rozanolixizumab (Rystiggo), a neonatal Fc receptor blocker, and zilucoplan (Zilbrysq), a complement C5 inhibitor.³ Maronati said physicians and researchers describe gMG as “a snowflake disease” because “every patient is different,” reflecting a bimodal age distribution with onset common among young women as well as older adults, more often men in that group.

“You cannot, with one mechanism of action, really solve the issue of all patients,” she said, describing cizutamig as a potential addition to that portfolio that works further upstream, targeting the B cells that generate autoantibodies before they mature into antibody-producing plasma cells.

Asked how a phase 2 trial might be designed, Maronati said UCB plans to retain the validated QMG and MG-ADL endpoints used across its gMG program and to study patient-reported outcomes, which she said UCB included in its phase 3 trials of both rozanolixizumab and zilucoplan. She said the company has not yet defined which gMG patient subtypes might respond best to cizutamig, describing the current data as supporting use in "a broad spectrum" of seropositive gMG patients rather than a narrower group, and said UCB is also evaluating which of several autoimmune indications beyond gMG to pursue next.

For more coverage of AANEM 2026, click here.

REFERENCES
1. Masri K, Zhao C, Song J, et al. Efficacy and safety of cizutamig, a BCMA×CD3 T-cell engager, in generalized myasthenia gravis: interim results from a phase 1b dose-escalation study. Presented at: 2026 AANEM Annual Meeting and MGFA Scientific Session; September 29-October 2, 2026; Orlando, FL.
2. UCB to acquire Candid Therapeutics, building upon its existing immunology pipeline with novel T-cell engagers. News release. UCB. Published May 3, 2026. Accessed November 6, 2026. https://www.businesswire.com/news/home/20260503595444/en/
3. UCB data presented at 2026 AANEM Annual Meeting and MGFA Scientific Session underscore leadership in advancing targeted treatments for gMG. News release. UCB. Published September 29, 2026. Accessed November 6, 2026. https://www.trivano.com/persbericht/ucb-data-presented-at-2026-aanem-annual-meeting-and-mgfa-scientific-session-underscore-leadership-in-advancing-targeted-treatments-for-gmg-763508.html