CLDN6 positive

Our data demonstrate that SAIL66, designed to engage CLDN6, CD3, and CD137, has the potential to enhance antitumor activity and provide a potent therapeutic option for patients with ovarian and other solid tumors expressing CLDN6. Clinical trials are currently underway to evaluate the safety and efficacy of SAIL66.

No signs of adverse effects from BNT142 RNA-LNP administration were observed in mice or cynomolgus monkeys. On the basis of these and other findings, a phase 1/2 first-in-human clinical trial has been initiated to assess the safety and preliminary efficacy of BNT142 RNA-LNP in patients with CLDN6-positive advanced solid tumors (NCT05262530).

More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.

P1, N=145, Recruiting, BioNTech Cell & Gene Therapies GmbH | Phase classification: P1/2 --> P1 | Trial completion date: Sep 2037 --> Jan 2040 | Trial primary completion date: Aug 2024 --> Jan 2027

P1, N=200, Recruiting, Second Affiliated Hospital of Guangzhou Medical University | Phase classification: P1/2 --> P1 | N=40 --> 200

P1/2, N=114, Recruiting, BioNTech Cell & Gene Therapies GmbH

P1/2, N=288, Recruiting, BioNTech SE

A repeat of the dose escalation is ongoing and will identify a RP2D for pivotal trials. ClinicalTrials.gov Identifier: NCT04503278 .

P1/2, N=114, Recruiting, BioNTech Cell & Gene Therapies GmbH | Trial completion date: Sep 2036 --> Sep 2037 | Trial primary completion date: Aug 2023 --> Aug 2024

High expression of CLDN6 mRNA is associated with the dysregulation of distinct biological pathways regulating cell growth, proliferation, and cell-matrix interactions. Clinically, the expression of CLDN6 protein is a valuable adverse prognostic marker in EAC and GAC.

The safety profile in terms of CRS, ICANS and DLTs observed is in line with previously reported observations. We intend to present data on up to 42 pts, with a data cut-off of 10.09.2023.

We report the development of a novel antibody-drug conjugate, CLDN6-23-ADC, that selectively targets CLDN6, a potential onco-fetal-antigen which is highly expressed in ovarian and endometrial cancers. CLDN6-23-ADC exhibits robust tumor regressions in mouse models of human ovarian and endometrial cancers and is currently undergoing Phase I study.

Additional sites will be opened in Europe, USA, and Asia in 2023. Clinical trial information: NCT05262530.

P1, N=178, Recruiting, Chugai Pharmaceutical | Not yet recruiting --> Recruiting

P1, N=178, Not yet recruiting, Chugai Pharmaceutical

P1/2, N=288, Recruiting, BioNTech SE | N=216 --> 288

P1/2, N=96, Recruiting, BioNTech Cell & Gene Therapies GmbH | Trial primary completion date: Sep 2022 --> Aug 2023

In chRCC CLDN6 expression is not associated with parameters of aggressiveness or survival. Due to the rare incidence of chRCC further studies with larger cohorts are warranted.

CLDN6 expression seems ubiquitous in all elements of GCT and is worthy of investigation as a diagnostic biomarker and therapeutic target. (Clinical trial information: NCT03760081).

P1/2, N=40, Recruiting, Second Affiliated Hospital of Guangzhou Medical University

P1/2; N=36 --> 96

P1/2, N=216, Recruiting, BioNTech SE | Not yet recruiting --> Recruiting

Functional evaluation of CLDN6X4-1BB BsAb indicated that the activation of 4-1BB signaling was dependent on CLDN6 expression on tumor cells and the activity was stronger than reference 4-1BB monoclonal antibody urelumab...From the safety perspective, there were no significant changes in liver enzymes or liver histopathology following repeated BsAb administration, suggesting little risks for liver toxicity commonly induced by other 4-1BB agonist antibodies.Conclusions We have successfully generated a novel CLDN6-targeted 4-1BB bispecific antibody which could induce potent 4-1BB stimulation and anti-tumor activity in a CLDN6-dependent manner while minimizing the risk of liver toxicity. Taken together, these data support further development of CLDN6 X 4-1BB bispecific antibody towards IND and clinical trial in 2022.

Furthermore, NBL-028 is designed upon a proprietary molecular scaffold with superior developability features, demonstrated by stability, yield and ease to purify. NBL-028 is currently at the stage of IND-enabling activities with the aim to enter clinical studies for treating Claudin 6 positive solid tumors in 1Q 2023.

CLDN6 CAR-T cells ± CARVac show an acceptable safety profile at doses tested and encouraging signs of clinical activity. Data from the completed dose escalation phase will be presented. Acknowledgements: BNT211-01 is funded by BioNTech Cell & Gene Therapies GmbH.Trial registration: Clinicaltrials.gov: NCT04503278.Ethics approval: Ethics & Institutional Review Board approvals were obtained from the respective participating countries prior to initiation of the trial.

P1/2, N=216, Not yet recruiting, BioNTech SE

Updated data from open cohorts will be presented. Clinical trial identification NCT04503278.

Manageable cytokine release syndrome (CRS, grade 1-2, the latter managed with Tocilizumab) without any signs of neurotoxicity have been observed in both patients of part 1 DL2. Updated data from open cohorts and especially for combination with CARVac will be presented. Clinicaltrials gov: NCT04503278

P1/2; N=36; Not yet recruiting; Sponsor:BioNTech Cell & Gene Therapies GmbH