NextCure Reports Preclinical Data for LNCB74 and Additional Clinical Biomarker Data for NC410 Combo at Society for Immunotherapy of Cancer Annual Meeting
NextCure (NXTC) presented preclinical data for LNCB74, a B7-H4-targeting antibody-drug conjugate (ADC), and additional biomarker data for NC410 combination therapy at SITC. LNCB74 showed promising results with strong anti-tumor activity in multiple tumor models and favorable safety profile, with IND filing expected by year-end. The NC410/pembrolizumab combination demonstrated clinical activity in MSS/MSI-L colorectal cancer patients, achieving 3 partial responses among 43 evaluable patients and disease control rates of 86% and 47% at 200mg and 100mg doses, respectively. Biomarker data supported NC410's mechanism of action in remodeling tumor microenvironment.
NextCure (NXTC) ha presentato dati preclinici per LNCB74, un anticorpo-coniugato del farmaco (ADC) che mira a B7-H4, e ulteriori dati sui biomarcatori per la terapia combinata con NC410 al SITC. LNCB74 ha mostrato risultati promettenti con un'ottima attività antitumorale in diversi modelli tumorali e un profilo di sicurezza favorevole, con la presentazione della domanda IND attesa entro la fine dell'anno. La combinazione NC410/pembrolizumab ha dimostrato attività clinica nei pazienti con cancro colorettale MSS/MSI-L, ottenendo 3 risposte parziali tra 43 pazienti valutabili e tassi di controllo della malattia dell'86% e 47% rispettivamente per dosi di 200 mg e 100 mg. I dati sui biomarcatori hanno supportato il meccanismo d'azione di NC410 nel rimodellare il microambiente tumorale.
NextCure (NXTC) presentó datos preclínicos para LNCB74, un conjugado de anticuerpo-fármaco (ADC) dirigido a B7-H4, y datos adicionales de biomarcadores para la terapia combinada con NC410 en el SITC. LNCB74 mostró resultados prometedores con
NextCure (NXTC)는 SITC에서 B7-H4를 표적으로 하는 항체-약물 접합체(ADC)인 LNCB74에 대한 전임상 데이터를 발표하였고, NC410 병용요법에 대한 추가 바이오마커 데이터도 공개하였습니다. LNCB74는 여러 종양 모델에서 강력한 항종양 활성을 보여주었으며 안전성 프로필도 우수하여 연말까지 IND 신청이 예상됩니다. NC410/펨브롤리주맙 병용요법은 MSS/MSI-L 대장암 환자에서 임상적 활성을 나타내어 43명의 평가 가능한 환자 중 3개의 부분 응답을 달성했으며, 각각 200mg 및 100mg 용량에서 질병 조절 비율은 86% 및 47%에 달했습니다. 바이오마커 데이터는 NC410의 종양 미세환경 재구성 작용 메커니즘을 뒷받침했습니다.
NextCure (NXTC) a présenté des données précliniques sur LNCB74, un conjugué anticorps-médicament (ADC) ciblant B7-H4, ainsi que des données supplémentaires sur les biomarqueurs pour la thérapie combinée NC410 au SITC. LNCB74 a montré des résultats prometteurs avec une forte activité antitumorale dans plusieurs modèles tumoraux et un profil de sécurité favorable, avec une demande IND attendue d'ici la fin de l'année. La combinaison NC410/pembrolizumab a démontré une activité clinique chez les patients atteints de cancer colorectal MSS/MSI-L, avec 3 réponses partielles parmi 43 patients évaluables et des taux de contrôle de la maladie de 86% et 47% pour des doses de 200 mg et 100 mg, respectivement. Les données de biomarqueurs ont soutenu le mécanisme d'action de NC410 dans le remodelage du microenvironnement tumoral.
NextCure (NXTC) hat präklinische Daten zu LNCB74, einem Antikörper-Arzneimittel-Konjugat (ADC), das auf B7-H4 abzielt, sowie zusätzliche Biomarker-Daten zur Kombinationstherapie mit NC410 auf dem SITC vorgestellt. LNCB74 zeigte vielversprechende Ergebnisse mit starker antitumoraler Aktivität in mehreren Tumormodellen und einem günstigen Sicherheitsprofil, wobei die Einreichung des IND-Antrags bis Ende des Jahres erwartet wird. Die Kombination aus NC410/Pembrolizumab zeigte klinische Aktivität bei MSS/MSI-L-Patienten mit kolorektalem Krebs und erreichte 3 partielle Ansprechen unter 43 auswertbaren Patienten und Krankheitskontrollraten von 86% bzw. 47% bei Dosen von 200mg und 100mg. Die Biomarker-Daten unterstützten den Wirkmechanismus von NC410 bei der Umgestaltung der Tumormikroumgebung.
- LNCB74 demonstrated strong anti-tumor activity with durable tumor regression in multiple tumor models
- LNCB74 showed favorable safety profile in cynomolgus monkeys up to 10mg/kg
- NC410/pembrolizumab combination achieved 3 partial responses in 43 evaluable patients
- 86% disease control rate achieved at 200mg NC410 dose
- Treatment was well tolerated in clinical trials
- Lower disease control rate (47%) observed at 100mg NC410 dose compared to 200mg dose
Insights
The preclinical data for LNCB74 shows significant promise in targeting B7-H4-expressing tumors. Key advantages include sub-nanomolar potency, selective tumor targeting and improved safety profile through the ConjuAll technology. The durable tumor regression at 3 mg/kg dosing and favorable toxicity profile up to 10 mg/kg in cynomolgus monkeys suggest a potentially wide therapeutic window.
For NC410, the combination therapy with pembrolizumab demonstrated meaningful clinical activity in MSS/MSI-L colorectal cancer patients, with disease control rates of 86% at the 200 mg dose. The biomarker data confirming immune infiltration and tumor microenvironment remodeling validates the mechanism of action. The imminent IND filing for LNCB74 by year-end marks a important development milestone.
The development of LNCB74 addresses a critical need in targeting B7-H4, which is highly expressed in multiple tumor types but in healthy tissues. The glucuronidase-cleavable linker technology and Fc mitigation strategy represent significant improvements over existing B7-H4 ADCs, potentially reducing off-target effects while maintaining efficacy. The NC410 combination data in MSS/MSI-L CRC is particularly noteworthy, as these patients typically have poor responses to immunotherapy. The 3 partial responses and high disease control rate in the 200 mg cohort suggest this combination could provide a new treatment option for this challenging patient population.
- Preclinical data for LNCB74 highlights its potential as therapeutic for treating multiple solid tumor indications; Investigational New Drug (IND) application filing expected by year-end
- Additional biomarker data support proposed mechanism of action of NC410
BELTSVILLE, Md., Nov. 05, 2024 (GLOBE NEWSWIRE) -- NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class and best-in-class therapies to treat cancer, today reports pre-clinical data from LNCB74, a B7-H4-targeting antibody-drug conjugate (ADC) being developed in partnership with LigaChem Biosciences (LCB) (KOSDAQ: 141080), and biomarker data from the NC410 combination study with pembrolizumab in patients with immune checkpoint inhibitor (ICI) naïve and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC). The data will be presented during poster sessions at the Society for Immunotherapy of Cancer (SITC) annual meeting.
“The preclinical data reported for LNCB74, our B7-H4 antibody-drug conjugate program, continue to reinforce its promise as a potential best-in-class therapeutic with advantages over other B7-H4 ADCs,” said Michael Richman, NextCure’s president and CEO. “We remain on track to submit an IND application to the FDA by year-end and intend to rapidly advance the program into clinical development.”
Preclinical Data on LNCB74 B7-H4 Antibody Drug Conjugate (ADC)
LNCB74 is a B7-H4 antibody conjugated to the microtubule disrupting payload monomethyl auristatin E (MMAE) with a drug-to-antibody ratio of 4 (DAR4). The ADC employs a glucuronidase-cleavable, site-specific linkage conjugated to an engineered cysteine in the antibody light chain via LigaChem Biosciences’ ConjuAllTM technology to increase stability in circulation, improve selective release of payload in tumor cells, and reduce payload release in non-tumor cells. LNCB74 incorporates an Fc mitigating mutation to minimize binding and uptake of LNCB74 by Fc receptor expressing immune cells. The ConjuAll technology, with its selective cleavage and release within tumor cells, combined with mitigation of off-target uptake via disabled Fc interactions, is engineered to improve the safety profile and therapeutic index of LNCB74 compared to other B7-H4 targeted ADCs.
Key findings:
- B7-H4 protein is highly expressed in multiple tumor indications. B7-H4 expression limited in normal healthy human tissues, providing a potential broad therapeutic index for a B7-H4 targeting ADC.
- LNCB74 shows specific binding to B7-H4 expressing tumor cells and is rapidly internalized in a target-dependent manner by cancer cells.
- LNCB74 mediates potent cytotoxicity, with sub-nanomolar to low nanomolar EC50 values on multiple B7-H4-positive cancer cell lines.
- LNCB74 demonstrates strong anti-tumor activity in multiple CDX and PDX tumor models. A single dose of 3 mg/kg resulted in durable tumor regression in multiple tumor models, suggesting activity comparable or superior to published B7-H4 targeting ADCs.
- LNCB74 demonstrates favorable PK and stability in rodents.
- LNCB74 was well tolerated in cynomolgus monkeys up to 10 mg/kg.
Phase 1b Study of NC410 in Combination with Pembrolizumab
The presentation includes additional clinical data for CRC patients from the Phase 1b portion of a Phase 1b/2 study evaluating NC410, a LAIR-2 fusion protein, in combination with pembrolizumab. The trial is evaluating the combination in ovarian cancer and ICI-naïve MSS/MSI-L CRC. Overall, the combination of NC410 and pembrolizumab continues to demonstrate clinical activity against MSS/MSI-L CRC, which is generally unresponsive to immunotherapy. Subjects who achieved clinical benefit of partial response or stable disease demonstrated durability of their responses that was clinically meaningful in this patient population.
Key findings:
- Of the 43 evaluable ICI-naïve MSS/MSI-L CRC patients without liver metastasis, there were 3 PRs as of the data cut-off of October 14, 2024.
- Disease control rates were
86% and47% for the 200 mg and 100 mg NC410 doses, respectively. - Biomarker data support proposed mechanism of action of NC410, showing remodeling of the tumor microenvironment, promotion of immune infiltration and anti-tumor activity.
- Treatment was well tolerated.
Poster Presentation Details:
Title: LNCB74 is a B7-H4 antibody-drug conjugate with a β-glucuronide linker-MMAE payload system to enhance therapeutic index in B7-H4 expressing cancers
Lead Author: Shannon M. Kahan
Abstract Number: 1051
Session Date & Time: Friday, November 8, 2024, 5:30 – 7:00 PM
Title: NC410 in combination with pembrolizumab improves anti-tumor responses by promoting collagen remodeling and tumor immunity in advanced ICI naive MSS/MSI-L CRC
Lead Author: Alina Barbu
Abstract Number: 632
Session Date & Time: Saturday, November 9, 2024, 7:10 – 8:30 PM
About NextCure, Inc.
NextCure is a clinical-stage biopharmaceutical company that is focused on advancing innovative medicines that treat cancer patients that do not respond to, or have disease progression on, current therapies, through the use of differentiated mechanisms of actions including antibody-drug conjugates, antibodies and proteins. We focus on advancing therapies that leverage our core strengths in understanding biological pathways and biomarkers, the interactions of cells, including in the tumor microenvironment, and the role each interaction plays in a biologic response. http://www.nextcure.com
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Statements made in this press release that are not historical facts are forward-looking statements. Words such as “expects,” “believes,” “intends,” “hope,” “forward” and similar expressions are intended to identify forward-looking statements. Forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those projected in any forward-looking statement. Such risks and uncertainties include, among others: our limited operating history and no products approved for commercial sale; our history of significant losses; our need to obtain additional financing; risks related to clinical development, including that early clinical data may not be confirmed by later clinical results; risks that pre-clinical research may not be confirmed in clinical trials; risks related to marketing approval and commercialization; and NextCure’s dependence on key personnel. More detailed information on these and additional factors that could affect NextCure’s actual results are described in NextCure’s filings with the Securities and Exchange Commission (the “SEC”), including NextCure’s most recent Form 10-K and subsequent Form 10-Q. You should not place undue reliance on any forward-looking statements. NextCure assumes no obligation to update any forward-looking statements, even if expectations change.
Investor Inquiries
Timothy Mayer, Ph.D.
NextCure, Inc.
Chief Operating Officer
(240) 762-6486
IR@nextcure.com
FAQ
What are the key findings from NextCure's LNCB74 preclinical trials?
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