Compass Therapeutics Presents Data on Enhanced Efficacy of CTX-471 in Combination with Tovecimig in Checkpoint-Refractory Models at the American Association for Cancer Research (AACR) Annual Meeting
Compass Therapeutics (NASDAQ: CMPX) presented promising preclinical data at the AACR Annual Meeting regarding the combination of CTX-471 and tovecimig in cancer treatment. The research demonstrated enhanced anti-tumor efficacy in checkpoint-refractory models.
The study showed that CTX-471 monotherapy was effective in multiple murine models resistant to immune checkpoint inhibitors. When combined with tovecimig, the treatment showed increased effectiveness through enhanced innate and adaptive anti-tumor immunity, improved tumor cell killing, and increased antigen presentation and interferon signaling.
The research utilized novel mouse tumor models engineered to mimic HLA loss in patients, including CT26B2m and MC38B2m knockout models. The combination therapy showed particular promise in cases where conventional checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 antibodies, have failed.
Compass Therapeutics (NASDAQ: CMPX) ha presentato dati preclinici promettenti al Congresso Annuale AACR riguardo alla combinazione di CTX-471 e tovecimig nel trattamento del cancro. La ricerca ha dimostrato un aumento dell’efficacia antitumorale in modelli resistenti agli inibitori dei checkpoint immunitari.
Lo studio ha evidenziato che la monoterapia con CTX-471 è risultata efficace in diversi modelli murini resistenti agli inibitori dei checkpoint immunitari. In combinazione con tovecimig, il trattamento ha mostrato una maggiore efficacia grazie a un potenziamento dell’immunità antitumorale innata e adattativa, un miglioramento nella distruzione delle cellule tumorali e un aumento della presentazione degli antigeni e della segnalazione dell’interferone.
La ricerca ha utilizzato nuovi modelli murini di tumore progettati per simulare la perdita di HLA nei pazienti, inclusi i modelli knockout CT26B2m e MC38B2m. La terapia combinata ha mostrato particolare efficacia nei casi in cui gli inibitori convenzionali dei checkpoint, come gli anticorpi anti-PD-1 e anti-PD-L1, non hanno avuto successo.
Compass Therapeutics (NASDAQ: CMPX) presentó datos preclínicos prometedores en la Reunión Anual de AACR sobre la combinación de CTX-471 y tovecimig en el tratamiento del cáncer. La investigación demostró una mayor eficacia antitumoral en modelos resistentes a inhibidores de puntos de control inmunitario.
El estudio mostró que la monoterapia con CTX-471 fue efectiva en varios modelos murinos resistentes a inhibidores de puntos de control inmunitario. Cuando se combinó con tovecimig, el tratamiento mostró una mayor efectividad mediante el fortalecimiento de la inmunidad antitumoral innata y adaptativa, una mejor destrucción de las células tumorales y un aumento en la presentación de antígenos y la señalización de interferón.
La investigación utilizó nuevos modelos de tumores en ratones diseñados para imitar la pérdida de HLA en pacientes, incluidos los modelos knockout CT26B2m y MC38B2m. La terapia combinada mostró especial promesa en casos donde los inhibidores convencionales de puntos de control, como los anticuerpos anti-PD-1 y anti-PD-L1, han fallado.
Compass Therapeutics (NASDAQ: CMPX)는 AACR 연례 회의에서 암 치료에 있어 CTX-471과 tovecimig의 병용에 관한 유망한 전임상 데이터를 발표했습니다. 연구 결과는 면역 체크포인트 저항성 모델에서 향상된 항종양 효능을 보여주었습니다.
연구에서는 CTX-471 단독 요법이 면역 체크포인트 억제제에 저항성을 가진 여러 마우스 모델에서 효과적임을 확인했습니다. tovecimig과 병용 시 선천 및 적응 면역 반응이 강화되고, 종양 세포 사멸이 증가하며, 항원 제시 및 인터페론 신호 전달이 향상되어 치료 효과가 더욱 높아졌습니다.
이번 연구는 환자의 HLA 손실을 모방하도록 설계된 새로운 마우스 종양 모델인 CT26B2m 및 MC38B2m 녹아웃 모델을 활용했습니다. 이 병용 요법은 항-PD-1 및 항-PD-L1 항체와 같은 기존 체크포인트 억제제가 실패한 경우에 특히 유망한 결과를 보였습니다.
Compass Therapeutics (NASDAQ : CMPX) a présenté des données précliniques prometteuses lors de la réunion annuelle de l’AACR concernant la combinaison de CTX-471 et tovecimig dans le traitement du cancer. La recherche a démontré une efficacité antitumorale accrue dans des modèles résistants aux inhibiteurs de points de contrôle.
L’étude a montré que la monothérapie par CTX-471 était efficace dans plusieurs modèles murins résistants aux inhibiteurs de points de contrôle immunitaires. En combinaison avec tovecimig, le traitement a montré une efficacité renforcée grâce à une immunité antitumorale innée et adaptative améliorée, une meilleure destruction des cellules tumorales et une augmentation de la présentation des antigènes ainsi que de la signalisation de l’interféron.
La recherche a utilisé de nouveaux modèles tumoraux murins conçus pour imiter la perte de HLA chez les patients, notamment les modèles knockout CT26B2m et MC38B2m. La thérapie combinée a montré un potentiel particulier dans les cas où les inhibiteurs classiques de points de contrôle, tels que les anticorps anti-PD-1 et anti-PD-L1, ont échoué.
Compass Therapeutics (NASDAQ: CMPX) präsentierte auf der AACR-Jahrestagung vielversprechende präklinische Daten zur Kombination von CTX-471 und tovecimig in der Krebsbehandlung. Die Forschung zeigte eine verbesserte antitumorale Wirksamkeit in Modellen, die gegen Checkpoint-Inhibitoren resistent sind.
Die Studie zeigte, dass die Monotherapie mit CTX-471 in mehreren murinen Modellen, die gegen Immun-Checkpoint-Inhibitoren resistent sind, wirksam war. In Kombination mit tovecimig zeigte die Behandlung eine gesteigerte Effektivität durch verbesserte angeborene und adaptive antitumorale Immunität, erhöhte Tumorzellabtötung sowie gesteigerte Antigenpräsentation und Interferon-Signalisierung.
Die Forschung nutzte neuartige Maus-Tumormodelle, die so konstruiert wurden, dass sie den HLA-Verlust bei Patienten nachahmen, darunter die Knockout-Modelle CT26B2m und MC38B2m. Die Kombinationstherapie zeigte besonders vielversprechende Ergebnisse in Fällen, in denen herkömmliche Checkpoint-Inhibitoren wie Anti-PD-1- und Anti-PD-L1-Antikörper versagt hatten.
- Demonstrated efficacy of CTX-471 monotherapy in checkpoint-inhibitor resistant models
- Enhanced anti-tumor efficacy when combining CTX-471 with tovecimig
- Potential new treatment option for patients who failed checkpoint inhibitor therapy
- Results are only from preclinical studies, requiring further clinical validation
- to specific mouse models, may not translate to human patients
Insights
Compass's preclinical data shows CTX-471/tovecimig combination overcomes checkpoint inhibitor resistance in mouse models, potentially addressing a major treatment gap.
The preclinical data presented by Compass Therapeutics at AACR demonstrates significant scientific progress in addressing a critical challenge in cancer immunotherapy: resistance to checkpoint inhibitors. Their CD137 agonist antibody (CTX-471) in combination with tovecimig (CTX-009) showed efficacy in sophisticated mouse models specifically engineered to be resistant to current immunotherapies like anti-PD-1 and anti-PD-L1 antibodies.
The research employed exceptionally relevant models including CT26B2m and MC38B2m knockout mice that mimic HLA loss in patients, as well as innovative models without the enhanced NK cell susceptibility bias that often complicates immunotherapy research. These models closely simulate clinically observed resistance mechanisms.
Mechanistically, the data reveals that this combination enhances multiple aspects of anti-tumor immunity: inflammasome activation, pyroptosis (inflammatory cell death), and interferon-mediated signaling pathways. This multi-faceted immune activation likely explains the efficacy against checkpoint-resistant tumors.
The clinical implications are significant - approximately
This research represents an important scientific proof-of-concept for Compass's approach to combination immunotherapy, but substantial development work and clinical validation will be required before potential application in patients.
- CTX-471 monotherapy demonstrated efficacy in multiple murine models, including models highly resistant to immune checkpoint inhibitors.
- Combining CTX-471 with tovecimig (CTX-009) markedly increased anti-tumor efficacy in these models.
- Tovecimig in combination with CTX-471 showed evidence of enhanced innate and adaptive anti-tumor immunity ranging from increased tumor cell killing to increased antigen presentation and interferon signaling.
- The combination of tovecimig and CTX-471 has the potential to be an effective therapeutic regimen in patients where checkpoint inhibitors have failed, including anti-PD-1 and anti-PD-L1 antibodies.
BOSTON, April 28, 2025 (GLOBE NEWSWIRE) -- Compass Therapeutics, Inc. (Nasdaq: CMPX), a clinical-stage, oncology-focused biopharmaceutical company developing proprietary antibody-based therapeutics, today announced its poster presentation entitled “Enhanced Efficacy of CTX-471, A CD137 Agonist Antibody, In Models of Immune Checkpoint Failure Via Simultaneous Blockade of Neo-Angiogenesis” at the American Association for Cancer Research (AACR) Annual Meeting, from April 25–30, 2025, at the McCormick Place Convention Center in Chicago, IL.
“We are encouraged by the preclinical data shared at AACR, which demonstrated increases in the tumoral immune infiltrate in several mouse models following CTX-471 monotherapy,” said Thomas Schuetz, M.D., Ph.D., Chief Executive Officer and Scientific Founder of Compass. “Our results also suggest that combining CTX-471 with a next-generation anti-angiogenic agent such as tovecimig might not only enhance therapeutic efficacy and duration of response to CTX-471, but may also provide clinical benefit to patients in whom checkpoint inhibitors have failed. We look forward to advancing our ongoing work in these programs, with potential application across multiple solid tumor types and patient populations.”
Tovecimig in combination with CTX-471 demonstrated compelling activity in multiple murine models, including novel models highly resistant to immune checkpoint inhibitors:
- CT26B2m and MC38B2m knockout mouse tumor models, engineered to mimic HLA loss in patients (B2m: beta-2 microglobulin).
- Two novel models of immunotherapy resistance without the enhanced NK cell susceptibility bias conferred by complete or targeted MHC-I loss:
- A murine model with CT26 cells containing an engineered deletion of the B2m gene that were passaged in tumor-experienced mice, establishing a line of CT26B2m-/- cells that escaped immune rejection (CT26 B2m knockout escapers, CT26B2m-/-E).
- A murine model containing an H-2k1 MHC-I locus knockout in MC38 cells, resulting in targeted homozygous loss (with the expression of the other MHC-I alleles, and therefore natural resistance to NK cells).
The combination of CTX-471 with tovecimig was effective in these mouse models where conventional immune checkpoint inhibitors show reduced activity. Mechanistically, the combination appears to enhance inflammasome activation, pyroptosis, and interferon-mediated signaling, potentially providing clinical benefit to patients in whom checkpoint inhibitors have failed.
A copy of the presentation materials can be accessed on the News & Events section under “Presentations” of the Company’s website at www.compasstherapeutics.com once the presentation has concluded.
About CTX-471
CTX-471 is a fully human monoclonal antibody that binds and activates a novel epitope of the co-stimulatory receptor CD137, also known as 4-1BB, a member of the tumor necrosis factor receptor superfamily. The antibody is currently being evaluated in a Phase 1b clinical trial in patients with solid tumors that have progressed after at least three months on an approved PD-1 or PD-L1 inhibitor. Initial results reported from a monotherapy cohort of the study included partial responses in melanoma, small cell lung cancer, and mesothelioma, and CTX-471 has been generally well tolerated. In preclinical studies, CTX-471 has demonstrated potent monotherapy activity against multiple syngeneic tumor models, including the generation of long-term functional immunological memory.
About Tovecimig (CTX-009)
Tovecimig is an investigational bispecific antibody that is designed to simultaneously block Delta-like ligand 4 (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization. Preclinical and early clinical data of tovecimig suggest that blockade of both pathways provides robust anti-tumor activity across several solid tumors, including colorectal, gastric, cholangiocarcinoma, pancreatic and non-small cell lung cancer. Partial responses to tovecimig as a monotherapy have been observed in heavily pre-treated patients with cancer who were resistant to approved anti-VEGF therapies. COMPANION-002, a Phase 2/3 trial of tovecimig plus paclitaxel versus paclitaxel monotherapy in patients with previously treated, unresectable advanced metastatic or recurrent biliary tract cancers (BTC) is ongoing (clinical trial information: NCT05506943).
About Compass Therapeutics
Compass Therapeutics, Inc. is a clinical-stage oncology-focused biopharmaceutical company developing proprietary antibody-based therapeutics to treat multiple human diseases. Compass’s scientific focus is on the relationship between angiogenesis, the immune system, and tumor growth. The Company’s pipeline of novel product candidates is designed to target multiple critical biological pathways required for an effective anti-tumor response. These include modulation of the microvasculature via angiogenesis-targeted agents, induction of a potent immune response via activators on effector cells in the tumor microenvironment, and alleviation of immunosuppressive mechanisms used by tumors to evade immune surveillance. Compass plans to advance its product candidates through clinical development as both standalone therapies and in combination with proprietary pipeline antibodies based on supportive clinical and nonclinical data. The Company was founded in 2014 and is headquartered in Boston, Massachusetts. For more information, visit the Compass Therapeutics website at https://www.compasstherapeutics.com.
Forward-Looking Statements
This press release contains forward-looking statements. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding Compass’s product candidates, including the therapeutic potential of tovecimig and CTX-471. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, Compass’s ability to raise the additional funding it will need to continue to pursue its business and product development plans, the inherent uncertainties associated with developing product candidates and operating as a development stage company, Compass’s ability to identify additional product candidates for development, Compass’s ability to develop, complete clinical trials for, obtain approvals for and commercialize any of its product candidates, competition in the industry in which Compass operates and market conditions. These forward-looking statements are made as of the date of this press release, and Compass assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Investors should consult all of the information set forth herein and should also refer to the risk factor disclosure set forth in the reports and other documents Compass files with the U.S. Securities and Exchange Commission (SEC) available at www.sec.gov, including without limitation Compass’s latest Annual Report on Form 10-K and subsequent filings with the SEC.
Investor Contact
ir@compasstherapeutics.com
Media Contact
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media@compasstherapeutics.com
617-500-8099
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