adc platform
The PLATFORM
Oncomatryx has developed its own platform of Antibody-Drug Conjugates (ADCs) targeting the tumor microenvironment. This is a new generation of drugs to treat once incurable metastatic solid tumors.
Precision drugs
Precision medicine is setting a milestone in the field of oncology. Drugs based on human monoclonal antibodies specifically designed to target cancer-associated proteins are reshaping the treatment.
In the last years of the 20th century, human monoclonal antibodies directed against therapeutic targets on tumor epithelial cells revolutionized cancer treatment. Already immersed in the 21st century, new therapeutic antibodies aimed at boosting the immune response against the tumor demonstrated efficacy in some tumors resistant to the first generation of antibodies.
And the conjugation of the first generation of antibodies with strong cytotoxic drugs generated a third wave of biotechnological drugs, Antibody Drug Conjugates (ADCs), which combined the specificity and safety of antibodies with much greater strength.
NOVEL TARGETS. NOVEL ANTIBODIES. NOVEL ADCs
Since war was declared on cancer nearly fifty years ago, significant advances have been achieved in the prevention and treatment of early stages of cancer. However, little progress has been made in the development of efficient tools to fight late and invasive stages of cancer.
The battlefield must be broadened.
There is increasing evidence supporting the development of precision drugs that target not only tumor epithelial cells, but also the Cancer-Associated Fibroblasts (CAFs), in the tumor microenvironment.
Our therapeutic approach is focused on the development of novel therapeutic antibodies and antibody-drug conjugates that target proteins located in the tumor microenvironment. A novel route to cancer treatment, directed not against tumor epithelial cells, but the Cancer-Associated Fibroblasts that promote their invasiveness, immunosuppression and drug resistance.
OUR CHALLENGE THROUGH THE TUMOR MICROENVIRONMENT
At the core of metastatic solid tumor resistance lies the complex tumor microenvironment, made up of endothelial cells, immune cells and cancer-associated fibroblasts (CAFs). Cancer cells interact with this microenvironment, becoming more resilient and posing a challenge to conventional therapeutic approaches.
A NOVEL GENERATION OF ADCs
At Oncomatryx, we’re leading a new revolution with a cutting-edge ADC platform specifically designed to tackle the unique challenges of the metastatic solid tumor microenvironment.
KEY STRENGTHS OF OUR PLATFORM
1. Targeted Antibodies against the Tumor Microenvironment: We have developed highly selective antibodies that are engineered to recognize and target specific proteins within the tumor’s microenvironment, particularly in Cancer-Associated Fibroblasts. This level of precision ensures our treatment zeroes in on the root of the problem.
2. Our own Cytotoxic Payload: Cytolysins, our own specialized payload, are cytotoxic agents designed to maximize therapeutic impact, avoid resistance, boost the immune system’s antitumor response, and minimize unwanted side effects on healthy surrounding tissues. Cytolysins were developed in collaboration with Tube Pharmaceuticals GmbH (Austrian Biopharmaceutical company led by prestigious german chemist Dr. Wolfgang Richter), later acquired by Oncomatryx in 2023.
WHAT SETS OUR ADC PLATFORM APART
PIPELINE
Our mission focuses on addressing unmet medical needs in oncology, particularly in metastatic solid tumors that are resistant to conventional chemotherapy, advanced immunotherapy and even modern ADCs. Driven by scientific excellence, we work tirelessly to discover and develop effective treatments. Our pipeline is a testament to our commitment to innovation and our hope to make a meaningful difference in patients’ lives.
We invite you to learn more about our work, including our tumor microenvironment-targeting ADCs—OMTX705, OMTX703, and OMTX707—their progress, and how together, we are paving the way toward a future where cancer can be treated more effectively and safely.
OMTX705
The antitumor efficacy of our anti-FAP ADC, OMTX705, was demonstrated in two different academic laboratories and three CROs, across various mouse xenograft models of pancreatic and other patient-derived metastatic solid tumors. OMTX705 caused 100% tumor growth inhibition as a monotherapy, achieving complete tumor regression in mice with a humanized immune system, and showed the greatest potency when combined with immunotherapy or chemotherapy.
OMTX705 is already in clinical trials in Europe and the USA, which is allowing us to gather very exciting data on its safety and antitumor efficacy in patients with previously incurable metastatic solid tumors.
THE TARGET – WHAT IS FAP?
FAP (Fibroblast Activation Protein) is a key protein in the interaction between the tumor and its microenvironment, specifically through the cancer-associated fibroblasts (CAFs). These cells play a crucial role in the progression of solid tumors, especially those with metastatic characteristics.
● It has a high capacity for internalization, facilitating the entry of the payload into the tumor-associated fibroblast.
● It is overexpressed in the peritumoral stroma of 90% of metastatic solid tumors.
● FAP expression has not been reported in healthy tissues, except for slight expression in adipocytes, smooth muscle, bone marrow, and the uterus.
● It is involved in extracellular matrix remodeling, tumor growth and metastasis.
Previous approaches blocking FAPα activity have failed in Phase II due to lack of efficacy. Our approach is not aimed at blocking FAPα, but at using it as a CAF-specific internalization vehicle for cytotoxic molecules.
THE ANTIBODY
OMTX005 anti-FAPα humanized IgG1 monoclonal antibody (mAb) binds specifically, in a concentration-dependent manner, to both human and murine FAPα, at subnanomolar EC50 values (0.33 and 0.25 nM) in vitro, in FAPα-transfected HT1080 cells and in primary Cancer Associated Fibroblasts from patients, as well as in vivo in tumor stroma of pancreas cancer patient-derived xenograft mice after i.p administration.
● OMTX005 anti-FAPα humanized mAb affinity and specificity are not affected by conjugation to Oncomatryx cytolysin payload.
● OMTX005 anti-FAPα humanized mAb is rapidly internalized within cells (85% after 60min)
THE PAYLOAD: CYTOLYSINS
Synthetic Cytolysins
● Synthetic Tetrapeptidic analogues of the natural class Tubulysins
● Low MW: 780 g/mol
● Not a substrate of Multiple Drug Resistance proteins
● Highly cytotoxic
● Anti-angiogenic
● Easy to conjugate
● Achievable by total synthesis in sufficient amount for preclinical and clinical development
● Functional group for linker technology can be modified
● Several linker technologies applicable
● Robust IP position
Different combinations of cytolysins and linkers were evaluated in vitro as well as in vivo models and Cytolysin-TAM558 was selected as the optimal structure for highest activity and stability
Novel MoA
PDX murine models
➟ 100% tumor growth inhibition and regression in Pancreatic, Gastric, Ovarian, Triple Negative Breast and Lung Cancer PDX murine models, with or without humanized immune systems, without significant toxicity.
➟ Demonstrated superiority over both classical chemotherapy and modern immunotherapy drugs currently in market, as a single agent and in combination therapies.
➟ Demonstrated superiority over other FAP-targeted ADCs bearing different payloads.
Non-human primates GLP-tox
Repeat Dose Toxicity
➟ Non-pivotal study: :
- MTD phase: 6 increasing dose levels up to 100mg/kg: No adverse effects at any dose
- FD phase: Two doses 80mg/kg day 1 and day 8: No adverse effects. TK analysis: OMTX705 – Cmax 2,180 µg/mL; t1/2 54.5h; AUC 99900h*µg/mL; CL 0.696mL/h/kg
➟ Pivotal study:
○ GLP study: GLP 28-day Repeat Dose Toxicity study in monkeys. OMTX705 was administered once a week, for four weeks, at 10, 30 and 80 mg/Kg
○ No observed adverse effects at any doses tested.
○ Cytolysin exposure was not detected at any OMTX705 dose level
○ 80mg/kg was considered the NOAEL and the HNSTD in monkeys
Clinical trials
Phase I dose escalation trial on highly invasive solid tumors and leiomyosarcomas.
➟ Primary objective: safety and tolerability.
➟ Dose escalation 3+3 design.
➟ Single agent.
➟ Combo with Pembrolizumab.
➟ IND and IMPD approved.
➟ First in Human EU Oct 2022.
➟ First in Human US May 2023.
COMPANION DX
INVASCAN: diagnosis and prognosis of Invasive Tumors
InvaScan is a new and precise tool for the diagnosis and prognosis of invasive tumors. It is an immunohistochemistry tissue staining system based on a monoclonal antibody that detects Collagen XI-α1, COL11A1, in biopsy samples of invasive carcinomas, optimized for use on standard platforms in pathology services.
TECHNICAL ADVANTAGES
1. It is specific to COL11A1 and it does not cross-react with other similar collagens, such as COL5A1. Additionally, it clearly marks cancer-associated fibroblasts.
2. It detects COL11A1 in samples from various tissues with high sensitivity, specificity, and reproducibility.
3. It is optimized for use in the automated staining platforms commonly used in pathology laboratories, facilitating its implementation in clinical practice.
4.Multicenter validations in Europe and the US have demonstrated its clinical utility for diagnosing and prognosing the invasiveness of colorrectal, pancreatic, kidney, breast, ovarian, and head and neck cancers.
COL11A1 has also been described as a useful biomarker for the diagnosis, prognosis, and prediction of chemoresistance in various types of tumors:
● Pancreatic cancer: COL11A1 was found in the desmoplastic stroma of pancreatic ductal adenocarcinomas, distinguishing them from chronic pancreatitis and ampullary carcinomas (García-Pravia et al. 2013. PloS ONE 8(10): 1-13).
● Colon cancer: COL11A1 was detected in the stroma of colonic polyps with malignant component, distinguishing them from benign polyps (Galván JA. et al. BMC Cancer 2014; 14:867).
● Breast cancer: COL11A1 was found in the desmoplastic stroma of infiltrating carcinomas, distinguishing them from benign inflammatory and sclerosing complex lesions. DMTX invaScan facilitates diagnosis of infiltrating breast tumors in biopsy core samples with high sensitivity and specificity (Fuentes-Martínez N. et al. Histol Histopathol. 2015; 30(1):87-93).
● Breast papillomas: Prognosis of recurrence and malignant recurrence of breast non-malignant papillary lesions. It has been validated by means of IHC on core needle biopsies of breast intraductal papillomas that were excised and followed up for longer than 5 years (Freire J. et al. BioMed Research International 2015; In Press).
● Head and neck cancer: COL11A1 was found in the desmoplastic stroma of squamous carcinomas in any localization, distinguishing them from benign lesions such as fibrosis, inflammation, leucocheratosis, ulcer, hyperplasia, etc.
● Kidney cancer: Collagen XI-α-1 was detected in the desmoplastic stroma of kidney carcinomas, distinguishing them from oncocytomas.
● Lung cancer: Collagen XI-α-1 was detected in the desmoplastic stroma of lepidic-pattern adenocarcinomas, which makes the differentiation of in situ adenocarcinomas from pulmonary fibrosis possible.
● Ovarian cancer: COL11A1 was detected in malignant ovarian tumors, distinguishing them from benign tumors and non-malignant lesions. Collagen-XI-α1 is also useful for the assessment of the invasiveness of borderline tumor implants. Increasing COL11A1 expression has been correlated with tumor invasiveness, metastasis and recurrence (Cheon, DJ. et al. Clin Cancer Res. 2014; 20(3):711-723).
● Bladder cancer: COL11A1 was detected in the stroma of invasive bladder carcinomas (pT2), distinguishing them from superficial tumors and benign lesions (Freire et al. 2014. Pathology Journal of the RCPA. 46:S135).
Additionally…
Companion Diagnostics for Oncomatryx Precision Drugs
We are developing and validating diagnostics to identify and monitor patients who are likely to benefit from treatment with our precision drugs targeting the tumor microenvironment.
