Pipeline

Artios is advancing an industry-leading pipeline of therapeutic candidates that target a broad range of solid tumors.

 

 

Artios’ lead candidate, alnodesertib (previously known as ART0380), is an orally administered, selective small molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR) with first- and best-in-class potential. It is designed to maximize the therapeutic window by selectively inducing DNA damage in sensitized cancer tissue while preserving DNA integrity in healthy tissue. It is further optimized for use in combination with a DNA-damaging therapy such as chemotherapy, to enhance anti-tumor activity and improve patient outcomes.

Mechanism of Action

ATR is an important signaling protein kinase that activates the cell’s response to DNA damage and replication stress that occur as cells multiply. ATR is the cell’s antidote for replication stress. It helps to stabilize the replication fork, the epicenter of DNA replication, and initiates DNA break repair, enabling subsequent cell division. Inhibiting ATR with alnodesertib thus removes the cancer cell’s ability to repair damaged DNA, leading to the selective death of cancerous cells.

 

Clinical Development of alnodesertib

Alnodesertib, in combination with low-dose irinotecan, is currently being evaluated in a Phase 1/2a clinical study to evaluate its potential in cancers with high endogenous replication stress.

The combination treatment has demonstrated a favorable safety profile, is well-tolerated, and has been shown to be suitable for long-term dosing. At the Phase 2 dose, it showed a meaningful duration of response and prolonged clinical benefit, with responses occurring in eight different ATM-deficient tumor types. Alnodesertib received U.S. FDA Fast Track designation, in combination with low-dose irinotecan, for treating patients with ATM-negative metastatic colorectal cancer in the third-line setting.

Clinical data with alnodesertib from our ongoing STELLA Phase 2 expansion cohorts are expected in 2026.

For more information, please click here.

 

---

ART6043 is the most advanced clinical Polθ program in the industry. It is a selective, orally bioavailable, small-molecule inhibitor of the polymerase domain of DNA polymerase theta (Polθ), a DNA repair enzyme that is preferentially expressed in cancer cells but is virtually absent in most healthy tissues.

Mechanism of Action

Some cancer cells, especially those with defective DDR pathways and are resistant to standard-of-care therapies, rely heavily on Polθ for survival. Polθ plays a key role in repairing DNA double-strand breaks through a process known as microhomology-mediated end joining (MMEJ). Many tumors use this repair mechanism frequently. For instance, cancer cells with DDR deficiencies such as BRCA1/2 mutations cannot repair DNA through the precise homologous recombination (HR) pathway. To compensate, these cells depend on alternative repair pathways like MMEJ, facilitated by Polθ.

By inhibiting Polθ, ART6043 disrupts the MMEJ repair pathway. This causes DNA damage to accumulate in cancer cells, ultimately leading to their death. Healthy cells, which do not rely on Polθ for DNA repair, remain unaffected.

Clinical Development

ART6043 is being evaluated in an ongoing Phase 1/2a study as monotherapy in patients with advanced or metastatic solid tumors that have a loss of function of known DDR genes. It is also being studied in combination with the PARP inhibitor, olaparib, in patients with a BRCA gene variant. Artios plans to initiate a Phase 2 trial with ART6043 in combination with olaparib.

Artios is also exploring the potential of Polθ with DNA damaging agents such as chemotherapies, ionizing radiation and radioligand therapy as well as with immuno-oncology medicines.

For more information, please click here.

 

---