Pipeline

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

 

ART0380 is an orally active, selective inhibitor of ataxia telangiectasia and Rad3-related protein (ATR) designed to maximize the therapeutic window and thereby 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 thus removes the cancer cell’s ability to repair damaged DNA, leading to the killing of cancerous cells.

Clinical Development of ART0380

ART0380 is being evaluated in the clinic as monotherapy and in combination with DNA damaging agents, to identify the optimal clinical regimen.

In the monotherapy setting, ART0380 is being studied in tumors with DDR deficiencies and/or in replication stress-vulnerable tumors in an ongoing Phase 2 expansion study in endometrial cancers.

ART0380, in combination with gemcitabine, a DNA-damaging agent, is being evaluated in an ongoing Phase 2 study in platinum-resistant ovarian cancer.

In the third setting, ART0380, in combination with irinotecan, is currently being evaluated in a Phase 1b proof-of-concept expansion study.

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.

 

---

Alternative Lengthening of Telomeres (ALT) is a telomere maintenance mechanism observed in 10-15% of all cancers. In cancer cells, this pathway is activated in response to telomere replication stress, ensuring genome stability and facilitating replicative immortality. ALT’s role in maintaining telomeres makes it a critical survival mechanism for highly replicating cancer cells. Artios’ ALT program is in the discovery phase, and the company is advancing the program to develop first-in-class therapies.