ATA230

ATA230 is a cytotoxic T lymphocyte (CTL) product candidate that is precision targeted against antigens expressed by the cytomegalvirus (CMV). ATA230 is in Phase 2 trials and has received orphan designation from EMA for the treatment of CMV infection in patients with impaired cell-mediated immunity.

We also intend to initiate an expanded access trial for patients with CMV infection or persistent CMV disease after allogeneic hematopoietic stem cell transplantation (HCT) or solid organ transplantation (SOT), and for whom there is no satisfactory alternative therapy.

We met with the FDA for an end of Phase 2 meeting to discuss late stage development of ATA230 for the treatment of anti-viral refractory or resistant CMV infection following either HCT or SOT.  Given the opportunity to pursue a conditional marketing authorization in the EU for ATA129, we have decided to prioritize at this time our EBV related programs ahead of ATA230.  Therefore, we intend to further evaluate ATA230 Phase 3 trial designs following the initiation of our ATA129 Phase 3 trials.

Cytomegalovirus (CMV)
CMV is a member of the herpesvirus family. The infection rate with CMV gradually increases throughout childhood, and once infected, an individual carries the virus for life due to its ability to establish a latent state of infection. It is estimated that CMV infection affects 50% to 90% of the global adult population. Patients with a compromised immune system, including bone marrow transplant (HCT) and solid organ transplant (SOT) patients, human immunodeficiency virus (HIV) patients, and to a lesser extent cancer patients, are at highest risk for developing significant disease syndromes caused by CMV, including interstitial pneumonia, gastrointestinal infection, central nervous system disease, hepatitis, retinitis, and encephalitis.

Antiviral drugs are important treatment options to treat and prophylax against (prevent) CMV infection, but emerging viral resistance to these drugs, and adverse effects such as kidney toxicity and a reduction in white blood cell count (impairing the ability to fight other infections) remain a challenge.

CMV Viremia and Disease after HCT
ATA230 has been studied in one Phase 1 clinical trial and is now being studied in two Phase 2 clinical trials including patients with CMV viremia and CMV disease, in each case refractory to antiviral drug treatment.

At the December 2016, ASH Annual Meeting, Dr. Susan Prockop, M.D. and colleagues reported Phase 2 results for ATA230.

  • Data from the Phase 2 trial described efficacy and safety of ATA230 in the treatment of 15 patients with documented CMV mutations conferring resistance to anti-viral therapies
  • Patients had received a median of 3 prior therapies before receiving ATA230
  • A response rate of approximately 70% was reported with 6 complete responses (CR) and 5 partial responses (PR)
  • An analysis of overall survival (OS) at 6 months in responders versus non responders demonstrated an OS of approximately 70% in responders (CR+PR) versus 25% in non-responders
  • There were 16 SAEs possibly related to CMV-CTL among 66 patients

We believe these data suggests a high response rate among patients with otherwise refractory CMV viremia and disease. Since these trials are ongoing, we expect that survival data may evolve with ongoing follow-up of the patients. Overall, ATA230 therapy was well tolerated. One patient developed possibly related de novo GvHD, or a flare-up of prior GvHD, in association with infusion of ATA230.

We met with the FDA for an end of Phase 2 meeting to discuss late stage development of ATA230 for the treatment of anti-viral refractory or resistant CMV infection following either HCT or SOT.  We intend to further evaluate ATA230 Phase 3 trial designs following the initiation of our ATA129 Phase 3 trials.