Endocyte, a provider developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy, announced updates on clinical development for EC1456, its folate receptor-targeted tubulysin cancer therapy, and EC1169, its prostate-specific membrane antigen targeted (PSMA-targeted) tubulysin prostate cancer therapy.

Endocyte will narrow the EC1169 development program to focus only on the cohort of taxane-exposed, metastatic castration-resistant prostate cancer (mCRPC) patients, for which a top-line efficacy assessment of the expansion phase of this phase 1 trial is expected before the end of 2017. An interim assessment confirmed clinical activity of the drug in the taxane-exposed cohort with a partial response in one patient, stable disease in other patients, and other markers of activity. Endocyte believes EC1169 may have benefit in taxane-exposed patients, with more advanced disease, where upregulation of PSMA increases with prior treatments. Endocyte will stop enrollment of taxane-naïve mCRPC patients in the EC1169 trial.

In addition, the company plans to stop enrollment in the EC1456 trial, where a careful assessment in folate receptor-positive (FR-positive) disease across multiple cohorts of patients and multiple dosing schedules did not yield the level of clinical activity necessary to support continued advancement of this agent. However, enrollment of a small number of patients in the EC1456 ovarian cancer surgical study will continue in order to inform other SMDC programs in development. Preliminary data to-date from the ovarian surgical study provides evidence that patients with FR-positive disease are being successfully identified with the use of the etarfolatide imaging agent, but the intratumoral levels of the EC1456 drug payload may be lower than predicted by pre-clinical models.

“Endocyte is a data-driven company, and we are committed to the disciplined management of clinical programs as the science guides us,” said Mike Sherman, president and CEO at Endocyte. “Recently gained insight into the safety and efficacy of EC1169 and EC1456, coupled with our commitment to the productive investment of capital, has led us to refocus efforts on our most promising programs, which include our CAR T-cell SMDC adaptor platform, our dual-targeted DNA crosslinker drug EC2629, and the cohort of taxane-exposed patients receiving EC1169.”

Endocyte is advancing its work with Seattle Children’s Research Institute aimed at bringing its CAR T-cell bi-specific adaptor molecule to the clinic in 2018. In addition, the company plans to file its IND for EC2629 in mid-2017, which includes a potent DNA-targeted warhead with clinically proven activity. To Endocyte’s knowledge, this is the first drug candidate designed to simultaneously target both tumor cells and tumor associated macrophages (TAMs), which contribute to disease progression by interfering with natural anti-tumor immune responses.

Endocyte also announced today plans to reduce its workforce by approximately 40% in order to better focus its resources on the company’s highest value opportunities, while maintaining key capabilities.

“As we refocus our clinical development efforts, we are also aligning our investments and resources to advance our most compelling pipeline programs to key inflection points," added Sherman. “We are very grateful for all the contributions over the years from our dedicated, talented team of employees, who have devoted so much of themselves towards helping advance our efforts to bring our innovative, targeted therapies to patients with cancer and other serious diseases. We’ll be working closely with those affected by the restructuring to support them through this difficult but necessary transition.”

Endocyte anticipates one-time charges of approximately $2.4 million related to termination benefits and the accelerated closure of the EC1456 trial. As a result of this restructuring, the company is revising its guidance for 2017 and now expects its cash balance at the end of 2017 to be approximately $105 million, with a more substantial positive impact from the restructuring beginning in 2018.