On October 24, 2019 Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company discovering and developing a new class of potent and selective precision oncology medicines for the treatment of patients with a wide range of solid tumor malignancies, reported the publication of several preclinical studies evaluating PEN-221 as a novel therapeutic for the treatment of small cell lung cancer (SCLC) (Press release, Tarveda Therapeutics, OCT 24, 2019, View Source [SID1234542504]). The publication, "Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer," was published in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
PEN-221 is a miniature drug conjugate comprising a peptide that is highly selective for somatostatin receptor 2 (SSTR2) conjugated to the potent tubulin inhibitor payload, DM1, via a tuned cleavable linker. SSTR2 is overexpressed on the surface of cancer cells in patients with a range of solid tumors including SCLC and neuroendocrine cancers.
"These studies demonstrate that the unique attributes of our PEN-221 miniature drug conjugate allow for deep tumor penetration, while limiting plasma and normal tissue exposure. We engineered PEN-221 to have these attributes in order to enable long-term dosing of our conjugate and cause durable tumor control, as was demonstrated in our published studies," said Mark Bilodeau, Chief Scientific Officer of Tarveda.
The publication shows a series of mouse xenograft efficacy studies where PEN‑221 treatment resulted in significant antitumor activity, including enduring and complete regressions in multiple SSTR2 positive SCLC models. PEN-221 treatment of SSTR2 positive SCLC xenograft tumors also showed potent and durable tumor inhibition superior to the currently used standard of care treatment for SCLC.
Additional studies elucidated how PEN-221 causes cell cycle arrest and tumor cell death. Mouse xenograft models demonstrated how the unique miniature conjugate structure of PEN-221 allows deep penetration into the tumor causing mitotic arrest while rapidly and durably delivering DM1, the toxic payload, into the tumor. The relatively short plasma exposure of PEN-221 and its DM1 payload limits damage to normal tissue, and PEN-221 was well tolerated in our Phase 1 study, which was presented at ASCO (Free ASCO Whitepaper) 2018.
Together, these results show that the unique attributes of PEN-221, including deep tumor penetration, rapid delivery of its toxic payload and limited exposure to normal cells may potentially offer distinct advantages in treating SCLC and GI neuroendocrine cancers compared to current therapeutic options.
"Based on the encouraging results from these studies, we initiated a Phase 1/2a clinical trial of PEN-221 in patients with a focus on both gastrointestinal neuroendocrine tumors and small cell lung cancer," said Jeffrey D. Bloss, Chief Medical Officer of Tarveda. "The Phase 1 portion of the study showed that PEN-221 was well tolerated with evidence of antitumor activity seen in multiple patients. We were encouraged by these results and initiated the Phase 2a portion of the study, which is currently enrolling patients with results expected in 2020."
About Small Cell Lung Cancer
Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancers in the U.S. with few new recent therapeutic options available despite over 60 agents that have been investigated in clinical trials. SCLC is an aggressive disease that spreads quickly and most patients with SCLC experience rapid disease progression before symptoms appear, resulting in about 7% survival at five years. In addition to the lack of early symptoms, the lack of early detection reduces the chances for an optimal therapeutic response.
About PEN-221
PEN-221 is a miniature drug conjugate consisting of a peptide ligand, that is highly selective in targeting SSTR2, joined through a cleavable linker to the potent cytotoxic payload DM1. SSTR2 is overexpressed on the cell surface of a range of solid tumors including neuroendocrine tumors and small cell lung cancer. In non-clinical experiments, PEN-221 binds with high affinity and selectivity to SSTR2. On binding, PEN-221 triggers SSTR2 internalization resulting in the accumulation of the DM1 payload in tumor cells followed by cell cycle arrest and apoptosis.
PEN-221 is being evaluated in Phase 2a expansion cohorts currently enrolling patients with midgut neuroendocrine tumors and small cell lung cancer (ClinicalTrials.gov Identifier: NCT02936323).