On December 19, 2024 Pyxis Oncology, Inc. (Nasdaq: PYXS), a clinical-stage company developing next-generation therapeutics for difficult-to-treat cancers, reported a portfolio prioritization, focusing resources on advancing its lead clinical program, PYX-201, a first-in-concept antibody-drug conjugate (ADC) with a microtubule inhibitor (optimized auristatin) payload that uniquely targets Extradomain-B Fibronectin (EDB+FN), a non-cellular structural component within the tumor extracellular matrix (Press release, Pyxis Oncology, DEC 19, 2024, View Source [SID1234649222]).

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In November 2024, Pyxis Oncology reported positive preliminary data from the ongoing Phase 1 dose-escalation study of PYX-201, evaluating its safety and efficacy in multiple solid tumor types. Among patients with HNSCC, PYX-201 achieved a confirmed 50% objective response rate (ORR) based on RECIST 1.1 criteria, including one complete response and a disease control rate (DCR) of 100% in six heavily pretreated HPV-positive and HPV-negative evaluable patients with a median of four prior lines of therapy.

Across six solid tumor types of interest at therapeutically active dose levels, including HNSCC, ovarian, non-small cell lung cancer (NSCLC), HR+/HER2- breast cancer, triple-negative breast cancer (TNBC), and sarcoma, PYX-201 (n=31) achieved a 26% ORR in the Phase 1 trial, with dose-dependent responses observed including patients who had previously progressed on taxanes. The data supports further development in both monotherapy and combination therapy expansion trials, including a frontline HNSCC study in combination with pembrolizumab, with patient dosing in both the monotherapy and combination therapy trials expected to begin in early 2025.

The portfolio prioritization further supports a robust development plan for PYX-201 in several dose expansion studies, including monotherapy in 2/3L HNSCC, in combination with pembrolizumab in 1/2L+ HNSCC, as well as pembrolizumab combination studies in other solid tumors including HR+/HER2- and triple-negative breast cancer. Preliminary data from these cohorts is expected across both the second half of 2025 and the first half of 2026.

Details on the PYX-201 Phase 1 dose-escalation trial and preliminary data presented in November are available on the Events & Presentations page in the Investor Relations section of Pyxis Oncology’s website at ir.pyxisoncology.com.

Pipeline Prioritization

Pyxis Oncology’s second clinical program, PYX-106 — a fully human IgG1 monoclonal antibody targeting Siglec-15 — is being deprioritized to allocate resources toward advancing the lead asset, PYX-201. As a result, Pyxis Oncology has decided to suspend further clinical investment in PYX-106, which was in-licensed from Biosion Inc., with Biosion retaining rights for Greater China.

To date, the Phase 1 monotherapy trial of PYX-106 enrolled 45 patients with advanced solid tumors. PYX-106 was observed as generally safe and well-tolerated across all tested doses, ranging from 0.5 mg/kg to 22.5 mg/kg. At this time, a maximum tolerated dose has not been established. The pharmacokinetic and pharmacodynamic results demonstrated dose-proportional pharmacokinetics, a half-life of 9 to 11 days, no detection of antidrug antibodies in a variety of heavily pretreated solid tumors across tested dose levels.

"Deprioritizing the PYX-106 clinical program as a monoclonal antibody represents a strategic and judicious use of our resources, allowing us to focus on advancing PYX-201," said Lara S. Sullivan, M.D., President and Chief Executive Officer of Pyxis Oncology. "We are excited about the potential of PYX-201, an innovative, first-in-concept ADC uniquely designed to target the tumor extracellular matrix. The positive preliminary PYX-201 Phase 1 data we presented last month reinforces our confidence in the promise of this program, particularly in addressing unmet needs in HNSCC in both monotherapy and combination therapy settings."