Pyxis Oncology Reports Positive Early Phase 1 Data for PYX-201

Pyxis Oncology, Inc. has shared promising early data from its ongoing Phase 1 clinical dose escalation study of PYX-201, an innovative antibody-drug conjugate (ADC) aimed at various solid tumors. This ADC, equipped with a microtubule inhibitor payload, uniquely targets Extradomain-B Fibronectin (EDB+FN) within the tumor extracellular matrix.

These encouraging results highlight significant clinical responses in six tumor types: head and neck squamous cell carcinoma (HNSCC), ovarian, non-small cell lung cancer (NSCLC), HR+/HER2- breast cancer, triple-negative breast cancer (TNBC), and sarcoma. PYX-201 has shown a confirmed 50% objective response rate (ORR) by RECIST 1.1 in HNSCC, including a complete response and 100% Disease Control Rate among six heavily pre-treated patients. This indicates its potential in both monotherapy and combination treatments.

Lara S. Sullivan, M.D., President and CEO of Pyxis Oncology, remarked that these positive data signify a crucial milestone for the company, showcasing PYX-201's potential to benefit patients with challenging cancers. The company is set to begin expansion trials for monotherapy in HNSCC in early 2025 and has also entered a new clinical trial collaboration with Merck (known as MSD outside the US and Canada). This partnership will assess the combination of PYX-201 with Merck's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), targeting HNSCC, HR+/HER2- breast cancer, TNBC, and sarcoma, with the first patients expected to dose in the first quarter of 2025.

The ongoing Phase 1 trial is open-label and multicenter, with 80 patients enrolled across various solid tumors. Patients receive doses of PYX-201 ranging from 0.3 mg/kg to 8.0 mg/kg, focusing on evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy. The median number of prior cancer therapies for patients enrolled is four, with some having undergone up to ten lines of treatment. The current identified dose range for PYX-201 is between 3.6 mg/kg and 5.4 mg/kg.

In HNSCC, significant clinical responses were observed. Among the evaluable patients treated within the identified dose range, a confirmed 50% ORR was noted, including a complete response and two partial responses by RECIST 1.1. Dr. Glenn J. Hanna from Dana-Farber Cancer Institute highlighted the potential of PYX-201 to provide meaningful responses in heavily pre-treated patients, underscoring its promising prospects across multiple cancer types, particularly head and neck cancer.

Pyxis Oncology's collaboration with Merck aims to evaluate PYX-201 in combination with KEYTRUDA® in first and second-line HNSCC, HR+/HER2- breast cancer, TNBC, and sarcoma. Both companies retain their commercial rights to their respective drugs.

The development plans for PYX-201 in HNSCC include a dose escalation and expansion study with preliminary clinical data expected in the latter half of 2025. Monotherapy studies in second and third-line HNSCC patients, experienced with platinum and PD-1 inhibitors or EGFR inhibitors, are also planned with data readouts expected in 2025 and 2026.

Additional encouraging responses were seen in other tumor types such as ovarian cancer, NSCLC, HR+/HER2- breast cancer, TNBC, and sarcoma, with several exploratory Phase 1 monotherapy expansions and combination studies planned. Expected preliminary clinical data from these studies is anticipated in the latter half of 2025 and into 2026. Preclinical studies of PYX-201 in combination with other agents in ovarian cancer and NSCLC are set to begin in 2025, followed by clinical trials with preliminary data expected in 2026.

PYX-201 has demonstrated a favorable tolerability profile in initial studies, with low instances of treatment-related adverse events leading to dose discontinuations or delays. The low incidence of severe adverse events supports its differentiated construct, which enhances molecular stability and ensures selective targeting of tumor tissue while minimizing effects on normal tissues.

Dr. Anthony Tolcher of NEXT Oncology noted that PYX-201's unique extracellular mechanism of action offers a significant opportunity for further development across a range of tumor types, both as a standalone treatment and in combination therapy settings. The safety data suggest PYX-201 could be safely combined with other treatments, including checkpoint inhibitors, to enhance patient responses.

Pyxis Oncology plans to present more detailed analyses during its investor event, highlighting the promising preliminary Phase 1 data for PYX-201.