While one might expect a positive readout from a biotech’s lead candidate to boost the company’s stock price, Pyxis Oncology’s shares—which have tumbled more than 40% this week—tell a different story.
The problem is, despite the company touting "encouraging" preliminary results in a range of solid tumors, including in tough-to-treat head and neck cancer, Pyxis’ antibody-drug conjugate (ADC) PYX-201 is “difficult to differentiate among emerging investigational drugs” in that indication, analysts at William Blair wrote in a note to clients Thursday.
Beyond head and neck squamous cell carcinoma (HNSCC), in which PYX-201 found the most success, the drug’s activity appears “modest” at best in other tumor types, the William Blair team pointed out. In light of the results, the analysts lowered their expected probability of success for Pyxis’ candidate from 35% to 10%.
PYX-201, which Pyxis originally in-licensed from Pfizer, is an ADC with an optimized auristatin payload designed to target part of the tumor extracellular matrix (ECM).
In phase 1 dose-escalation study results unveiled this week, the oncology prospect was able to generate clinical responses across six tumor types: HNSCC, ovarian cancer, non-small cell lung cancer (NSCLC), HR+/HER2- breast cancer, triple-negative breast cancer (TNBC) and sarcoma.
With early data now out in the wild, Pyxis has detailed plans to launch multiple additional trials, both for PYX-201 as a monotherapy and in combination with Merck & Co.’s immuno-oncology superstar Keytruda.
In HNSCC specifically, PYX-201—which was tested at a range from 3.6 mg/kg to 5.4 mg/kg—yielded a confirmed objective response rate of 50% among six heavily pretreated patients.
While the data look "encouraging" to cancer specialist Glenn J. Hanna, M.D., as quoted in Pyxis' press release, the team at William Blair struggled to see what sets PYX-201 apart from other candidates in head and neck cancer. Other candidates in the space include Merus’ bispecific petosemtamab and Pfizer and Genmab’s approved ADC Tivdak.
In the case of the latter drug, Pfizer and Genmab chose not to pursue further development for Tivdak as a monotherapy in head and neck cancer despite the med yielding a comparable confirmed response rate in a phase 2 trial, according to the William Blair team. This “suggests a high bar for commercial success for the cancer indication," the analysts wrote.
Still, Pyxis is rolling on with plans to launch a slate of additional studies in HNSCC, including two phase 1 trials of PYX-201 monotherapy in certain second- or third-line patients. The studies are slated to kick off in 2025’s first quarter, with data expected next year and in 2026.
The biotech is also teaming up with Merck to test PYX-201 and Keytruda together in a dose-escalation and expansion study in first- and second-line patients. That trial is also expected to be initiated in January, with Pyxis telegraphing a potential data readout by the second half of next year.
Aside from HNSCC, the company also pointed to "encouraging confirmed and unconfirmed responses" seen in other solid tumor types in the phase 1 trial.
Looking forward, Pyxis is plotting Keytruda combination studies in HR+/HER2- breast cancer, TNBC and sarcoma, plus preclinical trials of PYX-201 with “other agents” in ovarian cancer and NSCLC, the company said. Those preclinical studies are expected to commence in 2025.
In terms of safety, PYX-201 showed “favorable preliminary tolerability,” and few patients in Pyxis’ study discontinued the drug or experienced interruptions or delays caused by treatment-related adverse events (TRAEs), according to Pyxis. The study also showed a low incidence of grade 3 or 4 payload-related TRAEs and grade 1 or grade 2 adverse events, which Pyxis said points to the drug’s “attractive safety” for both monotherapy and combination therapy development.
Pyxis’ phase 1 dose-escalation study of PYX-201 has enrolled 80 patients across multiple solid tumor types. The trial participants have had a median of four lines of prior therapy.
The biotech’s phase 1 results come about a year after Pyxis rolled out layoffs and slimmed down its development footprint in a bid to pave a longer cash runway.
Last November, Pyxis revealed it would continue to focus on PYX-201 as its lead asset while pausing other early-stage research programs. At the same time, the company said it would cut 40% of its total head count, which stood at around 75 people a year ago, according to LinkedIn and Crunchbase.
Pyxis also said it had undertaken “monetization efforts” to maximize royalty streams for Apexigen, which the biotech purchased for roughly $10.7 million in an all-stock transaction last May. Pyxis said it was looking for partnerships for some of Apexigen’s programs that would not be advancing into the clinic under the new owner’s banner, plus antibody and ADC platform technologies with the potential to bring in additional funding.