ALX Oncology (ALXO) used the second day of the 12th Annual Cantor Fitzgerald Global Healthcare Conference to outline the biomarker-driven strategy behind its lead program, Evorpacept (EVO), and provide updates on its EGFR antibody-drug conjugate candidate ALX2004.
Evorpacept employs a dual mechanism combining a "dead Fc" segment designed to block the CD47 "don't eat me" signal with an Fc-active antibody that provides targeted immune activation. CEO Jason said the CD47 pathway has historically been difficult to target because it is how healthy cells communicate with the immune system, and cancer exploits that same signal.
Jason told analysts the key question has been whether CD47 can function as a biomarker rather than merely a therapeutic target. Five clinical data sets have been cited to support the approach, including combinations with Herceptin, zanidatamab, and rituximab, alongside the randomized ASPEN-06 gastric cancer study and a HER2-positive breast cancer study conducted with Jazz Pharmaceuticals.
In ASPEN-06, objective response rate was roughly 40 percentage points higher in CD47-high patients compared with CD47-low patients. Progression-free survival hazard ratio reached 0.39 in the randomized cohort. In the HER2-positive breast study, all five identified responders overexpressed CD47, including one complete response.
For context, real-world data from more than 600 second-line HER2-positive breast cancer patients presented at ESMO showed a standard-of-care objective response rate of 14% to 15% and a median progression-free survival of just 3 to 4 months. ALX Oncology estimates about half of the post-progression HER2-positive population is CD47-high, translating to roughly 20,000 patients in its core market.
The company is moving forward with the ASPEN-09 Phase II study, which plans to enroll 80 to 120 patients receiving EVO combined with trastuzumab and chemotherapy across both CD47-high and CD47-low subgroups. A Phase III base-case design would randomize patients to EVO plus trastuzumab and chemotherapy versus trastuzumab and chemotherapy alone, with accelerated approval reserved only for unusually strong data, Jason said.
A companion diagnostic using immunohistochemistry on tumor tissue was initiated about a year ago in partnership with Ventana. Cutoffs under investigation include IHC 2–3 and IHC 3.
On ALX2004, an EGFR-directed antibody-drug conjugate, the company selected the milatuzumab epitope originally developed by EMD Serono after extensive screening, aiming to avoid the on-target skin toxicities seen with cetuximab and panitumumab. Dose escalation began approximately a year ago at Moffitt Cancer Center and MD Anderson, progressing from 1 mg/kg through 2, 4 and above 4 mg/kg over the summer. The expected therapeutic window sits around 4 mg/kg.
An initial safety and tolerability update covering at least 20 patients across lung, head and neck, colorectal and esophageal cancers is expected in the second half of 2024, with proof-of-concept response data targeted for mid-2025 in second- and third-line head-and-neck and lung cancer patients.
No revenue, cash burn, quarterly financials or runway figures were discussed. Cantor analyst Lee Waczak moderated the session. Analyst price targets for ALXO were noted in the $4 to $6 range, with the stock listed at a beta of 0.4.
