Bicycle reported updated Phase 1 dose escalation data today for BT5528, it's bispecific peptide conjugate, in advanced solid tumors that express positive EphA2. The first data is from ovarian and urothelial. This is actually very good news because the approach is more akin to what THTX is doing with a PDC than the ADC approach. This is also a peptide Bicycle uses for deliver, but the target is different, although it also is more prevalent the more advanced the cancer is like Sort1. I don't know enough about it to know if it's also internalizing it and helping it to pass resistance. I thought it would be best to paste their exact release since it also shows you what you can discuss, even with a small set of dosage trial patients.
As JFM will note, they DO discuss having done staining afterward to understand the expression and if the patient is considered "evaluable". In the CS Q&A Levesque did, he mentioned they would get sortilin expression data afterwards, but we haven't heard about it. You'll see the results are compared to an ADC that wasn't as effective as their PDC. The responses are not all that dissimilar to what we saw with TH1902, nor the safety issues. They described it as "demonstrateing anti-tumor activity" and a "differentiated tolerability", which is a nice way to describe your safety advantages. Anyway, here's how another very similar company in a similar part of the trial releaseed their data. The ORRs and such are a bit lower than what we've seen, the safety is better, and there was one CR for ovarian. All in, shows that PDC approach is something differnent and they have it working. Bodes well for Th1902 conceptually. It's up around 3% and has an $800mil market cap.
"BT5528, a BTC targeting EphA2, a target for which prior antibody-based approaches have been unsuccessful, has demonstrated anti-tumor activity and differentiated tolerability. Bicycle has established an RP2D dose (6.5mg/m2 every other week) and is enrolling ongoing expansion cohorts.
- Preliminary signs of anti-tumor activity observed. A total of 45 patients (15 at RP2D 6.5mg/m2 every other week) were dosed with a median of four prior lines of therapy. Expression of EphA2 was evaluated retrospectively using an immunohistochemistry (IHC) assay.
- Amongst these patients, anti-tumor activity was observed in urothelial and ovarian cancer patients.
- A total of 21 ovarian cancer patients were dosed. Of these, nine response evaluable patients were determined to be EphA2-positive based on the IHC assay. The median prior lines of therapy for these nine patients was four.
- Among these nine late-line ovarian cancer patients, six patients (67%) were observed to have a reduction in target lesions, including one patient with a complete response (CR) and one with a partial response (PR) under Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, resulting in a disease control rate (DCR) of 67% and an overall response rate (ORR) of 22%.
- A total of eight urothelial patients were dosed. Of these, three response evaluable patients were determined to be EphA2-positive based on the IHC assay and of these three patients, two were observed to have tumor reductions constituting a PR under RECIST version 1.1 (ORR and DCR of 67%).
- BT5528 well-tolerated at RP2D of 6.5mg/m2 every other week. Low, or no, levels of incidence of neutrophil count decrease, peripheral neuropathy, skin rash and eye disorders were reported. Low-grade GI treatment-related events were those most commonly reported amongst the 15 patients at this dose. There were three Grade 3 and above events at the RP2D: diarrhea (n=1, 7%) and anemia (n=2, 13%). In addition, and in contrast to the toxicities observed with EphA2 ADCs, Bicycle has observed no signs of treatment-related coagulopathy to date in any patient.
- Bicycle advancing BT5528 in ongoing expansion cohorts. In June 2022, Bicycle announced the dosing of the first patient in the part B dose expansion portion of the Phase I/II trial. Up to 56 patients will be enrolled in the initial expansion cohorts, with the ability to further expand enrollment based on results from these cohorts. Dose expansion is taking place in urothelial (n=14) and ovarian (n=14) cancers as well as in a basket cohort of other solid tumors (n=28), including non-small cell lung, triple-negative breast, head and neck, and esophageal cancers."