BTAI: Encouraging Data for BXCL701 in Heavily Pretreated mCRPC Patients…

By David Bautz, PhD

NASDAQ:BTAI

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Encouraging Data for BXCL701 in Heavily Pretreated mCRPC Population

On September 15, 2021, BioXcel Therapeutics, Inc. (BTAI) announced that data from the ongoing Phase 1b/2 clinical trial of BXCL701 in patients with metastatic castration-resistant prostate cancer (mCRPC) was presented at the 2021 European Society for Medical Oncology (ESMO) Congress (the poster can be found here). BXCL701 (talabostat) is an oral small molecule immunomodulator designed to activate the innate immune system through inhibition of dipeptidyl peptidase (DPP) 8/9 and fibroblast activation protein (FAP). Its purpose is to initiate inflammation in the tumor microenvironment, thus potentially turning “cold” tumors “hot” and making them more amenable to immunotherapy treatment.

The following image gives an overview of the Phase 1b/2 trial. The Phase 2 portion of the trial consists of two patients cohorts: mCRPC with either therapy-induced neuroendocrine (t-NEPC) or adenocarcinoma phenotype. The current data up date is for the adenocarcinoma cohort.

The following table lists the patient characteristics for all those enrolled as of July 8, 2021. As can be seen, this is a very heavily pretreated population with a mean number of 5.3 prior therapies, almost all having had prior androgen signaling inhibitors, and all having received prior taxane chemotherapy.

The best responses recorded for each patient are indicated in the following table. A few highlights from the table include:

• 1 confirmed and 2 unconfirmed partial responses (PR) for an objective response rate (ORR) of 16%

• A disease control rate (PR + stable disease [SD] + non-complete response [CR]/non-progressive disease [PD]) of 63%

• A PSA50 (representing a ≥50% reduction in PSA level from baseline) of 17%

To put these numbers in perspective, when pembrolizumab was evaluated as a monotherapy in a similar patient cohort the DCR was 12%, the ORR was ~5%, and the PSA50 was 6% (Antonarakis et al., 2019).

The following table gives a summary of the six (23%) composite responders, who had either a PSA50, a circulating tumor cell (CTC) conversion from ≥5/7.5 mL to ≤5/7.5 mL, or RECIST 1.1 response. All of the composite responders had a decrease in tumor size, with three of the patients exhibiting a partial response (1 confirmed, 2 unconfirmed).

Lastly, the following table provides a summary of the adverse events, with all those listed being reported by ≥3% of patients. The majority of the events were low grade and importantly there was no indication that BXCL501 potentiates any adverse events typically seen with immune checkpoint inhibitors. One patient who initiated dosing with 0.3 mg BID experienced Grade 3 hypotension, however step-up dosing was then implemented for all new patients with BCXL701 0.2 mg BID on Day 1 through Day 7 and escalation was permitted to 0.3 mg BID if no treatment emergent AEs greater than Grade 1 or no skipped doses due to hypotension or orthostasis occurred during the first week of treatment.

Conclusion

The data presented by BioXcel on BXCL701 in a very heavily pretreated mCRPC population are very encouraging, particularly when viewed in relation to monotherapy pembrolizumab. While difficult to compare data across different clinical trials, pembrolizumab did not show robust activity in a mCRPC population and it appears as though BXCL701 may be potentiating its activity. Since BXCL701 is predicted to turn “cold” tumors “hot”, with prostate cancer known to be immunologically “cold”, and the majority of the responders not having strong predictive markers of pembrolizumab response (e.g., PD-L1 low or MSI stable), these data are indicative of BXCL701 causing inflammation in the tumor microenvironment and increasing the susceptibility to immune checkpoint therapy. We look forward to additional updates from this study. With no changes to our model our valuation remains at $110.

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