The $45M financing last August has given Essa enough funding (~$80M cash) to now pursue combination trials with standard of care anti-androgen drugs used in prostate cancer. The company has specifically mentioned they are in discussions for potential collaborations with each of the 3 lutamides and abiraterone (view Oppenheimer presentation here @ 27min mark).
Remember the partners who have the agents are all large pharma:
- enzalutamide (Xtandi) is marketed by Pfizer
- apalutamide (Erleada) is marketed by JnJ’s Janssen
- darolutamide (Nubeqa) is marketed by Bayer
- abiraterone (Zytiga) is marketed by JnJ’s Janssen but also faces generic competition
With Pfizer leading the August financing and having first right access to Essa’s data (read more here), they are first in line for Essa’s combination therapy. The other names mentioned above are also in discussions, according to the company.
Basis for Combination Therapy
Existing anti-androgen therapies, including Pfizer’s Xtandi, block the ligand binding domain so that androgen cannot activate the androgen receptor (AR) and stimulate prostate tumor growth (more detail here).
EPI-7386 targets the other end of the AR domain, called the N-terminal domain (see below). Combining existing anti-androgen therapies with Essa’s novel MoA drug would block multiple domains and theoretically prevent androgen from binding to the receptor. This combination approach could be more effective at stopping tumor growth, compared to just monotherapy.
Essa’s plan is to target 3rd line mCRPC patients with their monotherapy and will work with combinations to move into earlier lines of therapy.
New Pre-Clinical Data Backing Combination Therapy
Combination treatment of Essa’s EPI-7386 with currently approved apalutamide and darolutamide inhibited the androgen-receptor pathway, according to RNA expression in VCap xenograft cells that were treated.
The graphs below show a suboptimal dose of EPI-7386 in combination with the 2 lutamides against androgen receptor splice variants resistant to currently approved drugs. The combination (3 bars to the furthest right for each dataset) inhibits expression of these genes that contribute to resistance, showing potential superiority of combination therapy. This is an early sign (preclinical) that EPI-7386 combo can overcome resistance with mCRPC.
Phase 1 Data in Early 2021
Essa will report monotherapy Phase 1 data in early 2021. Thus far, 4 sites have been activated for dose escalation part of the Phase 1 study. The company estimates (listen @ 28min mark here) to have some early pharmacology, safety, and tolerability data by ASCO GU (mid-Feb 2021). The full data set is expected by ASCO (early-June 2021).
PropThink contributors are LONG EPIX
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