Innocrin Pharmaceuticals raises $28 million to develop best-in-class CYP17 inhibitor

Innocrin Pharmaceuticals has completed a $28 million Series D financing round led by Eshelman Ventures and Fred Eshelman with participation of Novartis Venture Fund, Lilly Ventures, Hatteras Venture Partners, Intersouth Partners, and A&B Equity Holdings.

Innocrin is a spin-out of Viamet Pharmaceuticals. The company is developing a CYP17 inhibitor, VT-464, for the treatment of castration-resistant prostate cancer (CRPC). CYP17 is a validated target for the treatment of CRPC. Johnson & Johnson’s Zytiga (abiraterone acetate), an approved CYP17 inhibitor, generated annual sales of $2.24 billion in 2014. Innocrin believes VT-464 is a best-in-class CYP17 inhibitor.

CYP17 is a protein with two enzymatic functions: 17α-hydroxylase and 17,20-lyase. Lyase inhibition reduces the biosynthesis of androgens that drive cancer cell growth. However, hydroxylase inhibition elevates progestogens and mineralocorticoids, resulting in secondary mineralocorticoid excess. VT-464 is the most lyase-selective CYP17 inhibitors reported to date.

lyase IC50 (nM) hydroxylase IC50 (nM) h/l ratio Ref
abiraterone 15 2.5 0.17 [1]
VT-464 69 670 9.7 [1]
galeterone 23 73 3.2 [2]

Interim results from the Phase I/II trial (INO-VT-464-CL-001) were presented at the ASCO2015 Genitourinary Cancers Symposium[3]. 73% of treatment-naïve patients received 300-600 mg BID VT-464 had PSA30 responses. PSA responses were observed in 2 of 7 patients who have failed Xtandi (enzalutamide) as well.

Abiraterone has been shown to cause mineralocorticoid excess syndrome characterized by hypokalemia (88%), hypertension (40%), and fluid overload (31%)[4]. No mineralocorticoid excess syndrome was observed in the VT-464 Phase I/II trial.

Meanwhile, Tokai Pharmaceuticals (NASDAQ: TKAI) is developing a selective CYP17 lyase inhibitor known as galeterone. The company announced positive interim results from the phase II trial (ARMOR2) of galeterone in June 2014. Similarly, 82% of treatment-naïve patients achieved PSA30 responses. Tokai anticipates initiating the pivotal clinical trial in 2015H1.

[1] Bioorg Med Chem Lett. 2014, 24(11), 2444-2447.
[2] Cancer Research. 2013, doi: 10.1158/1538-7445.AM2013-83.
[3] J Clin Oncol. 2015, 33, (suppl 7; abstr 187).
[4] J Clin Oncol. 2009, 27(23), 3742-3748.


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