BEIJING – Androgen receptor (AR)-related disease specialist Kintor Pharmaceutical Ltd., of Suzhou, China, is looking to raise up to HK$1.861 billion (US$240 million) in a Hong Kong IPO to advance its small-molecule AR antagonists, proxalutamide and pyrilutamide, both of which have first- and best-in-class potential.

The pre-revenue biotech is issuing a total of 92.3 million shares globally at an offer price between HK$17.8 and HK$20.15. Its stock will start trading on the HKEX under the ticker 9939 on May 22.

“Hong Kong is an international financial center and a sophisticated global capital market,” Kintor’s chief financial officer, Lucy Lu, told reporters at a press conference on May 11. “Considering the company’s competitive edge and promising prospects, we chose Hong Kong as our primary listing destination.”

For an innovation-driven biotech based in China, Kintor said the HKEX offers direct access to the international capital markets, which will enhance the company’s fundraising capabilities and channels and broaden its shareholder base.

Kintor’s IPO comes at the time when Hong Kong retail investors have been enthusiastic about pre-revenue biotech stocks. Innocare Pharma Ltd. and Akeso Inc., two biotech companies that went public in February and April, have so far seen their share prices rise by 59% and 50.8%, respectively.

Established in 2009, Kintor has positioned itself to strategically focus on AR-related diseases with substantial unmet medical needs. It boasts a pipeline of five clinical-stage candidates, and proceeds from the IPO are expected to help the biotech prepare to launch its first product this year.

Two promising AR antagonists

Kintor’s lead product is proxalutamide, which, pending positive data, it aims to start marketing in China by 2021. Kintor plans to use around 42% of the net proceeds from the IPO to develop and commercialize the drug, which has so far shown clinical results pointing to potential efficacy in prostate cancer patients who have not succeeded with marketed AR-targeting drugs Xtandi (enzalutamide, Astellas Pharma Inc.) and Zytiga (abiraterone, Johnson & Johnson).

Proxalutamide is a second-generation AR antagonist with a dual-acting mechanism that effectively inhibits AR activity by binding to AR and exhibits the biological effect of reducing AR expression in vivo and in vitro, which in turn decreases the frequency with which cancerous cells are produced. In studies so far, proxalutamide has demonstrated a favorable safety profile, with no incidence of triggering seizures, a side effect known to existing AR inhibitors, among more than 600 users in clinical trials. The drug also showed a higher AR antagonist binding affinity and no induction effect on enzyme CYP1A2, CYP2B6 and CYP3A4, which Kintor said makes it suitable for combination therapy.

Currently, proxalutamide is undergoing phase III trials in China and phase II trials in the U.S. for metastatic castration-resistant prostate cancer (mCRPC) and is also in clinical trials for breast cancer. Kintor plans to complete the interim analysis of phase III data and apply for an accelerated NDA for mCRPC in China this year.

Upon NDA approval, proxalutamide could be the first domestically developed second-generation AR antagonist to compete against enzalutamide, which has been marketed as Xtandi in China since November 2019.

To maximize proxalutamide’s potential value, Kintor is also exploring combination therapies that combine the drug candidate with abiraterone and a PARP inhibitor, respectively, for mCRPC.

Another lead product in development is pyrilutamide, which Kintor plans to advance to phase II trials for androgenetic alopecia in the second half of this year, using 28% of the net proceeds from the IPO.

A topical AR antagonist, pyrilutamide is designed to address the shortcomings of minoxidil and finasteride. It is being developed to locally block androgen-mediated signaling instead of reducing androgen level systematically. Its metabolite has substantially reduced AR agonist activity in vivo, thereby limiting its side effects. In comparison, minoxidil may trigger an allergic reaction to propylene glycol as well as orthostatic hypotension, while finasteride may lead to adverse sexual side effects.

Kintor is also developing pyrilutamide for acne vulgaris, with phase I trials expected to start next year.

Three other drug candidates in clinical development include angiogenesis inhibitor ALK-1 for hepatocellular carcinoma and liver cancer, mTOR kinase inhibitor detorsertib for metastatic solid tumors, and hedgehog/SMO inhibitor GT-1708F for leukemia and basal cell carcinoma.

ALK-1 is in phase II trials in Taiwan for metastatic HCC as a combination therapy with PD-1 drug Opdivo (nivolumab, Bristol Myers Squibb Co.). Detorsertib is in phase I trials in China for metastatic solid tumors, and GT-1708F is expected to enter the clinical phase this year.

To enrich its pipeline, Kintor also emphasizes in-licensing promising assets as part of its strategy. “We look at commercial-stage products to develop in greater China that will complement our drug candidates,” Kintor CEO Tong Youzhi said at the press conference. “We also consider high-risk assets that have global value and we aim at the global rights.”

Prior to this IPO, Kintor has completed five investment rounds that raised a total of $94.46 million. The IPO is backed by Huatai International, UBS and China International Capital Corporation.

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