BEIJING – Suzhou-based Alphamab Oncology Co. Ltd. (HK:9966), which aims to bring the first PD-L1/CTLA4 bispecific antibody to China, saw its share prices jump almost 30% on its debut on the Hong Kong Stock Exchange (HKEX) on Dec. 12, 2019, ending the year on a positive note for the pre-revenue biotech.

With a listing price at HK$10.2 per share, Alphamab raised HK$1,829.9 million (US$234.4 million) through its global offering on the HKEX. Backed by Morgan Stanley, CLSA and Jefferies, the biotech startup saw its shares oversubscribed by 192 times in Hong Kong.

Alphamab is the eighth pre-revenue biotech listed in Hong Kong this year, and also the 13th since the bourse overhauled its listing regime in April last year. The biotech company filed for listing with the HKEX this July, soon after a series B financing round that secured $60 million.

The biotech attracted seven cornerstone investors on this IPO, namely Matthew Funds, Orbimed Funds, Greenwoods Asset Management Limited, Morgan Stanley Asia Limited, Lake Bleu Prime Healthcare Master Fund Limited, Luye Pharma Group Ltd. and Taikang Life Insurance Co. Ltd.

“We’re leading in the bispecific antibody space, with our PD-L1/CTLA4 bispecific antibody KN-046 and anti-HER2 bispecific antibody KN-026,” Alphamab’s CEO Ting Xu told BioWorld regarding the encouraging response from the market. He said investors are drawn by Alphamab’s “cutting-edge” clinical programs, especially its KN-046.

“[Going public in Hong Kong] is an exciting start for us,” said Xu, adding that the proceeds will support the company for the next few years to accelerate Alphamab’s clinical programs and development of R&D platforms to create technological breakthroughs.

In the interest of bringing its core assets to the market as quickly as possible, Alphamab will spend 75% of the proceeds on its key drug development programs.

Confident in its lead product KN-046, Alphamab will use around half of the proceeds to develop and commercialize the drug candidate, which is currently in phase Ib/II stage in China and Australia.

“We can prove the advantages of our KN-046 [with the proceeds],” Xu noted.

KN-046 is the world's first PD-L1/CTLA4 bispecific antibody and the only one with multiple indications in phase II clinical trials. Alphamab sees it as a potential blockbuster and has positioned it as the backbone of the second generation of tumor immunotherapy.

Striving for the first mover advantage, the company plans to submit the first BLA for KN-046 in China for third or later-line unresectable/metastatic nasopharyngeal cancer in 2021. It has set aside 10% of the proceeds from the IPO for its launch.

Results from phase I clinical trials showed that KN-046 has a favorable safety profile and early efficacy signals for nasopharyngeal cancer, especially in subjects with high PD-L1 expression, as well as gastrointestinal cancers, including pancreatic cancer.

Currently, KN-046 is also in phase II clinical trials in China for more indications, namely non-small-cell lung carcinoma (NSCLC), triple-negative breast cancer (TNBC) and esophageal squamous-cell carcinoma (ESCC), which Alphamab may expand into a global trial.

The biotech company said preliminary results from phase II trials for the second-line or later-line NSCLC subjects and the first-line TNBC subjects indicate promising efficacy of KN-046 for these two indications, especially as a combination therapy with chemotherapy.

For KN-046, Alphamab will initiate a phase Ib clinical trial for ulcerative colitis, melanoma and small-cell lung cancer in the first quarter next year, as well as a phase II clinical trial for pancreatic cancer in the first quarter of 2020.

Also included in Alphamab’s pipeline are anti-HER2 bispecific antibody KN-026 to target HER2-positive breast cancer and gastric cancer, biosimilar candidate KN-019 referencing Nulojix (belatacept, Bristol-Myers Squibb Co.) to treat prophylaxis of kidney transplants and rheumatoid arthritis, and subcutaneous PD-L1 antibody KN-035 (envafolimab).

The company is also developing four bispecific antibodies with undisclosed targets.

China has yet to approve any bispecific antibodies so far. China Insights Consultancy predicts the first anti-PD-(L)1/CTLA-4 bispecific antibody will be launched in China in 2022. The market size of this drug is estimated to be $0.1 billion in China in 2022, then grow to $2.9 billion in 2030 at a CAGR of 47.5%.

Away from the overcrowded PD-1 race, bispecific antibodies are a new playing field for the Chinese drug makers.

In China, there are two PD-(L)1/CTLA-4 bispecific antibody candidates in clinical trials, namely Alphamab’s KN-046 and Akeso Biopharma Inc.’s AK-104.

This month, Akeso also filed for a pre-revenue listing with the HKEX after a $150 million series D financing round that closed last month.

The Guangdong-based biotech also boasts its own bispecific antibody candidates, with an aim to advance its AK-104 to compete with Alphamab’s KN-046. Akeso is also developing AK-112, which is said to be the world's first PD-1/VEGF bispecific antibody.

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