Shanghai-based I-Mab Biopharma Co. Ltd. became the first IPO out of the gate this year, pricing its IPO of about 7.4 million American depositary shares (ADSs) – each 10 representing 23 ordinary shares of the company, par value $0.0001 per share – at $14 each, within the planned range of $12 at the low end and $15 at the high. But the stock’s performance might not have been all investors hoped, as shares (NASDAQ:IMAB) closed at $12.50 Jan. 17.

Gross proceeds for the firm, which is focused on immuno-oncology and autoimmune diseases, are estimated at about $103.7 million. I-Mab granted underwriters an option to buy more ADSs, which could bring the total haul to about $119.2 million. Jefferies LLC and China International Capital Corp. Hong Kong Securities Ltd. are acting as joint book-running managers, with China Renaissance Securities Ltd. and Huatai Securities Inc. serving as lead managers.

It’s been awhile since the U.S. market has seen an IPO that originated in China. That happened in 2017 when Shanghai-based Zai Labs Ltd. went public, reaping gross proceeds of about $150 million. A rule change in the spring of 2018 by the Hong Kong Stock Exchange allowed more pre-profit companies to list there, but some saw I-Mab’s decision to go the U.S. route as evidence of a shift. Firms such as U.S.-based Grail Inc. and Stealth Bio Therapeutics Inc. made U-turns and listed in the U.S. after considering Hong Kong as an option. I-Mab, for its part, has been otherwise successful at pulling down money since it was formed in 2017 via the merger of Third Venture Biopharma Co. Ltd. and Tasgen Biotech Co. Ltd. The most advanced prospect in the pipeline is TJ-202, a CD38 antibody, licensed from Morphosys AG, of Planegg, Germany. The compound is undergoing two registrational trials, including a third-line monotherapy trial and a second-line combination therapy trial, in multiple myeloma (MM) in greater China. The company submitted an IND application to the National Medical Products Administration (NMPA) in October 2019 for a phase Ib trial in systemic lupus erythematosus.

In SEC paperwork, I-Mab said that “TJ-202, if approved, is potentially highly differentiated compared with the currently marketed CD38 antibody.” That’s Darzalex (daratumumab, Johnson & Johnson), which gained its first go-ahead from the FDA in November 2015. “Under a similar pre-medication condition with dexamethasone, anti-pyretics and anti-histamines, TJ-202 has demonstrated a significantly shorter infusion time and lower infusion reaction rate,” I-Mab said. “Second, unlike [Darzalex], TJ-202 does not down-regulate CD38 expression on the surface of bone marrow myeloma cells in vitro, maintaining sensitivity of myeloma cells to TJ-202 for repeated treatments.” Specifically, TJ-202 is undergoing tests as a third-line monotherapy and a registrational trial paired with lenalidomide as a second-line therapy, both in patients with MM. “We aim to submit an NDA for TJ-202 as a third-line monotherapy in 2021, followed by another NDA submission for TJ-202 as a second-line combination therapy,” the company said.

Also in the hopper is long-acting growth hormone TJ-101, for which I-Mab is working toward submitting an IND application this year for a phase III registrational trial in China. There’s also enoblituzumab, for which the company expects to submit an IND application, also this year, for a registrational trial or a phase II experiment. Last summer, I-Mab and Rockville, Md.-based Macrogenics Inc. entered a collaboration and license agreement to develop and commercialize the immune-optimized, anti-B7-H3 monoclonal antibody that incorporates Macrogenics’ Fc optimization technology platform. Enoblituzumab, the companies noted, represents one of the most advanced programs in development directed against B7-H3, a target for which no agent is approved. I-Mab obtains regional development and commercialization rights in mainland China, Hong Kong, Macau and Taiwan. In all, as I-Mab pointed out in an SEC filing, “the investigational drugs in our China portfolio are positioned for a series of new drug applications in China, with the submission of the first [one] expected in 2021.”

Hyleukin lookin’ good

Last fall, the company scored a string of IND approvals in China. At the beginning of the month, the NMPA gave the green light for trials of its TJD-5 candidate, described as a novel CD73 antibody, in patients with advanced solid tumors. It’s in a phase I/II dose-escalation study and a cohort expansion study of TJD-5 monotherapy or TJD-5 with toripalimab in patients with advanced or metastatic cancers. PD-1 antibody toripalimab, from Shanghai-based Junshi Biosciences Co. Ltd., gained approval from the NMPA in late 2018. About two weeks after the TJD-5 trial clearance, I-Mab chalked two more IND wins with TJ-202.

Also in development is TJ-301, which the company said represents potentially a distinctive IL-6 blocker for ulcerative colitis (UC) and other autoimmune diseases. In-licensed from Ferring Pharmaceuticals Inc., of Parsippany, N.J., TJ-301 was well-tolerated in three trials conducted in Germany involving 128 subjects, including two phase I experiments and one phase IIa biomarker study, called Future. No apparent dose-related adverse events turned up, and promising effects were observed. I-Mab has a phase II study ongoing in Taiwan, South Korea and China, with data due this year. After clinical efficacy and differentiation are validated for UC, the firm aims to develop TJ-301 in other inflammation indications where the pathogenic role of IL-6 is known.

I-Mab’s TJ-107 is touted as the first long-acting recombinant human IL-7 drug with possible use in cancer treatment-related lymphopenia and cancer immunotherapy. The candidate is known to boost T lymphocytes by increasing their number and functions, and exclusive rights in greater China were acquired from Seoul, South Korea-based Genexine Inc. in late 2017, when the drug was known as Hyleukin. The drug, which was the subject of a $548 million deal, may prove an oncology-care agent to treat cancer treatment-related lymphopenia, and has proved its mettle in synergizing with a PD-1 antibody in a tumor animal model potentially through increased T-lymphocyte activation and proliferation. I-Mab is conducting a phase Ib trial in China to determine a suitable dose range, and intends to submit a clinical trial application for a phase II venture in cancer patients this year.

No Comments