Generally speaking, the R&D and review of innovative drugs are guided by clinical value, and the intrinsic value of innovative biopharmaceutical companies also needs to be confirmed by reliable R&D results.
Therefore, among the 18A companies in Hong Kong stocks, there is such a "treasure company": when investors are still judging the positive impact of its AKT track results on the company's valuation, it has come up with its self-developed activin receptor II antibody LAE102, which is expected to be used for muscle gain and fat loss; when the secondary market is studying the potential of LAE102 in combination with GLP-1RA, this company has shown its "unique secrets" in the field of NASH and anti-liver fibrosis.
This company is Laika Pharmaceutical (02105). At the 2024 Global NASH-TAG Conference held in the United States last week, it announced its self-developed bifunctional NK-aHSC engager drug discovery platform targeting activated hepatic stellate cells, as well as the anti-liver fibrosis preclinical data of the LAE105 antibody designed based on the platform technology.
Oncology, metabolism, and liver fibrosis, these three seemingly unrelated fields are integrated into one biotech, but they are so logical, which is closely related to the scientific research background and experience of the company's founder, Dr. Lv Xiangyang, and his team.
The lack of space in the therapeutic field of NASH has led to fierce competition
According to Zhitong Financial APP, among the many new drug research and development directions, the research and development of NASH-related targeted drugs has always been known to the global industry with a high threshold. Given the huge clinical needs and treatment gaps in the field of NASH, Evaluate Pharma has predicted that the global NASH drug market will reach $40 billion by 2025. The improvement in the degree of fibrosis has been one of the key indicators to measure the effectiveness of NASH drugs. In addition to NASH indications, liver fibrosis is also an important cause of liver cancer or liver failure.
In this context, LAE105 antibody is a potential first-in-class new drug to improve liver fibrosis and may be applied to other fibrotic diseases with similar mechanisms.
It is worth mentioning that most of the drug development on the market today focuses on reducing liver fat or alleviating fibrosis by blocking a signaling pathway during hepatic stellate cell activation.
Compared with the efficacy of the current multi-technology route of NASH investigational drugs, the high-dose group of semaglutide, which is currently popular in the market, is not as effective as Inventiva's pan-PPAR agonist, and Akero's FGF21 class drug showed that the improvement in liver fibrosis in the published phase IIb clinical data was also less than expected. The only one that may be the first to "hit the line" is Madrigal's Resmetirom, an oral small molecule thyroid hormone receptor-β (ΤRβ) agonist that has received accelerated and priority approval from the FDA. It remains to be seen whether the FDA will approve resmetirom as the first drug approved for the treatment of NASH in the first quarter.
Differentiated innovation allows Laikai to achieve a breakthrough in fibrosis treatment
In contrast, Laekna Pharma has found a different way, hoping to alleviate fibrosis by using its own immune system.
From the perspective of mechanism of action, activated hepatic stellate cells (aHSCs) are the main source of hepatic muscle fibroblasts, and the accumulation of aHSCs is also the main cause of liver fibroblasts. Previously, the use of genetic manipulation or pharmacological methods (e.g., ADC, CAR-T) to deplete aHSCs has demonstrated antifibrotic effects in various animal models.
In order to apply the above findings to clinical practice, Laekna has independently developed and established a world-leading and unique drug discovery platform that uses the body's own immune system to eliminate aHSCs.
With the support of this technology platform, Laekna Biopharma's self-developed LAE105 can recruit and activate immune cells (such as NK cells) after binding to aHSC surface proteins, thereby using the body's own immune system to eliminate aHSCs, thereby alleviating liver fibrosis. In addition to improving liver fibrosis, it may also be applied to other fibrotic diseases with similar mechanisms, and is a potential first-in-class new drug. In the future, relying on this platform, Laikai will also be able to continuously develop more optimized anti-liver fibrosis drug precursors in the future.
Not only in liver fibrosis, activated myofibroblasts play a key pathogenic role in many diseases, including fibrotic diseases, autoimmune diseases, and tumors. Elimination of these cells has shown efficacy in preclinical animal models. This technology platform targets the removal of myofibroblasts, which has a wide range of applications.
Laka's unique NASH scientific research advantages
Laikai's scientific research accumulation in NASH and liver fibrosis did not happen overnight. As early as the beginning of the company's establishment, the founder Dr. Lv Xiangyang set this strategic direction, and established a macromolecule laboratory and R&D team for this purpose.
Dr. Xiangyang was a member of the American Society for the Study of Liver Diseases. He worked for Novartis USA for many years before returning to Shanghai in 2007 to co-establish Novartis (China) Biomedical Research Co., Ltd. (CNIBR). At that time, he strongly supported Novartis China to establish a new drug research and development platform for liver diseases, and later served as the project R&D leader, building a global scientific research team from scratch and conducting a number of new drug innovation and translational medicine research. According to official information, he also won the Novartis VIVA Award in 2012 and was awarded the honorary title of "Novartis Leading Scientist".
Later, he left Novartis and founded Laikai Pharmaceutical, still not forgetting his original intention. In his view, liver disease is a high-incidence disease unique to Chinese, and there has been no breakthrough drug in the global NASH field. Therefore, he hopes to accelerate the breakthrough of new drugs for liver fibrosis with the solid knowledge of the scientific research team, new R&D concepts and original technology platforms.
Another key figure is Dr. Scott L. Friedman, Advisor to the Scientific Committee of Laica Therapeutics, who is currently the Dean of the School of Therapeutic Development and Chief of the Department of Hepatology at the Icahn School of Medicine at Mount Sinai in New York. Dr. Friedman was one of the first scholars in the world to isolate and identify hepatic stellate cells. Dr. Minhua Zhang, one of the authors of this poster and senior director of biology of Laikai's early R&D team, also graduated from Icahn School of Medicine at Mount Sinai. With the blessing of Dr. Friedman, it is more convenient for Laikai to establish a platform for aHSC removal.
Relying on technical barriers based on the blue ocean of tens of billions, the company has achieved short, medium and long-term balance
From a market perspective, there is a large patient base in the treatment area of NASH alone, and a large number of unmet clinical treatment needs. According to Frost & Sullivan's forecast, if new NASH drugs are approved in the future, the global NASH drug market will reach $10.7 billion in 2025 and $32.2 billion in 2030, with a compound annualized growth rate of 41.8% and 24.6% during the period. In addition to reducing liver fibrosis, LAE105 can also be combined with drugs to lower liver lipids, so as to achieve more efficient disease remission against NASH.
A look at Laekna Therapeutics' recent milestones:
In terms of clinical progress, the data of the Phase 1b clinical trial of breast cancer related to its core product afuresertib combined with fulvestrant have been released at the San Antonio Breast Cancer Congress, confirming an objective response rate (ORR) of 30% and a median progression-free survival (PFS) of 7.3 months, which is nearly double the PFS of fulvestrant monotherapy for 3-4 months, and the clinical benefit is significant. At present, the company has begun to initiate a phase III pivotal trial.
In the field of independent research and development, LAE102 is the world's first activin receptor II antibody independently developed by Laekna, which was approved by the FDA for IND in 2023, and the Chinese CDE has also accepted its new drug clinical trial application, which will preliminarily evaluate the anti-tumor activity of LAE102 and its effect on changes in body weight, muscle mass and fat mass.
The successful selection of the LAE105 antibody and the NK-aHSC conjugative drug discovery platform into the global NASH-TAG conference fully reflects the high recognition of its research results by the international liver disease research community, and also reflects the innovative gold content of LAE105 antibody and the R&D strength of Laek's hard core. This undoubtedly provides a strong endorsement for the smooth follow-up research and development and final product commercialization of Laikai.
In the words of the founder, Dr. Lv Xiangyang, he hopes to achieve such a balance - the products that the company has the potential to launch in the near future, and there are more innovative projects and breakthrough innovative drug pipelines in the medium and long term, forming a healthy cycle.