Editor's note: On May 9, the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China approved Laekna Therapeutics' LAE102 (ActRIIA monoclonal antibody) for the treatment of obese patients. So far, LAE102 has been approved by both China and the United States. Affected by this news, the next day's trading, Laekna Pharmaceutical's share price rose by 22.29%, fully reflecting investors' optimistic expectations for the future commercialization potential of LAE102. Such a positive market response not only brought capital support to Laekna Pharmaceutical, but also injected strong confidence into the company's future R&D and marketing activities. The company said it is accelerating preparations for the Phase I clinical trial and will soon start recruiting subjects for obesity.
Back in mid-2017, when Lv Xiangyang took the young doctor Zhang Ruipeng to start the first project - early research on ActRII-related targets in the Laikai Pharmaceutical Laboratory established by himself, he did not expect that the diet drug track would be in full swing in 2024. Laikai's laboratory is very small, which is completely incomparable with his time in a foreign company, but in the hearts of the team, the enthusiasm for entrepreneurship and scientific research is burning.
If we want to review and summarize Dr. Lv's nearly 20 years of R&D experience in multinational pharmaceutical companies, there are two points worth mentioning: first, he was awarded the "Novartis Leading Scientist" award by Novartis VIVA in 2012; The other is that he is one of the co-inventors of the FDA's breakthrough therapy Bimagrumab (ActRII monoclonal antibody), which is currently used for potential fat-loss and muscle-preserving indications, and Bimagrumab's company was acquired by Eli Lilly for about $1.9 billion last year.
But Lu Xiangyang still resolutely decided to step out of the comfort zone of foreign companies and start his own business, because he has always wanted to make several real new molecules, new mechanisms, and new concept drugs in his own hands. Since the establishment of Laekna Pharma, on the one hand, he has advanced the anti-tumor AKT inhibitor introduced from Novartis to phase III clinical trial, which is the guarantee of Laekna's recent revenue and profitability; On the other hand, Laikai's early team never stopped making independent discoveries.
On May 9, Laekna Pharma announced that its self-developed LAE102 (ActRIIA monoclonal antibody) has received IND approval from CDE for the treatment of obesity patients. Some people say that this is a "hot spot", Lu Xiangyang and the team smiled indifferently - after 7 years of accumulation, they finally accumulated a lot.
1. The current situation of diet drugs: weight loss? Inadequate! Gaining muscle and losing fat is the future
Let's first look at a set of data, according to the World Health Organization, the number of obese people in the world will exceed one billion in 2022, accounting for about one-eighth of the total global population. Of these, about 159 million are obese children or adolescents aged 5 to 19 years and 879 million are adults.
Francesco Blanca, Director of WHO's Department of Nutrition and Food Safety, said, "Obesity is a worldwide problem today. Morgan Stanley estimates that the global obesity drug market is expected to exceed $54 billion by 2030.
The continuous rise in the global obesity population, coupled with the explosion of the "weight loss miracle drug" semaglutide (GLP-1) and Jia Ling's "hot and hot" weight loss fever, have directly driven the rapid development of the weight loss product market, and the stock prices of Eli Lilly and Novo Nordisk continue to hit new highs.
However, although GLP-1, known as the "miracle drug for weight loss", leads the market for weight loss drugs, studies have shown that nearly 40% of the weight lost by subjects with this type of drug is muscle, and muscle loss increases the risk of cardiovascular diseases, osteoporosis and other diseases.
So, fat loss alone is not enough. The value of the target as a companion target for GLP-1 "next level" is gradually emerging, and ActRII is an emerging target.
Unlike GLP-1 drugs, which simply lose muscle, ActRII monoclonal antibody can reduce fat accumulation and promote muscle gain by blocking ActRII signals.
2. Competitive landscape: The world's only two potential drugs for obesity indication under development ActRII
Activin通路在肥胖、肌肉萎缩、肺动脉高压和肿瘤学方面均具有重要意义。 作为一种在脂肪和肌肉细胞中都有表达的激活素受体,ActRII(activin type II receptor/激活素II型受体,包括ActRIIA/ActRIIB)其传导信号的活化,会引起肌肉萎缩和脂肪的累积。
In other words, blocking this pathway is expected to increase the body's muscle mass while reducing fat accumulation.
From the perspective of the global competition landscape of ActRII targets, although there are many drugs developed for this target, most of the drugs under development are mainly for indications such as hematological diseases, pulmonary hypertension and cancer, and most of them exist in the form of ActRIIA/B fusion proteins. In this field, ActRII antibody drugs for obesity indications and have entered the clinical research stage are relatively scarce, and there are only two drugs purchased by Eli Lilly, Bimagrumab, and LAE102, which are independently developed by Laekna Therapeutics.
Bimagrumab has been preliminarily tested for its effect on muscle gain and fat loss. According to the results of a phase II study of bimagrumab in patients with type 2 diabetes mellitus and obesity or overweight, compared with placebo, bimagrumab was able to reduce fat mass by about 20.5% and increase fat-free body mass by 3.6% compared with placebo.
In addition, week 44 was the last dose of bimagrumab based on the frequency of dosing every four weeks, so the week 48 outcome was the primary endpoint data. As you can see from the graph below, unlike many incretin-based therapies, patients did not observe weight gain within 8 weeks of stopping treatment. To date, safety data from bimagrumab have shown that side effects include muscle cramps and diarrhoea, which occur early in treatment and are mostly mild.
Source: Open information
At the same time, the Phase 2b clinical study of bimagrumab in combination with semaglutide in the treatment of obesity has also completed patient enrollment, and the topline data is expected to be read out in the second half of 2024.
Source: Open information
Unlike Bimagrumab, Lachem's LAE102 is a monoclonal antibody that selectively targets ActRIIA, specifically targeting ActRIIA targets and plays a vital role in muscle regeneration and lipid metabolism.
The positive results of preclinical studies further confirm the potential of LAE102: when LAE102 is combined with GLP-1 receptor agonists such as semaglutide, it not only further reduces fat, but also significantly reduces muscle loss that GLP-1 receptor agonists may induce.
According to Laika's latest announcement and 2023 annual report, LAE102 has received IND approval for obesity indications in China and the United States, and the company is fully prepared to start the clinical study of LAE102 as soon as possible. It can be judged that if the follow-up clinical trial of LAE102 goes smoothly and achieves positive results, it is expected to become a breakthrough drug for the treatment of obesity. At the same time, this also reaffirms the innovation ability and R&D strength of Laekna in the field of biomedicine.
3. The next step: Laikai's muscle-gaining, fat-reducing and anti-aging follow-up products are endless
Taking the next step, LAE102, as a potential world-first ActRIIA monoclonal antibody, is not limited to the treatment of obesity - the pleiotropy of LAE102 makes it potentially valuable in many fields such as muscle regeneration, immune activation, hematopoietic development, and tumor growth control.
In addition, there are at least two antibodies for muscle regeneration and other disease indications in the pipeline of drug candidates independently developed by Laekna, a successor to LAE102, including LAE103, a selective antibody for ActRIIB, and LAE123, a dual-target inhibitor for ActRIIA/IIB. According to the company's 2023 annual report, the Laekna team has accumulated extensive experience and deep expertise in this specific area and is developing additional drug candidates to maximize the value of targeting the ActRII receptor.
Old age and weakness are irresistible natural laws for human beings, and one of the major manifestations is the loss of muscle mass - muscle tissue will have physiological deterioration with age, mainly manifested as a decrease in muscle mass, which is medically called muscle atrophy.
According to a study published by the Beijing Municipal Health Commission, adults will gradually lose muscle mass (including muscle strength) from the age of 40, especially after the age of 75, and muscle mass may decrease by 15% every 10 years. The prevalence of sarcopenia ranges from about 5% to 13% in the 60 to 70 year old population, while it soars to 11% to 50% in the 80 and older population.
The Chinese population is rapidly aging, and a drug target that promotes muscle regeneration may help address these concerns and problems. In the author's opinion, this indicates that LAE102 and its follow-up products are expected to become a revolutionary drug with both muscle and fat loss and anti-aging functions in the field of innovative drugs in the future, and its future imagination space may not be underestimated.
4. Summary
Overall, in the next weight loss track competition of Incretins such as GLP-1Ra, muscle-building therapy has begun to take the lead, and Laekna Pharmaceutical, which holds the world's first LAE102, has shown its unique advantages and growth.
From an investment perspective, as Laekna continues to promote the clinical progress of LAE102 and other drugs under development, it is believed that the follow-up company will continue to bring more surprises in the development of innovative drugs, and its positive market performance and performance growth will eventually be reflected in the capital market.