Since the development of Wegovy by Novo Nordisk was proven to be safe and effective in controlling weight, and was approved by the US FDA to treat obese patients in 2021, the weight loss drug market has gradually become a hot spot for industry investment. Following Smeglutide, Mounjaro (tirzepatide) from Eli Lilly and Company is expected to be approved for the treatment of obese patients by the end of this year.In addition to large pharmaceutical companies, many biotechnology companies are also focusing on the development of weight loss drugs, with many focusing on non glucagon like peptide-1 (GLP-1) based therapies.Based on industry media STAT's reports and other publicly available materials, introduce to readers how these emerging biotechnology companies have innovative strategies to establish themselves in the weight loss market.
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Not only lose weight, but also gain muscle
Although approved weight loss drugs can reduce weight in obese patients, they also cause muscle loss in patients. According to clinical trial results, approximately 40% of the weight loss in obese patients is fat-free. Some doctors are concerned that elderly people taking this medication may become weaker and more prone to accidents.
The under development therapy biomagrumab developed by Versanis Bio is expected to break this challenge.Bimagrumab is a potential "first in class" monoclonal antibody that targets the activin type 2 receptor (ActRII).ActRII is an activator receptor expressed in both fat and muscle cells. The activation of ActRII receptor signaling can lead to muscle atrophy and fat accumulation in adipose tissue,so targeting this pathway is expected to drive fat loss while increasing the muscle composition of the patient's body.In a 48 week phase II clinical trial, compared with placebo,bimagumab can cause about 22% fat mass loss and 4.5% fat free weight increase in overweight or obese patients with type 2 diabetes.In addition, unlike many incretin based therapies, patients did not observe any weight gain within 12 weeks of discontinuing treatment.So far, the safety data of bimarumab shows that its side effects include muscle spasms and diarrhea, which occur in the early stages of treatment and are mostly mild.
In addition to Versanis, Italian startup Resalis Therapeutics is also focusing on fat cells.Resalis' lead project RES-010 is an antisense oligonucleotide (ASO) therapy that inhibits miR-22 microRNAs. MiR-22 plays a key role in regulating fat metabolism and energy consumption.In many concept validation experiments on rodents and non human primates, RES-010 has demonstrated good tolerance and sustained efficacy.According to industry media STAT, senior executives at Resalis pointed out that in preclinical studies, drugs only cause loss of fat storage, while muscle quality is not affected.Resalis is expected to launch a human clinical trial of RES-010 in early 2024.
Natural fat reduction to avoid side effects
According to STAT statistics, more than half of the 80 currently under development weight loss therapies are based on targeted GLP-1 receptors. The activation of GLP-1 receptor can stimulate insulin production, inhibit glucagon secretion, reduce appetite and food intake, and ultimately achieve weight loss. However, such therapies often lead to side effects such as nausea and vomiting, and for some patients, the side effects of these drugs are unbearable. In a large clinical trial, 5% of participants had to stop taking medication due to side effects.
Swiss startup Aphaia Pharma wants to change this situation by developing a "natural" weight loss method. Dr. Steffen Sebastian Bolz, Chief Scientific Officer of Aphaia, pointed out that when the cells in the lower part of the small intestine are stimulated by nutrients in food, they release a series of hormones, sending a satiety signal to the brain and simultaneously producing other metabolic effects. However, in obese patients, nutrients do not reach this area, but are absorbed at a higher level in the intestine, which also leads to high blood sugar levels in the patient.APH-012, a leading project developed by Aphaia, is an oral microbead that can release glucose in the lower part of the small intestine to stimulate nutrient sensing cells to release hormones (including GLP-1) and control various steady-state and metabolic functions, such as appetite, hunger, satiety, glucose metabolism, energy consumption, etc.Through the design of microspheres, the glucose released by APH-012 will not be absorbed in the upper part of the small intestine, nor will it enter the systemic circulation, which is a key safety design for patients with diabetes. Compared to other therapies based on synthetic GLP-1 receptor agonists, these therapies have the potential to produce fewer side effects by promoting the secretion of natural hormones.
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Kallyope also adopts principles similar to Aphaia therapy.Kallyope focuses on identifying and developing weight loss metabolic therapies targeting the gut brain signaling axis, and the company collaborates with Aardvark Therapeutics.The latter is a start-up company that develops targeted therapies called "bitter receptors" in the gut, and has found that these receptors can trigger the release of hormones such as GLP-1Dr. Brett Lauring, Chief Medical Officer of Aphaia, stated in an interview that this type of therapy has similar effects to weight loss surgery that alters an individual's digestive system. this type of therapy has similar effects to weight loss surgery that alters an individual's digestive system.
The challenge for innovative weight loss therapies is ...
Having a differentiated and innovative drug pipeline is key to the success of new therapies, but biotechnology companies still face many challenges when entering the field of weight loss therapies. For example, unlike the development of cancer therapies, regulatory authorities have stricter safety standards for weight loss drugs. Therefore, when developing weight loss therapies, the industry often needs to conduct larger clinical trials to prove the safety and efficacy of ongoing therapies, which is a significant burden for many biotechnology companies. In addition, existing approved therapies have shown impressive weight loss effects. Therefore, Dr. Randy Seeley, director of the Michigan Nutrition and Obesity Research Center, stated that the new therapy needs to demonstrate a therapeutic effect of at least about 20% weight loss while also demonstrating benefits for heart health in order to highlight its advantages.
In addition to examining the single drug therapeutic effects of new therapies, many biotechnology companies are also examining the effectiveness of their in research products combined with existing approved drugs.For example, Versanis is conducting a clinical 2b trial to examine the efficacy of its lead drug bimarumab and smeglutide combined therapy in obese or overweight patients without diabetes. In addition, some studies have shown that patients taking GLP-1 alone may experience an increase in another intestinal hormone, ghrelin (commonly known as hunger hormone), which may be one of the reasons for weight recovery in patients after discontinuing treatment. In the Phase 2a clinical trial of Aardvark's lead project ARD-101, there are indications that drug treatment can reduce levels of hunger hormones.
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Dr. Tien Lee, CEO of Aardvark, said, "Like treating other diseases, we ultimately need a combination of drugs to achieve the best weight loss effect.Nowadays, many people are focused on developing the next generation GLP-1 drug, but in fact, it can also promote the therapeutic effect of obesity in many other aspects."
According to incomplete statistics from WuXi KangDe last year, at least 31 therapies in the weight loss field are in clinical phase 2, phase 3, pre registration, and already on the market.The types of therapeutic targets in Phase 2 clinical development are more diverse and the mechanisms are more novel, including controllable metabolic accelerators, neuropeptide YY5 receptors, and IKK ε/ TBK1, activin type II receptor, etc. These data suggest from another perspective that the industry is exploring weight loss therapies beyond the GLP-1 signaling pathway
Data source: Public information
Let's look forward to more innovative, effective, and safe monotherapy and combination therapies being approved as many biotechnology companies increase their investment in weight loss drug development, making weight loss no longer a challenge for many people!
