A company that has won the favor of Sequoia, Eli Lilly Asia Ventures, WuXi AppTec and other well-known institutions and industrial capital, and has an IPO on the cusp of the GLP-1 boom, surged 73% on the first day of listing, with a total market value of 900 million US dollars......
When the instability of the market is concretized, the high-quality targets stacked with countless good news will also "return to the pre-liberation period" due to a clinical data that has no obvious benefit.
On February 3 this year, when Structure Therapeutics landed on the NASDAQ and closed up 73% on the first day, Zhen Li, an investor in the secondary market, believed that the valuation of U.S. stocks for Chinese concept stocks may be "breaking the ice". But what Zhen Li didn't expect was that yesterday, the latest data of the phase 2a clinical trial of the core product small molecule GLP-1 receptor agonist GSBR-1290 for the treatment of type 2 diabetes released by Structure Therapeutics was lower than market expectations, especially compared with the same variety of Eli Lilly, and did not show better benefits, resulting in the stock price of Structure Therapeutics falling nearly 50% before the market, close to the issue price, and the market value was "evaporated" by more than $1 billion.
However, what makes Zhen Li even more puzzled is that the founding team has gathered a number of well-known figures in the industry and created a differentiated platform; it has completed two rounds of financing in less than a year and the amount of financing is among the best; a biotech favored by Sequoia Capital, Qiming Venture Capital and other domestic and foreign investment "bigwigs" can be said to have a deep background, why can't the stock price withstand a "flying disaster", is it itself overvalued, or is the market sentiment at work?
"Can't cross" the faucet Eli Lilly
In fact, the latest Phase 2a clinical data of GSBR-1290 released by Structure Therapeutics is still positive, and for type 2 diabetes, GSBR-1290 was reduced by 1.01% and 1.02% in HbA1c (glycosylated hemoglobin index) and 3.51% and 3.26% in body weight at 12 weeks of treatment in the 45mg and 90mg dose groups, respectively. In terms of weight loss, the weight loss in the 120mg dose group and the placebo group was 5.55% and 0.82% and 4.74% respectively in the 8-week treatment group.
Although the weight loss data is positive, the 2a clinical data is not only less competitive with Eli Lilly's oral small molecule GLP-1 drug Orforglipron, but also not as good as the data disclosed by GSBR-1290 in the 1b clinical trial.
In fact, Structure Therapeutics' GSBR-1290 has been wearing a halo from birth to its phase 1 clinical trial, and now the company's stock price fell off a cliff due to the failure of clinical data to meet expectations, which is the embodiment of the huge psychological gap after investors are full of expectations.
After Novo Nordisk's semaglutide has brought amazing clinical benefits and market sales, the competition for long-acting injectable dosage forms is almost coming to an end, and the giants have opened up the battlefield of oral dosage forms.
On the one hand, oral small molecules are expected to break through the defects of large molecule GLP-1 that are unstable and easily degraded, on the other hand, Novo Nordisk dominates the field of peptide GLP-1 with semaglutide, and the SNAC technology from Emisphere, which it has acquired, has made semaglutide almost unattainable in terms of effectiveness and safety.
In this case, oral small molecule GLP-1 has become a differentiated battlefield opened up by latecomers. At present, only Eli Lilly's Orforglipron has rushed to Phase III, and the GSBR-1290 of Structure Therapeutics has been able to enter Phase II clinical trials, which is actually in the echelon with rapid progress, in addition to him, TTP273 from Huadong Medicine has completed Phase II clinical trials in the world.
It is reported that after completing the phase I single ascending dose (SAD) study of GSBR-1290 in 2022, the phase 1b clinical study of GSBR-1290 was released on September 29 this year, and the average body weight of the 90mg dose group was reduced by 4.9 kg by day 28, a decrease of 4.9% compared with placebo. This clinical result not only makes investors believe that the company is a GLP-1 "treasure" worth excavating, but also makes GSBR-1290 a "potential stock" for Eli Lilly in the field of oral small molecules. By the end of the day, Structure Therapeutics' stock price rose 35% to $50.42 per share, with a market capitalization of $1.929 billion.
From the data, it can be seen that the Phase 2a results announced by Structure Therapeutics are not as good as the Phase 1b results, not to mention the final results of the Phase II clinical trial that Eli Lilly's Orforglipron has achieved. It is reported that Eli Lilly's Orforglipron in phase 2 clinical trial, at 12 weeks of treatment, HbA1c decreased by 1.5%, and after 36 weeks of administration of the highest dose of 45mg, it helped patients lose an average weight of 14.7%.
However, this is not the final and complete result, and Structure Therapeutics said in the announcement that it expects to release full 12-week weight loss data in the second quarter of 2024, and the Phase 2b study will also be launched in the second half of 2024.
From a more macro point of view, the front of Suntech GSBR-1290 is not only the mountain of Eli Lilly's Orforglipron, but also full of various MNC players such as Roche and AstraZeneca, and the value of an oral small molecule GLP-1 is no longer just the PK with placebo in the clinical trial process, but the competition with external giants.
The oral peptide field cannot be inserted, and oral small molecule GLP-1R agonists have naturally become a "cost-effective" choice to avoid the technical threshold. In 2018, with a down payment of only US$50 million, Eli Lilly obtained the global development and commercialization rights of the LY3502970 "produced" by Roche's Sino-foreign pharmaceutical platform, making it the current Orforglipron, the world's fastest-growing oral small molecule GLP-1R agonist.
To date, Orforglipron has initiated a number of Phase III clinical trials for diabetes and weight loss indications, and it is worth noting that in September this year, Eli Lilly also initiated the ACHIEVE-3 study, a Phase III clinical trial of the efficacy and safety of Orforglipron head-to-head Novo Nordisk oral semaglutide in patients with type 2 diabetes who are poorly controlled by metformin.
Eli Lilly has undoubtedly become a "leader" in the field of small molecule GLP-1, which is difficult for the industry to achieve, and it is also worth looking forward to who will win the "second-in-command" position next. MNC such as AstraZeneca and Roche have also entered the game in recent years.
In November, AstraZeneca announced a partnership with Chinese biotechnology company Chengyi Biotech to develop a small-molecule GLP-1 receptor agonist ECC5004 for the treatment of obesity, type 2 diabetes and other cardiometabolic diseases, with an initial payment of US$185 million and a total of more than US$2 billion. ECC5004 has achieved preliminary results from Phase I clinical trials, is well tolerated compared to placebo, and promotes blood glucose and weight reduction.
Not long ago, Roche also acquired Carmot for a total of more than $3 billion, and one of the company's core assets is a small molecule GLP-1 receptor agonist CT-996, which is still in phase 1 clinical trials.
It is worth mentioning that Pfizer's previously announced termination of the GLP-1 R&D pipeline Danuglipron is also an oral GLP-1R receptor agonist, although it met the primary endpoint, but due to the high incidence of adverse events, the development of the twice-daily dosage form was terminated.
With many "labels",
What is the strength of Structure Biotech?
At present, although Structure Therapeutics has suffered setbacks in the capital market due to GSBR-1290, the fastest oral small molecule GLP-1 receptor agonist in the research pipeline, it is gradually "high-rise" in the long run.
Aside from this plunge, in the four years since its establishment, most of the time it has gone smoothly. Behind it is nothing more than the capital market's call for "true innovation", and a strong founding R&D team, differentiated platforms and pipelines have become the key.
First of all, the founding team of Structure Biosciences can be said to have a great history, which was co-founded by Dr. Raymond Stevens and Rich Friesner, the founder of Schrödinger, a well-known AI pharmaceutical listed company, with Raymond Stevens as the CEO.
Raymond Stevens' resume is a testament to its achievements. He is a pioneer in structure-based drug discovery and structural genomics, and has been involved in the discovery and development of several therapeutic molecules, which have led to the development of several breakthrough drugs, including Palnziq for the treatment of phenylketonuria (PKU), which was developed by BioMarin Pharmaceutical and approved for marketing in 2018.
Not only that, but he also founded Receptos, the company that developed Zeposia, a GPCR agonist targeting the S1PR1 receptor, which was approved in 2020 for the treatment of multiple sclerosis and ulcerative colitis in 2021. At the same time, the industry-renowned scientist has also contributed to the academic community and helping to incubate biotechs, and has helped students successfully launch several biotech start-ups, including Syrrx (acquired by Takeda), MemRx (acquired by Chiron/Novartis), Receptos (acquired by Celgene/Bristol-Myers Squibb) and Ruiyi (now Bird Rock Bio).
Building on Raymond Stevens' proven expertise, Structure Therapeutics has created a cutting-edge technology platform built with structure-based drug discovery and computational chemistry focused on structure-based drug discovery and the challenging target GPCR (G-protein-coupled receptor) to design differentiated small molecule therapeutics to overcome the limitations of biologics and peptide therapies targeting this receptor family.
Not only the CEO, but most of the senior management members of Structure Biotech are also experienced and quite resistant. For example, Chief Scientific Officer Xichen Lin has nearly 20 years of industry experience in drug discovery and development, and has successfully developed a number of pre-clinical, phase I and phase II drugs. It is worth mentioning that Lin Xichen was the head of external innovation in the Asia-Pacific region of Novo Nordisk, the "GLP-1 pioneer". Mark Bach, Chief Medical Officer, is an expert in the field of pediatric endocrinology with 30 years of clinical research and drug development experience, and has extensive experience building and leading global clinical teams, and has successfully brought multiple innovative drugs to the global market.
This may also be indirectly reflected in the R&D pipeline. Structure Therapeutics' first bet is GLP-1R, one of the members of the GPCR family, and GSBR-1290 has become the fastest oral small molecule GLP-1 receptor agonist in its research and development.
Under this platform, in addition to focusing on the next-generation GLP-1R drug candidate, Structure Therapeutics is currently in clinical trials for another fast-progressing drug candidate, ANPA-0073. This small molecule product targets the apelin receptor (APJR) and has the potential to treat idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension (PAH).
The early solid R&D platform and pipeline layout, as well as the "endorsement" of the star team, may become the key to the subsequent success of the capital market of Structure Biotech, and it is not an exaggeration to call it a "capital darling". Looking at the past rounds of financing of Structure Therapeutics, it has been bet on by more than 20 well-known investment institutions and peers, including Sequoia Capital, Qiming Venture Partners, Hillhouse, F-Prime, Eli Lilly Asia, Schrödinger, BVF and other investment "bigwigs".
Even in the two years when the capital winter of the pharmaceutical industry intensified, Structure Biotech also performed extraordinarily, and in the context of the industry's special encouragement of "true innovation" and "differentiation", it completed two rounds of financing in less than a year, first completing a $100 million Series B financing in October 2021, and then completing another $33 million oversubscription financing in August 2022.
At the beginning of this year, Structure Therapeutics took the lead in breaking the "U.S. stock IPO nightmare" and became the first biotech to be listed on the U.S. stock market in 2023, and successfully landed on the NASDAQ in February this year. On the first day of listing in the United States, it still became a "special case" in the past two years, and the capital market gave the company extremely positive feedback.
A set of data can back it up. At the close of trading on the first day, the stock price of Structure Biotech soared by 73.33%, and the total market value reached $905 million at that time.
In addition, catching up with the popularity of the GLP-1 track, in the GLP-1 oral track that large MNCs such as Novo Nordisk and Eli Lilly are competing to catch up, with the heavy investment of many well-known investment institutions and large pharmaceutical companies, the GLP-1 track that Structure Therapeutics is betting on has directly triggered a phenomenal reaction this year, almost every company wants to have a GLP-1, and Structure Biotech has also become a "sweet spot" in the capital market, with this halo, the market value has repeatedly soared.
A strong founding team, a differentiated platform, a highly anticipated pipeline, and a strong investment institution "platform...... This makes Structure Biotech favored by the secondary market. At present, the high expectations for "true innovation" are not met, and the market value has suddenly "evaporated" by more than 1 billion US dollars, which has poured cold water on the company.