Exclusive Interview with Dr. Shi Dongfang of New Element Pharma: Accelerating Phase III Clinical Trials for Gout Drug ABP-671 to Deliver a Globally Valuable Innovation

On December 12, Bloomberg cited sources as saying that Amgen has agreed to acquire Horizon Therapeutics at $116.5 per share, for a total of $27.8 billion, making this transaction the largest M&A deal in the global pharmaceutical industry in 2022. Previously, Horizon Therapeutics had disclosed that three major global pharmaceutical giants—Johnson & Johnson, Amgen, and Sanofi—were discussing potential competing bids.

According to Horizon Therapeutics’ financial report, its revenue this year is approximately $3.6 billion. Among its portfolio, Krystexxa, the company’s highly anticipated flagship gout medication, generated $570 million in sales last year. Following the FDA’s approval in July 2022 for an expanded indication allowing combination therapy with methotrexate, annual sales are projected to reach as high as $1.5 billion.

Regarding gout medications, another deal this month has also drawn significant attention: On December 15, 2022, Innovent Biologics entered into a strategic collaboration and licensing agreement with LG Chem for Tigulixostat, an innovative late-stage clinical drug developed by LG Chem for the treatment of hyperuricemia in gout patients, with a total transaction value of $660 million.

Amid the continuously expanding gout market, major pharmaceutical companies both in China and abroad are taking a series of strategic actions. The potential of various new gout drugs is increasingly evident, the time for commercialization has arrived, and the race to capture market share is about to begin.

Among the numerous companies poised to enter the field of novel gout drug development, Atom Therapeutics’ ABP-671 is particularly noteworthy. Clinical data from the United States, Australia, and China demonstrate that ABP-671 exhibits robust efficacy in lowering serum uric acid levels, along with a favorable safety and tolerability profile.

To gain further insights, VCBeat’s New Medicine channel conducted an exclusive interview with Dr. Shi Dongfang, Founder, Chairman, and CEO of Atom Therapeutics.

Currently, the number of individuals with hyperuricemia and the prevalence of gout are showing a significant upward trend both globally and in China, indicating broad growth potential for the anti-gout medication market.

Gout significantly impairs patients' quality of life and can precipitate other comorbidities. The prevalence of hyperuricemia and gout has been rising year by year, with a trend toward affecting younger populations, making it the second most common metabolic disease after diabetes mellitus. Globally, the number of individuals with hyperuricemia and gout reached 1.05 billion in 2021, including over 100 million gout patients. In the United States, there are more than 10 million gout patients, while China is estimated to have over 35 million. As a chronic condition, gout requires the vast majority of patients to adhere to long-term treatment, often involving lifelong medication. According to Frost & Sullivan’s forecasts, the global market for gout medications is projected to achieve annual sales of USD 7.05 billion by 2025. Therefore, the gout drug market holds substantial potential.

However,Current gout medications demonstrate limited efficacy and pose significant safety risks, failing to meet the needs of patients requiring long-term pharmacotherapy. Historically, global R&D activity for novel gout therapies was sluggish, which is a primary reason why the few gout drugs introduced in recent years have been able to command high prices in the market.

Current gout medications can be classified into three categories: URAT1 inhibitors, xanthine oxidase inhibitors, and uricase.

Currently marketed drugs fall far short of meeting clinical needs in terms of efficacy and safety, which has also madeAtom Therapeutics is firmly advancing the development of anti-gout medications.

Currently, numerous gout medications developed by pharmaceutical companies are in various stages of clinical trials. Key domestic companies include Hengrui Medicine, Yifang Biopharma, Haichuang Pharma, Simcere Pharmaceutical, and Atom Therapeutics, while major overseas companies include AstraZeneca, JW Pharmaceutical, and LG Chem.

According to the US guidelines for gout management, the serum uric acid (sUA) level in patients with gout should be maintained below 6 mg/dL (360 μmol/L); furthermore, the guidelines strongly recommend targeting an sUA level below 5 mg/dL (300 μmol/L). In contrast, the UK and Australian guidelines for gout treatment recommend maintaining sUA levels below 5 mg/dL (300 μmol/L). Sustaining sUA levels within the range of 4–5 mg/dL (240–300 μmol/L) over the long term facilitates the continuous dissolution of tophi and monosodium urate crystals in the joints and soft tissues of gout patients. This process reduces the frequency of acute gout flares and decreases the size and number of clinically detectable urate crystal deposits, ultimately achieving a functional cure for patients with gout.

Atom Therapeutics’ ABP-671 is a URAT1 inhibitor. Results from the Phase IIa clinical trial in Australia and the Phase I/IIa clinical trials in China demonstrated that over 85% of gout subjects in the lowest dose group achieved the primary clinical endpoint, defined as serum uric acid (sUA) levels <6 mg/dL (or 360 μmol/L). In one of the intermediate dose groups, 92% of subjects achieved the primary endpoint of sUA <6 mg/dL. Among the three high-dose groups, 100% of subjects met the primary clinical endpoint.

Of greater note is the favorable attainment rate of ABP-671 for the secondary endpoint of serum uric acid (sUA) <5 mg/dL (or 300 μmol/L). In the lowest-dose group of ABP-671, over 60% of subjects achieved sUA levels <5 mg/dL; in one mid-dose group, 72% of subjects reached sUA levels <5 mg/dL; and in all three high-dose groups, the attainment rate for sUA <5 mg/dL was 100%. This level of efficacy is difficult to achieve with any currently marketed drugs.

In terms of safety, ABP-671 demonstrated a favorable safety and tolerability profile. All adverse events (AEs) were Grade 1 or Grade 2, with the majority being Grade 1, comparable to the placebo group. No serious adverse events occurred, and no hepatotoxicity, nephrotoxicity, or cardiotoxicity was observed.

"Following the news of Horizon’s acquisition at a premium and Innovent’s introduction of Tigulixostat for the Chinese market, Dr. Shi Dongfang, Founder of Atom Therapeutics, and Mr. Jin Wenqing, Executive Vice President of the company, stated that the core team is highly confident in Atom Therapeutics’ ABP-671 project."Based on current clinical data, a single daily dose of 2 mg of ABP-671 may demonstrate superior efficacy compared to the maximum daily dose of 80 mg of benzbromarone and febuxostat.“We will advance the Phase III clinical study of ABP-671 as soon as possible, while accelerating its development for other indications.” Atom Therapeutics is also advancing its innovative drug for the treatment of acute gout attacks, with Phase I clinical trials expected to begin in the third quarter of 2023.

Since its establishment in 2012, Atom Therapeutics has quietly dedicated itself to drug development, carving out a R&D path focused on creating innovative drugs with global commercial value. “Many domestic projects are confined to the Chinese market; however, under the volume-based procurement (VBP) policy, the profit margins for ‘China-only’ new drugs are not high, making it difficult to reflect their true market value. In contrast, for an innovative drug with a global market, 85–90% of its profits come from overseas.” Against this backdrop, even with high-quality drug candidates, the slim profits in the domestic market are insufficient to support subsequent R&D efforts for innovative pharmaceutical companies. Therefore, after initial exploration, Atom Therapeutics clarified its strategic direction: to develop high-quality drugs with global commercial value.

It is no easy feat for Chinese pharmaceuticals to break into the global market. Industry practitioners are well aware of the gaps between domestic and international drug R&D, with many current Chinese drugs failing to achieve “me-better” status. Beyond the intrinsic quality of new drugs, “first-mover advantage” presents another inevitable challenge. Even “me-too” drugs struggle to enter overseas markets; if there is little difference in efficacy and safety, physicians tend to prefer established drugs they have used for years.

How to Develop Best-in-Class Drugs in the Current Impetuous New Drug R&D Industry?

Unlike some of the fervent innovative drug companies that have recently emerged, Dr. Shi Dongfang, with nearly 30 years of industry experience, clearly understands that advancing five or six pipelines simultaneously may not be advisable for small biotech firms. First and foremost, funding is the initial hurdle. The cost of developing a drug from preclinical stages through Phase I and II clinical trials can range from 100 to 200 million RMB, but once it enters Phase III clinical trials, the expected expenditure could reach around $100 million, or even more. Small biotechs are unlikely to sustain pushing numerous product pipelines into Phase III clinical trials.

Therefore, for biotech companies, strategic selection is more critical than sheer effort. Dr. Shi believes that rather than pursuing a low success rate across numerous projects, Atom Therapeutics prefers to maintain a leaner pipeline to ensure higher drug development success rates, while proactively preparing for Phase III clinical trials and market launch. Developing innovative drugs with differentiated value and best-in-class potential has always been the core objective of Atom Therapeutics.

During the Phase III clinical trial stage, Atom Therapeutics adopts a model of “early-stage independent R&D plus late-stage joint development with international pharmaceutical companies.” The company plans to seek large pharmaceutical enterprises globally as partners to jointly advance the project. This approach not only helps share a portion of the R&D costs but also signifies the first step toward entering the international market, as gaining recognition from major global pharmaceutical companies at this stage is crucial. Later, leveraging the mature business models and global sales networks of these international giants will effectively boost post-launch sales revenue.

Currently, Atom Therapeutics' core patent for ABP-671 has been granted in over 70 countries and regions.

Doing the right thing at the right time, without rushing for quick success, is a rare quality in this era. Atom Therapeutics is precisely such a company.

Mr. Jin Wenqing, Executive Vice President and another core member of the team, was also an investor during Atom Therapeutics’ angel financing round and joined the company in 2015. He holds Dr. Shi’s selection and management of the drug pipeline in highest regard. From an investor’s perspective, a company’s potential is judged not by the size of its pipeline, but by whether it possesses projects with the potential to become blockbuster drugs. In other words, investors prioritize success rates and market potential above all else.

Regarding team recruitment, Dr. Shi also believes that a company should build a team appropriate to its current stage of development; assembling a full, top-tier team too early is a waste of both capital and talent resources.

Regarding financing, while some companies may adopt a “raise as much as possible” strategy, Atom Therapeutics prefers to “raise only what is currently needed,” ensuring adequate cash flow.Currently, investors in Atom Therapeutics’ Series A through C rounds include prominent investment institutions such as Cathay Capital, Livzon Pharmaceutical Group, Xicheng Jinrui, Sequoia Capital, GTJA Innovation Investment, Youxuan Capital, Zhongyu Capital, Fortune Capital, Yifeng Capital, Yuanhe Holdings, and Qiandao Group. With steady and solid progress, Atom Therapeutics is poised to advance its core product, ABP-671, into Phase III clinical trials. The company has also launched a new round of financing, expected to be completed by March 2023. Atom Therapeutics plans to initiate an IPO at the earliest opportunity to prepare for its long-term development.