Avidence Therapeutics Files IPO Prospectus Highlighting Its Breakthrough Long-Acting Intra-Articular Platform for Osteoarthritis

Small-molecule drugs are generally considered to be administered primarily via the oral route. In recent years, an increasing number of international pharmaceutical companies have turned their attention to the development of long-acting injectable small-molecule drugs.

“Some argue that the chemical design of small-molecule drugs has matured and reached a bottleneck, making further innovation difficult,” Dr. Li Ang, founder of Avidence Therapeutics, told VCBeat. “In fact, many blockbuster pipelines of multinational pharmaceutical companies still consist of small-molecule drugs, particularly long-acting injectable small molecules, which have emerged prominently in recent years.” Conventional wisdom holds that antibody drugs exhibit slower metabolic rates, allowing for therapeutic effects lasting two weeks, one month, or even two to three months after injection. In contrast, small-molecule drugs are rapidly metabolized, with half-lives of less than one day, and are cleared from the body within a week, rendering them unsuitable for long-acting injectable formulations.

This is indeed the case. There are over 3,000 small-molecule drugs on the market, yet fewer than 20–30 are formulated as long-acting injectables. Many small-molecule drugs are developed for oral administration, with rapid metabolism intentionally designed into their structures, making them unsuitable for long-acting injectable formulations from a medicinal chemistry perspective. However, the recent surge in long-acting injectable antiretroviral therapies for HIV/AIDS, which are projected to generate several blockbuster drugs with annual sales exceeding $1 billion each, has rekindled interest in the development of long-acting injectable small-molecule drugs.

For instance, companies such as Gilead and Merck are developing HIV pre-exposure prophylaxis (PrEP) agents administered via monthly, bimonthly or quarterly, or even semi-annual injections. After intramuscular or subcutaneous administration, these drugs form water-insoluble crystals that dissolve slowly in the body, thereby achieving sustained suppression of viral replication. For chronic conditions like HIV infection, lifelong oral regimens often lead to missed doses or medication fatigue. In contrast, long-acting injectable formulations can prevent viral replication and transmission during periods without drug coverage, representing a promising strategy in the fight against AIDS.

More long-acting small-molecule drugs require the empowerment of advanced drug delivery technologies and the use of biodegradable polymer materials to achieve sustained and controlled release, thereby delivering therapeutic effects that last for weeks or even months. For example, Janssen’s Invega Sustenna modifies oral paliperidone by encapsulating it in a polymeric matrix; upon intramuscular injection, it provides durable efficacy lasting one to three months for the treatment of atypical psychosis. Given the difficulties psychiatric patients face in adhering to self-administered medication regimens, regular long-acting injections deliver exceptional efficacy in controlling disease onset.

Leveraging the unique advantages of long-acting formulations, Avidence Therapeutics has innovatively developed a long-acting intra-articular injection platform targeting chronic pain associated with osteoarthritis. The company has developed a series of formulations that optimize clinically validated drug targets for localized joint delivery with sustained release over three to six months. Although oral anti-inflammatory drugs demonstrate significant efficacy in reducing inflammation and alleviating pain, they are associated with severe cardiovascular and gastrointestinal side effects. The FDA mandates boxed warnings highlighting potentially life-threatening risks, including myocardial infarction, cerebral thrombosis, gastrointestinal bleeding, and perforation. The FDA emphasizes that such medications must be used at the lowest effective dose for the shortest duration possible, as long-term use leads to an cumulative increase in the risk of adverse effects. These systemic side effects significantly narrow the patient population that can benefit from treatment, thereby limiting both dosage and therapeutic efficacy.

Avidence Therapeutics’ intra-articular injection approach has successfully addressed its safety concerns. In a rat model of osteoarthritis, the intra-articularly administered drug demonstrated analgesic efficacy comparable to that of steroids. In a beagle dog pharmacokinetic study, the drug exhibited sustained and stable release for 3–6 months following intra-articular injection, with blood concentrations more than 100-fold lower than those observed with oral administration, thereby sufficiently eliminating potential cardiovascular and gastrointestinal risks and achieving best-in-class advantages. The product is currently undergoing GMP manufacturing and pre-IND preparations.

Notably, in the lucrative osteoarthritis market, total sales remain staggering despite the severe side effects associated with traditional oral anti-inflammatory drugs. As early as 2003, the combined global sales of COX-2 inhibitors, including Celebrex, Vioxx, and Valdecoxib, exceeded $9 billion. Although subsequent discoveries of cardiovascular risks associated with these drugs led to restrictions on their use, such limitations have not hindered the sustained growth in demand within the osteoarthritis treatment market. The market is projected to achieve a compound annual growth rate (CAGR) of 8.1%, with demand expected to reach $10.3 billion by 2025.

The company’s R&D achievements stem from Dr. Li Ang’s deep expertise in joint diseases and biomaterials. Dr. Li earned his Ph.D. in Biomedical Engineering from Columbia University in New York, where he studied under Professor Gordana Vunjak-Novakovic, a member of both the U.S. National Academy of Engineering and the National Academy of Medicine. Dr. Li has focused on the role of cartilage extracellular matrix in the pathogenesis of arthritis and has explored the interactions between various biomaterials and cartilage production, differentiation, and degeneration. By integrating decades of experience from multiple international pharmaceutical experts, the company has propelled long-acting drug delivery technologies to the forefront of small-molecule drug development.

“Focus breeds excellence; craftsmanship polishes premium products.” In the future, Avidence Therapeutics will continue to focus on innovation in long-acting small-molecule drugs, fully leveraging the significant advantages of long-acting formulations for chronic diseases. The company aims to expand its applications beyond osteoarthritis into broader therapeutic areas and advance clinical development, thereby pioneering a new landscape for small-molecule therapeutics.