Furong Biologics Files for IPO: Advancing FL115, a Best-in-Class IL-15 Superagonist in Phase I Trials Across the U.S. and China

Recently, the cytokine drug industry has reached a major milestone. On April 22, N-803 (brand name: Anktiva), an interleukin-15 (IL-15) superagonist developed by immunotherapy company ImmunityBio, received FDA approval for marketing, becoming the first IL-15 superagonist approved by the FDA.

Cytokines are a class of small-molecule proteins with broad biological activities and serve as key participants in immune regulation.With the rapid development of tumor immunotherapy, the importance of cytokine drugs in immunotherapy is increasingly evident, becoming a key strategy for humans to regulate the immune system and achieve desired immune responses.。

Despite significant clinical advances in cytokine research, the use of cytokines as immunotherapeutic agents still faces developmental challenges. Due to their inherent properties, cytokine drugs often exhibit short half-lives, broad activity profiles, and pleiotropic effects. Continuous administration can easily lead to systemic toxicity, and achieving selective activation at specific sites remains difficult, thereby limiting their therapeutic efficacy.

Suzhou Forlong Biotechnology Co., Ltd. (hereinafter referred to as “Forlong”) is an innovative R&D enterprise committed to overcoming the key challenges hindering the development of cytokine-based therapeutics.Founded in April 2019 and headquartered in Suzhou High-Tech Zone, the company is an innovative enterprise driven by synthetic immunology technology, focusing on the development of protein drugs such as cytokines.。

To date, Forlong has established an integrated synthetic immunology technology system and, building on this foundation, developed four core technology platforms, achieving significant breakthroughs in the long-acting formulation and detoxification of cytokines. Supported by its core technologies and professional team, the company has built a diverse pipeline of candidates under development. Among them,The lead candidate in the pipeline, FL115, an IL-15 tumor immune agonist, is advancing most rapidly. It has currently received clinical trial approval from both the CDE and the FDA, and clinical trials are underway for the treatment of advanced locally unresectable or metastatic solid tumors.。

Notably, Forlong’s professional expertise and R&D achievements have garnered favor from the investment community.In February 2023, Forlong completed its Series A financing round, raising over RMB 100 million., further accelerating the development of its cytokine-based tumor immunotherapy drugs.

Established less than five years ago, Forlong has rapidly built its technology platform and laid out its R&D pipeline, backed by a core team with decades of deep expertise in innovative drug development and extensive industrialization experience.

The company’s core team comprises top-tier scientists and industry experts in the field of protein therapeutics, possessing robust capabilities in translating scientific research into practical applications. Multiple research achievements have been licensed to major international pharmaceutical companies and have advanced into clinical translation stages, with total licensing fees amounting to hundreds of millions of yuan. Importantly,The company is backed by the Shanghai Synthetic Immunology Engineering Technology Research Center, an internationally renowned protein drug discovery laboratory.。

Leveraging the team’s profound understanding of immunology and decades of R&D experience in protein engineering, Forlong has developed an internationally leading integrated synthetic immunology technology system, from which four major technology platforms have been derived—Fbody long-acting technology platform, Fc engineering platform, synthetic novel cytokine platform, biomolecular artificial evolution platform。

Forlong’s 4 Core Technology Platforms | Image source: Forlong

Technologies such as library-based high-throughput screening for directed evolution of immune molecules, computer-aided design-enabled directed evolution of novel immune molecules, and structural adaptability studies of artificial immune molecules,Forlong has achieved a technological breakthrough by establishing a library display technology based on ultra-large-capacity immune molecule libraries. This platform enables the application of multiple evolutionary pressures and multi-functional screening, allowing for multi-dimensional optimization of protein therapeutics, particularly cytokines, thereby comprehensively meeting their drugability requirements.。

Taking Fbody long-acting technology as an example, Forlong employs directed evolution through multi-functional screening,Screening from 25 billion mutants to obtain an Fc monomer with high safety, high yield, and long half-life, which is a rare Fc monomer internationally with excellent druggability.Notably, the Fc monomer screened by Forlong has overcome the application limitations of Fc fusion proteins, enabling its use with recombinant proteins that are incompatible with Fc fusion, such as complex proteins, dimers, and trimers. Furthermore, due to its improved safety profile and lower production complexity and cost, it holds corresponding application value in the iteration and upgrading of mature recombinant protein products.

IL-15 is a pleiotropic cytokine that activates T cells, B cells, and NK cells, and mediates their proliferation and survival. It plays a crucial role in both innate and adaptive immunity, making it a highly sought-after therapeutic target. However, native IL-15 has a short half-life and low monomeric bioactivity, resulting in poor druggability. Therefore, the use of Fc fusion proteins to extend its half-life has become a mainstream molecular design strategy. Nevertheless, bivalent Fc fusion proteins present certain challenges, such as the risk of excessive immune activation leading to cytokine storm, and systemic toxicity induced by Fc effector functions including ADCC, ADCP, and CDC.

Forlong has overcome these challenges and developed FL115, a novel long-acting IL-15 superagonist, based on its Fbody long-acting technology platform.。

FL115 is a soluble sFc fusion protein that offers the advantages of a long half-life, low molecular weight, strong penetration into solid tumors, a simple and robust manufacturing process, and lower production costs. Notably, during the screening of Fc monomers, the R&D team knocked out all sites capable of binding to Fcγ receptors.Therefore, the single-arm FL115 is less likely to cause cytokine storm or induce systemic toxicity, demonstrating a high safety profile.。

The company’s R&D team discovered during preclinical studies that data from head-to-head comparative studies with N-803 showed the safe dose of FL115 to be dozens of times higher than that of N-803; therefore, with efficacy equivalent to or significantly greater than that of N-803,FL115 is poised to significantly broaden the therapeutic window, emerging as a safer and more effective next-generation IL-15 superagonist for cancer immunotherapy, while expanding into additional indications.。

Currently, FL115 is undergoing a Phase I clinical trial in the United States for the treatment of advanced locally unresectable or metastatic solid tumors (NCT06130722), with the first patient dosed on December 12, 2023, U.S. time. Existing clinical data demonstrate that FL115 has a favorable safety and efficacy profile, showing potential to become a best-in-class (BIC) therapy. Furthermore,The second dose cohort in this clinical trial has been escalated to 10 µg/kg (the maximum intravenous dose of N-803 in Phase I clinical studies). At this dose level, no serious adverse reactions were observed in patients, and the treatment remained safe.。

On March 5 this year,FL115 Injection Has Received Implied Approval for Clinical Trials from the CDE (Acceptance No.: CXSL2300885) and Is Planned to Undergo Clinical Trials for the Treatment of Advanced, Locally Unresectable or Metastatic Solid Tumors, the study, led by Professor Zhang Li from the Sun Yat-sen University Cancer Center, has begun patient recruitment.

Regarding future development, Forlong stated that the company’s focus is on advancing the R&D of its IL-15 pipeline candidate, FL115, with the aim of bringing clinical benefits to more patients. In addition,The company is actively advancing external collaborations for its technology platform., has currently entered into a collaboration with a renowned pharmaceutical company to apply its proprietary Fbody core technology to the development of other protein therapeutics, jointly creating next-generation long-acting biologics to benefit more patients