Heterodimeric interleukin 15

SHANGHAI & SUZHOU, China--(BUSINESS WIRE)--Forlong Biotechnology, a clinical-stage biotech company focusing on developing transformative cytokine therapies for patients with severe unmet needs, today announced that it has entered into a collaboration agreement with Shanghai Henlius Biotech, Inc., (2696.HK) (“Henlius”) to develop innovative cancer immunotherapy with an engineered cytokine. Under the terms of the agreement, Forlong will fuse a monoclonal antibody against a specific target selected by Henlius in a site-specific manner, with an engineered cytokine. In exchange, Forlong will receive an undisclosed upfront sponsor fee and research milestone payments, and upon reaching a predetermined development milestone, further licensing fee payments. Forlong has developed a portfolio of engineered cytokines aiming to activate specific subpopulations of the immune system. FL115 is an interleukin-15 (IL-15) superagonist to stimulate natural killer (NK) cells and memory T cells, showing favorable safety profile and preliminary clinical responses in multiple Phase I studies in China and US, and is currently being advanced to combo therapy with PD-(L)1 antibodies in Phase I for patients with advanced solid tumors and combo therapy with Bacillus Calmette-Guérin (BCG) in Phase II for patients with nonmuscle invasive bladder cancer (NMIBC). FL116 is a human anti-programmed cell death protein 1 (PD-1) antibody site-specifically fused to an interleukin-18 (IL-18) variant with minimal binding affinity to the IL-18 binding protein (IL-18BP), to preferentially activate T cells expressing both PD-1 and IL-18 receptors, and is in Preclinical Development Candidate Stage. Early research programs include cytokine-fusion proteins to activate naïve T cells and others being developed with proprietary Syntokine® Synthetic Cytokine Platform and AI-driven Intelligent Biomolecular Discovery Platform. “Recent progress in cancer immunotherapy has shown tremendous advancement in harnessing power of engineered cytokines through fusion with target proteins to activate desired segments of the immune system with precision,“ said Dong Wei, Ph.D., Chief Executive Officer of Forlong Biotechnology, “we are very excited by this collaboration, and will continue to further develop cytokine fusion proteins for target-specific immunostimulatory activity to significantly improve therapeutic outcome, through our internal programs such as FL115 and FL116 as well as additional partnership in the future”. "We are pleased to collaborate with Forlong Biotech to explore new frontiers in cancer immunotherapy," said Jijun Yuan, Ph.D., Chief Scientific Officer of Henlius. "By leveraging Forlong's synthetic cytokine platform for engineered cytokines and Henlius' profound expertise in the ​full-cycle​development of biologics, we will join forces to accelerate the development of novel therapies that can bring clinical benefits to cancer patients." About Forlong Biotechnology Forlong Biotechnology is a clinical-stage biotech company focusing on developing transformative cytokine therapies for patients with severe unmet needs. It has established four proprietary synthetic immunology platforms: Fbody® Long-acting Technology Platform, Fc engineering platform, Syntokine® Synthetic Cytokine Platform and AI-driven Intelligent Biomolecular Discovery Platform. Its lead candidate FL115 is interleukin-15 (IL-15) super agonist with best-in-class potential, currently being advanced to combo therapy with PD-(L)1 antibodies in Phase I for patients with solid tumors and combo therapy with Bacillus Calmette-Guérin (BCG) in Phase II for patients with nonmuscle invasive bladder cancer (NMIBC). Its second candidate FL116 is a human anti-programmed cell death protein 1 (PD-1) antibody site-specifically fused to an interleukin-18 (IL-18) variant with minimal binding affinity to the IL-18 binding protein (IL-18BP), and has demonstrated potent tumor-killing efficacy in multiple in vivo tumor models sensitive or resistant to immune checkpoint inhibitors. About Henlius Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 9 products have been approved for marketing worldwide, and 4 marketing applications have been accepted for review in China, the U.S. and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP. Henlius has pro-actively built a diversified and high-quality product pipeline covering about 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include HANSIZHUANG (serplulimab, trade name: Hetronifly® in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANLIKANG (rituximab), the first China-developed biosimilar, and denosumab Bildyos® and Bilprevda®. What’s more, Henlius has conducted over 30 clinical studies for 19 products, expanding its presence in major markets as well as emerging markets.

ANKTIVA, a first-in-class, lymphocyte-stimulating agent, works synergistically with BCG to activate and proliferate natural killer (NK) and T cells, helping eliminate cancer Already approved in the U.S. and designated as a Breakthrough Therapy by the FDA, this marks ANKTIVA’s first marketing approval outside the U.S. ANKTIVA plus BCG offers a new option for eligible patients among the 16,400 to 18,000 people diagnosed with NMIBC in the UK each year 1 CULVER CITY, Calif.--(BUSINESS WIRE)--ImmunityBio, Inc. (NASDAQ: IBRX) today announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for ANKTIVA® (nogapendekin alfa inbakicept-pmln) in combination with Bacillus Calmette-Guérin (BCG) for the treatment of certain bladder cancer patients. This is the first marketing approval outside the U.S. for this novel lymphocyte-stimulating agent. “With the MHRA’s authorization of ANKTIVA plus BCG, we can now offer our immunotherapy outside the U.S. to help patients with a disease that, if not effectively treated, can lead to bladder removal,” said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. “This immune-boosting, lymphocyte-stimulating agent, the first of its kind, is central to our Cancer BioShield platform, which is designed to restore immune function and support long-term disease control.” “ImmunityBio is honored to have received this important authorization from the UK MHRA. In light of the United States Most-Favored-Nation Prescription Drug Pricing policy implemented on May 12, 2025, we are actively evaluating our go-to-market strategy for the UK,” said Richard Adcock, CEO and President of ImmunityBio. ANKTIVA is a first-in-class IL-15 agonist that activates and proliferates natural killer (NK) cells and CD4+ and CD8+ T cells. It is designed to restore immune competence by reversing lymphopenia—a condition in which cancer and conventional therapies, such as chemotherapy, radiation and checkpoint inhibitors, reduce the number and function of immune cells. Restoring immune function is essential for immunosurveillance, immunogenic cell death, and sustained tumor control. The BioShield platform’s effectiveness can be monitored using a routine complete blood count (CBC). ANKTIVA was designated a Breakthrough Therapy by the FDA and received approval from both the FDA and MHRA based on its safety and efficacy outcomes of complete response (CR) and duration of response (DOR). In a single-arm, multicenter trial, 77 evaluable patients received ANKTIVA with BCG for up to 37 months. As of the November 2023 data cutoff, the duration of complete response for some patients exceeded 47 months and remains ongoing. These extended duration of complete responses beyond 24 months with ANKTIVA and BCG surpasses the benchmark for meaningful clinical results set by experts from the International Bladder Cancer Group. ImmunityBio has also submitted regulatory applications to the European Medicines Agency (EMA) to expand availability of ANKTIVA across the 27 European Union (EU) member states, as well as Iceland, Norway and Liechtenstein. About NMIBC CIS Bladder cancer is the 10th most commonly-diagnosed cancer globally,2 and in the UK, the Action Bladder Cancer UK estimates approximately 23,000 patients are diagnosed annually.1 At the time of diagnosis, about 80% of cases are non-muscle invasive bladder cancer (NMIBC), wherein the cancer is found only on the inner layer of the bladder wall.3 The standard therapy for NMIBC is intravesical instillation (delivery to the bladder via a catheter) of Bacillus Calmette-Guerin (BCG).4,5 BCG is a benign bacteria that induces an immune response in the bladder in proximity to the cancer cells, leading to clearance of the cancer in many patients. In ~30-40% of patients, however, BCG will fail, and in ~50% that initially respond, cancer will recur.6 About ANKTIVA The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response. ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and drives the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones. The proliferation of the trifecta of these immune killing cells and the activation of trained immune memory results in immunogenic cell death, inducing a state of equilibrium with durable complete responses. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in-vivo. ANKTIVA was approved by the FDA in 2024 for BCG-unresponsive non-muscle invasive bladder cancer CIS with or without papillary tumors. For more information, visit Anktiva.com. INDICATION AND IMPORTANT SAFETY INFORMATION FROM THE FDA LABEL INDICATION AND USAGE: ANKTIVA is an interleukin-15 (IL-15) receptor agonist indicated with Bacillus Calmette-Guerin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. WARNINGS AND PRECAUTIONS: Risk of Metastatic Bladder Cancer with Delayed Cystectomy. Delaying cystectomy can lead to the development of muscle invasive or metastatic bladder cancer, which can be lethal. If patient with CIS do not have a complete response to treatment after a second induction course of ANKTIVA with BCG, reconsider cystectomy. DOSAGE AND ADMINISTRATION: For lntravesical Use Only. Do not administer by subcutaneous or intravenous routes. Instill intravesically only after dilution. Total time from vial puncture to the completion of the intravesical instillation should not exceed 2 hours. USE IN SPECIFIC POPULATIONS: Pregnancy: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ADVERSE REACTIONS: The most common (≥15%) adverse reactions, including laboratory test abnormalities, are increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills and pyrexia. For more information about ANKTIVA, please see the Full Prescribing Information at www.anktiva.com. You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact lmmunityBio at 1-877-ANKTIVA (1-877-265-8482) About ImmunityBio ImmunityBio is a vertically-integrated biotechnology company developing next-generation therapies and vaccines that bolster the natural immune system to defeat cancers and infectious diseases. The Company’s range of immunotherapy and cell therapy platforms, alone and together, act to drive and sustain an immune response with the goal of creating durable and safe protection against disease. Designated an FDA Breakthrough Therapy, ANKTIVA is the first FDA-approved immunotherapy for non-muscle invasive bladder cancer CIS that activates natural killer cells, T cells, and memory T cells for a long-duration response. The Company is applying its science and platforms to treating cancers, including the development of potential cancer vaccines, as well as developing immunotherapies and cell therapies that we believe sharply reduce or eliminate the need for standard high-dose chemotherapy. These platforms and their associated product candidates are designed to be more effective, accessible, and easily administered than current standards of care in oncology and infectious diseases. For more information, visit ImmunityBio.com (Founder’s Vision) and connect with us on X (Twitter), Facebook, LinkedIn, and Instagram. References: Action Bladder UK. Non-muscle invasive bladder cancer. May 2021. Available at: https://actionbladdercanceruk.org/library/files/ABCUK%20An%20Introduction%20to%20NMIBC%20May%202021.pdf World Cancer Research Fund. Bladder Cancer Statistics. 2022. Available at: https://www.wcrf.org/preventing-cancer/cancer-statistics/bladder-cancer-statistics/ Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer. Canadian Urological Association Journal, 4(1), 56–64. https://doi.org/10.5489/cuaj.777 Holzbeierlein J, Bixler BR, Buckley DI, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline: 2024 amendment. J Urol. 2024;10.1097/JU.0000000000003846. Grabe-Heyne, et al. Intermediate and high-risk non-muscle-invasive bladder cancer: an overview of epidemiology, burden, and unmet needs. Front Oncol. 2023 Jun 2;13:1170124. doi: 10.3389/fonc.2023.1170124. Kodera A, Mohammed M, Lim P, Abdalla O, Elhadi M. The Management of Bacillus Calmette-Guérin (BCG) Failure in High-Risk Non-muscle Invasive Bladder Cancer: A Review Article. Cureus. 2023 Jun 26;15(6):e40962. doi: 10.7759/cureus.40962. PMID: 37503461; PMCID: PMC10369196. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, such as statements regarding clinical trial data and potential results and implications to be drawn therefrom, the belief that the MHRA authorization leads to increased revenue, the expectation that the EAP as previously reported will enable access to ANKTIVA for patients across all solid tumor types who have exhausted first-line therapy including chemo, radiation or immunotherapy, the RMAT designation as previously reported and potential results therefrom and regulatory submissions in connection therewith, the belief that ALC levels and NLR levels obtained from a CBC are predictors of clinical benefit and outcomes relating to overall survival, the belief that improving ALC levels and NLR levels correlates with enhanced overall survival and clinical benefit, the belief that reversal of lymphopenia correlates with improved survival, clinical trial and expanded access program enrollment, data and potential results to be drawn therefrom, anticipated components of ImmunityBio’s Cancer BioShield platform, the development of therapeutics for cancer and infectious diseases, potential benefits to patients, potential treatment outcomes for patients, the described mechanism of action and results and contributions therefrom, potential future uses and applications of ANKTIVA alone or in combination with other therapeutic agents for the prevention or reversal of lymphopenia, potential future uses and applications of ANKTIVA alone or in combination with other therapeutic agents across multiple tumor types and indications and for potential applications beyond oncology, potential regulatory pathways and the regulatory review process and timing thereof, the application of the Company’s science and platforms to treat cancers or develop cancer vaccines, immunotherapies and cell therapies that has the potential to change the paradigm in cancer care, and ImmunityBio’s approved product and investigational agents as compared to existing treatment options, and the impact of the MHRA on the Company’s ex-United States go to market strategy, including in light of the recently implemented United States Most Favored Nation pricing policy on the Company’s go-to-market strategy in the United Kingdom, among others. 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Such information may be limited or incomplete, and ImmunityBio’s statements should not be read to indicate that it has conducted a thorough inquiry into, or review of, all potentially available relevant information. 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