Tian'an Biopharma's HongKa® – The World’s First Immune-Based Biologic for Persistent High-Risk HPV Infection Enters Expert Consensus and Files IPO Prospectus

On March 4, 2025, the eighth annual International HPV Awareness Day was observed, aiming to raise public awareness of the hazards of human papillomavirus (HPV) and to promote the prevention and elimination of cervical cancer.

In fact, China has been making continuous progress. In 2009, cervical cancer screening was included in the national major public health service programs, and "two-cancer screening" (for breast and cervical cancers) was implemented for eligible women in rural areas. In 2019, vaccination efforts were advanced. In 2023, ten departments, including the National Health Commission, jointly formulated the Action Plan for Accelerating the Elimination of Cervical Cancer (2023–2030), to further accelerate the process of eliminating cervical cancer.

On the other hand, according to the 2023 ICO/IARC Report on HPV and Related Diseases in China, cervical cancer ranked third among female malignancies in terms of both incidence and mortality rates among women aged 15–44 years in China in 2020. The latest data released by the National Cancer Center in 2022 indicated that the incidence of gynecological cancers in China continued to rise, with 119,300 new cases and 37,200 deaths from cervical cancer annually. In other words, the onset of cervical cancer in China is showing a trend toward affecting younger populations.

However, the current HPV screening rate for women aged 35–64 in China is only 36.8%, which remains significantly below the interim target of 70% screening coverage by 2030, indicating that prevention and control efforts still face substantial challenges. Meanwhile, current screening methods have notable drawbacks: procedures such as cervical cytology (TCT) and colposcopy rely heavily on physician experience, and their invasive nature often causes patient discomfort and psychological stress.

Furthermore, early-stage cervical cancer is generally asymptomatic, and the prognosis following detection of carcinoma in situ is quite favorable, with a five-year survival rate reaching 100%. As the disease progresses to the middle and late stages of cervical cancer, symptoms such as vaginal bleeding, abnormal vaginal discharge, and compression-related manifestations—including urinary frequency, constipation, lower extremity edema, ureteral obstruction, hydronephrosis, and uremia—may occur. In advanced stages, systemic signs of failure, such as anemia and cachexia, may present. Once cervical cancer progresses to invasive carcinoma, it advances rapidly; without treatment, patients may die within 2 to 5 years.

Therefore, the last line of defense lies in the treatment phase.

Cervical cancer is primarily caused by persistent infection with high-risk human papillomavirus (HPV). One approach involves developing a novel immunotherapy to replace traditional ablative and traumatic treatments, targeting individuals with compromised local cervical immunity who require pharmacological intervention. By enhancing local immune function in the cervix, this therapy can effectively clear HPV, reverse cervical lesions, and achieve optimal therapeutic outcomes.

Nr-CWS, namely the topical Nocardia rubra cell wall skeleton (Hongka®), is an innovative drug with independent intellectual property rights and a National Medical Products Administration (NMPA) approval number, developed by Shenyang Shengbaokang Biological Pharmaceutical Co., Ltd. (hereinafter referred to as “Shengbaokang Bio”). It has obtained 35 domestic and international invention patents. As a world-first and internationally leading biological product, it effectively fills the gap in biologic therapies for local cervical HPV infection and will become a new alternative to surgical treatment for cervical precancerous lesions.

*Nocardia rubra* is a Gram-positive bacterium that was initially discovered in soil and has garnered attention due to its unique biological characteristics and potential medical value.

In the 1970s, scientists in the United States and Japan discovered the cell wall skeleton of Nocardia rubra while searching for ideal antigens against malignant tumors. Its cell wall skeleton (Nr-CWS) is the primary immunologically active component, composed of mycolic acid, arabinogalactan, and peptidoglycan, among others. It can activate the immune system and possesses immunogenicity.

Notably, studies have shown that Nr-CWS influences the progression of cervical cancer by enhancing the antitumor activities of macrophages and dendritic cells. It also reduces the expression of the PD-L1 gene.

However, the application of Nr-CWS was limited at that time, primarily due to its suboptimal performance in the treatment of solid tumors. Fortunately, this important study did not go unnoticed.

In 1998, the Ministry of Health of China approved the New Drug Certificate for Nr-CWS, as well as its drug production approval number. In 2002, the project “Topical Nocardia rubra Cell Wall Skeleton” was approved by the State Development Planning Commission as a “High-Tech Demonstration Project.” In 2003, the State Food and Drug Administration approved topical Nocardia rubra cell wall skeleton as a national Class II biological new drug.

It is worth mentioning that in 2004, the “Topical Nocardia rubra Cell Wall Skeleton” project was included by the National Development and Reform Commission in the “Special Program for the Development of High-Tech Industries to Revitalize the Old Industrial Base in Northeast China (First Batch).” In February of the same year, Tian’an Bio passed the on-site GMP certification inspection organized by the State Food and Drug Administration; in August, it received the Pharmaceutical GMP Certificate issued by the State Food and Drug Administration.

Image source: Tianan Bio

In 2005, during the clinical application of Nr-CWS, the core team at Shenyang Shengbaokang Biological Pharmaceutical Co., Ltd. further confirmed its significant efficacy in clearing HPV, as well as its therapeutic effects on skin ulcers, herpes zoster, and fungal infections. The company began applying for domestic and international invention patents. Focusing on HPV treatment, Nr-CWS has engaged in comprehensive, long-term research into its pharmacological mechanisms and continuous statistical observation of clinical efficacy in collaboration with universities, research institutes, and clinical units. Thus commenced the journey of Shenyang Shengbaokang Biological Pharmaceutical Co., Ltd. and its Hongka® product.

As a non-specific immunomodulator, Hongka® enhances the immune activity of macrophages and natural killer cells in the body, effectively promoting the phagocytosis and killing of pathogens by immune cells, thereby improving the human body’s resistance to infection.

Specifically, Hongka® is first absorbed through the wound surface at the lesion site, releasing immunomodulatory signals into the body to activate the immune activity of non-specific immune cells, such as macrophages and natural killer (NK) cells.

Secondly, it stimulates local immune cells to secrete various cytokines, thereby enhancing local cervical immune function and exerting antiviral and anti-infective effects. Meanwhile, it interferes with the transcription and replication of HPV within the nucleus of human cells and initiates apoptosis in diseased cells, leading to the shedding of HPV and lesioned tissue along with cellular turnover.

Finally, Hongka® can rapidly eliminate local inflammation, repair damaged cervical epithelium, accelerate the healing of lesioned tissues, and significantly enhance cervical immunity.

Clinical trial results demonstrate that Nr-CWS significantly increases the number of T cells, including CD4+ and CD8+ T cells, in cervical tissue. It promotes macrophage proliferation, migration, and phagocytic function, while simultaneously reducing the expression of PD-1/PD-L1. Furthermore, by targeting FPR3 on the surface of dendritic cells (DCs) and activating Th1-type immune responses, Nr-CWS elevates levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-α). This increase in immune cell activity exerts an effective antiviral immune response against HPV.

Image source: Shenyang Shengbaokang Biological Pharmaceutical Co., Ltd.

The target population for the Hongka® product comprises individuals unable to clear HPV infection through their own immune response and who require pharmacological intervention. Indications include simple HPV infection, chronic cervicitis with HPV infection, low-grade squamous intraepithelial lesion (LSIL) of the cervix with HPV infection, high-grade squamous intraepithelial lesion (HSIL) of the cervix with HPV infection (in patients unwilling to undergo surgery), persistent HPV infection following LEEP or CKC procedures, and persistent HPV infection after cervical cancer surgery.

2017 was a year of great significance for Tianan Biologics.

Under the leadership of Academician Lang Jinghe from Peking Union Medical College Hospital, thirteen hospitals (14 centers) successively initiated a clinical study on “The Efficacy and Safety of Topical Nocardia rubra Cell Wall Skeleton in Patients with Persistent High-Risk HPV Infection of the Cervix.” This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled a total of 555 participants, including 368 in the experimental group and 187 in the control group.

The results of this trial were officially published in the Chinese Journal of Obstetrics and Gynecology in July 2023.

The results showed that at 12 months post-treatment, the clearance rates for HPV types 16, 18, 52, and 58 in the experimental group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively, whereas those in the control group were 21.6% (11/51), 11.1% (1/9), 35.1% (13/37), and 20.0% (8/40), respectively. Comparisons of clearance rates for different HPV types between the two groups revealed statistically significant differences (all P < 0.001).

In 2022, Tian'an Bio, as a participating research unit in the National 14th Five-Year Plan Major Science and Technology Special Project, undertook the research on "Development and Safety Evaluation of New Fertility-Sparing Treatment Regimens for Gynecologic Malignancies."

Notably, in May 2024, the Chinese Expert Consensus on the Application of Topical Immunomodulators for Persistent High-Risk Human Papillomavirus Infection (hereinafter referred to as the “Consensus”), jointly developed by 27 clinical gynecology, epidemiology, and virology experts across China, was officially published in the Chinese Journal of Obstetrics and Gynecology. The release of this Consensus not only contributes to responding to the “Healthy China 2030” initiative and the WHO’s goal of “eliminating cervical cancer by 2050,” thereby reducing the incidence of cervical precancerous lesions and cervical cancer caused by persistent HR-HPV infection, but also provides academic guidance for the standardized clinical application of topical immunomodulators (Nr-CWS).

Overall, the four major therapeutic advantages constitute the product strength moat of Red Card®—

Scientific Basis of Etiological Treatment:HPV exhibits high epitheliotropism, and HPV infection is non-systemic. In light of this characteristic, advanced immunotherapy concepts are employed to clear the HPV virus by enhancing local cervical immunity, thereby replacing traditional disinfection-based products and surgical approaches, with a profile of safety and no side effects.

Superiority of Therapeutic Efficacy:NMPA-approved biological agent; endorsed by China’s most authoritative official guidelines for evidence-based pharmacological treatment of HPV and CIN, achieving a 91% efficacy rate in clearing persistent HPV infection and a histological normalization rate of over 95% in HSIL.

Efficacy of Route of Administration:Professional nurses administer medication to allow the drug to act directly on the lesion site, enabling precise treatment for the management of cervical lesions and clearance of HPV infection.

Rationality of the Topical Medication Course:A 20-day treatment course, compared to the three-month regimen required by other products, significantly reduces the duration of medication administration for patients and alleviates their anxiety.

Building on this foundation, Shenyang Shengbaokang Biological Pharmaceutical Co., Ltd. is also expanding the application scenarios and exploring further possibilities for Hongka®.

In 2019, Tian’an Bio collaborated with Peking University School of Stomatology to evaluate the efficacy and safety of Hongka® in treating oral erosive lichen planus, a condition classified by the World Health Organization as a precancerous lesion. In 2021, Tian’an Bio initiated a multicenter collaborative study on “Hongka® for the Treatment of Diabetic Wounds.” Meanwhile, multiple research papers on Hongka® regarding HPV infection, cervical therapy, and basic research have been published in top-tier journals such as Frontiers in Immunology in the United States. Currently, Tian’an Bio is developing Hongka® as a new drug for the treatment of erosive oral lichen planus, diabetic foot ulcers, and radiation-induced skin ulcers. Additionally, Hongka® intimate care products have been confirmed for development and market launch, representing a novel application of an existing medication.

Furthermore, Hongka® has demonstrated remarkable efficacy in the treatment of radiation-induced skin ulcers. In August 2024, the Center for Drug Evaluation (CDE) of the National Medical Products Administration approved a clinical trial application for Hongka® in the treatment of radiation-induced skin injuries.

On the other hand, with the imminent completion and commissioning of Shenyang Shengbaokang Biological Pharmaceutical Co., Ltd.’s fully intelligent production base for red yeast rice-derived products, Hongka® is also leading the intervention for high-risk HPV into the era of “immunotherapy.”