In the initial story, VGX-3100 carried great hope and aura.

Unlike preventive vaccines from companies such as Merck and GSK, VGX-3100 is a therapeutic vaccine aimed at clearing high-risk HPV-16/18 infections and reversing related precancerous lesions. Its core competitiveness lies in its unique mechanism of action and delivery system.

The vaccine is based on synthetic DNA encoding HPV virus E6/E7 proteins, and is introduced into the human body through intramuscular injection supplemented by electric pulse delivery technology. Electric pulses can instantly form microchannels on the cell membrane, greatly improving the efficiency of DNA molecules entering the cell and the subsequent sustained expression level of antigens. The DNA vector selected during design poses no risk of integration into the human genome, ensuring basic safety.

After entering the cell, DNA will guide the synthesis of E6/E7 cancer proteins, thereby activating the body's specific CD8+T cell immune response, while linking CD4+B cells to participate in immune regulation, accurately killing HPV infected cells, and potentially forming long-term immune memory, thereby reducing the risk of recurrence from the root.

Inovio designed two key phase III trials for VGX-3100- Reveal1 and Reveal2, with the core objective of validating its therapeutic efficacy for high-grade squamous intraepithelial lesions (HSIL) of HPV-16/18 positive cervix.

In March 2023, the Reveal2 trial data was released, instantly casting a shadow over this vaccine. Due to the small sample size, the difference between the preset biomarker positive patient subgroup and the placebo group did not reach statistical significance. Dramatically, in the original population, the medication group achieved the primary endpoint with a response rate of 28.6%.

This' self defeating 'was interpreted by the market as a' clinical setback ', and Inovio's stock price plummeted on the same day, casting a big question mark on the global outlook of VGX-3100.

However, few people have noticed that behind this "disappointment" data lies a key positive signal: among all enrolled subjects, the HPV virus clearance rate in the VGX-3100 treatment group reached 37.3%, and 27.6% of patients achieved both virus clearance and lesion regression, both of which were significantly better than those in the placebo group.

More importantly, this trial confirms for the first time the feasibility of therapeutic HPV vaccines reversing precancerous lesions by activating the immune system.

The FDA has seen positive efficacy signals in the trial, but also pointed out that in order to consider approval, VGX-3100 needs to undergo at least another confirmatory trial in the biomarker positive population.

In the face of high additional investment, Inovio, which is highly financially constrained, has finally decided not to advance clinical trials for indications for cervical precancerous lesions in the United States in 2023, and has placed its hopes on Beijing Oriental Life Sciences in China.

Based on the potential of effectiveness and safety data, Dongfang Lue has chosen to rise to the challenge and vowed to rewrite the treatment pattern of HPV with VGX-3100.

As early as 2018, Dongfang Lue reached an agreement with Inovio to acquire exclusive rights to the production, sales, and development of VGX-3100 in China (including Hong Kong, Macau, and Taiwan).

The huge unmet demand is an important consideration for Eastern Strategy.

In 2020, WHO officially launched the Global Strategy for Accelerating the Elimination of Cervical Cancer, which sets three core goals for 2030: achieving a 90% HPV vaccination rate for 15-year-old girls, a 70% coverage rate for high-quality cervical cancer screening for women under the age of 45, and a 90% coverage rate for the treatment of cervical cancer and precancerous lesions.

As a high-risk country for cervical cancer, China's prevention and control work began in the late 1990s, and in 2023, the "Action Plan for Accelerating the Elimination of Cervical Cancer (2023-2030)" was introduced, elevating it to an important level of the "Healthy China" strategy.

In the chain of cervical cancer prevention and control, high-grade squamous intraepithelial lesions (HSIL) are the precursor lesions of cervical cancer, and their effective treatment is the key to blocking cancer progression. According to Frost&Sullivan data, there are over 7 million patients with cervical precancerous lesions infected with HPV-16/18 in China, and the actual number of patients treated exceeds 2 million.

At present, the mainstream surgical therapies in clinical practice, such as LEEP knife and cold knife cone cutting, can quickly remove visible lesions, but there is a clear "treatment ceiling": not only is it an invasive operation, but it can also cause permanent damage to the cervix, leading to postoperative complications such as bleeding and infection. Moreover, it can only treat local lesions and cannot eliminate latent HPV virus, resulting in a postoperative recurrence rate of up to 15% -30%, which puts the improvement of treatment coverage in a dilemma of "treating symptoms without addressing the root cause".

More importantly, in recent years, cervical cancer has gradually become younger, and preserving fertility has become an urgent need for cervical cancer treatment.

In contrast, non-surgical treatment options such as VGX-3100 provide a new pathway to protect cervical tissue while curing lesions.

This strategy does not require traumatic operations and aims to eliminate the virus at its root, reverse lesions, and provide long-term protection by inducing immune memory, especially suitable for young women with fertility preservation needs. Meanwhile, its operation is relatively simple and easier to promote in primary healthcare institutions, providing a feasible path for substantially improving the treatment coverage of cervical precancerous lesions.

In 2021, Dongfang Lue launched an independent multicenter, randomized, double-blind, placebo-controlled phase III clinical trial of VGX-3100 in China, focusing on the Asian population. By June 2025, all 207 patients had been enrolled in the trial, and as expected, the data will be unblinded in the second quarter of 2026.

This means that if positive results are obtained, the achievement of VGX-3100, the first HPV therapeutic vaccine for cervical precancerous lesions, is expected to be realized in China. And Dongfang Lue and Fosun Pharma will also lead their peers for at least a five-year window period.

Public information shows that there have been over 90 related clinical trials worldwide, involving more than 30 candidate products, but no product has been officially approved for marketing so far.

VGX-3100 carries the hope of curing HPV, and the core requirement of therapeutic HPV vaccines is to eliminate infected cells, which relies on a strong and long-lasting cellular immune response, which is the natural home ground of the DNA platform.

The DNA platform emerged in the early 1990s, with genetic engineering mediated DNA delivery triggering immune responses as its core. It was the first to achieve breakthroughs in the field of veterinary biopharmaceuticals, landing four approved vaccines and verifying the commercial feasibility of the technology.

Unfortunately, the first generation DNA vaccines with naked plasmids as the core have low delivery efficiency and limited antigen expression, making it difficult to stimulate sufficiently strong immune responses, especially in cellular immunity, which did not fully meet expectations.

In recent years, the immunogenicity of DNA vaccines has been significantly improved in clinical trials through the introduction of delivery technologies such as promoter optimization, codon adjustment, and electroporation. Research has been conducted in areas such as infectious disease prevention and cancer immunotherapy, especially in the "primary immunization enhanced" immunization strategy, which has shown potential and become an important development branch of nucleic acid diagnosis and treatment technology in the biopharmaceutical field.

The outstanding advantage of DNA vaccines lies in their high safety, as they do not rely on chemical delivery systems such as lipid nanoparticles, thereby avoiding potential carrier accumulation toxicity risks. In addition, due to its low cost and storage resistance, DNA vaccines are particularly suitable for areas with limited adaptation resources.

In contrast, the advantages and limitations of mRNA platforms are equally evident. MRNA technology has demonstrated unparalleled research and development speed in response to sudden infectious diseases, and has achieved great success in the field of preventive vaccines. However, in terms of therapeutic vaccines for chronic infections (such as HIV, HPV) or cancer, they have not yet accumulated clinical validation results of the same scale, and their long-term immune efficacy and safety still need more data to be confirmed.

However, traditional technological pathways such as peptide and protein vaccines have inherent deficiencies in immunogenicity, limited strength in inducing cellular immunity, and difficulty in ensuring the persistence of immune responses, often requiring repeated administration for reinforcement. This is a significant shortcoming in the treatment of chronic infectious diseases.

This difference in mechanism determines the unique strategic value of DNA platforms in the field of therapeutic vaccines.

Based on its unique administration method and the mechanism advantage of inducing broad and persistent cellular immunity with specificity, in addition to HPV related lesions, the DNA platform provides a potential technological option for disease fields such as chronic viral infections and tumor immunotherapy through antiviral and anti-tumor cell immunotherapy.

It should be pointed out that DNA platforms also have clear technical difficulties. Due to the large molecular weight of plasmid DNA, simple injection is difficult to efficiently penetrate the cell membrane and enter the cell interior, making delivery efficiency a key bottleneck that restricts its effectiveness.

The intelligent electric pulse delivery system adopted by Dongfang Lue forms reversible micropores on the cell membrane through millisecond level electric pulses, which can significantly improve the efficiency of DNA cell introduction and effectively solve the core bottleneck of DNA vaccine delivery. It is currently one of the validated key enabling technologies in this field.

If VGX-3100 passes the critical validation period, the commercialization of DNA therapy vaccines is expected to open up, and the treatment of various diseases including HPV will enter a new era.

Thanks to the DNA drug development platform, the imagination of VGX-3100 goes far beyond HSIL.

This vaccine mainly activates human cellular immunity and has therapeutic potential for multiple organs in the human body affected by HPV infection or cancer. Currently, it has obtained Phase II clinical approvals for multiple indications such as anal precancerous lesions and vaginal precancerous lesions.

It is worth mentioning that VGX-3100 is the first clinical therapy for the above-mentioned diseases in China. Moreover, the development of this therapy for indications such as precancerous lesions of the external genitalia and tumors of the oral and pharyngeal regions has also been planned.

In addition to VGX-3100, Dongfang Lue has also laid out multiple pipelines for therapeutic DNA vaccines targeting chronic persistent infections and tumors on this technology platform.

Dongfang Lue's deep cultivation and meticulous research and development of VGX-3100 and DNA platform is not an isolated case, but rooted in a comprehensive rise and innovation leading Chinese new drug ecosystem.

The passive pattern of 'approval from abroad and China following suit' is gone forever, and China is transitioning from innovation 'following' to 'leading'.

According to the National Healthcare Security Administration, by 2025, China's pipeline for developing and innovating new drugs will account for 30% of the world's total, ranking second in the world; Significant achievements have also been made in terms of market launch, with 11 new drugs approved in China, including 4 independently developed by our country. According to other data, from 2015 to 2024, China's original research and development of innovative drugs accounted for 24% of the global market, second only to the United States, becoming an important force in the source innovation of global innovative drugs.

The leap in clinical research capabilities has become the core support for the rise of innovative drugs in China.

At the ESMO Annual Meeting in 2025, 448 Chinese research abstracts were selected (accounting for 15.3% of the global total), with 35 oral presentations and 23 breakthrough abstracts being outstanding. At the recently concluded 2026 JPM conference, China's power once again reached its peak, with over 30 pharmaceutical companies appearing and 7 making their voices heard at the main venue.

It is worth mentioning that China's IIT research has gained recognition and reference from the American industry and regulatory authorities. Fudan GEB-101, Huaxi WGc-0201 and other IIT studies have successfully obtained FDA clinical trial approval, and their efficient clinical translation models have been referenced by American pharmaceutical companies and regulatory agencies, promoting the optimization of their own clinical processes and actively seeking cooperation, completely reversing the previous situation of China's unilateral borrowing from the West.

It is evident that from submitting case reports 20 years ago and conducting limited bridging trials 10 years ago, to now leading international multicenter research and appearing at top global events, China's clinical research has achieved a revolutionary leap and continues to lead the world in scale and efficiency.

The National Medical Products Administration revealed that in 2026, precise measures will be taken to strengthen service support for innovative drugs with new mechanisms and targets throughout the entire chain of communication and exchange, clinical trials, registration and application, and review and approval, in order to help innovative drugs make their debut in China. This means that the regulatory level changes from following the FDA to daring to be the first in the world, which is bound to promote a new round of local innovation.

The story of Dongfang Lue saving the "first HPV therapeutic vaccine" is a representative of the rise of "Eastern" power. The 'hard bones' that make overseas give up are rejuvenating on the fertile ground of innovation in China and are expected to reach new heights.