Exclusive Interview with Frost & Sullivan Entrepreneurs
True Biology was established inIn 2012, the company was a biotechnology enterprise driven by innovative research and development, focusing on the development, production, and commercialization of innovative drugs for major diseases such as viral infections and tumors. The company adheres to the orientation of meeting unmet clinical needs, concentrates on the fields of antiviral and anti-tumor research, and is committed to addressing key challenges such as drug resistance and insufficient efficacy through mechanism innovation. The company's core management team has rich experience in international innovative drug research and development and transformation, providing solid support for continuous innovation.
In the field of viral infections, the company's core product Azvudine has been conditionally approved for useHIV infection and COVID-19 treatment, with the latter becoming the first domestically approved oral drug in this field. Moreover, Azvudine, with its dual mechanism of 'inhibiting viral replication + immune regulation,' shows potential clinical value in areas where immunological recovery is incomplete. The ongoing product CL-197 has long-acting characteristics and is expected to achieve once-weekly dosing, improving treatment compliance.
In the oncology field, the company has expanded its antitumor indications around AZD9291 and is advancing its collaboration withThe development of PD-1 monoclonal antibody combination therapies aims to break through the limitations of current immunotherapy. In addition, the company is simultaneously deploying innovative directions such as non-camptothecin structure TOPO1 inhibitors, ADCs, and peptide radioconjugated drugs (PRCs), developing unique drug pipelines targeting tumor resistance and heterogeneity.
Real Biotech has established a complete production and commercialization system, with core products achieving wide terminal coverage. In the future, the company will continue to advance the development of innovative pipelines to enhance clinical value and accessibility.
Against this backdrop, Frost & Sullivanfrost &Frost & Sullivan, hereinafter referred to as 'Frost & Sullivan', invited Dr. Du Jinfan, Chairman, CEO and CSO of Zhenre Biology, to participate in a dialogue and exchange, focusing on the company's R&D strategy and product layout.
Exclusive Interview Guest PROFILE 
·Dr. Du Jinfa
·Chairman of Real Biotech
·CEO and CSO
·Recognized by the Chinese government"National Distinguished Expert"
One of the inventors of the revolutionary hepatitis C treatment drug sofosbuvir
The drug has been hailed asThe Galen Prize, known as the 'Medicine Nobel Prize'.
The contribution to the treatment of hepatitis C has been hailed by the journal Cell as one of the most significant public health achievements of our time.
01
Focus on unmet clinical needs and build an innovative R&D system driven by both antiviral and anti-tumor strategies
@Frost & Sullivan China Healthcare Business Unit
In your previous career, you have been involved in the research and development of key drugs for AIDS treatment- Enquetiapine, this drug is still one of the main medications used for treating AIDS patients globally. Later, the hepatitis C cure drug sofosbuvir was developed, creating significant social and economic benefits. Looking back on this experience, what is your deepest takeaway? How have these experiences influenced your return to China?
@Dr. Du Jinfang
The most profound realization is that when making medicine, one must create products that can truly address unmet clinical needs and benefit human health. This cannot be achieved without genuine pharmaceutical innovation. Innovation requires the courage to be ahead of others and to venture into uncharted territories.
Challenging the impossible has always been a core aspect of my new drug research and development practice. At Zai Lab, before embarking on each project, we ask: What is the most troubling issue for patients in this field, and how do we solve it? Therefore, in response to unmet clinical needs, we have deployed a series of unique drug pipelines.
@Frost & Sullivan China Healthcare Business Unit
Real Biotech has long focused on antiviral and anti-tumor fields. Could you please share the company's core judgments on research and development direction choices? How does the company identify tracks with truly unmet clinical needs? Additionally, the company has established nucleoside drugs,The TOPO1 inhibitor and XDC, as well as other diversified R&D platforms, how do these platforms collaborate with each other, and what key roles have they played in enhancing the overall R&D success rate?
@Dr. Du Jinfang
Real Biotech focuses on the fields of antiviral and anti-tumor research, with R&D directions centered on unmet clinical needs. It prioritizes the layout of disease tracks with high disease burden, prominent drug resistance issues, and existing therapeutic bottlenecks, focusing on solving key pain points that have not been met clinically.
Among them, the nucleoside platform serves as the underlying core, fully exploring the value of Azvudine in anti-infection and anti-tumor applications, focusing on unmet clinical challenges such as immune reconstruction deficiency and immunosuppression.
New non-hypogalatinizing agentsTOPO1Inhibitor platform, overcoming traditional toxin resistance from the source, available as a monotherapy or as part of a new generationADC high activity toxin;
XDCDual load platform layoutADCs coupled with peptide radionuclides (PRCs) target innovative targets that have not yet been addressed by drugs in the oncology field, offering innovative solutions for tumor heterogeneity and resistance development.
The three major platforms form a collaborative R&D pattern through underlying technology interoperability, complementary mechanisms, and resource sharing, providing continuous support for the company's long-term innovative development.
02
Deepen antiviral strategies, expand on immune reconstruction deficitsThe therapeutic value of INR) and leads the innovative direction of long-acting HIV
@Frost & Sullivan China Healthcare Business Unit
Azvudine, the core product of the company, has been commercially launched in the field of antiviral therapy and has accumulated relatively sufficient data in clinical trials and real-world settings. How do you evaluate its clinical value and competitive advantage within the current treatment system?
@Dr. Du Jinfang
Azvudine, with its low dose, high activity, dual target, and immunomodulatory comprehensive characteristics,The HIV treatment system has unique advantages and broad clinical value.
Clinical trial data shows,Azvudine 3 mg has an antiviral effect comparable to lamivudine 300 mg, achieving effective viral suppression at a low dose. At the same time, the drug has dual targets to inhibit viral replication.+The unique mechanisms of immunomodulation not only enrich existing treatment options but alsoThe global unmet need for HIV immune reconstitution provides an important research direction and potential solutions.
@Frost & Sullivan China Healthcare Business Unit
Why do real organisms focus on immune reconstitution insufficiency?Regarding the issue of (INR), how do you view the clinical value and future treatment directions in this field?
@Dr. Du Jinfang
ImmunodeficiencyINR is a globally recognized clinical challenge in the field of HIV treatment, with significant unmet needs.
According to the 'Guidelines for the Diagnosis and Treatment of AIDS in China ((2024 Edition). After ART treatment, the immune abnormalities of some patients can return to normal or near-normal levels, achieving immune function reconstruction. However, there are still 10% to 40% of patients who cannot fully achieve immune reconstruction even after long-term viral suppression. Compared with those who have achieved complete immune reconstruction, these patients have a higher incidence and mortality rates of opportunistic infections, non-AIDS complications, tumors, etc. Currently, there is a global lack of effective treatment drugs for patients with incomplete immune function reconstruction, and there is an urgent unmet clinical need.
Related work has been carried out by real organismsAccording to IIT research, positive data were observed in subjects after treatment with Azvudine, which will be further validated through larger-scale clinical studies, aiming to provide new treatment pathways for this field.
03
Give full play to the advantages of dual mechanisms, promote combined immunotherapy, and expand the space for tumor indications
@Frost & Sullivan China Healthcare Business Unit
Azvudine has expanded its application scope from the field of anti-infection to anti-tumor therapy,How does the 'dual mechanism' play a role in tumor treatment? What are its unique advantages?
@Dr. Du Jinfang
Azvudine passes"Direct tumor suppression+immune regulationThe dual mechanism exerts a broad-spectrum anti-tumor effect. On one hand, azvudine can terminate DNA chain elongation and interfere with the function of enzymes related to cancer cell nucleic acid synthesis, directly inhibiting tumor cell proliferation. On the other hand, it can reduce the infiltration of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and promote CD8⁺ T cells, CD4⁺ T Cell infiltration and proliferation reshape the immunosuppressive microenvironment, activating the body's own anti-tumor immune response.
Compared with anti-tumor drugs that rely solely on a single mechanism, azvudine combination therapy can achieveThe synergistic effect of '1+1>2' can particularly transform 'cold tumors' into 'hot tumors', breaking through the bottlenecks of immune therapy resistance and non-response, and possesses significant differential advantages in the treatment of broad-spectrum solid tumors.
@Frost & Sullivan China Healthcare Business Unit
this yearIn February, the clinical trial of azvudine combined with PD-1 monoclonal antibody for the treatment of advanced solid tumors was approved by the National Medical Products Administration. What are the core considerations behind the company's decision to advance this combination therapy? How do you evaluate the potential for this combination regimen to be applied in a broader patient population?
@Dr. Du Jinfang
Our choice for this direction is mainly aimed at breaking through the current clinical bottlenecks in immunotherapy. Taking colorectal cancer as an example, there are approximatelyRMB 2.03 million, of which approximately 95% are microsatellite-stabilizing (MSS) patients. These patients are basically ineffective with PD-1 monotherapy and face the dilemma of having no effective immunotherapy options for a long time.
A clinical trial initiated by a researcher has shown that azvudine in combinationPD-1 inhibitors and anti-VEGFR drugs are used for patients with microsatellite stable colorectal cancer who have received multiple lines of treatment: In the non-liver metastasis subgroup, the disease control rate was 100% in the higher dose group, the objective response rate was 40%, and the average treatment duration reached 33.9 weeks, showing positive data in terms of clinical efficacy and treatment persistence.
Based on clear mechanism synergy and positivityIIT data suggests that this combined approach holds promise for transforming 'cold tumors' into 'hot tumors', breaking through the immune treatment bottleneck for refractory tumors such as MSS colorectal cancer, and has significant application potential in a broader population of patients with advanced solid tumors.
04
Focusing on the challenges of drug resistance and heterogeneity, we are building a diversified conjugation and small molecule innovation platform
@Frost & Sullivan China Healthcare Business Unit
companyThe TOP1 inhibitor platform adopts a non-camptothecin structure and has an advantage in overcoming drug resistance. What is your view on the strategic significance of this platform in next-generation anti-tumor drugs?
@Dr. Du Jinfang
Currently exceedsEighty percent of ADC drugs use taxanes as their toxins, and most of these drugs develop resistance after a period of treatment. We aim to develop a drug with a completely new chemical structure to provide an effective solution for this type of drug-resistant tumor.
Preclinical research results indicate that the newTopo1 inhibitor, ZSSW-136, has an inhibitory activity against drug-resistant tumors that is 400 times greater than that of irinotecan in patient-derived xenografts. In animal models of drug-resistant tumors, it can completely inhibit tumor growth. The results of this study are currently being published. Notably, it can be used alone as a small molecule compound for drug development or as the toxin of a new generation of ADCs, leading to the development of a series of novel ADCs antitumor drugs effective against existing ADC-resistant tumors.
@Frost & Sullivan China Healthcare Business Unit
In the field of novel conjugated drugs, the company has made arrangementsIn the ADC and PRC directions, such as PSMA dual payload ADCs and GRPR-targeted PRC pipelines. Why did the company choose these two targets?
@Dr. Du Jinfang
The company's layout in the field of novel conjugated drugs always focuses on innovative targets that have not yet been addressed in oncology, aiming to meet unmet clinical needs and develop innovative solutions for the challenges of tumor heterogeneity and resistance.
Among them,PSMA is a validated antigen with high tumor specificity, limited expression in normal tissues, and efficient internalization capabilities. Based on the characteristics of this target, ZS-1005, a dual payload ADC candidate drug with an innovative mechanism, has been designed by Zhenbio. It currently exhibits excellent tumor growth inhibitory capabilities and good safety profiles in mouse models of prostate cancer and other diseases.
andGRPR is expressed at low levels and in limited distribution in normal tissues, but it is highly expressed in various human solid tumors including lung cancer, breast cancer, prostate cancer, some gastrointestinal tumors, and neuroblastoma. It may be involved in promoting tumor growth and progression, making it a highly promising therapeutic target. Our candidate drug ZS-2004, developed based on this target, has observed excellent efficacy and safety data in animal trials and is currently undergoing further preclinical studies.
@Frost & Sullivan China Healthcare Business Unit
real organismsWhat are the core technical advantages of ADC 'Dual Payload' design? What specific value can it bring to clinical practice?
@Dr. Du Jinfang
Dual payload design is a key technological innovation for real organisms to cope with tumor heterogeneity and resistance risks.In the ADC field, this design achieves simultaneous killing of tumor cells in different cell cycles by precisely delivering two toxins with different mechanisms of action to tumor cells. It also takes into account antigen-expressing and antigen-lowly expressing subpopulations, effectively addressing the challenges posed by tumor heterogeneity.
At the same time, this strategy can delay or overcome the risk of single pathway resistance at the source. The synergy of these two mechanisms is expected to enhance the therapeutic index and safety margin, providing a more durable response for clinical practice. This design aims to ensure the effectiveness and safety of treatment, further improving long-term benefits for patients.
05
From product commercialization to industry evolution, gain insights into future technology trends and competitive landscape
@Frost & Sullivan China Healthcare Business Unit
From a commercialization perspective, what do you believe are the company's most core strengths in terms of production capacity, access, and channels? Especially against the backdrop of the gradual advancement of Azvudine's new indications, how will these strengths be translated into future growth drivers?
@Dr. Du Jinfang
From a commercialization perspective, the company has established an integrated, replicable, and rapidly scalable commercial support system across three major sectors: production capacity, access channels, and distribution networks. This can provide a stable guarantee for the long-term development of Azvudine and the company's overall innovation pipeline.
Firstly, there is guaranteed self-production capacity through scale-up and compliance. The company has completedGMPCertify a modern production base with stable and large-scale supply capabilities, capable of supporting the sales of existing indications and rapid expansion of new indications in the future. Ensure that supply, quality, and costs are controllable.
Secondly, the medical insurance access and price advantage are prominent. Azvudine has been included in the national medical insurance catalog, with stable prices and significant policy and cost advantages. This enhances the accessibility of the drug, laying the foundation for its rapid hospitalization and increased usage in new indications.
Thirdly, in terms of channels and commercialization capabilities, the company has established a commercial network covering medical institutions nationwide, off-campus platforms, and online platforms. It has also assembled a professional team with relevant experience, capable of providing implementation and promotion support for more innovative products based on AZD307.
At the same time, Zhenre Biology adheres to its commercial strategy of 'rooted in China, radiating globally'. Focusing on the global layout of Azvudine, it targets advantageous markets such as Africa, Southeast Asia, Europe, and America. Through localized cooperation and rapid registration, it achieves overseas presence, expands cross-regional revenue sources, and ensures sustainable profitability. Subsequently, with the clinical breakthrough of Azvudine in new indications such as tumors, combined with the cooperation and expansion of innovative pipelines such as ADCs, PRCs, and TOPO1 inhibitors, it further opens up larger market spaces, forming a matrix of core product iteration + innovative pipeline, serving as a long-term growth engine through collaboration.
