Exclusive Interview with Adlai Nortye CEO Carsten Lu: Efficient Integration of Global Resources to Accelerate First-in-Class Oncology Drug Development

At the recently concluded 2019 European Society for Medical Oncology (ESMO) Annual Congress, Adlai Nortye presented the latest clinical findings of AN0025 in Barcelona, Spain, announcing its Phase 1b clinical data as a neoadjuvant therapy for locally advanced rectal cancer.

Current rectal cancer patients, particularly those at high risk of recurrence, urgently need new treatment options. In this study, AN0025 combined with standard therapy was used as neoadjuvant treatment for patients with high-risk locally advanced rectal cancer. Among 25 evaluable patients with high-risk locally advanced rectal cancer, nearly 40% either did not require surgery or achieved pathological complete response in postoperative specimens. In contrast, the best historical data for patients with similar enrollment criteria showed a rate of no more than 20%.

Dr. Lars Birgerson, Chief Development Officer of Adlai Nortye Biopharma and President and CEO of Adlai Nortye USA, stated at ESMO that AN0025 holds a unique leading position in the EP4 target research landscape. “Phase 1b clinical data have demonstrated the favorable tolerability of AN0025 in combination with chemoradiotherapy and as consolidation chemotherapy following radiotherapy, as well as encouraging clinical outcomes in the treatment of locally advanced rectal cancer.”

It was revealed that Adlai Nortye Biopharma plans to immediately initiate a randomized clinical trial of AN0025 in combination with radiochemotherapy. “We believe that its combination with multiple therapeutic modalities, including immune checkpoint inhibitors for the treatment of various solid tumors, holds significant application prospects,” pointed out Dr. Birgerson.

Adlai Nortye Biopharma, headquartered in Hangzhou, Zhejiang, began its transformation into an innovative drug developer in 2016. As a clinical-stage global biopharmaceutical company, it is dedicated to developing differentiated and innovative oncology therapeutics. In addition to AN0025, Adlai Nortye has two other investigational new drugs, AN2025 and AN1004, which are among the fastest-moving programs globally and are currently in clinical trials. How did a startup biopharmaceutical company achieve such remarkable clinical milestones in just over three years? Recently, VCBeat interviewed Lu Yang, Founder, Chairman, and CEO of Adlai Nortye, to explore this question.

Lu Yang, Founder, Chairman & CEO of Adlai Nortye

Lu Yang is a serial entrepreneur, and Adlai Nortye Biopharma represents his third venture in the biopharmaceutical sector. In his previous two startups, Lu Yang led his teams to rapidly secure industry leadership through a steady, precise, and decisive strategy—a playbook for success that he is now continuing at Adlai Nortye Biopharma.

“2019 was a pivotal year for Adlai Nortye Biopharma and for me personally, as well as a year of fruitful achievements.” Lu Yang was extremely busy in 2019; our interview could only be conducted during the brief interval between his two flights.

Progress of Adlai Nortye’s Clinical Pipeline

In January of this year, Adlai Nortye Biopharma entered into an agreement with global pharmaceutical giant Merck & Co. to jointly conduct clinical trials evaluating the combination of AN0025 and pembrolizumab (Keytruda®) for the treatment of solid tumors. Lu Yang told VCBeat that combination therapy has become a prevailing trend in oncology drug development. By seizing this opportunity to collaborate on the clinical co-administration of AN0025 with a blockbuster monoclonal antibody, Adlai Nortye is well-positioned to significantly facilitate the future expansion of AN0025’s indications and market reach.

Engaging in clinical collaborations with multinational pharmaceutical giants is one of Lu Yang’s efficient strategies for new drug development. “Through such partnerships, the company can achieve rapid growth.” Adlai Nortye Biopharma has collaborated with leading international pharmaceutical companies, including Merck & Co., Novartis, and Eisai Co., Ltd. of Japan. In just over three years, the company has built a product pipeline with international competitiveness and accelerated the clinical development of its products.

In February, Adlai Nortye Biopharma’s other clinical-stage investigational new drug, the oncolytic virus product AN1004 (Pelareorep), received clinical trial approval from the National Medical Products Administration (NMPA). An open-label, randomized, multicenter Phase III clinical trial of Pelareorep in combination with paclitaxel for the treatment of advanced/metastatic breast cancer will be conducted in China.

According to Lu Yang, a Phase II clinical trial of pelareorep for metastatic breast cancer found that its combination with paclitaxel doubled overall survival in patients with ER+/PR+/HER2- breast cancer. Furthermore, the U.S. FDA has approved the use of a Special Protocol Assessment (SPA) for its Phase III clinical trial in metastatic breast cancer and granted it Fast Track designation.

In March this year, Adlai Nortye Biopharma presented preclinical data on AN2025 (Buparlisib), a potential therapeutic agent for head and neck squamous cell carcinoma (HNSCC, hereinafter referred to as “head and neck cancer”), at the 7th International Conference on Innovation in Head and Neck Cancer. Currently, although the combination of immune checkpoint inhibitors and chemotherapy is becoming the first-line treatment regimen for head and neck cancer, approximately 80% of patients still experience disease progression after treatment. AN2025 specifically addresses the substantial unmet clinical need in the second-line treatment setting for head and neck cancer. Data indicate that AN2025 holds significant potential for treating tumors that are non-responsive or resistant to PD-1 inhibitors.

In fact, prior to this, AN2025 had already been granted FDA Fast Track designation and is poised to enter global multicenter Phase III clinical trials. Lu Yang pointed out that animal study results indicate AN2025 can be used in patients whose disease progresses after first-line immunotherapy, “which represents a significant unmet clinical need.”

“AN2025 is the company’s most advanced product in its current R&D pipeline,” Lu Yang told VCBeat. The company is preparing for Phase III clinical trials of AN2025, which are planned to enroll nearly 500 patients at more than 120 sites worldwide, with the product expected to reach the market in 2022.

In Lu Yang’s words, Adlai Nortye is striving to participate in the global oncology treatment revolution through its strategic layout in the field of tumor therapy. “In terms of preclinical research, we have accumulated more than ten preclinical candidate compounds, represented by AN3005 (an intravenously administered STING agonist) and AN4005 (an oral PD-L1 inhibitor).”

New drug development carries a very high risk of failure. Lu Yang mitigates this risk through a multi-pipeline strategy, noting, “After weighing the risks, we can achieve a balance where ‘if one area underperforms, another may succeed.’”

In Lu Yang’s strategic plan, Adlai Nortye Biopharma has two products poised to enter global multicenter Phase III clinical trials, with another two products about to enter the clinical development stage. He aims to drive the annual entry of 1–2 novel original drugs into clinical trials, thereby establishing a sustainable development model that enhances clinical efficacy and mitigates risks through a diversified pipeline portfolio across different stages.

Secondly, we aim to foster synergies between our products under development and existing marketed immune checkpoint inhibitors, as well as among our own product portfolio. “There are numerous indications in the oncology field. The company’s oncology therapeutics feature broad-spectrum activity. As clinical research progresses, the specific indication areas for each product will become increasingly defined. Overlapping indications across multiple products will constitute the primary focus of the company’s future market strategy.”

Finally, in terms of R&D strategy selection, Lu Yang organically integrated independent research and development with external licensing. By leveraging external licensing, Adlai Nortye Biopharma rapidly enriched its product pipeline, thereby mitigating the risks associated with prolonged drug development cycles. Meanwhile, the company strengthened its in-house R&D capabilities, accelerating the progression of licensed products into subsequent clinical stages while providing the core momentum for sustainable corporate growth.

Around 2015, China’s innovative drug industry entered a golden age of development. Against the backdrop of numerous national policies and supporting regulations introduced to encourage drug innovation, an increasing number of overseas-returning professionals came back to start businesses in China, while industrial support services such as contract research organizations (CROs) became increasingly sophisticated. “It can be said that the timing, geographical advantages, and human resources were all in place.” Lu Yang has always believed that developing innovative drugs is not something that can be achieved through individual efforts alone.

Since its founding over three years ago, Adlai Nortye Biopharma has established an international R&D and management team. Its executive leadership and core R&D team, comprising more than 30 professionals, are all from top-tier global pharmaceutical companies. Most of these scientists held managerial positions at major multinational pharmaceutical firms, where they were engaged in preclinical project research and clinical development.

In Lu Yang’s view, there are three main reasons why Adlai Nortye Biopharma attracts talent. First, Adlai Nortye is driven by its mission to transform cancer into a chronic disease or even achieve a cure. In recent years, oncology treatment technologies, particularly tumor immunotherapy, have witnessed rapid advancements. Scientists, recognizing the potential for cancers to be cured or managed as chronic conditions in the future, have flocked to join the entrepreneurial wave in oncology therapeutics.

Second, Adlai Nortye fosters a highly open corporate culture. Lu Yang stated that although he may not match these scientists in terms of specialized expertise, he is eager to learn, engage in collaborative discussions with them, and fully consider their opinions and insights.

Furthermore, Lu Yang aims to build Adlai Nortye Biopharma into a world-class biopharmaceutical company. Developing innovative drugs with global competitiveness has been a principle established by Lu Yang since the inception of Adlai Nortye Biopharma. In his view, new drugs that merely involve slight modifications to the chemical structures of breakthrough medicines cannot generate genuine market competitiveness. “Products must be based on approval for marketing through European and American drug regulatory authorities, and must be innovative drugs capable of meeting clinical needs and achieving global sales.” Undoubtedly, such positioning holds greater appeal for these returnee scientists.

“We will launch our IPO plan at the appropriate time.” Lu Yang’s vision for Adlai Nortye Biopharma’s future development path has become increasingly clear. Previously, Adlai Nortye Biopharma completed its Series A and Series B financing rounds in 2015 and 2018, respectively, raising tens of millions of U.S. dollars in total. The company is currently undergoing its Series C financing round.