Kaidi Medical Targets the Multi-Billion-Dollar Solid Tumor Market with Precision Antigen Selection and CAR Library Platform

Since the advent of cellular immunotherapy, the treatment of hematological malignancies has become a highly competitive "red ocean" market fiercely contested by pharmaceutical companies. The presence of single targets and well-defined mechanisms of action has drawn numerous innovative enterprises to the hematologic oncology sector. However, in clinical practice, approximately 90% of cancer incidence is attributable to solid tumors, making the solid tumor treatment market a hundred-billion-RMB industry that significantly surpasses that of hematological malignancies.

Despite the enormous market potential, a significant gap persists in actual clinical practice. Unlike CAR-T therapy for hematological malignancies (e.g., acute lymphoblastic leukemia), which already has the clinically validated drug Kymriah on the market, solid tumors have yet to yield any immunotherapy modalities that have truly "broken through." Consequently, clinical management of solid tumor patients remains largely confined to conventional chemotherapy and radiotherapy, alongside interventions such as immune checkpoint inhibitors and targeted therapies.

Compared to hematologic malignancies, the challenges in developing immunotherapies for solid tumors lie in how to overcome the immunosuppressive effects of the tumor microenvironment, how to facilitate the infiltration of immune cells into the tumor interior, and how to enable immune cells to undergo massive proliferation and exert potent cytotoxic effects after penetrating the tumor tissue. All of these factors constitute the technical barriers in the development of anti-solid-tumor therapeutics.

These challenges present precisely the opportunities that Nanjing Kaidi Biotechnology Co., Ltd. has identified. Dr. Dai Hongjiu, founder of Kaidi Biotech, holds a Ph.D. from the Institute of Life Sciences, Chinese Academy of Sciences. He subsequently conducted postdoctoral research at the University of Illinois, the University of California, and the University of Nebraska-Lincoln, focusing on cancer pathogenesis, GPCRs and neurodevelopment, and T-cell immunity. He has established a profound research foundation in cellular immunotherapy and the mechanisms of solid tumor development; subsequently, Dr. Dai transitioned into the industry as a Senior Scientist at GenScript Biotech, where he accumulated extensive experience in both scientific research and industrial applications.

Dr. Dai Hongjiu, Founder of Kaidi Medical, Co-Authors Research Featured on the Cover of *Science*

“In my view, live biotherapeutics are highly promising therapeutic agents. While most conventional drugs are cleared after undergoing metabolism in the human body, live biotherapeutics are the only class of drugs capable of in vivo expansion and sustained persistence. Particularly driven by advances in synthetic biology, live biotherapeutics in cell and gene therapy will represent a major trend of our era,” Dr. Dai Hongjiu said. “Moreover, there remains a significant gap in the clinical treatment of solid tumors. Influenced by environmental and dietary factors, the number of cancer patients in China continues to rise year by year. Yet, patients still lack access to optimal clinical medications and a satisfactory treatment experience, which has become my founding mission for establishing Kaidi Medical.”

Conquering cancer is by no means an easy task; it is no exaggeration to say that its difficulty is as immense as constructing the International Space Station.

Referring to the aforementioned numerous barriers in conquering solid tumors, Dr. Dai Hongjiu explained that, first, we must ensure that the living drug (CAR-T) can rapidly expand in vivo; second, we must guarantee that CAR-T cells can effectively traffic through the bloodstream. Once these two fundamental prerequisites are secured, we must then focus on equipping CAR-T cells with superior tumor infiltration capabilities and ensuring their sustained persistence within the tumor.

Based on this therapeutic rationale, Kaidi Medical is primarily focusing its efforts in two directions to tackle solid tumors: 1- Development of tumor-specific targets; 2- Screening of CAR library constructs, 3- Universal CAR R&D platform.

Kaidi Medical's Anti-Cancer Solutions

In terms of target selection, Kaidi Medical has independently developed a tumor-specific target platform “FIS-SAGS^TM”, screening for highly specific tumor targets, such as those that are highly expressed on the surface of tumor cells but are not expressed or are expressed at low levels in normal tissues. Secondly, regarding the CAR library, Kaidi Medical has developed a CAR library construct screening platform, "KD-SmCAR^TM", the library contains numerous antibody sequences, intracellular signaling domains, and related components that were independently discovered and engineered by the company and are protected by proprietary intellectual property rights, which can be used to screen for the most suitable CAR construct for viral packaging and transduction into immune cells.

Through this platform-based screening approach, a stringent selection process can identify the most optimal specific targets and CAR molecules. In 2016, Nanjing Kaidi Biotechnology Co., Ltd. successfully established this technological platform, enabling the company to screen through hundreds to thousands of target libraries and isolate molecules with the most favorable data across all parameters. Dr. Dai Hongjiu, the company’s founder, vividly describes it as a proprietary IP platform. By permuting and combining different functional sequences, a vast, IP-protected candidate library is constructed.

Based on the “FIS-SAGS” tumor-specific target development platform, Kaidi Medical has initially targeted the NKG2DL target. Kaidi Medical is also the only company in China to hold full intellectual property rights for the CAR targeting this target.

NKG2D is one of the primary activating receptors on natural killer (NK) cells that mediates target cell cytotoxicity by binding to NKG2D ligands (NKG2DL) on target cells. There are eight known NKG2D ligands, primarily comprising MICA, MICB, and ULBP1-6. These ligands are highly expressed on the surface of various tumor cells, such as HCC, GBM, and PC, but are virtually undetectable in normal human tissues. The binding affinity between NKG2D and its ligands ranges from 10⁻⁸ to 10⁻⁷ M. Consequently, targeting NKG2DL enables highly efficient tumor cell killing with essentially no toxicity to normal tissues.

Focusing on the NKG2DL target, Kaidi Medical has independently developed the KD-025 clinical pipeline. Founder Dr. Dai Hongjiu stated that KD-025 is undergoing simultaneous dual filing in both China and the United States. Considering the differing commercial prospects of specific oncology markets in each country and the urgency of improving patient survival outcomes, KD-025 will primarily focus on clinical research and regulatory submissions for glioma in the U.S., while in China, it will concentrate on liver cancer and colorectal cancer.

In the eradication of gliomas, Kaidi Medical has completed the world's first preclinical breakthrough study on KD-025, demonstrating its ability to specifically eradicate gliomas and glioma stem cells. The tumor clearance efficacy reached 100%, enabling long-term tumor-free survival in animal models. The related research findings have been published in the *Journal for ImmunoTherapy of Cancer* (Impact Factor: 13.751), filling a domestic gap and providing an urgently needed therapeutic option for patients with advanced malignant glioma.

In the field of liver cancer, Kaidi Medical's KD-025 pipeline has completed the world's first breakthrough preclinical study, achieving an efficacy rate of over 80% in specifically eliminating liver cancer cells. CAR-T cells derived from liver cancer patients demonstrate in vivo tumor-killing efficacy equivalent to those derived from healthy donors. Currently, research in this area is rarely reported domestically or internationally; however, Kaidi Medical published its research findings in the academic journal *Cancer Immunology Research* (Impact Factor: 11.151) as early as 2019, filling a domestic research gap.

Dr. Dai Hongjiu, founder of Kaidi Medical, told VCBeat that the company’s most advanced pipeline candidate, KD-025, is currently in the expedited IND application stage. It is expected to obtain approval in the third quarter of 2022, after which clinical trials will be initiated sequentially. In addition to KD-025, Kaidi Medical has also developed KD-182, an oncology pipeline targeting gastric and pancreatic cancers, based on its core technology platform. KD-182 is also expected to complete its IND filing and enter clinical trials by the end of next year or early the following year.

Focusing on the patients themselves, and considering urgent clinical needs as well as patient well-being during treatment—this was the most profound takeaway from my conversation with Dr. Dai Hongjiu, founder of Kaidi Medical. “Kaidi Medical does not aim to develop a blockbuster drug in a red-ocean market that subjects patients to a grueling treatment regimen of repeated infusions. Instead, we prioritize simplifying the drug’s manufacturing process, lowering production costs, and keeping pricing within patients’ financial reach. We are committed to ensuring that patients who have exhausted all other clinical options can benefit from our therapies, and that they can complete their treatment through a simpler administration route.”

Kaidi Medical 2700M²GMP R&D Center

We have every reason to believe that new drugs developed from a patient-centric perspective will ultimately be widely accepted by the market. Kaidi Medical is also progressively developing cutting-edge cellular therapies for solid tumors, including off-the-shelf CAR-T, dual-target CAR-T, CAR-NK, and CAR-MO. Focusing on the R&D of novel CAR-T therapies and antibody-based drugs for solid tumors, the company is simultaneously advancing the development of broad-spectrum mRNA vaccines for COVID-19. To date, it has filed dozens of patent applications and secured 8 granted patents.

It is reported that Nanjing Kaidi Biotechnology Co., Ltd. has secured tens of millions of RMB in funding and is currently undergoing a new round of financing valued at hundreds of millions of RMB. The raised capital will be primarily allocated to accelerating IND applications for its pipeline portfolio, constructing a GMP R&D center, covering personnel expenses, and other related initiatives.

As the investor behind Kaidi Biotechnology,Wang Haining, Founding Partner, Longmen CapitalAgreed: "CAR-T cell therapy has emerged as one of the most prominent research directions in the life sciences in recent years, and is also one of the tracks most concentrated with pharmaceutical innovation projects. Although many companies are engaged in CAR-T research, their efforts are predominantly focused on hematological malignancies, resulting in severe target crowding."

Since its inception, Kaidi has been dedicated to CAR-T therapy research for solid tumors, conducting extensive and valuable work in target identification, sequence optimization, and genetic engineering. Its publications and data are highly compelling, and its clinical studies are robust and rigorously conducted.

"When we first invested in Kaidi, the company was still in its early stages, but Dr. Dai gave me a strong sense of alignment. He possesses an excellent scientific and industrial background and is one of the most driven scientists I have ever encountered. Within the highly complex CAR-T ecosystem—spanning research, clinical development, and CMC—it is precisely this relentless drive, coupled with solid and rigorous scientific research, that makes breakthroughs possible. We also look forward to Kaidi’s continued innovation and hope to see its novel therapies reach the market at the earliest opportunity."

Longmen Capital is a specialized venture capital institution in the pharmaceutical and healthcare sector, focusing on early-stage and growth-stage investments in pharmaceutical and biotech innovation. The team members possess interdisciplinary academic backgrounds in medicine, pharmacy, biology, and finance, along with extensive experience in healthcare venture capital and industry operations. Since its establishment in 2017, Longmen Capital has invested in over 30 innovative healthcare enterprises, with assets under management nearing RMB 3 billion.