First Patient Achieves Over 3 Years of Cancer-Free Survival with Boya Bio's Non-Viral PD1-Targeted CAR-T Therapy BRL-201

Sep 27, 2023 16:00 CST Updated 16:00

BRL Medicine

Cell and Gene Therapy Drug Developer

Recently, BRL Medicine Inc. (hereinafter referred to as "BRL Medicine"), which focuses on gene and cell therapy, has collaborated with the First Affiliated Hospital of Zhejiang University School of Medicine to carry outThe World's First"Clinical Trial of PD1 Knockout Non-Viral Site-Specific Integration CD19-CART Cell Therapy for Relapsed and Refractory Non-Hodgkin's Lymphoma"First Patient Subject"Mr. Sun"(Pseudonym)Completed the latest follow-up, all examination items met the standards, and the disease remained in continuous complete remission.Cancer-free survival for over 3 years to date.It is worth mentioning that the CAR-T treatment product Mr. Sun received is developed by BRL Medicine based on its independent research and development.Non-viral Site-specific Integration CAR-T Platform (Quikin CART)^®）Targeting CD19The non-viral PD1-CAR-T product (pipeline code: “BRL-201”) is the world's first autologous CAR-T cell product that achieves targeted integration of the genome at the PD1 site and knocks out the PD1 gene without using a viral vector.This research achievement was published on August 31, 2022, in the international top journalNatureIt was published and rated as "One of the Ten Major Research Advances in Hematology in China in 2022" and "Major Medical Progress in China in 2022".

"Breaking the Shackles of Relapse and Refractory Conditions, Reigniting the Hope of Life"

In April 2018, Mr. Sun from Guangdong began to experience the darkest moment of his life. After discovering a lump on his neck that did not disappear, he went to the First Affiliated Hospital of Guangdong Pharmaceutical University for examination. Following imaging observations and a biopsy of the neck lump, Mr. Sun was diagnosed with "diffuse large B-cell lymphoma." What he thought would be a routine check-up left the 40-year-old Mr. Sun feeling despair for the first time in his life. "When the doctor confirmed that I had malignant lymphoma, I completely fell apart. This result was something I never expected. Normally, I am someone who rarely catches a cold. I thought after decades of hard work, my career had finally entered an upward trajectory, and it was time to enjoy the fruits of my success, but suddenly I was plunged into an abyss. However, for the sake of my wife and children and their support and encouragement, I have to face the treatment positively."Mr. Sun recalled.

As a result, Mr. Sun underwent two years of cancer chemotherapy and received multiple rounds of different chemotherapy regimens during this period. However, the treatment outcomes were unsatisfactory, as the disease briefly improved but then relapsed.Mr. Sun stated,"At that time, I lived in a third- or fourth-tier city in Guangdong, more than 200 kilometers away from the nearest provincial capital, Guangzhou. Looking back on those two years of traveling for chemotherapy, it was truly an unforgettable experience. The support from family and friends kept me going. After completing the first round of chemotherapy, the original tumor had receded, but subsequent PET-CT scans showed residual areas that still needed to be addressed, meaning complete remission hadn’t been achieved. A few months later, the tumor regrew in the same place. Then, in early 2020, the cancer cells began to metastasize to the stomach and mesentery. Following multiple episodes of severe gastric bleeding, I underwent a total gastrectomy, which caused significant inconvenience in daily life and brought immense suffering. At that point, my attending physician said that if no new targeted drug became available, I likely only had a few months left."Fortunately, after many twists and turns, I contacted Dean Huang He of the First Affiliated Hospital of Zhejiang University School of Medicine. Luckily, I was able to join the clinical study on CAR-T treatment that he is conducting in collaboration with BRL Medicine, which has allowed me to extend my life. Now, I can even see my son get admitted to Tsinghua University—it feels like a dream. I am very grateful to the doctors and BRL Medicine for giving me a chance to be reborn.”

"Mr. Sun's" recent lifestyle photos show that he has fully regained his health after receiving BRL-201 CAR-T therapy, frequently engaging in sports and traveling, and enjoying a normal life.

BRL-201 Shows Significant Efficacy, Tumor Cell Lesions Completely Disappear

In May 2020, Mr. Sun, as the first patient in the BRL-201 clinical trial, officially received cell infusion. To date, he has achieved complete remission (CR) and has been cancer-free for over three years.Before receiving BRL-201 treatment, Mr. Sun was a patient who had undergone 14 rounds of chemotherapy, 20 rounds of radiotherapy, a total gastrectomy, and had lymphoma metastasized throughout the body, with the disease progressing to the terminal stage; in the most recent follow-up, all of Mr. Sun's blood tests and PET-CT scans met the standards, his condition has stabilized, and he has now embarked on a healthy life.

Seeing patients receive treatment, recover, and return home, Dean Huang He, the Principal Investigator (PI) of this clinical study, stated:"Non-Hodgkin lymphoma is a malignant tumor of the hematologic system that originates in lymphoid tissue, accounting for 80%-90% of all lymphomas. Although patients often achieve remission after initial treatment, recurrence frequently follows. Despite the approval of CAR-T products for clinical treatment of relapsed or refractory non-Hodgkin lymphoma, the overall efficacy remains limited. However, based on the results of this clinical study,BRL Medicine's Non-Viral Targeted Integration CAR-T Product Demonstrates Excellent Safety and Efficacy in Clinical Treatment.The first patient, Mr. Sun, was discharged after being hospitalized for only 14 days. No drug-related adverse events of grade 2 or higher were observed during the entire CAR-T treatment process, including the most common cytokine release syndrome and neurotoxicity associated with CAR-T therapy.After infusion, CAR-T cells can rapidly expand in the body and persist for a prolonged period.Three years have passed, and there are no cancer cells in the patient's body. The CAR-T cells are still patrolling and monitoring lymphoma, bringing long-term benefits to the patient. Besides Mr. Sun, more than twenty other patients have participated in this project, all achieving good results. Currently, the registered clinical trial of BRL Medicine’s non-viral CAR-T cell therapy is proceeding actively, showing significant efficacy for specific types of lymphoma. It is hoped that it will be launched soon to benefit patients. At the same time, we hope that BRL Medicine can develop more and better products for a wider range of indications to help more cancer patients.

BRL Medicine InnovativeCAR-T Therapy: A Promising Future

BRL-201TherapySafer, More Effective, More Accessible。BRL-201, indicated for relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL), is developed using BRL Medicine's self-developed non-viral targeted integration CAR-T platform (Quikin CART).^®) The CAR-T product developed by BRL Medicine received IND approval in China on December 14, 2022, officially entering the registration clinical stage.

Product Advantages:

Low cost, can benefit more patients

BRL-201 utilizes the 2020 Nobel Prize-winning CRISPR/Cas9 gene editing technology to precisely edit the PD1 site in T lymphocytes and insert a CAR molecule targeting CD19 in tumor cells, all without the use of viral vectors. The non-viral production process significantly reduces the high costs associated with using viral vectors and simplifies the complex manufacturing process.

Fast preparation, suitable for patients with rapid progression

From the perspective of production technology, the preparation time for traditional CAR-T products is relatively long, which significantly increases the waiting time for patients in need of treatment. It also means that such CAR-T products cannot be used for patients with very fast tumor progression. However, BRL Medicine's BRL-201 product adopts a non-viral manufacturing method with a simple process. In just one step, it achieves both sustained CAR expression and regulation of endogenous genes in T cells, greatly reducing the overall preparation time for CAR-T products. The preparation can be completed in as little as three days, significantly improving production capacity and allowing timely treatment for patients with rapidly progressing tumors.

Safer, ensuring the uniformity of the product

Non-viral targeted integration allows each CAR sequence to be precisely inserted into a specific site of the genome, avoiding the oncogenic risks caused by random insertion and maximizing the safety and efficacy of the CAR-T product. In the BRL-201 clinical trial (IIT) for the treatment of relapsed/refractory non-Hodgkin lymphoma, no CAR-T-related neurotoxicity or cytokine release syndrome above grade 2 was observed in the 21 patients treated, demonstrating the excellent clinical safety of BRL-201.

More Effective, Breaking the Shackles of Recurrence and Refractoriness

Clinical research results of BRL-201 have demonstrated the product’s outstanding clinical efficacy, representing the best clinical outcomes in terms of high remission rates and low toxicity side effects among global CAR-T cell therapies for refractory and relapsed lymphoma to date. The long-term benefits for patients are significantly higher than those of existing similar virus-based CAR-T products. According to the latest clinical data, the mPFS has improved from 2.9-12.8 months (existing virus-based CAR-T) to 20.8 months (BRL Medicine's BRL-201 CAR-T). Single-cell sequencing results indicate a high proportion of memory T cells within the BRL-201 cell product, which exhibit enhanced anti-tumor immune function, allowing the infused CAR-T cells to persist over the long term.

As a company focusing on the research and development and transformation of gene therapy and cell therapy drugs, BRL Medicine has been adhering to technological innovation, continuously overcoming industry barriers, and implementing a multi-pipeline strategic layout. In the future, BRL Medicine will continue to focus on patients and work with clinical experts to fully promote the transformation and implementation of multiple clinical research results, providing better treatment options for a wide range of patients and benefiting patients with genetic diseases, malignant tumors, and autoimmune diseases worldwide.

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About BRL Medicine

BRL Medicine Inc. is committed to becoming a global leading cell and gene pharmaceutical company in the era of new commercial civilization. With the mission of "leading innovation with gene editing technology, developing breakthrough therapies, and benefiting all humanity," BRL Medicine, relying on its self-developed center and the "Shanghai Gene Editing and Cell Therapy Research Center" co-built with universities, has generated more than 100 patent achievements so far. Five projects are conducting investigator-initiated clinical trials in eight well-known hospitals, three projects have been approved for IND and have officially entered the registration clinical trial stage, and several other projects are in the IND application stage. Among them, gene editing therapy for β-thalassemia, non-viral...PD1Site-specific integration CAR-T, as well as UCART and other projects, have achieved excellent clinical results, demonstrating global leadership andNature、Nature Medicine、Nature biotechnology...and published multiple academic papers in well-known academic journals. BRL Medicine has established five proprietary technology platforms: a gene-editing technology innovation platform, a hematopoietic stem cell platform, a non-viral targeted integration CAR-T platform, a universal cell platform, and an enhanced T-cell platform. It also owns a 7000-square-meter GMP pilot production base and a nearly 200-person operations team, effectively ensuring that innovative research achievements can be quickly transformed and applied. BRL Medicine continuously drives rapid updates and iterations of its R&D products based on patient needs and clinical feedback. With an open, sharing, and win-win attitude, BRL Medicine is working with global innovative biopharmaceutical ecosystem companies to accelerate the transformation and implementation of innovative drugs for the benefit of patients worldwide suffering from genetic diseases, malignant tumors, and autoimmune disorders!

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