Science

Who can ride the cycle? The "Saga" of CAR-T therapy in China

Legendary Bio was founded in Nanjing in 2014, and was incubated internally by Kingsray Bio, the "world's largest gene synthesis" provider. At the beginning, Legendary Biologics was located in Nanjing, doing research quietly and was once unknown.

What really made Legendary Biologics "break the circle" was its heavyweight partnership with multinational giant Johnson & Johnson in 2017.

At the end of February 2022, Legendary Biologics' BCMA-targeting CAR-T product, Cedar Key Orenzai (CARVYKTI), was officially approved by the FDA and is the first CAR-T product approved for marketing in the United States in China. This is an epoch-making milestone for China's cellular gene therapy industry.

Legendary Biologics is targeting the potential of cell therapy in treating diseases that are considered incurable, such as hematological malignancies, solid tumors and infectious diseases.

Development History

Who can ride the cycle? The "Saga" of CAR-T therapy in China

▲Legendary Biology Major Milestones

2014

Legendary Bio was established

2016

First patient with relapsed, refractory multiple myeloma (RRMM) treated clinically with LCAR-B38M, China, March

2017

Results of an ongoing early clinical trial of LCAR-B38M presented at the ASCO Congress in June

Signed a global partnership and licensing agreement with Janssen, a pharmaceutical company owned by Johnson & Johnson, in December

2018

In March, the Phase II IND (clinical study application) for LCAR-B38M passed NMPA review

In May, the FDA approved the Phase Ib/II IND for JNJ-4528

2019

In April, the European Medicines Agency (EMA) granted PRIME certification to cilta-cel priority drugs

In December, the US FDA granted cilta-cel Breakthrough Therapy Designation (BTD) certification

2020

In May, announced a collaborative research and licensing agreement with Noile-Immune Biotech

In June, Nasdaq IPO, raising $487 million, known as "the first CAR-T stock in China"

In August, cilta-cel received CDE (Center for Drug Evaluation) approval for breakthrough therapies

2021

Received accelerated review of FDA and EMA Biologics License Application (BLA)/Marketing Authorization Application (MAA) for cilta-cel in February

In June, announced the establishment of a high level manufacturing site in Belgium to expand global manufacturing capabilities for innovative cellular therapies

In September, based on an IND application approved by the U.S. FDA, will begin a Phase I clinical trial of investigational cell therapy LB1901 for the treatment of adults with relapsed/refractory peripheral T-cell lymphoma (PTCL), or cutaneous T-cell lymphoma (CTCL)

2022

In February, Legendary Bio's self-developed CAR-T product cilta-cel was approved for marketing by the FDA, becoming the first original Chinese CAR-T cell therapy product to be marketed in the US.

Financing History and Equity Structure

As a majority-owned subsidiary of Kingsley Biologics, Legendary Biologics has a relatively concise financing history with only three milestones including the IPO, although each of them has been good.

  • In March 2020, received $150 million in strategic investment from Hudson Bay Capital, Johnson & Johnson Ventures, Eli Lilly Asia Fund, Vivo Capital, RA Capital and others. Valued at $1.95 billion after the investment.
  • In June 2020, the Nasdaq IPO went public, raising $487 million.
  • In May 2021, we received $500 million in strategic financing from High Tide Capital, and High Tide took a stake in Kingsley Biologics and Legendary Biologics, a subsidiary of Kingsley.

Who can ride the cycle? The "Saga" of CAR-T therapy in China

According to the announcement made by Kingsway Biologicals in May 2021, Kingsway Biologicals currently holds 52.12% equity interest in Legendary Biologicals, which is the holding company of Legendary Biologicals, while High Tide Capital holds 9.45% equity interest in Legendary Biologicals.

Management Team

By the end of 2021, Legendary Bio has 1,000+ employees in the US, China and Europe.

In terms of management structure, Legendary Biologics is structured into two lines, the U.S. and China, coordinated by Dr. Ying Huang, CEO and CFO.

In terms of the background of the executive team, experience in multinational pharmaceutical giants is basically the standard.

Legendary Biologics' executive team has undergone several upheavals.

In 2018, Dr. Yuan Xu joined Legendary Biologics as Chief Executive Officer. Prior to joining Legendary Biologics, Dr. Yuan Xu served as Senior Vice President at Merck Sharp & Dohme in the US, where he was responsible for R&D and commercialization. Under Yuan Xu's stewardship, Legendary Bio's U.S. team has rapidly expanded and made significant progress in the development of CAR-T products.

In June 2020, Legendary Bio was successfully listed on the NASDAQ market in the United States.

In August 2020, Kingsway announced that Dr. Yuan Xu resigned for personal reasons. And Dr. Fangliang Zhang, the founder of Legendary Biologics Holding Company - Kingsray Biologics, resigned as CEO of Kingsray and took over the role of CEO and CEO of Legendary Biologics.

Who can ride the cycle? The "Saga" of CAR-T therapy in China

Dr. Zhang Fangliang's experience is quite legendary.

  • From 1995-2002, Dr. Fangliang Zhang served as Chief Scientist at Schering-Plough (acquired by Merck Sharp & Dohme).
  • In 2002, Dr. Fangliang Zhang co-founded Kingsway Biologicals, which was listed on the Main Board of the Hong Kong Stock Exchange in 2015. Currently, Kingsway Biologics has a market capitalization of HK$56.9 billion. (Market capitalization is as of June 21, 2022)
  • In 2014, he founded Legendary Biologics, a subsidiary of Kingsley Biologics, to expand the business scope of Kingsley Biologics. Dr. Fangliang Zhang has served as Chairman of the Board of Directors of Legendary Biologics since May 2015.

Dr. Fangliang Zhang holds a PhD in Biochemistry from Duke University.

In September 2020, Dr. Fangliang Zhang was placed under residential surveillance due to the "smuggling controversy". Legendary Biologics changed its CEO in a hurry again and was replaced by Chief Financial Officer Ying Huang. At the same time, the position of Chairman of the Board of Legendary Biologics was replaced by Wang Ye.

In November 2020, Fangliang Zhang was arrested on suspicion of smuggling goods that are prohibited by the import and export regulations of Chinese law.

In February 2021, Fangliang Zhang was released on bail by the regulatory authorities, and at the time of Kingsway's announcement, no formal charges had been filed against him.

On May 2, 2022, Kingsway announced that Dr. Fangliang Zhang, Nanjing Kingsway Biotechnology Co., Ltd. and three employees and one former employee who had handled the Group's import and export activities had been notified by the Zhenjiang Municipal People's Procuratorate that the investigation had been reviewed and the Procuratorate had decided not to bring any proceedings against any entity or individual thereof. Dr. Fangliang Zhang is back at liberty as a non-executive director of Kingsway and the chairman of the Risk Management Committee and the Strategy Committee.

Who can ride the cycle? The "Saga" of CAR-T therapy in China

Dr. Ying Huang has served as Legendary Bio's Chief Financial Officer since July 2019 and as Chief Executive Officer since September 2020. on December 30, 2021, Dr. Ying Huang joined Legendary Bio's Board of Directors as a Class I Director.

Before joining the legendary

  • As Managing Director and Head of Biotech Equity Research at Bank of America Securities from August 2014-July 2019, he led a team of analysts covering more than 30 biotech companies, including Amgen, Gilead, Sunbase, Boeing Health and others.
  • Prior to joining Bank of America Securities, he worked at Wells Fargo (formerly Associated Bank), Credit Suisse, Gleacher and Barclays.
  • Earlier, he was the Chief Scientist of Schering-Plough's (now Merck Sharp & Dohme) Chemical Research Division, focusing on the development of small molecule drugs in the therapeutic areas of cardiovascular and central nervous system, and co-author of several patents and peer-reviewed publications.

Dr. Ying Huang studied at the Junior Program of the University of Science and Technology of China and Columbia Business School, and received his PhD in Bioorganic Chemistry from Columbia University.

Who can ride the cycle? The "Saga" of CAR-T therapy in China

Sally Wang has served as Chairman of the Board of Legendary Bio since November 2020.

From Wang Ye's experience at Legend Bio Holdings' parent company Kingsway Bio, she is a marketing "warrior".

  • From August 2002, when he joined Kingsray as Sales Account Manager to his current position as Chairman of Legendary Biologics, Wang has held various positions at Kingsray, including Sales Account Manager, Director of Sales and Marketing, Vice President of Operations, Executive Vice President of Operations, Chief Operating Officer, and President.

Meanwhile, Wang Ye graduated from Wuhan University with a B.S. and M.S. in Microbiology, and also worked as an environmental monitoring engineer at Futian District Environmental Protection Monitoring Station in Shenzhen from July 1993 to July 2000. After joining Kingsley, Wang received a Master's degree in Computer Science from the University of Bridgeport in 2003 and an Executive MBA from China Europe International Business School in 2014.

Core Technology Executives

Legendary Biologics has built a global research team of over 370 researchers who identify potential cellular targets and create and evaluate a broad portfolio of product candidates.

As the "first major inventor of CAR-T technology in China", Dr. Xiaohu Fan, the original co-founder and chief scientist of Legendary Biologics, is the main supporter of its CAR-T product technology.

However, on April 2, 2022, Legendary Bio announced the appointment of Dr. Guowei Fang as Senior Vice President, Global Head of Research and Early Development, replacing Dr. Xiaohu Fan, who left the company on March 30. Dr. Guowei Fang will be responsible for directing Legendary Biologics' research and development efforts in China, the U.S. and Ireland, advancing a multiple pipeline of products targeting hematologic and solid tumors.

Dr. Guo-Wei Fang has extensive experience in the fields of oncology and immunology.

  • Prior to joining Legend, he served as Senior Vice President of Research and Development at Zymeworks, where he was responsible for novel technology platform development and the development of multifunctional biologics and antibody drug coupling combinations.
  • Previously, served as head of R&D at Pharmacyclics, an AbbVie company, where he led discovery and early development efforts.
  • Prior to joining Pharmacyclics, he worked at Genentech and AbbVie, focusing on oncology research and discovery.

Dr. Guowei Fang received his PhD in biochemistry, cell biology and tumor biology from the University of Colorado at Boulder and did his postdoctoral research in cell biology and cancer biology at Harvard Medical School. Prior to entering the pharmaceutical industry, Dr. Fang taught at Stanford University, where he led the cancer research program.

Who can ride the cycle? The "Saga" of CAR-T therapy in China

Dr. Lida Pacaud joined Legendary Biologics in January 2021 as Vice President of U.S. Clinical Development.

Prior to joining Legendary Biologics, he served as Global Clinical Program Leader and Executive Medical Director of Novartis' Cell & Genetics Division, where he led the clinical development of KYMRIAH, the world's first approved CAR-T therapy. Prior to that, Lida worked at Roche and Wyeth.

Dr. Lida Pacaud holds an MD degree and pediatric certification from the Tbilisi State Medical University and was trained in pediatric oncology and hematology in France.

Commercialization Executives

Who can ride the cycle? The "Saga" of CAR-T therapy in China

Steve Gavel has served as Vice President of Business Development for Legendary Biologics USA and Europe since July 2018. He has over 28 years of commercial experience in biotech startups, leading pharmaceutical and medical device organizations.

  • Previously, Gavel worked at Sunbase (acquired by BMS) where he led the commercial development activities of the bb2121 program for CAR-T in the US.
  • Prior to joining Sunbase, he served as Senior Marketing Director at Takeda Pharmaceuticals' Oncology Division, where he led the marketing strategy and execution of Takeda's best-selling drug VELCADE.
  • Earlier, he held several sales, marketing and market access leadership positions at Syntex, Immunex, Johnson & Johnson and IMS Health.

Gavel received his bachelor's degree in finance and business administration from Millersville University in Millersville, Pennsylvania, USA.

Who can ride the cycle? The "Saga" of CAR-T therapy in China

Chong Yang has served as vice president of business development for Greater China since July 2018.

Previously, held a variety of sales and marketing leadership roles with increasing responsibilities at multinational pharmaceutical companies including Roche Oncology, Bayer Oncology and Novartis Oncology. Has over 17 years of commercial experience and extensive expertise in promoting and launching products including GLIVEC, NEXAVAR, AVASTIN and RITUXAN in the China market.

Yang Chong received his medical degree from Nanjing University, China, and served his surgical residency at Zhongda Hospital, Southeast University, China.

Product Pipeline

Legendary Bio's goal is to advance the use of cellular therapies in hematological oncology, solid tumors, and infectious diseases. And Legendary Bio's product pipeline is thus built.

Nature of R&D (self-research/introduction)

Who can ride the cycle? The "Saga" of CAR-T therapy in China

▲Legendary Bio Product Pipeline

Among all of Legendary Biologics' pipeline, the most advanced is the CAR-T product cetakiolensai (CARVYKTI, cilta-cel), which targets BCMA, the CAR-T product approved for the U.S. market in late February 2022.

In addition to Cedar Key Orenside, Legendary Bio's pipeline includes eight other CAR-T cell therapy products entering the clinic, as well as an undisclosed program targeting infectious diseases.

Among them.

  • LB1905 is exploring allogeneic CAR-T therapies.
  • LB1902, LB1904 and LB1908 are being explored for efficacy in solid tumors, mainly in the direction of gastric and breast cancers.

Product Technology

Who can ride the cycle? The "Saga" of CAR-T therapy in China

▲ 4 core technologies of Legendary Bio

Legend Bio currently has four core technologies: CAR-T, including universal CAR-T; TCR-T; CAR-NK; and γδ-T. All are cutting-edge technologies in cell therapy.

CAR-T cells and TCR-T cells are both genetically engineered T cells.

CAR-T cell therapy, which works by recognizing membrane surface antigens (e.g. CD19, BCMA, etc.), is highly effective in hematological tumors. Several companies have been working hard to try to break the bottleneck in solid tumors. Several CAR-T products have been approved.

TCR-T technology, the main mechanism is to enable the modified T cells to express TCR (T cell receptor) that effectively recognizes tumor cells, thus directing the T cells to kill the tumor cells. Only one product has been approved worldwide.

  • On January 25, 2022, the FDA approved Kimmtrak for use in adult patients with HLA-A*02:01 positive unresectable or metastatic uveal melanoma (mUM). The product was developed by Immunocore, a British biotechnology company.

CAR-NK technology, through genetic engineering modifications, expresses chimeric antigen receptors (CARs) on the surface of NK cells that can bind to tumor-specific antigens and specifically recognize tumor cells with specific antigens after infusion, triggering an immune response to remove tumor cells. Currently, CAR-NK cell therapy is at the earliest clinical stage.

T cells are divided into two major categories, αβ T cells (e.g. CD4, CD8, etc.) and γδ T cells, depending on the TCR. Human peripheral blood lymphocytes are dominated by αβ T cells, and γδ-T cells generally account for only 1%-5%. γδ-T cells, the natural surveillance cells of the immune system, are capable of identifying and targeting tumor cells. γδ-T cells also play a role in bridging the innate and adaptive immune systems. γδ-T cell therapy is currently the most advanced and only in the clinic.

Product Pipeline Strategy

▐ Policy benefits, rapid testing of product candidates in patients

To encourage innovation, China's State Drug Administration (NMPA) has introduced a policy benefit: after consultation and under the supervision of a scientific advisory board and ethics committee, Chinese clinicians may initiate clinical testing of experimental cellular therapies in their hospitals without obtaining NMPA approval for formal experimental new drugs.

Legend works with clinicians and hospitals to conduct trials to international standards to support future global regulatory filings and partnerships. This approach allows Legend Bio to rapidly test Legend's product candidates directly in patients, quickly identifying promising candidates and advancing them to clinical trials for registration in China, the U.S., Europe and Japan.

Correspondingly clinically, Legendary Biologics has adopted a global clinical development strategy.

▐ Best-in-class product advancement to "frontline applications

Legendary Bio's CAR-T products are very potent.

In December 2021, Legendary Biologics presented the latest clinical data for cilta-cel at the ASH.

  • Results from the CARTITUDE-1 clinical trial showed that 97 patients with R/R MM treated with CARVYKTI achieved an overall remission rate (ORR) value of 98%, a complete remission rate (CR) of 83%, and a progression-free survival (PFS) rate of 61% at 24 months during a median follow-up time of 21.7 months.

Who can ride the cycle? The "Saga" of CAR-T therapy in China

These data reaffirm the product's best-in-class clinical trial data. Due to the strength of the product, cilta-cel has been granted Breakthrough Drug Designation/Orphan Drug Designation/Priority Drug Designation in several countries.

Who can ride the cycle? The "Saga" of CAR-T therapy in China

With the approval of cilta-cel in the U.S., Legendary Biologics will seek to advance cilta-cel to frontline therapies in approved indications in the future and, at the same time, seek approval for additional indications.

▐ Exploring "all the possibilities" of cellular therapy

Legendary Biologics will advance the development of cell therapy in other pipelines such as hematological tumors, solid tumors and infectious diseases to explore more possibilities of cell therapy - different development plans and related trials have been initiated for hematological tumors, solid tumors and infectious diseases.

  • In September 2021, Legendary Biologics has begun a Phase 1 clinical trial of its investigational cell therapy LB1901.

▐ Introduction of differentiated CAR-T production line

In addition to advancing its own products, Legendary Biologics has been very careful to collaborate on differentiated technologies.

In May 2020, Legendary Biologics announced a collaboration agreement with Noile-Immune Biotech, an innovative cancer immunotherapy biologic company.

  • Working together on two specific cancer targets, Legendary Biologics has the right to apply Noile-Immune's core PRIME (Proliferation inducing and migration enhancing) technology to its cell development pipeline to develop CAR-T and/or TCR-T cell therapies that secrete IL-7 and CCL19.

The principle of *PRIME technology is to genetically engineer T cells to express cytokines and chemokines (such as IL-7 and CCL19.) IL-7 can maintain T cell stability while promoting T cell proliferation, while CCL19 can recruit peripheral T cells and dendritic cells into lymphoid tissue.

  • At the same time, Legendary Bio will pay Noile-Immune approximately $70 million for a portion of the development, regulatory and commercial milestone payments, while Noile-Immune will also be entitled to royalties on commercial sales of the product.

This partnership with companies with differentiated technologies will be able to enrich its technological routes.

Business layout

The first commercial launch of Legend Bio's self-developed CAR-T product cilta-cel in the U.S. is another proof that Chinese innovative drugs have their own place in the international arena.

This is the first CAR-T product approved for marketing in the U.S. in China, and a key point in the transformation of Legendary Bio from Biotech to Bio Pharma eight years after its founding.

Product Commercialization

Who can ride the cycle? The "Saga" of CAR-T therapy in China

▲Kingsray Biologicals - Legendary Biologicals 2021 Revenue Data

Who can ride the cycle? The "Saga" of CAR-T therapy in China

▲ Legendary Bio 2021 Financial Data

In 2021, Legendary Biologics external revenue was $86.4 million, +14.1% year-over-year ($75.7 million for the full year 2020). Revenue is primarily derived from the continued recognition of upfront and milestone payments in Legendary Bio's partnership with Johnson & Johnson.

At the same time, Legendary Biologics had a net loss of approximately $390 million as it is still at the stage where the drug is just coming to market. Adjusted net loss was approximately $350 million.

  • The loss was primarily due to continued growth in cilta-cel clinical trials and product development expenses - including approximately $200 million for cilta-cel clinical trials in the U.S. and China; and $110 million in R&D expenses for other pipeline programs. Total R&D investment was $310 million, +34.9% year-over-year.

In 2022, Legendary Biologics completed the end-line commercialization filing for the CARVYKTI product, and Legendary Biologics and Janssen's commercialization team will soon begin sales of the product, with Legendary Biologics and Janssen jointly responsible for the marketing push and a 50:50 revenue split.

According to Dr. Ying Huang, CEO of Legendary Biologics, at the J.P. Morgan Health Forum earlier this year, Cedar Key Orenza is expected to advance into the early-line multiple myeloma treatment market in the future, with an expected peak sales of $5 billion.

  • CARVYKTI is priced at $465,000 in the U.S. market; Bristol-Myers Squibb's CAR-T product Abecma, which also targets BMCA, is priced at $419,500 and will generate $164 million in revenue in 2021.

Regional Commercialization

Who can ride the cycle? The "Saga" of CAR-T therapy in China

▲ Legendary Bio Production Base

Immediately following the commercialization approval, capacity building will also be one of Legendary Bio's priorities in the next phase.

  • Legendary Biologics has built GMP-grade manufacturing plants in the U.S. and China to supply CAR-T products for clinical trials.
  • The commercial GMP production facility in Raritan, New Jersey, USA is also operational.
  • is building future commercial capacity sites in Belgium and China. Among them, the Belgian production site was announced in June 2021 and is expected to be fully operational in 2023.

Commercialization Strategy

▐ Leveraging the power of top global pharmaceutical companies

The success of Legendary Biologics' model of "collaborating with a major international pharmaceutical company (Johnson & Johnson) to promote R&D & commercialization" points to a relatively feasible path for Chinese innovative drugs to go abroad.

At the 2017 American Society of Clinical Oncology Annual Meeting (ASCO), Legendary Biologics presented the results of its CAR-T cell therapy LCAR-B38M for multiple myeloma. The results showed an objective remission rate of 96% in 25 patients who participated in the treatment for more than one year. Because the research results were so outstanding, Legendary Biologics immediately became the talk of the town at that time. It attracted the attention of several pharmaceutical companies, including Johnson & Johnson.

In December 2017, Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, and Legendary Biologics signed a global strategic collaboration agreement to co-develop CAR-T cell therapies. Legendary Biologics became famous in one go.

  • Under the agreement, Legendary Biologics received an upfront payment of $350 million and is entitled to additional payments as development, manufacturing, regulatory and sales milestones are reached. Legendary Biologics and Janssen share costs and profits on a 50/50 basis in global markets other than Greater China, and on a 70/30 basis in Greater China (Legendary Biologics/Janssen).

Who can ride the cycle? The "Saga" of CAR-T therapy in China

▲Process of cooperation with Johnson & Johnson

Based on the milestones already reached, Legendary Biologics has received $600 million in upfront and milestone payments from Johnson & Johnson. It is recognized by the industry that Johnson & Johnson's participation has significantly enhanced the advancement of Cedar Key Orenza to market.

With the approval of the product, the channel will be "divided" between Johnson & Johnson and Legendary Biologics - Legendary will participate in the promotion of the product in the U.S., with Johnson & Johnson focusing on community sales and Legendary Biologics specializing in the promotion of the product in the U.S. hospital market.

▐ Ample cash reserves

Legendary Biologics currently has an overall strong cash reserve of.

  • At the end of 2020, Legendary Bio had cash reserves of $693 million.
  • At the end of 2021, Legendary Bio had cash reserves of $890 million.
  • In Q1 2022, Legendary Bio reached two combined $50 million milestones.

The focus of Legendary Biologics is on R&D, manufacturing and commercialization of cell therapy end-products. Sufficient cash reserves will not only help Legendary Biologics accelerate its pipeline, but also its commercialization.

▐ Forward-looking, multi-level layout of commercial production centers

For CAR-T products, manufacturing is a major challenge. This is evident from the production difficulties faced by Kymriah (from: Novartis), the world's first approved CAR-T product.

  • Novartis' Kymriah took patients an average of 52 days from leukocyte removal to infusion of CAR-T cells in the clinical trial (Belinda study), while Gilead Yescarta's clinical trial (Zuma-7 study) took patients 29 days.
  • Some data show that 40% of registered patients never receive Kymriah injections, and most pass away due to disease progression during the long manufacturing process.

And as you can see from the capacity building mentioned above, Legendary Biologics has built plants in layers based on preclinical, early commercialization, and potential future expansion, which lays the foundation for the commercialization it will undertake.

▐ Diversified commercialization team based on geography

Starting back in 2018, Legendary Bio began building its commercialization team.

In July 2018, Steve Gavel, Vice President of Business Development, U.S. and Europe, and Steve Gavel, Vice President of Business Development, Greater China, Legendary Bio

Yang Chong's appointment represents the beginning of Legendary Bio's preparation for commercialization.

With the approval of the product, Legendary Biologics priced the product at $465,000, which is higher than comparable marketed products (referring to targeted BCMA products). The pricing of the existing product is covered by both commercial and Medicare in the U.S. when considered in terms of ability to pay.

At the same time, Legendary Bio has recruited and built a small but sophisticated commercialization team in the past 6-9 months, mainly to develop large hospitals and treatment centers (similar to China's tertiary hospitals), with the goal of covering 75%-80% of such medical institutions in the US.

Challenges

Legendary Biologics also faces a number of challenges.

Challenge 1: Legendary Bio's own clinical trials and filing capabilities are in question

Because Cedar Key Orense is partnered with Johnson & Johnson, the industry has questions about Legendary Biologics' own ability to conduct clinical trials and filings.

The main reason for this is the slow clinical advancement in the domestic market.

  • In 2018, Cedar Key Orense became the first CAR-T product to enter the clinic in China. However, it has not been approved so far.
  • In contrast, Fosun Kite and WuXi Juno's CAR-T have been approved in China.

Legendary Biologics explained that initially there was no manufacturing site in China that needed to meet GMP standards, so the company spent some time on renovating the GMP-compliant manufacturing plant and production. In addition, there was a slight delay in patient enrollment in 2020 due to the impact of the new crown epidemic. Currently, Legend Bio is actively communicating with CDE to complete enrollment and filing.

Challenge 2: The successor to the product pipeline

Judging from the current production line, the successor of the legendary creature Sidaki Orense has not yet appeared.

The fastest progressing CAR-T product is currently targeting CD4, which entered Phase I clinical in September 2021.

Challenge 3: Can the team remain stable with a major change in senior management?

As mentioned in the previous executive update, shortly after Legendary Biologics' NASDAQ listing, Dr. Yuan Xu, who had served as CEO for more than two years, left the company in August 2020, followed by the "fiasco" of Dr. Fangliang Zhang, founder of Kingsway Biologics. Legendary Biologics sought to quell the stock price volatility by quickly replacing the Chairman of the Board as well as the CEO.

At the end of February 2022, Legendary Biologics CAR-T products were approved in the U.S. In early April 2022, the "soul" of Legendary Biologics, co-founder and Chief Scientific Officer Xiaohu Fan, left the company. In an interview after his departure, Dr. Fan Xiaohu said, "I will take a break and then start again, and will still focus on cell therapy in the future." This once again triggered a hot debate in the market.

Based on the fact that CAR-T is one of the areas where Chinese pharmaceutical innovation is most likely to be on par with the international market, the advancement of CAR-T has everyone's blood boiling.

But this innovative technology also needs more breakthroughs. Several breakthrough directions are currently recognized as follows.

(1) Develop generic CAR-T, improve the process of CAR-T, and make CAR-T a drug that is "well used and affordable".

(2) Use of CAR-T therapies for solid tumors to enter a broader market.

(3) Discovery of new targets. The current CAR-T research is basically centered on CD19 and BCMA, are there more and better targets that have not yet been discovered?

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