Article Archives - WuXi Advanced Therapies

Pioneering Scalable Solutions in AAV Manufacturing and Testing for Gene Therapy

Posted on June 25, 2024June 25, 2024 by Weiheng Su

Gene therapy represents a frontier in medical science, offering the prospect of cure for previously incurable genetic disorders. Central to this promise are adeno- associated virus (AAV) vectors, the vehicles for delivering therapeutic genes to patients’ cells. However, the commercial success and accessibility of gene therapies hinges on overcoming significant challenges in scalability and testing.

The Scalability Challenge in AAV Manufacturing

The scalability challenge in AAV manufacturing is a critical bottleneck hindering the wider application and commercial viability of gene therapies. Traditional AAV production methods are associated with low yields and recoveries, making the process expensive and inefficient. These challenges stem from the complex biological requirements for AAV vector production, including the need for specific helper viruses and the intricate balance of conditions required for effective replication and packaging of the therapeutic gene. As demand for gene therapies grows, the industry grapples with how to scale up production without compromising quality or increasing costs prohibitively. This situation creates barriers to patient access and places significant financial and logistical strain on healthcare systems worldwide, emphasizing the urgent need for innovative solutions to enhance scalability and reduce the overall cost of gene therapy manufacturing.

We have repeatedly heard from industry veterans that AAV production using the triple transfection system is not a logical fit for affordable gene therapy access for patients or feasible gene therapy manufacturing at scale for drug developers. The gene therapy sector has been on a mission to pursue a game changing solution.
Weimin Valenti – Executive Director of Strategic Alliances and Licensing, and TESSA franchise leader at OXGENE, a WuXi Advanced Therapies company.

The WuXi Advanced Therapies Solution

At WuXi Advanced Therapies we have developed Tetracycline- Enabled Self-Silencing Adenovirus (TESSA^®) technology, a ground-breaking approach to AAV manufacturing. TESSA^®technology transforms the process by enabling transfection-free, scalable production of AAV vectors at Good Manufacturing Practice (GMP) grade in HEK293 cells. This innovative solution significantly reduces costs and complexity, ensuring adenoviral contamination-free AAV production, with patient safety enhanced through the self-silencing of helper adenoviruses. With TESSA^®, overall yields can increase more than tenfold due to the combination of improved yield with a significantly higher percentage of full AAV capsids.

TESSA^® Pro, an advanced version of this scalable AAV production process, delivers substantial improvements in AAV manufacturing by lowering levels of host cell DNA and reverse packaging contamination. This benefit is evidenced by a study that was completed by Bridge Bio and shared during a webinar conducted in October of 2023 titled ‘Alleviating production bottlenecks in AAV manufacture via platform innovation’ (insights. bio). In practical terms, the TESSA^® Pro process has generated up to 23 times more AAV material compared to the 3-plasmid process, with final AAV material quality also favoring TESSA with 100% full capsids versus 51% from the 3-plasmid process.

Recognizing the benefits of the TESSA^® technology, Janssen Biotech, Inc., now Johnson & Johnson (J&J) Innovative Medicine, recently entered into a licensing agreement with WuXi and have successfully implemented the TESSA^® process, from cloning and virus vector recovery to AdV and AAV production.

Major advance over the state of the art, and competitive in that respect with the best Sf9 platform yields I’ve seen. All in all, my conclusion is that TESSA is a strong contender for anyone considering development of a scalable AAV platform.
Gene therapy expert from a leading pharmaceutical company.

A Partner in Innovation

At WuXi Advanced Therapies we integrate our innovative AAV manufacturing with a comprehensive development and testing platform. By linking process development, assay development, biosafety testing, viral clearance, and product release testing with manufacturing, we ensure the quality and safety of gene therapies. This seamless integration of advanced testing methodologies from early development through to commercialization is crucial for meeting regulatory standards at scale, effectively bridging the gap between scalable production and the market’s demand for safe and effective gene therapies.

Our ethos is to work in close collaboration with our customers, partnering with pharmaceutical and biotech companies to foster innovation in gene therapy. This collaboration extends beyond transactional service provision, addressing industry- wide challenges and pushing the boundaries of gene therapy development and commercialization. Through these partnerships, we leverage our extensive expertise and cutting- edge technology to help bring transformative gene therapies to market, reinforcing our role as a strategic ally in the quest for novel treatments.

Looking Forward: The Future of Gene Therapy Manufacturing and Testing

The future of gene therapy manufacturing and testing is poised for transformative changes. Innovative technologies, changes in the regulatory environment, and the drive towards personalized medicine are expected to shape the landscape. WuXi Advanced Therapies is at the forefront of these developments, ready to lead with ground-breaking solutions that meet the sector’s evolving needs. Our commitment to innovation ensures we will continue to play a pivotal role in advancing gene therapy, making treatments more accessible and effective for patients worldwide.

As we progress through this transformative era of personalized medicine and gene therapy, adopting technological advancements for scaling up manufacturing of these innovative drugs will be critical for their success, and also expand their reach to more patients. TESSA is a breakthrough and built from decades of cumulative virology research, from Atchison’s first identification of AAV particles as contaminants in adenovirus preparations in 1965, to the significant efforts by veterans such as Muzyczka, Samulski, Xiao, Gao, and Grimm, in vectorizing AAV and their attempts to exploit its natural helper, the adenovirus, in generating these efficient gene delivery particles.

We believe TESSA is a significant game-changer for manufacturing AAV medicines, more economically, and help propel them to the clinic and patients.
Weiheng Su, Head of AAV at WuXi Advanced Therapies and inventor of TESSA technology

In Conclusion

Overcoming scalability and testing challenges is crucial for the broader accessibility and efficacy of gene therapies. At WuXi Advanced Therapies we tackle these challenges head on, offering innovative solutions and partnerships to navigate the complexities of gene therapy development and commercialization. Our work not only advances the field but also promises a future where treatments are more readily available to those in need. Partner with WuXi Advanced Therapies to leverage our expertise and technology for the betterment of healthcare outcomes worldwide. Get in touch today and we’ll arrange a time for you to meet with our scientists to learn more. You can also download a copy of this article.

Five Best Practices to Adapt and Improve Quality Control Programs for CGTs

Posted on April 29, 2024July 2, 2024 by Audrey Chang

To launch a successful GMP program for biologics, a robust quality control (QC) release testing protocol is essential. QC testing, which is mandated by global regulatory authorities, helps ensure that a product meets scientific specifications and reaches patients safely. Though each program will have unique parameters, QC testing should gather data to answer the following questions:

Identity: Have you produced the correct product?
Purity: What manufacturing and product byproducts are present?
Strength: What is the potency and quantity of your product?
Safety: Is your product safe and free of unwanted adventitious agents, e.g. Virus, bacteria, and mycoplasma?
Product Quality Attributes: Have you demonstrated that product specific attributes are present?

As biologics continue to diversify beyond monoclonal antibodies (mAbs) and recombinant proteins to include cell and gene therapies (CGTs), QC programs are shifting to accommodate the unique challenges associated with these advanced and novel therapeutics.

Recognizing Important Shifts

CGTs require adaptive and advanced assays for characterization and safety assessments; in many instances, the assays historically used for biologics do not fit the needs of these novel therapies. For example, mycoplasma has long been an area of key testing concern due to its ability to pass through standard sterilization filters. The standard mycoplasma culture-based assay takes 28 days to complete. This cycle is incompatible with the short shelf life of CGT products; as a result, the industry has pivoted to PCR testing for mycoplasma in CGTs, which can be completed in just a few days.

Empty/full ratios for viral vectors are another critical quality characteristic that has been challenging to characterize in the GMP setting thus far. To date, Analytical ultracentrifugation (AUC) has served as the best assessment of empty, full, and partial populations on the market, and as the identification of these ratios grows increasingly vital, AUC will continue to be an important implement for QC programs.

Several other considerations, including defining the critical quality attributes of raw materials and navigating evolving regulatory guidance, have left CGT developers and manufacturers looking for greater insight into how best to design their QC approach.

Identifying Five Best Practices for QC Programs

As you strive to design a strategic QC program, assess how you can leverage the following five best practices in your approach:

Align to Your Risk Assessment:To mitigate risk, begin with a GMP mindset from the start, including sourcing well-characterized cell lines and raw materials while accounting for scale in your processes.
Take a Quality by Design (QbD) Approach: Implementing QbD processes entails several deliberate choices, including ensuring you have the inventory necessary for your product lifecycle, creating a reference standard, and tracking trends as you set specifications.
Leverage Templates and Platforms: Utilizing a templated or platformed approach helps you minimize variation in your process and establish streamlined validations, defined assay parameters, and a thorough understanding of each step.
Gain Proximity to the Manufacturing Floor: The closer the QC lab’s proximity to the manufacturing floor, the better. The goal is to implement real-time, continuous testing in parallel with your manufacturing process.
Participate in Knowledge Sharing: Disseminating key findings between stakeholders across the industry ― particularly around data, technology, and regulatory interactions ― yields major benefits for everyone, including patients.

Where Can I Learn More?

If you’d like more insight into improving your QC program, Dr. Audrey Chang, Executive Director at WuXi Advanced Therapies, recently hosted a webinar in which she highlighted the difficulties of developing QC programs for CGTs and her recommendations for how to improve them. You can watch the full webinar here or contact us to schedule a time to speak with her directly.

6 Key Questions to Cover When Selecting Your Cell Banking Manufacturing Partner

Posted on April 28, 2024June 4, 2024 by Mitch Gore

The purpose of cell banking is to provide cells of a specific genetic and phenotypic profile for use in the production of disease therapies in adequate quantities for the lifespan of the therapeutic. Cell banks and cell lines used for pharmaceutical products are governed by regulatory agencies worldwide.

Cell banks can be research cell banks (RCB), master cell banks (MCB), working cell banks (WCB), and end of production cell banks (EOPCB). Research cell banks are the result of extensive modification and selection processes that provide the seed stock for the MCB.

Expanding from RCB to MCB, and ultimately, to WCB involves a significant transition of growing cells under research conditions to growing cells using GMP-compliant processes. A large part of what changes during this transition is the extensive testing required to ensure genetic and phenotypic consistency, safety, purity, and functionality. In addition, when creating MCB and WCB especially, there needs to be proper documentation produced for support of regulatory requirements.

Choosing the right cell banking service provider is critical to the speed and success of the production of the therapeutic. Whether you are a small academic medical center provider or a large therapy developer or CDMO, here are six key questions you should be asking to help understand how well your needs will be addressed.

Do they have experience with your cell type?

It’s vital to choose a manufacturing partner that has demonstrated experience with your cell type and the growth and production targets you need to meet to support your program. Only a provider with prior experience will be able to knowledgeably assess their ability to deliver.

Common cell types used in cell banking include:

Human

Embryonic Retina (PER-C6)

Spleen

Kidney (MRC-5)

Neuroblastoma cells

Embryonic Kidney (HEK 293)

Umbilical cord

Murine

Hybridoma

Hybridoma Sp2/0

Myeloma (NSO)

Monkey

Africa Green Monkey (VERO)

Rhesus Monkey (LLC MK2)

Insect

Drosophila S2

Fall armyworm Sf9

Hamster

Ovary (CHO)

Canine

Kidney (MDCK)

Chicken

Embryo

2. What is the anticipated timeline and approach?

Even the most robust cells and cell expansion protocols are subject to unknown pitfalls when transferring from provider to a manufacturing partner. Putting emphasis on the technical transfer of the cell bank expansion characteristics from the start will help avoid issues.

Make sure there is a clear and well documented understanding of the expected growth characteristics and a plan to test those before proceeding to the actual manufacturing runs. Minimally, the provider should be proposing that test runs be conducted for at least several passages, with cell counts and viability recorded at each passage.

The timeline for the pre-bank verification can vary, but it’s typically completed in approximately three weeks. Following that, MCB or WCB GMP production is typically three weeks. Two to six additional weeks are needed for testing and two to four weeks for document production should also be included in the timeline.

3. How will the partner manage in-process and release testing?

Understanding how your manufacturing partner will manage the testing of your cell bank during and after the production run is critical to ensure successful project execution. The timeline required for post-bank testing should be established early in the discussion with the provider.

Special attention should be given to the in-process testing as it’s vital to gauge the progress and health of the cells at each passage. The results may indicate a need to adjust expansion plan parameters. At harvest and vialing there may be a need for quick turnaround of test results (STAT testing) to facilitate conditional release. Make sure your provider can perform STAT testing when needed.

Examples of the types of tests used for cell banking include:

Pre-Bank Sterility and Mycoplasma
Adventitious Viral Screening
Animal-derived Raw Material vVruses
Specific Virus Screening (Sf-rhabdovirus, Calicivirus, retroviruses, etc.)
Cell Morphology
Post-Bank Viability and Usability
Post-Bank Sterility and Mycoplasma
Cell Line Identification
Stability Testing

4. Is the testing done in-house or outsourced?

Find out if your provider will outsource the testing or if they have integrated testing capabilities. In-house testing alleviates the need to ship samples to a secondary site. This will significantly impact the turnaround time for results and can also influence the number of vials needed for testing.

Your provider should be willing and able to advise you on the appropriate release tests for MCBs, WCBs, EOBCs, and genetic testing for stability studies. Their testing services need to include STAT testing, conditional release, pre- and post-bank testing, all within a proven and robust quality system.

5. What is the provider’s approach to materials management?

An often-overlooked aspect of cell banking projects is materials management.

Finding a manufacturing partner who can quickly develop the Bill of Materials (BOM) and source the media, media additives, specific culture containers, and culture systems will help avoid delays.

You may have to consider alternative materials, so choose a cell banking partner that can help suggest, source, and test the new components. It’s important to be sure that your provider has extensive experience in materials management for all types of cell banking and be willing to collaborate with you to quickly obtain and test alternative components.

6. Can the provider analyze for phenotypic / genetic drift?

Phenotypic and genetic drift is a potential risk in cell banking and ensuring that this has not happened should be part of the process. Make sure your provider has knowledge of the appropriate methods to access morphological and genetic changes. These can include microscopic evaluation, short tandem repeat profiling, growth curve comparisons, and testing for mycoplasma presence.

In conclusion, careful consideration of your cell banking service provider is critical to the success and speed of your journey from discovery to commercial manufacturing. The ideal cell banking service provider has experience with the cell types, systems, and testing needed for your project. Importantly, those services and capabilities should also be part of an integrated development, GMP production, and testing workflow.

WuXi Advanced Therapies has been providing cell banking services, testing, and regulatory support for over 20 years. We can support your cell banking needs at any point in the journey from discovery to commercial production. Our teams also have extensive capabilities and experience in gene therapy and cell therapy processes, furthering our understanding of cell bank use. We conduct all manufacturing and testing from our state-of-the art facilities in Philadelphia, PA. Get in touch today to discuss your cell banking requirements.

WuXi Advanced Therapies Receives FDA Approval to Manufacture Iovance’s AMTAGVI^™ (lifileucel) for Advanced Melanoma

Posted on February 20, 2024June 13, 2024 by Amy Lamperti

AMTAGVI™ is the first and only one-time, individualized T cell therapy to receive U.S. FDA approval for a solid tumor cancer.

PHILADELPHIA, PA. February 20, 2024 – WuXi Advanced Therapies (WuXi ATU), a wholly owned subsidiary of WuXi AppTec, today announced that the U.S. Food and Drug Administration (FDA) has approved its Philadelphia site to begin the analytical testing and manufacturing of AMTAGVI for Iovance, which received FDA accelerated approval of its Biologics License Application (BLA) on February 16, 2024.

AMTAGVI is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. AMTAGVI is also the first and only one-time, individualized T cell therapy to receive U.S. FDA approval for a solid tumor cancer.

With this announcement, WuXi ATU’s Philadelphia site becomes the first U.S. external manufacturing site and the first third-party contract testing, development, and manufacturing organization (CTDMO) to be approved by the FDA to support the commercial manufacturing and release of an individualized T cell therapy for a solid tumor cancer.

“We congratulate Iovance on this major milestone in their quest to address unmet patient needs in the treatment of advanced melanoma. WuXi ATU has partnered with Iovance since 2015, and we are thrilled to help them through each step of the drug development pipeline – from research to clinical manufacturing to FDA approval,” said Edward Hu, Chief Executive Officer of WuXi ATU and Vice Chairman of WuXi AppTec. “We are proud of our track record of enabling healthcare innovators to advance medical discoveries and deliver groundbreaking treatments to patients globally.”

Iovance, (NASDAQ: IOVA) is headquartered in San Carlos, California with an FDA-approved built-to-suit custom manufacturing facility, the Iovance Cell Therapy Center (iCTC), adjacent to WuXi ATU in the Navy Yard Philadelphia. The company is committed to innovating, developing, and delivering tumor infiltrating lymphocyte (TIL) cell therapies, including gene-edited cell therapies, for patients with cancer.

“The accelerated approval of AMTAGVI is the first step in realizing Iovance’s ambition to usher in the next generation of cell therapy by bringing this breakthrough to patients with advanced solid tumors,” said Frederick Vogt, Ph.D., J.D., Interim Chief Executive Officer and President of Iovance. “Given the significant unmet needs in the advanced melanoma community, we are proud to offer a personalized, one-time therapeutic option for these patients. WuXi ATU has partnered with us to manufacture this cell therapy for close to a decade. It is a great benefit to both Iovance and the healthcare community to have a contract testing, development, and manufacturing partner adjacent to our facilities. Working together our teams can make a meaningful difference for patients.”

About Iovance Biotherapeutics, Inc.

Iovance Biotherapeutics (NASDAQ: IOVA) aims to be the global leader in innovating, developing and delivering tumor infiltrating lymphocyte (TIL) cell therapies for patients with cancer. We are pioneering a transformational approach to cure cancer by harnessing the human immune system’s ability to recognize and destroy diverse cancer cells in each patient. The Iovance TIL platform has demonstrated promising clinical data across multiple solid tumors. Iovance’s AMTAGVI™ is the first FDA-approved T cell therapy for a solid tumor indication. We are committed to continuous innovation in cell therapy, including gene-edited cell therapy, which may be a promising option for patients with cancer. For more information, please visit www.iovance.com.

About WuXi Advanced Therapies (WuXi ATU)

As the advanced therapies business unit of WuXi AppTec, WuXi Advanced Therapies is a Contract Testing, Development and Manufacturing Organization (CTDMO) that offers advanced platforms and end-to-end solutions that enable the discovery, development, testing, manufacturing, and commercialization of cell and gene therapies. Our services and solutions accelerate time to market and support customer programs around the world. For more information visit www.advancedtherapies.com.

About WuXi AppTec

As a global company with operations across Asia, Europe, and North America, WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable the pharmaceutical and healthcare industry around the world to advance discoveries and deliver groundbreaking treatments to patients. Through its unique business models, WuXi AppTec’s integrated, end-to-end services include chemistry drug CRDMO (Contract Research, Development and Manufacturing Organization), biology discovery, preclinical testing and clinical research services, and cell and gene therapies CTDMO (Contract Testing, Development and Manufacturing Organization), helping customers improve the productivity of advancing healthcare products through cost-effective and efficient solutions. WuXi AppTec received AA ESG rating from MSCI in 2023 and its open-access platform is enabling more than 6,000 customers from over 30 countries to improve the health of those in need – and to realize the vision that “every drug can be made and every disease can be treated.”

CONTACTS

WuXi Advanced Therapies

Amy Lamperti
Executive Director, Global Marketing
amy.lamperti@wuxiapptec.com

WuXi AppTec

Davy Wu
Executive Director, Brand & Corporate Communications
mediainquiries@wuxiapptec.com

Iovance Biotherapeutics, Inc.

Sara Pellegrino, IRC
Senior Vice President, Investor Relations & Corporate Communications
650-260-7120 ext. 264
Sara.Pellegrino@iovance.com

Jen Saunders
Director, Investor Relations & Public Relations
267-485-3119
Jen.Saunders@iovance.com

WuXi Advanced Therapies Supports First Investigational CD19 CAR-T Therapy Approved by China’s NMPA

Posted on November 8, 2023June 4, 2024 by Amy Lamperti

SHANGHAI, November 8, 2023 – WuXi Advanced Therapies (WuXi ATU), a global Contract Testing, Development and Manufacturing Organization (CTDMO) congratulates its customer, Juventas Cell Therapy, on achieving China’s NMPA approval for Juventas’ New Drug Application (NDA) for Inaticabtagene Autoleucel (CNCT19 Injection), which is indicated for the treatment of adult relapsed and refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

Unique CTDMO Model Accelerates Market Approval Process

As a crucial partner of Juventas Cell Therapy, WuXi ATU has played a critical role in the development and production of key raw materials such as plasmids and lentivirus. The services encompassed process development, support for the IND and BLA filings, registration testing, on-site inspections, market approval, and providing comprehensive CTDMO services to ensure seamless commercial production.

Since 2018, WuXi ATU has worked alongside Juventas Cell Therapy. In August 2023, WuXi ATU received the “Outstanding Supplier of 2022” by Juventas for WuXi ATU’s contributions in developing and manufacturing Inaticabtagene Autoleucel.

Leveraging the advantages of its CTDMO platform, WuXi ATU empowered Juventas to expedite the project across various facets and accelerate the approval for Inaticabtagene Autoleucel. It took only four years from IND submission to NDA acceptance.. As a result, WuXi ATU became the first Cell and Gene Therapy CDMO in China to pass a lentiviral vector on-site inspection by the Center for Food and Drug Inspection of the China NMPA (CFDI).

QbD Concept Embedded, Ensuring Process and Quality

CAR-T cell therapy, representing tumor immunotherapy, was recognized as the top scientific breakthrough of 2013 by Science. As a “living drug”, CAR-T cells exhibits high complexity and variability. Its production process includes (i) two key raw material production: plasmid production and lentiviral vector production and (ii) CAR-T cell drug production, each of which involves multidimensional, multi-input, and multi-output factors. Therefore, from the initial stage of process design and development, Juventas Cell Therapy and WuXi ATU adhered to the concept of “Quality by Design” (QbD) throughout the drug’s entire lifecycle. The QbD process involves applying a scientific and systematic development approach to efficiently transform laboratory-prepared processes into GMP manufacturing processes that meet IND filing requirements and, ultimately, achieve BLA approval for commercial production. By applying the QbD, Juventas Cell Therapy and WuXi ATU considered the impact of key raw materials on final product quality, as well as its impact on patient efficacy and safety from the early stages of process design.

This approach attempts to mitigate future risks and the high costs associated with changes by doing the following: Fully understanding of the unique requirements for downstream cell products, setting quality target product profile (QTPP) for key raw materials, identifying critical quality attributes (CQA), systematically developing laboratory-scale process models for multivariate experimental research to determine critical process parameters (CPP) and design space, and ultimately establishing an overall control strategy. This strategy has been validated at the commercial production scale, ensuring the robustness of the manufacturing process and the stability of product quality.

About Juventas

Established in June 2018, Juventas Cell Therapy Ltd, a biopharmaceutical company powered by cutting-edge cell and gene technologies, has become the leader of innovative CGT drug development in China. Juventas’ innovation is stemmed from its integrated R&D platforms including CAR, iPSCs, and gene-editing technologies. With more than 10 drug candidates in its pipeline, featured with solo, dual, or multiple target autologous CAR-T and universal cellular products, Juventas is well on its way to fulfil its mission – providing novel solutions to unmet clinical needs in the treatment of blood cancers, solid tumors, and other diseases.

Beside self-driven innovation, Juventas is open for domestic and international collaborations, and has developed close partnership cooperation with China national top scientific institutes and clinical research centers, to diligently translate frontier science and technology advancement into bedside therapies/treatments.

In Nov. 2023, Juventas’ first core product – Inaticabtagene Autoleucel (CNCT19) was approved by NMPA, for the treatment of adult B-cell relapsed and refractory acute lymphoblastic leukemia (B-ALL).

About WuXi Advanced Therapies (WuXi ATU)

As the advanced therapies business unit of WuXi AppTec, WuXi Advanced Therapies is a Contract Testing, Development and Manufacturing Organization (CTDMO) that offers integrated platforms to transform the discovery, development, testing, manufacturing, and commercialization of cell and gene therapies. Our services and solutions accelerate time to market and support customer programs around the world. For more information, please visit https://wuxiadvstg.wpenginepowered.com.

Cabaletta Bio and WuXi Advanced Therapies Announce Expansion of GMP Manufacturing Agreement to Include CABA-201

Posted on August 22, 2023June 4, 2024 by Amy Lamperti

– Agreement expansion facilitates preparation for commercial readiness for CABA-201, enabling treatment of patients in multiple planned clinical trials with separate parallel cohorts –

– Partnership for CABA-201 builds on existing manufacturing agreement for clinical trial supply of MuSK-CAART for MusCAARTes™ trial –

PHILADELPHIA, August 22, 2023 – Cabaletta Bio, Inc. (Nasdaq: CABA), a clinical-stage biotechnology company focused on developing and launching the first curative targeted cell therapies for patients with autoimmune diseases, today announced that it has entered into certain work orders relating to Good Manufacturing Practice (GMP) manufacturing under its existing master services agreement with WuXi Advanced Therapies (WuXi ATU), a global Contract Testing, Development and Manufacturing Organization (CTDMO). As part of the agreement, WuXi ATU will serve as a cell processing manufacturing partner for the planned global clinical development of CABA-201 in multiple indications, including potential late-stage clinical trials and commercial readiness activities for CABA-201.

“We have had a successful collaboration with WuXi ATU over the past two years for the GMP compliant production of novel cell therapies. Based on this initial collaboration, we chose to expand our partnership to include WuXi ATU as a manufacturer for our CABA-201 clinical programs,” said Gwendolyn Binder, Ph.D., President of Science and Technology of Cabaletta. “WuXi ATU’s dedicated production capacity for CABA-201 supports our planned global expansion and commercial preparedness efforts and will enable us to dose patients in multiple clinical trials with separate parallel cohorts, while maintaining a capital-efficient manufacturing strategy.”

Under the terms of the agreement, WuXi ATU will provide GMP manufacturing of CABA-201, a 4-1BB-containing fully human CD19-CAR T cell investigational therapy, to support any of Cabaletta’s planned clinical trials, including the previously announced separate Phase 1/2 clinical trials of CABA-201 for the treatment of patients with systemic lupus erythematosus and idiopathic inflammatory myopathies, or myositis. In addition, WuXi ATU will continue to serve as the Company’s cell processing manufacturing partner for the MusCAARTes™ Phase 1 clinical trial of MuSK-CAART.

“We are delighted to expand our partnership with Cabaletta to advance the development of CABA-201 for patients with autoimmune diseases,” said David Y. H. Chang, Ph.D., President and Chief Technology Officer of WuXi ATU. “We look forward to applying our expertise in cell and gene therapy manufacturing to better support our customers to bring potentially life-saving treatments faster to patients in need.”

About Cabaletta Bio
Cabaletta Bio (Nasdaq: CABA) is a clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies that have the potential to provide a deep and durable, perhaps curative, treatment for patients with autoimmune diseases. The CABA™ platform encompasses two strategies: the CARTA (chimeric antigen receptor T cells for autoimmunity) strategy, with CABA-201, a 4-1BB-containing fully human CD19-CAR T, as the lead product candidate being evaluated in systemic lupus erythematosus and myositis, and the CAART (chimeric autoantibody receptor T cells) strategy, with multiple clinical-stage candidates, including DSG3-CAART for mucosal pemphigus vulgaris and MuSK-CAART for MuSK myasthenia gravis. The expanding CABA™ platform is designed to develop potentially curative therapies that offer deep and durable responses for patients with a broad range of autoimmune diseases. Cabaletta Bio’s headquarters and labs are located in Philadelphia, PA.

About WuXi Advanced Therapies (WuXi ATU)
As the advanced therapies business unit of WuXi AppTec, WuXi Advanced Therapies is a Contract Testing, Development and Manufacturing Organization (CTDMO) that offers integrated platforms to transform the discovery, development, testing, manufacturing, and commercialization of cell and gene therapies. Our services and solutions accelerate time to market and support customer programs around the world. For more information, please visit www.advancedtherapies.com

Forward-Looking Statements
This press release contains “forward-looking statements” of Cabaletta Bio within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including without limitation, express or implied statements regarding its expectations regarding: Cabaletta’s ability to capitalize on and the potential benefits of the expanded scope of its collaboration with WuXi ATU; Cabaletta’s ability to grow its autoimmune-focused pipeline; its plans around CABA-201, including its ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner and advance the separate Phase 1/2 clinical trials of CABA-201 in each indication; the Company’s business plans and objectives; the progress and results of its MusCAARTes™ Phase 1 trial, including Cabaletta’s ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner, and progress the trial; the expectation that Cabaletta Bio may improve outcomes for patients suffering from systemic lupus erythematosus, myositis, MuSK-associated myasthenia gravis, or other autoimmune diseases as well as its expected therapeutic benefits; and the ability to accelerate Cabaletta’s pipeline and develop meaningful therapies for patients, including in collaboration with academic and industry partners and the ability to optimize such collaborations on its development programs.
Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to regulatory filings and potential clearance; the risk that signs of biologic activity or persistence may not inform long-term results; Cabaletta’s ability to demonstrate sufficient evidence of safety, efficacy and tolerability in its preclinical studies and clinical trials of DSG3-CAART, MuSK-CAART and CABA-201; the risk that the results observed with the similarly-designed construct employed in the recent Nature Medicine publication, including due to the dosing regimen, are not indicative of the results we seek to achieve with CABA-201; risks related to clinical trial site activation or enrollment rates that are lower than expected; risks related to unexpected safety or efficacy data observed during clinical studies; risks related to volatile market and economic conditions and public health crises; Cabaletta’s ability to retain and recognize the intended incentives conferred by Orphan Drug Designation and Fast Track Designation for its product candidates, as applicable; risks related to Cabaletta’s ability to protect and maintain its intellectual property position; risks related to fostering and maintaining successful relationships with Cabaletta’s collaboration and manufacturing partners; uncertainties related to the initiation and conduct of studies and other development requirements for its product candidates; the risk that any one or more of Cabaletta’s product candidates will not be successfully developed and/or commercialized; and the risk that the initial or interim results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Cabaletta’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Cabaletta’s most recent annual report on Form 10-K as well as discussions of potential risks, uncertainties, and other important factors in Cabaletta’s other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Cabaletta undertakes no duty to update this information unless required by law.

WuXi ATU and T-MAXIMUM Announce Strategic Partnership of Cooperation for MT-027 UCAR-T

Posted on June 6, 2023June 4, 2024 by Amy Lamperti

June 6, 2023 – Boston, Massachusetts. WuXi Advanced Therapies (WuXi ATU), a global Contract Testing, Development and Manufacturing Organization (CTDMO), and T-MAXIMUM today signed a strategic collaboration agreement. WuXi ATU will provide integrated testing, development and manufacturing and IND filing services for T-MAXIMUM’s UCAR-T product MT-027.

MT-027 is a universal allogeneic CAR-T cell therapy product targeting B7-H3 for the treatment of recurrent high-grade glioma. It has obtained Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA).

“We are delighted to be a strategic partner with WuXi ATU,”said Dr. Xiaoyun Shang, CEO of T-MAXIMUM. “T-MAXIMUM’s mission is to develop UCAR-T product for patients in need, and we are glad to take the full advantage of WuXi ATU’s CTDMO platform to accelerate MT-027 testing, process development, manufacturing and IND filing. In the future, we also desire to deepen our collaboration on more pipeline products.”

Xiaoping Wang, Co-founder and Director of T-MAXIMUM, and Dr. Yong Fan, Chief Technology Officer and Senior Vice President of Global Regulatory Affairs, attended the signing ceremony and visited the WuXi ATU’s Philadelphia site.

“We are grateful for T-MAXIMUM’s trust in WuXi ATU to provide integrated CTDMO services for T-MAXIMUM’s UCAR-T product MT-027. UCAR-T, as an important modality of cell therapy products, has great potential to offer patients more readily available ‘off-the-shelf’ cell therapy treatment.” Edward Hu, Chairman and CEO of WuXi ATU said, “WuXi ATU will work together with T-MAXIMUM to accelerate MT-027’s development to bring this life saving treatment to patients in need efficiently.”

T-MAXIMUM & WuXi Advanced Therapies Contract Signing Ceremony. The second on the left is Edward Hu, Chairman and CEO of WuXi ATU, the third on the left is Dr. Angela Chen, Chief Business Officer of WuXi ATU , the first on the left is Dr. David Chang, former Chief Technology Officer of WuXi ATU, and the third on the right is Dr. Xiaoyun Shang, CEO of T-MAXIMUM, the first on the right is Xiaoping Wang, Co-founder and Director of T-MAXIMUM, the second on the right is Dr. Yong Fan, Chief Technology Officer and Senior Vice President of Global Regulatory Affairs of T-MAXIMUM.

About MT027
MT027, an allogeneic chimeric antigen receptor T-cell (UCAR-T) therapy targeting B7-H3, is prepared using T cells from healthy donors. As a next-generation off-the-shelf CAR-T product, MT027 can be immediately and readily available for patients, addressing the common challenges of autologous cell therapies such as lengthy preparation cycles, insufficient capacity, and patients’ T cells not meeting the manufacturing criteria, which often result in many patients unable to receive CAR-T therapy timely. Additionally, the expected medical costs are significantly reduced, relieving patients’ financial burden.

MT027 is developed through genetic modification techniques, where CAR targeting B7-H3 is expressed on the surface of gene-edited T cells, which avoids the GvHD and HvGR that may arise from interactions between exogenous T cells and the patient’s own immune system with promising safety and efficacy in the treatment of recurrent high-grade gliomas.

T-MAXIMUM Biotech
T-MAXIMUM Biotech is dedicated to the development of universal cellular drugs, exploring the treatment of “incurable” diseases with cellular drugs as the ultimate form of medication. The team is composed of renowned experts in the field of immunotherapy and gene editing and senior industry professionals in the field of biopharmaceuticals. The company’s core technology platform, gene-edited allogeneic immunotherapy, adopts the 3.0 version of its completely independent intellectual property rights to achieve allogeneic universal CAR-T cell therapy, addressing the risk of graft-versus-host disease and rejection of allogeneic immune cells, and the obtained allogeneic CAR-T cells persist well in patients. The company is currently focusing on advanced malignant tumors, and its first product pipeline for recurrent gliomas has achieved validation of efficacy and safety in preliminary clinical studies. The company plans to promote the launch of at least one product to the market and multiple products into clinical phase II in the next five years.

T-MAXIMUM Biotech always adheres to the corporate philosophy of “integrity innovation, quiet water flowing deep, and collaborative integration”, overcoming the difficulties to solve the clinical problem of no cure, to be the real original innovation, and to be a globally leading innovative company in cell therapy, to provide the means for “incurable” diseases.

Clinical Phase I/II IND Approval! The first cell therapy project in Korea supported by WuXi Advanced Therapies receives MFDS approval

Posted on March 16, 2023June 4, 2024 by Amy Lamperti

Wednesday March 8, 2023 – TICAROS, a Korean CAR-T developing biotech in partnership with WuXi Advanced Therapies (WuXi ATU) received IND approval from the Korean Ministry of Food and Drug Safety (MFDS).

WuXi Advanced Therapies is a global Contract Testing, Development and Manufacturing Organization (CTDMO). WuXi ATU has delivered solutions through the OXGENE plasmid optimization, GMP lentivirus manufacturing and IND application filling, for TICAROS’ new CAR-T cell therapy product in Korea. In this collaboration, WuXi ATU supported customer not only for the process development and manufacturing of LVV for the CAR-T product, but also prepared the IND filing documentations with high quality and speed to obtain MFDA approval for phase I and phase II clinical trials in one application. This greatly accelerates the TICAROS’s efforts to develop new cell therapy product to patients in need.

Mr. Jae Won Lee, CEO of TICAROS, said: “I am very grateful to WuXi ATU for its excellent work in the development of our next-generation CAR-T cell therapy. The cooperation with WuXi ATU in the Oxford UK, China sites has greatly improved the speed of our drug development.”

“Congratulations to TICAROS for the approval of CAR-T IND in Korea, and appreciate TICAROS’ recognition of WuXi ATU CTDMO services.” Edward Hu, Chairman and CEO of WuXi ATU said, “This is the first IND approval supported by WuXi ATU in Korea. WuXi ATU’s one-stop CTDMO service platform will continue to empower cell and gene therapy innovation companies, support global customers to accelerate the development, testing and manufacturing of innovative cell and gene therapies for patients in needs.”

TICAROS’ New CAR-T Cell Therapies

TICAROS’ next generation immunotherapies is being developed for intractable haematologic malignancies and advanced solid tumors. TICAROS’ cutting-edge platform technologies include CLIP CAR (Clamping-based Immunological Synapse Potentiating CAR) Technology, a strategy to stabilize immune synapse between CAR-T cells and target tumor cells by modifying CAR structure, which results in maximized efficacy of CAR-T cells and CONVERTER CAR Technology, which enables selective inhibition of CTLA4 only in tumor-specific CAR-T cells without affecting other T cells in patients’ blood. Thus, the selective inhibition of CTLA-4 only in CAR-T cells potentiates CAR-T activity without causing serious autoimmunity.

About TICAROS Co., Ltd (TICAROS)

TICAROS Co.Ltd is a biotech which develops next generation immunotherapies for both hematological and solid cancers. Recently, alongside with antibody techniques, immuno-oncology therapies are evolving into novel cellular therapeutics which harbor immune cell therapies and gene therapies together. Especially, the outstanding clinical efficacy of CAR-T cell therapies and the potential for successful TCR-T therapies are leading a new era of cancer therapeutics. TICAROS develops matchless CAR-T and cell therapeutics for cancer treatment, by leveraging accumulated experiences and technologies of immunologists at Seoul National University, College of Medicine. We hope that these efforts will lead to a novel breakthrough in treatment of not only intractable hematologic malignancies, but also of advanced solid tumors.

About WuXi Advanced Therapies (WuXi ATU)

About WuXi AppTec

As a global company with operations across Asia, Europe, and North America, WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable global pharmaceutical and healthcare industry to advance discoveries and deliver groundbreaking treatments to patients. Through its unique business models, WuXi AppTec’s integrated, end-to-end services include chemistry drug CRDMO (Contract Research, Development and Manufacturing Organization), biology discovery, preclinical testing and clinical research services, cell and gene therapies CTDMO (Contract Testing, Development and Manufacturing Organization), helping customers improve the productivity of advancing healthcare products through cost-effective and efficient solutions. WuXi AppTec received AA ESG rating from MSCI in 2021 and its open-access platform is enabling more than 5,800 collaborators from over 30 countries to improve the health of those in need – and to realize the vision that “every drug can be made and every disease can be treated.” Please visit: http://www.wuxiapptec.com.

WuXi Advanced Therapies Announces Licensing Agreement with Janssen

Posted on August 12, 2022June 4, 2024 by Amy Lamperti

August 11, 2022 – PHILADELPHIA, PA. WuXi Advanced Therapies (WuXi ATU), a wholly owned subsidiary of WuXi AppTec, today announced a licensing agreement with Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson (“Janssen”). Under this agreement, WuXi ATU will license to Janssen its TESSA™ technology, a high-performance system that can produce 10 times more adeno-associated viral (AAV) vectors than traditional AAV manufacturing systems. Janssen will also have access to work on WuXi ATU’s proprietary clonal suspension HEK293 cell line. This agreement was facilitated by Johnson & Johnson Innovation.

AAV vectors are commonly used for the delivery of gene therapies to patients due to their ability to transduce numerous cell and tissue types. WuXi ATU’s TESSA™ technology responds to industry demand for large scale AAV manufacturing by producing higher quality AAV particles more efficiently. WuXi ATU has also successfully scaled up the TESSA™ technology to 200L; this achieved a 10-fold higher yield and a significantly higher percentage of full AAV capsids, greatly reducing overall AAV production costs compared to traditional plasmid-based AAV production systems.

“We are honored that Janssen selected WuXi ATU’s TESSA™ technology.” said David Chang, CEO of WuXi Advanced Therapies. “We remain committed to improving the TESSA™ platform to produce faster and more cost effective AAV products for patients.”

As a Contract Testing, Development and Manufacturing Organization (CTDMO) with global operations, WuXi ATU will continue to enhance its capability and capacity to help customers develop and deliver life-changing cell and gene therapies faster for patients in need.

About WuXi Advanced Therapies (WuXi ATU)

About WuXi AppTec

Media Contact:
Davy Wu | mediainquiries@wuxiapptec.com

WuXi Advanced Therapies Testing Facility To Receive EMA GMP Certificate for New Philadelphia Facility

Posted on January 7, 2022June 4, 2024 by Amy Lamperti

January 07, 2022 – Philadelphia. WuXi Advanced Therapies (WuXi ATU) announced it has successfully completed a remote European Medicines Agency (EMA) inspection for its advanced therapies testing facility at 400 Rouse Boulevard in its Philadelphia Navy Yard Campus, and received confirmation that the issuance of GMP certificate is in progress. This certification will not only mark an important milestone for WuXi ATU, the advanced therapies business unit of WuXi AppTec, on its global quality system, but it will underscore its commitment to providing cell and gene therapy Contract Testing Development and Manufacturing Organization (CTDMO) services with the highest standards for customers.

The issuance of GMP certificate followed a remote inspection conducted by Ireland’s Health Products Regulatory Authority (HPRA) in December 2021. The comprehensive inspection covered Virology and Mycoplasma Quality Control testing and the facility’s entire quality system. The positive inspection outcome will support ongoing submissions to the EMA for new biologics and cell and gene therapy products from our global commercial partners.

The new state-of-the-art testing facility, which officially opened two months ago, has tripled WuXi ATU’s capacity for testing to meet the growing demand among the cell and gene therapy industry. The Biosafety Testing team has significant expertise in assay development, biologics safety testing, viral clearance and commercial lot release assays and will benefit from increased capacity with this new testing facility expansion in Philadelphia.

“At WuXi ATU, delivering the highest quality standards for our customers and meeting global regulatory standards are among our top priorities.” said Dr. David Chang, Chief Executive Officer of WuXi ATU. “The EMA certificate for biosafety testing at our new Philadelphia facility is a testimony to our commitment to being a trusted partner to our customers. As demand for cell and gene therapies grow, we will further enhance our CDMTO platform to better enable customers in Philadelphia and beyond to bring ground-breaking therapeutics to patients as quickly, reliably and consistently as possible.”

As a CTDMO with global operations, WuXi ATU’s unique business model integrates powerful testing capabilities with its advanced therapies process development and manufacturing platforms, such as TESSA technology for AAV manufacturing and XLenti stable solutions for lentiviral manufacturing. This allows all assay development, biosafety, viral clearance, and product release testing to be completed in-house, shortening customers’ timelines for the approval of advanced therapies. WuXi ATU has supported more than 1,700 customer submissions for biosafety testing through industry-leading testing and analytical assay development, enabling the delivery of more effective and accessible advanced therapies to patients.

About WuXi Advanced Therapies (ATU)

WuXi Advanced Therapies, a global Contract Testing Development and Manufacturing Organization (CTDMO), is the advanced therapies business unit of WuXi AppTec and offers integrated platforms to transform the discovery, development, testing, manufacturing, and commercialization of cell and gene therapies for customers worldwide. Our technologies, automation platforms and service solutions advance pre-clinical research and accelerate the timeline to GMP manufacture, while integrated GMP manufacturing and testing platforms reduce time to market, maintaining high titres, high levels of quality assurance and full regulatory compliance. Ultimately, our complete end-to-end solutions support pioneering companies to deliver breakthrough cell and gene therapies to the patients who need them. For more information, please visit www.advancedtherapies.com.