**[Challenge]** Even with high-purity samples like cell culture samples, accurately characterizing extracellular vesicles (EVs) is not easy. Interference from lipoproteins, cellular debris, and protein aggregates poses challenges. Additionally, the complexity of biological fluids, limited sample volumes, and the presence of rare EV subpopulations further complicate the analysis. **[Solution]** Our Leprechaun separates EVs on Luni consumables, allowing for the measurement of particle size and concentration, and simultaneous analysis of up to four surface or internal markers. It can be applied to samples of less than 25µL, does not require sample purification, and offers sensitivity up to 5×10⁵ particles/mL, single particle analysis, and EV size measurement down to 35nm. **[Demonstration]** In this webinar, we will introduce how Leprechaun combines single particle interference measurement with immunofluorescence imaging to achieve comprehensive analysis of any EV sample. It is also possible to confirm the loading efficiency of cargo carried by EVs, distinguish whether proteins are soluble or EV-derived, and obtain a breakdown of all EV subpopulations.

We have launched a new product. Please check the link below for details.

**[Issue]** The evolution of LNPs is progressing more rapidly than ever, largely due to modifications in particle formulations. However, the formulations to be tested are complex in composition and involve a vast number of combinations, making large-scale screening difficult to achieve. Furthermore, there is the subsequent challenge of transferring to production. Evaluations are also required to be accurate, comprehensive, and high-throughput. **[Webinar Overview]** In this webinar, we will explain how our Sun series can accelerate the exploration and development of LNPs, based on the latest research findings and user case studies in LNP formulations. We will also introduce Stunner, which enables high-speed and accurate LNP evaluations.

Our company will be exhibiting at the 25th Annual Meeting of the Protein Science Society, which will be held from June 18 (Wednesday) to June 20 (Friday), 2025. At our booth, we will introduce groundbreaking solutions for the research and development of proteins and antibody drugs, including the Aunty stability evaluation device, which can also be automated. We invite you to visit our booth. Dates: June 18 (Wednesday) - June 20 (Friday), 2025 Venue: Akurie Himeji Details: https://aeplan.jp/pssj2025/

Unchained Labs, Inc. will exhibit at the 41st Annual Meeting of the Japanese DDS Society, which will be held from June 17 (Tuesday). At our booth, you can see a wide range of products, from the manufacturing of lipid nanoparticles (LNP) to their characterization, as well as products for ADC and the evaluation of extracellular vesicles. Additionally, on the first day of the event, July 17, we will also hold a presentation by exhibiting companies. All of our staff sincerely look forward to your visit. Event Name: 41st Annual Meeting of the Japanese DDS Society Date: July 17 (Tuesday) - July 18 (Wednesday) Venue: Makuhari Messe International Conference Hall Details: https://procomu.jp/dds2025/ <Exhibiting Company Presentation> July 17 (Tuesday) around 15:28

CPhI Japan Exhibition & Seminar! April 9 (Wednesday) - 11 (Friday) @ Tokyo Big Sight Unchained Labs, Inc. will be exhibiting in the biopharmaceutical zone at CPhI Japan this year as well. Additionally, we will hold a seminar on the second day! Please visit our booth at Tokyo Big Sight. <Exhibitor Seminar> Date and Time: April 10 (Thursday) 13:00-13:30 Venue: 5B "Stability Evaluation of Biopharmaceuticals - Towards a New Era of High-Speed and High-Throughput" *No prior reservation required, free of charge.

Stability testing of proteins and formulations can feel overwhelming when screening large numbers of candidates or conditions. Traditional tools often lack flexibility, provide only partial information, or have low throughput, wasting valuable time. Aunty is the world's fastest and highest throughput protein stability assessment tool. By setting up to 96 samples on a plate, Aunty processes thermal denaturation and aggregation tests at an astonishing speed. Using fluorescence measurements, SLS (Static Light Scattering), and DLS (Dynamic Light Scattering), it analyzes the entire plate every minute, allowing for instant access to detailed stability data. You can screen large numbers of candidate molecules and conditions and repeat experiments as many times as needed. Aunty delivers unprecedented detailed stability assessments with overwhelming speed and data resolution. In this webinar, we will provide a detailed explanation of the flow from experimental setup to data analysis with Aunty. You will see the analysis of Tm (melting temperature), Tagg (aggregation temperature), and colloidal stability, and experience high-resolution stability data like never before!

We have launched a new product. Please check the link below for details.

Our company will be exhibiting at BioJapan 2023, which will be held from Wednesday, October 11. At our booth, you can see the protein structural stability evaluation device, Uncle, as well as technical data on Leprechaun, which can analyze lentiviruses and exosomes, and a mysterious new product. Additionally, on the first day, we will have a lecture by Professor Nagamori from the University of Tokyo on the broad drug discovery support provided by Uncle. We invite you to come to Pacifico Yokohama! Exhibition details: ■ Dates: October 11 (Wednesday) to October 13 (Friday), 2023 ■ Venue: Pacifico Yokohama ■ Booth #: B-36 Seminar details: "Evaluation methods for physical properties enabling broad drug discovery support from small molecule drugs to antibody drugs" ■ Date: October 11 (Wednesday) ■ Time: 14:30 - 15:30 ■ Location: Annex Hall F203 ■ Details and pre-registration: https://biojapan2023.jcdbizmatch.jp/Lookup/jp/Seminar/u0?ke=unchained

This seminar is jointly hosted by Kitahama Seisakusho Co., Ltd. and Unchained Labs, Inc. In the field of LNP creation technology, we will introduce a technique for producing monodisperse nanoparticles such as LNPs using the microfluidic devices from ParticleWorks (formerly Blacktrace), which became a brand of Unchained Labs in July of this year. Additionally, we will present various automation devices that leverage Unchained Labs' strengths in biopharmaceutical research and gene therapy in the evaluation and post-processing technology, offering solutions to the challenges faced by researchers in biopharmaceutical analysis and gene therapy drug development through these products. <Presentation 1> Streamlining LNP formulation development using microfluidic technology Moriho Fukai, Kitahama Seisakusho Co., Ltd. <Presentation 2> A tool that significantly enhances the efficiency of buffer exchange and characterization of biopharmaceutical samples using lipid nanoparticles Yuji Senoo, Unchained Labs, Inc.

Our company will be exhibiting at the CPhI Japan 2022 (Bio Live), an international pharmaceutical development exhibition, starting from April 20 (Wednesday). At our booth, you can see the actual protein stability evaluation device, Stunner. Additionally, visitors to our booth will receive an original Unchained Labs tote bag as a gift! We look forward to seeing you there.

In the development of vectors such as LNP (lipid nanoparticles) and AAV (adeno-associated viruses), buffer exchange is an important step and presents various challenges. LNP requires rapid exchange, while AAV necessitates improvements in recovery rates and concentration, so a single solution is not always optimal. Unagi is a buffer exchange and concentration device developed to accommodate biopharmaceuticals and biomolecules for gene therapy, utilizing pressure-based ultrafiltration/diafiltration (UF/DF) technology. Unagi achieves precise buffer exchange and concentration without compromising sample recovery rates. It also allows for the selection of regenerated cellulose (RC) membranes and polyethersulfone (PES) membranes, and customization of capacity and orbital mixing, providing data results under various conditions. In this webinar, you will see the final exchange values, concentration values, and analytical characteristics for LNP and AAV under various conditions. Please check out the power and flexibility of Unagi.

In this webinar, we will introduce the "Unchained Ecosystem," which combines the technology of Unchained Labs to achieve an efficient workflow for formulation development utilizing high-throughput approaches, small-volume microfluidics, and automation. In the first part, we will explain an overview of our ecosystem and each of our products. In the second part, we will present how IGM Biosciences efficiently identifies stable formulations and rapidly identifies optimized monoclonal antibody (mAb) formulations using this ecosystem. Additionally, we will discuss our efforts to integrate automation at the front end of this workflow and the automation of the data lake at the back end. *This webinar is a recording of an event held in the United States this September, with Japanese subtitles.*

Unchained Labs, Inc. will exhibit at the 2nd Annual Meeting of the Japanese Society for Antibody Research, which will be held from December 1 (Friday) to December 3 (Sunday). At our booth, you will be able to see our antibody stability evaluation device, Uncle, as well as innovative products for antibody and antibody drug research and development, such as Unagi, which automates the cumbersome buffer exchange process. Additionally, visitors to our booth will receive original merchandise from our company as a gift! All of our employees are sincerely looking forward to your visit. Event Name: 2nd Annual Meeting of the Japanese Society for Antibody Research Date: December 1 (Friday) - December 3 (Sunday), 2023 Venue: Leica Nankoku Hall (directly connected to JR Kagoshima Chuo Station) Booth: #29 Details: https://antibodysociety.jp/%e5%ad%a6%e8%a1%93%e9%9b%86%e4%bc%9a%e3%81%b8%e3%81%ae%e6%a1%88%e5%86%85/

Researchers of lipid nanoparticles (LNPs) spend a tremendous amount of time on screening, optimization, and scaling up experiments to achieve optimal performance, spot-on targeting, and controlled release of active pharmaceutical ingredients (APIs). Factors such as solubility, pH stability, payload release, and encapsulation all depend on particle size, shape, and structure. In other words, to obtain the correct formulation, it is necessary to explore a vast number of formulation parameters and process parameters one by one, but even if a perfect formulation is found, scaling up usually means switching equipment and re-optimizing settings. In this webinar, we will introduce Sunny Suite, an automated high-throughput screening platform designed to reduce the time spent on screening, optimizing, and scaling up experiments for LNP formulations.

The concentration of lipid nanoparticles is an important parameter that should be known for all batches of particles, but existing methods either cannot handle throughput, require dilutions that affect accuracy, or take a lot of time. Additionally, keeping the particles at the appropriate size is a common goal, but it is difficult to detect all aggregates in the sample, and collecting size data for all samples is quite challenging. Regarding payload quantification, most solutions rely on complex interrupted workflows, expensive dyes, and wasteful standard curves. In this webinar, you will learn how our newly updated Stunner can perform not only size determination and concentration quantification of LNPs but also payload quantification, providing unique information from various nanoparticle applications. *This webinar is a Japanese translation and presentation of the content "Stop guessing. Get fast LNP quant and sizing on Stunner," composed by Nelis Denys, M.Sc., Market Manager at Unchained Labs, Inc.*

CPhI Japan Exhibition & Seminar! April 17 (Wednesday) - 19 (Friday) @ Tokyo Big Sight Unchained Labs, Inc. will be exhibiting in the biopharmaceutical zone at CPhI Japan this year as well. This time, we will also hold an exhibitor seminar on the first day! Please come visit our booth at Tokyo Big Sight. <Exhibitor Seminar> April 17 (Wednesday) 11:30 - 12:00 【5B】 "Unchained Ecosystem Supporting Drug Development and Scale-Up with Lipid Nanoparticles" *No prior reservation required, free of charge.

Unchained Labs, Inc. will exhibit at the 39th Annual Meeting of the Japanese Society of Pharmaceutical Sciences, which will be held from May 23 (Thursday) to May 25 (Saturday). At our booth, you can see a wide range of products from the manufacturing to the characterization of lipid nanoparticles (LNP), covering both the development and manufacturing phases. Additionally, on the third day, we will hold a luncheon on the same topic. All of our employees sincerely look forward to your visit. Event Name: 39th Annual Meeting of the Japanese Society of Pharmaceutical Sciences Date: May 23 (Thursday) - May 25 (Saturday) Venue: Kobe International Conference Center Booth: #20 Details: https://procomu.jp/apstj2024/ <Luncheon Seminar> May 25 (Saturday) 12:15 - 13:15 Room 401 + 402 "Accelerating the Development of Lipid Nanoparticle Formulations: High-Throughput Manufacturing Condition Evaluation and Analytical Applications"

Our company will be exhibiting at the 24th Annual Meeting of the Protein Science Society, which will be held from June 11 (Tuesday) to June 13 (Thursday), 2024. At our booth, we will introduce groundbreaking solutions for the research and development of proteins and antibody drugs, including the stability evaluation device Uncle. We invite you to visit our booth. Dates: June 11 (Tuesday) - June 13 (Thursday), 2024 Venue: Sapporo Convention Center Booth: #31 Details: https://aeplan.jp/pssj2024/

<Announcement of Interphex Exhibition and Product Technology Seminars> Our company will be exhibiting at the Interphex BioPharmaceuticals EXPO again this year. Additionally, we will be presenting at product technology seminars on the first and second days of the exhibition! We invite you to come to Tokyo Big Sight. Exhibition Details: Name: Interphex Week Tokyo (26th Edition) Date: June 26 (Wednesday) - 28 (Friday), 2024 Venue: Tokyo Big Sight Booth: 46-17 (East Hall 6), diagonally across from Cytiva's booth Product Technology Seminar 1 "Solutions for Completely Mastering Lipid Nanoparticles (LNP)" ● June 26 (Wednesday) 11:40 - 12:10 ● Venue: Exhibitor Seminar Room 6 (East Hall 5) Product Technology Seminar 2 "How to Achieve Automation in Chemical Research" ● June 27 (Thursday) 12:30 - 13:00 ● Venue: Exhibitor Seminar Room 7 (East Hall 6)

Unchained Labs, Inc. will exhibit at the 40th Annual Meeting of the Japanese DDS Society, which will be held from July 9 (Thursday). At our booth, you can see a wide range of products covering everything from the manufacturing of lipid nanoparticles (LNP) to their characterization, spanning from the development phase to the manufacturing phase. Additionally, on the first day of the event, July 9, we will also hold a presentation by exhibiting companies. All of our employees sincerely look forward to your visit. Event Name: 40th Annual Meeting of the Japanese DDS Society Date: July 9 (Tuesday) - July 11 (Thursday) (Company exhibitions will be on the 10th and 11th) Venue: Tsukuba International Congress Center Booth: #9 Details: https://procomu.jp/dds2024/index.html <Exhibiting Company Presentation> July 9 (Tuesday) around 14:30 Room F, Conference Room 202 "Introduction of a platform that covers everything from the development, manufacturing, to characterization of LNP formulations."

Our company will be exhibiting at the 30th Annual Meeting of the Japanese Society of Gene and Cell Therapy, which will be held from July 16 (Tuesday) to July 18 (Thursday), 2024. At our booth, we will introduce groundbreaking solutions for gene therapy research and development, including the stability evaluation device Stunner and the Leprechaun, which can evaluate the physical properties of lentiviral exosomes. We invite you to visit our booth. Event Name: 30th Annual Meeting of the Japanese Society of Gene and Cell Therapy Date: July 16 (Tuesday) - July 18 (Thursday) Venue: Pacifico Yokohama Conference Center Booth: #18 Details: https://square.umin.ac.jp/jsgct2024/

Our company will be exhibiting at BioJapan 2024, which will be held from Wednesday, October 9. At our booth, we will showcase lipid nanoparticle (LNP) related products, as well as groundbreaking analytical devices for research and development in gene therapy and biopharmaceuticals. We invite you to visit us at Pacifico Yokohama! Exhibition details: ■ Dates: October 9 (Wednesday) - October 11 (Friday), 2024 ■ Venue: Pacifico Yokohama ■ Booth #: D-97

Our company will be exhibiting at the 41st Medicinal Chemistry Symposium, which will be held from November 20 (Wednesday). Unchained Labs will propose the automation of chemical research through customizable automation devices. We look forward to seeing you at the venue! Exhibition details: ■ Dates: November 20 (Wednesday) to 22 (Friday), 2024 *Corporate exhibitions will be held on the 20th and 21st for two days ■ Venue: Kyoto Terrsa ■ Details: https://mcs2024.jp

In vector development, understanding the ratios of various particles such as titers, Empty/Full, and impurities like aggregates, as well as stability, are essential evaluation criteria. We will introduce analytical methods that can perform these assessments with high precision, quickly, and conveniently using a small sample size, primarily focusing on AAV vectors. ◾️ Details and registration here >> https://eventory.cc/event/interphexonline24/schedule?day=14888 ◾️ Event name: INTERPHEX Online Conference 2024 Gene Therapy Day ◾️ Date and time: November 29 (Friday) 15:30 - 16:00 ◾️ Speaker: Takuma Iwasaki, Field Application Scientist, Unchained Labs, Inc. ◾️ Organized by: INTERPHEX Secretariat 【Pre-registration required, free of charge】 *This seminar is part of the Gene Therapy Day program at the INTERPHEX Online Conference 2024 organized by the INTERPHEX Secretariat.

We will be releasing a recorded video of the presentation from the Jihousha seminar on "Trends in Drug Discovery and Development of Biopharmaceuticals" held in June this year for a limited time! **"New Solutions" for the Evaluation of Physical Properties and Stability of Biopharmaceuticals Provided by Unchained Labs** ■ Overview Antibody-drug conjugates (ADCs) are biopharmaceuticals that have garnered attention due to their pharmacological activity and the excellent specificity of antibodies. However, evaluating their characteristics is very challenging due to the rarity of samples and their tendency to aggregate. In this webinar, we will introduce the platform from Unchained Labs that allows for the quantification, quality assessment, aggregation, conformation, and colloidal stability checks of ADCs and DARs in small amounts and high throughput, making it easy to optimize formulation conditions. ■ Speaker: Yuji Senoo | Field Application Scientist, Unchained Labs, Inc. ■ Availability: Until Tuesday, December 3, 2024 ■ For more details and to watch, click here >> https://go.unchainedlabs.com/l/907652/2024-10-23/zbln1

Creating perfect lipid nanoparticles (LNPs) requires technology. Testing flow rates and formulations one by one to find the appropriate size of LNPs is time-consuming and wastes valuable payload. Additionally, scaling up often requires new workflows, and there are always such challenges in new gene therapy research. Nunchuck is a groundbreaking platform that combines two critical steps necessary for producing LNPs of optimal size: Total Flow Rate (TFR) screening and LNP formulation exploration. It can screen eight types of TFRs in just 10 minutes, quickly finding the sweet spot and allowing immediate production of LNPs with capacities ranging from 0.5 to 200 mL. Moreover, the produced LNPs can be quickly evaluated for physical properties, such as payload measurement, using Stunner. This webinar will introduce how to conduct TFR screening suitable for the purpose of creating size-tunable, high-quality RNA-LNPs and how to scale up. We will also demonstrate how to evaluate the produced LNPs with Stunner.

You can view the upcoming webinars and recordings of past webinars on our website (currently only English webinars are available. Japanese webinars will be announced as they become available). Website: https://www.unchainedlabs.com/webinars/

Buffer exchange and concentration of biological products and gene therapy samples can take away your focus and precious time, even if it's just a few samples. Furthermore, achieving the goals of exchange and concentration intricately is always a challenging task. In this webinar, you will see how easy it is to set up buffer exchange and concentration for biological products and gene therapy samples using our new product, UNAGI. We will showcase an example of how UNAGI provides accurate and consistent buffer exchange for mAbs and proteins. Speaker: Field Application Scientist, Unchained Labs Yuki Ooshiro

Is the concentration quantification of proteins and nucleic acids always measured for each sample? Quantification for each sample is time-consuming and labor-intensive, and there are also issues regarding accuracy. Lunatic is a next-generation spectrophotometer that can perform high-throughput quantification of up to 96 samples with just 2uL of sample volume in about 5 minutes. In this webinar, we will discuss why Lunatic is the optimal UV/Vis spectrophotometer for the concentration quantification of proteins and nucleic acids, including the principles behind it.