SK Biopharmaceuticals was the first pharmaceuticals company in South Korea to carry out the entire process from discovering innovative new drug candidates, develop and commercialize a molecule in the field of epilepsy and successfully get New Drug Approval by FDA without partnering or licensing-out.
NDA is significant as a starting point for products to be released into the market, and through this session, Dr. Cho would like to introduce Korea's first in-house new drug approval and commercialization case by sharing the NDA approval process and its strategy of XCOPRI, a product launched in the US by SK Biopharmaceuticals.
In addition, Dr. Cho will present how commercialization of a product is closely related with clinical development process and how key clinical data has been developed as key marketing message in the market, providing the new treatment options for healthcare professionals and patients.

CAR-T therapies are autologous, meaning that cells are?taken from a patient?to create an individualized treatment. A major challenge is creating a uniform product that achieves the same results every time.
In other words, the patients are in different stages of their tumors, and also in different stages of treatment, however, the final product specifications are pretty similar.
In order to solve these difficulties, this presentation intends to promote patient-centered CAR-T development.

Patient-Centric CAR-T Development
- Strategies to address the manufacturing challenges
- Patient-Centric Specification
- Equipment Selection based on Quality Risk Management

The most common movement disorders in the world are essential tremors and Parkinson's disease. These movement problems are caused by different etiologies and have consequently been treated with a variety of medications and surgical procedures. Despite differing etiologies, aberrant muscle tension and contraction can explain the symptoms of several illnesses. CaV3.1 T-type Ca2+ channels are hypothesized to play a crucial role in the genesis of core dysfunction in these three movement disorders. Injection of CaV3.1 antisense-oligo nucleotides (ASO) intrathecally effectively decreases motor symptoms in animal models of essential tremor and Parkinson's disease. CaV3.1 ASO may be a versatile medication for lowering the primary symptoms of movement disorders, allowing physicians to focus on individual variation in the development of these conditions.

Gene therapy has been highlighted as next generation therapeutics and many pharmaceutical companies are developing genetic therapeutics. Even though gene therapy has infinite potential, it has challenge in terms of delivery. Naked genetic material is impossible to be delivered into cells, so proper delivery system is required for efficacy of gene therapy. Broadly using delivery platforms like LNP, AAV has limitation for tissue specificity, immunogenicity, encapsulation, and scalability. Polymer nanoparticle is novel gene delivery system to overcome those limitations. Genedit is actively developing Polymer nanoparticle and has numerous polymer library named Nanogalaxy™ platform. Nanogalaxy™ platform is generated through iteration research cycle and proved great transfection efficiency of genetic materials in rodent and non-human primates. This technology will lead unlocking the potential of genetic drugs.

Neurodegenerative diseases (NDDs) are age-related disorders characterized by progressive neurodegeneration and neuronal cell loss in the central nervous system. Neuropathological conditions such as the accumulation of misfolded proteins can cause neuroinflammation, apoptosis, and synaptic dysfunction in the brain, leading to the development of NDDs including Alzheimer's disease (AD) and Parkinson's disease (PD). MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression post-transcriptionally via RNA interference. Recently, some studies have reported that some miRNAs play an important role in the development of NDDs by regulating target gene expression. MiRNA-485 (miR-485) is a highly conserved brain-enriched miRNA. Overexpression of miR-485-3p induces the pathological changes of AD with induction of amyloid-beta, Tau protein deposition and microglia activation, and suppression by antisense oligonucleotide (ASO) reverses these effects including clearing of amyloid-beta and Tau, reduction of neuroinflammation and induction of neuroprotection and neurorestoration. BMD-001 is a polyionic nanoparticle structured to carry the ASO targeting miR-485-3p and sized to cross the blood-brain barrier. A surface ligand targeting the LAT1 receptor was added, and entry into CNS was highly increased. Importantly, and unlike other ligand-amended CNS delivery systems, the BBB receptor is also expressed by microglia, neurons, and astrocytes, facilitating the ultimate benefit of this approach. Finally, this drug complex now called BMD-001 shows recovery of cognitive function in AD disease-model animals treated intravenously.

Understanding the genetic etiology of neurological disorders can advance precision medicine by providing genetic diagnosis and targeted therapy. In the past, germline mutations, which are transmitted from parents or newly arise from parental germ cells, were considered as major genetic causes for neurological disorders. However, we and other groups have shown that somatic mutations in the brain, which can arise from neural stem cells during development or over aging, account for a significant fraction of many brain diseases ranging from neurodevelopmental, neurodegenerative, and neuropsychiatric to neoplastic diseases. Identification of disease-causing somatic mutations or mutated genes can provide new insight into molecular pathogenesis and therapeutic targets for neurological disorders with unprecedented therapeutic options. Regarding targeted therapy, RNA therapeutics such as antisense oligonucleotide (ASO) and small interfering RNA (siRNA) are emerging as promising therapeutic tools for treating genetic neurological disorders. While the number of either approved or investigational ASO and siRNA drugs indicated for neurological disorders with germline mutations is on a steep rise, such RNA therapeutics can also be attractive modalities against neurologic disorders with somatic mutations. In this seminar, I will highlight various neurological diseases caused by brain somatic mutations and introduce Sovargen’s ASO pipelines targeting these conditions.

Blood-brain barrier (BBB) is a major hurdle to deliver various therapeutic modalities such as antibodies, peptides, and oligonucleotides for treating brain diseases. The development of an innovative shuttle platform to penetrate BBB is a large unmet need and receptor-mediated transcytosis is the most notable biological mechanism for BBB penetration. Here we introduced the aptamer-based technology which can effectively transport various types of drugs to the brain. We discovered the aptamer that is highly selective for transferrin receptor (TfR) which is one of the promising targets for BBB transcytosis. TfR aptamer showed the target selectivity with the affinity of ~14nM to human TfR and cross-species reactivity. Both in vitro and in vivo experiments demonstrated that the aptamer itself successfully penetrated the artificial endothelial layers and brain BBB. TfR aptamer were simply conjugated to antibodies, the most largest therapeutic modality, with aptamer-to-antibody ratio of 1~2, and in vivo experiments demonstrated the efficient brain delivery of therapeutic antibodies. The results based on the characterization of its biological and biochemical properties suggested that TfR aptamer is very suitable and widely applicable as a BBB shuttle.

Messenger RNA (mRNA)-based drugs have emerged as a relatively new concept in drug development. The potential of mRNA-based therapeutics that can express almost all proteins, combined with excellent safety and flexible production processes, has been actively studied in various diseases. Over the past decade, clinical development using mRNA therapeutics has been rapidly expanding into various fields including cancers as well as infectious diseases. mRNA, a major component of mRNA therapeutics is synthesized through in vitro transcription (IVT) using a DNA template encoding therapeutic proteins or antigens and bacteriophage RNA polymerase. When injected mRNA enters the cell, it is expressed as a protein in the cytoplasm and functions as a soluble protein as well as an intracellular and transmembrane protein, which is a revolutionary extension to the targets that were previously considered undruggable. Recently, two mRNA vaccines were recently approved for the first time to prevent COVID-19 infection and have proven to be more effective than expected. Since these results lead to the expectation that high efficacy will be reproduced in the treatment of various diseases including cancers, mRNA-based therapeutics will be actively studied in clinical practices as a next-generation new drug modality.

Drug development process is long journey taking more than 5 years. Even with heavy efforts made by different stakeholders on drug development, the products often underperform or fail due to lack of proper roadmap to follow from the start through development, approval and launch. For successful drug development and to bring innovative therapeutics to patients with unmet medical needs, it is critical to begin the development with end in mind.

The Target Product Profile (TPP) and Clinical Development Plan (CDP) are strategic development process tools that describe high-level concept of the drug product goal and the path. Implementation of a robust and disciplined TPP and CDP can not only guide the product’s path forward, but also help to drive alignment in cross-functional strategies, leading to more effective and cohesive product development. The TPP should be developed early in the development process, outlining differentiation of the product compared to competitors, how the drug can be positioned in the competitive landscape, and other important product-specific attributes. CDP needs to be developed to efficiently achieve the TPP. The TPP and CDP are fluid, dynamic documents, and as more details become available throughout the development process, a more complete TPP and CDP evolve.

The current presentation will detail how TPP and CDP can be developed and utilized during the course of clinical development and their value.

Interest Areas: US/EU orphan drug designations, expedited drug development pathways, fast track approvals

Abstract Keywords: Orphan drugs, fast track, breakthrough therapy, priority review, new drug approvals (NDAs), new biologic approvals (BLAs), accelerated approval, priority medicines (PRIME), accelerated assessment, conditional marketing authorization

Objective:
Present the expedited drug development programs overview inclusive of orphan drug designations introduced and practiced by global regulators to support enhancement in the efficiency of innovative drug therapy review and approval in addressing unmet medical needs

Content:
Drug development is a long journey taking extensive 10 to 15 years of clinical development and regulatory submission/review activities. For patients left without treatment options particularly under serious conditions and/or life-threatening situation, acceleration of innovative therapies engaging molecular genetics, immunology and rare disease research, etc. has become more critical.

In order to accommodate such urgent and unmet medical needs, global regulators such as US FDA and EU EMA have been proactive to support in speeding up the process for development of innovative new therapies. Recent efforts put forth on novel trial designs, novel endpoints, and expedited pathways altogether are breaking down barriers between industries pursuing such new drug development and patients in need.
Furthermore, such global regulators have been playing the critical roles in developing several good review practice tools to enhance the efficiency of drug therapy review and approval where we will discuss such overall expedited development programs with each trend analysis of orphan drug designation, priority review, fast track designation, accelerated approval and breakthrough therapy designation.

K-CAB is Korea’s 30th NME drug that is classified as a P-CAB drug. It has received approval in Korea in July 2018 with indications for ERD, NERD, GU, HP eradication, and maintenance of healed ERD. With 5 indications, K-CAB has the most indications approved out of all the P-CAB drugs in Korea.
There are 4 P-CAB drugs that have been approved worldwide (revaprazan, vonoprazan, tegoprazan and fexuprazan) and 3 out of the 4 have been developed in Korea, with vonoprazan being the exception. Korea is currently pioneering the development of P-CAB drugs.
Although proton pump inhibitors (PPIs) are prescribed as the main treatment for gastroesophageal reflux disease, P-CABs, which meet the unmet needs of PPIs are anticipated to be the main next generation treatment of GERD with high expectations to replace PPIs in the GERD treatment market.

K-CAB was launched in Korea during March of 2019 and recorded sales of more than 20 billion KRW in the first year. The success in Korea provided the confidence to challenge the global market, with global development and licensing-out activities commencing in January 2020.
As a result, K-CAB has been successfully licensed out to 34 countries and was launched in China under the brand name ‘Taishinzan (compound name, Tigolasan)’ this April, announcing K-CABs appearance to the global stage.
In addition to China, K-CAB is currently under development in the US by a company that specializes in GI development and has recently completed the EoP2 meeting. K-CAB is also looking for opportunities in Europe having completed the EMA SA meeting.
With global development of K-CAB progressing at a very fast pace, K-CAB is working towards reaching 100 countries and 2 trillion global sales.

This concludes the introduction and development history of K-CAB.
May K-CAB’s on-going success story aid companies that are looking to succeed in globalization of drug products and or global business.

New drug development is full of complex decision makings. Of all the considerations for the decisions, there is no doubt that patients' need should be the most important element. Then what are necessary steps to translate the patients' need into solid clinical development program? It is the place where marketing and clinical development meet. Marketing is one of the key principles in new drug development. Key steps are following. 1)Understanding the patients' journey and need, 2)understanding the new molecule's benefit, 3)Mapping out the current medical practices, 4)Predicting future medical practices based on competitive landscape, 5)Selecting a patient group to serve by the new medicine 6)Clarifying differentiations the new molecule can provide within the selected patient group( Differentiate or Die). These steps needs to be reiterated going through different stages of clinical development.

The discovery and development of new medicines is a long, complex and rigorous process. It’s crucial to have differentiated clinical and regulatory strategy in drug development for the successful commercial outcome. Any company developing a new pharmaceutical or biotechnology derived product requires to ensure it achieves its strategic goals such as regulatory and commercial success. Only if the perspectives of all relevant disciplines are integrated into the development plan can the project truly reflect corporate goals. Multidisciplinary and aspirational approach and effort from all members of the development team, are extremely valuable and predictive of the success of any program.
Drug discovery and development is a staged process aligned within a regulated environment that is also staged. The activities within this process are not linear, often occurring in a reiterative and parallel fashion. To ensure effective communication with either internal or external stakeholders at right time, it’s important to set up a strategic plan how to identify the key differentiating features and competitive positioning of developing drug, who and when should be involved at this staged process.
Clinical Development Plan (CDP), which can be viewed as the map of how to get there is considered as the core document for the development team to provide the conceptual framework for scientific, commercial rationale, the entire clinical trials program to support regulatory approval for the intended indication, regulatory consideration, market access strategy based on competitive advantage as well as target product profile (TPP). It can be used to address issues early in the product development process and prevent late-stage development failures. Clinical trial plan should be conducted in consideration of other aspects in the CDP to generate the information necessary to support the label claims which are directly connected with regulatory and commercial success.

Statistics in clinical research is a fundamental key to establish a valid clinical trial design and also a commercial success. It is very important to collaborate with statisticians from the very early stage of clinical development not only for a statistical analysis development but also in establishing an objective framework and protocol development. In this presentation, general concepts in this aspect will be discussed.

For the successful commercialization of new product, timely cross functional collaboration is critical for solid strategy development and execution across the product development cycle. When clinical trial is designed, it’s often focused on the requirement for the regulatory approval. However, even after regulatory approval, medicine may not be accessible to patients especially in countries with national reimbursement mechanism and in these countries, reimbursement approval so called market access is critical step for patient access. Clinical trial sets the base for market access in both access requirements and key access elements perspective. Eligibility criteria, comparator and outcome measure are 3 crucial elements in clinical trial as those dynamically impact on access requirement of clinical, cost effectiveness and budget impact and also on key access elements of time, price and population. Eligibility criteria highly impacts on reimbursement population and unmet need of patient group affects urgency and priority for the reimbursement. Also, size of patient population determines budget impact, which is one of major requirement for the reimbursement review. For reimbursement approval, clinical and cost effectiveness relative to comparator need to be shown and therefore, usage, effectiveness and cost of comparator highly impacts on reimbursement decision. To prove clinical and economic effectiveness showing value of new product, optimal outcome measure is also crucial and if selected outcome measure is not acceptable as the access requirement, reimbursement approval may not be granted or delayed until sufficient evidence is provided, which ultimately impacts on patient access. As clinical trial design is this much fundamental for the reimbursement approval, market access input is necessary for patient access and new product commercialization. The input can be made from the early development phase, but most critical point will be phase III trial design. For the proposal on 3 main elements, market access strategy needs to be built based on thorough assessment addressing potential payers’ questions and it needs to be aligned as cross functional team. The recognition of the importance on market access and early engagement will enable effective new product commercialization with optimal patient access.

The investment in life science industry has been increasing dramatically over past years, and many great biotech/medtech companies have formed and are successfully developing attractive assets and products. The presentation will focus on investigating recent global and Korean investment market trend, and further analyzing in different angle view to predict the future direction of the investment. Also, it will help to resolve questions on the reason for the interest and the investment in particular areas by the institutional investors.

While investing in the biotech field for 7 years as one of the investors in the major VC field, I have seen many CEO's and Companies making mistakes. Not knowing which choices may effect how on their future funding. I would like to deliver some keywords for the Biotech companies and distinguish which will effect Good or Bad to their future funding.

While the biotech industry has experienced a substantial correction in the past year, the view is that the biotech industry will survive this downturn and eventually thrive again because of the biopharmaceutical ecosystem’s unique importance to solving some of the world’s greatest unmet needs. The industry’s fundamentals remain strong, and demand for innovation and underpin growth strategies will continue to attract global capital and talent. Biotech companies that focus on innovation to help address unmet medical needs of the future and can deliver a promising outlook for revenues will be able to navigate current downturn market successfully. In this presentation, we are sharing, based on our experience, essential factors to overcome and attract capital from ever increasingly competitive global capital market.

Status of the Korea bio industry in the stock market, and the latest trends in IPO market. Further deep dive into the process and different tracks of technology special listing and the strategy for success, which is important track for Korea bio-ventures.

This presentation introduces CHA Vaccine Institute (CVI)’s adjuvant platform technology and pipelines, and shares insights from its recent IPO process. CVI is a research-oriented biotech company, with expertise on therapeutic and prophylactic vaccines, as well as immuno-therapeutics for cancer.
The institute has its own patented adjuvant platform technology, based on TLR 2 and 3 ligands. Vaccine adjuvant ? the word originating from Latin adjuvare, meaning ‘to help, or to aid’ ? is a substance that increases or modulates the immune response to a vaccine, helping to create a stronger immune response in vaccine recipients.
Using this adjuvant platform, CVI has been developing novel vaccines and therapeutic vaccines for infectious disease, including hepatitis B vaccine (both therapeutic vaccine for chronic hepatitis B patients and prophylactic vaccine for non-responders), shingles vaccines (both prophylactic and therapeutic) and influenza vaccine for the elderly. More vaccines are under development using our technology. We are researching cancer therapeutic vaccine and cancer immune-therapeutics next.
Finally, as the CEO of CVI, I will also share my experience in the IPO process with a special emphasis on our technological potential. Last year, CVI was successfully listed on the KOSDAQ market based on the merits of our adjuvant platform. I hope the experience will provide unique insight into the process to both researchers in immunology and investors in biotech and pharmaceutical companies.

-Company Introduction
-KONEX & KOSDAQ Listing process: Why& How?
-KONEX & KOSDAQ Listing process: Pros & cons
-Take home message

A special purpose acquisition company (SPAC) is a company without commercial operations and is formed strictly to raise capital through an initial public offering (IPO) or the purpose of acquiring or merging with an existing company. It has a business purpose that allows unlisted companies that cannot enter the stock market for various reasons to easily enter the stock market. SPACs offer various advantages for companies that have been planning to go public. After imposing the SAPC system in 2010, a total of 114 companies completed the merger by April 2022.
Kainos Medicine, Inc. was established in 2007 and completed an IPO on the KOSDAQ market by SPAC in 2020. Considering the huge cost and funds required to commercialize the developed product, IPO by SPAC can be another channel that can finance easier for bio companies.