mAI BioCurie

Genetic medicines – spanning cell, gene, and nucleic acids therapies (“CGT”) – have the unprecedented potential to treat and cure rare genetic diseases, cancer, and many other devastating diseases. However, the future of CGT is seriously hampered by a very real and practical challenge in development and manufacturing.

There are over 7,000 known rare hereditary diseases that afflict more than 30 million Americans and 400 million people worldwide. Collectively, people living with a rare disease represent one of the largest underserved patient communities, with only 5% of known rare diseases having an approved treatment. To date, FDA has approved over 30 CGTs that address serious diseases including rare genetic diseases and terminal cancers, laying the groundwork for this new therapeutic paradigm. Gene therapy targeting rare inherited diseases that affect smaller populations will pave the way for addressing diseases that affect large populations, such as cardiovascular, autoimmune, neurological, and infectious diseases. With over 2000 clinical trials globally underway, there is a potential tsunami of ~300–400 product FDA approvals in the next few years. These medicines could save millions of lives and alleviate the lives of millions more who live with debilitating chronic conditions. Consequently, CGT is the fastest growing biopharma sector and is projected to reach $62.5B by 2032.

Unfortunately, the high molecular complexity of CGTs combined with the fast-growing demand has created production challenges that threaten the future of this sector:

• Low scalability, inefficiency, poor reproducibility, and a high manual labor component result in extremely high cost of goods (COGs) and protracted timelines, which is problematic given the compressed timelines for CGT development.
• Acute capacity and workforce shortfall are recognized across the industry as major bottlenecks and pain points for CGT.
• Low reproducibility, poorly defined quality metrics, and inadequate data analytics hamper the quality, safety, and efficacy of these new emerging therapies.
• Billions of dollars are wasted annually in direct costs and lost revenue.
• Most importantly, millions of patients who could benefit from CGTs cannot get access.

These issues have led to major shortfalls and delays in getting approved lifesaving CGT products to patients, resulting in patient deaths. Notably, even companies like Johnson & Johnson and Bristol Myers Squib, which have respectively developed incredibly efficacious cell therapies Carvytki® and Abecma® to treat blood cancers, are facing major manufacturing challenges (“This Cancer Therapy is Lifesaving, but There Isn’t Enough of It”, WSJ, September 21, 2023). Patients “lucky” enough to get access to a CGT face price tags ranging from ~$0.5M–3.5M per patient, which Medicare and other payers are reticent to cover.

Healthcare systems must start preparing for the challenge of ensuring that all patients, not just a select few with financial means and privileged access to technology, can benefit from these therapies. This demands an innovative technological solution to bring these lifesaving therapies from niche into mainstream medicine.

We have developed the first AI-driven solution to address the manufacturing bottleneck – the difference between doing “cool science” and making innovative therapies that are lifesaving, accessible, and equitable.

BioCurie is pioneering mechanistic AI (mAI™) to revolutionize cell and gene therapy (CGT) manufacturing to make these lifesaving therapies faster, better, and cheaper. The BioCurie mAI Platform™ is the first scalable AI-driven software platform for CGT process development and manufacturing. Our solution will enable biopharma companies and contract manufacturers to drive down the time, cost, and risk of CGT production, while improving product quality, safety, and commercial viability. It enables developers and manufacturers to accurately predict the best production conditions for their cell, gene, and nucleic acid therapy products. Without having to be experts in AI or machine leaning (ML), our end-users can utilize an intuitive graphical user interface that empowers them to deploy best-in-class AI/ML modeling technology and allow them to focus on R&D and commercial objectives. By conducting millions of in silico experiments, our AI-driven software provides end-users with optimized manufacturing conditions for their specific CGT, leading to faster, better, and cheaper CGT production. It does this by enabling applications that are critical for clinical and commercial success such as process optimization, scale-up, tech transfer (across sites), automation, process monitoring, and root cause analysis (troubleshooting). In doing so, we will transform the current state of CGT production from today’s labor-intensive, brute-force “hit-or-miss” approach to a new data-driven paradigm. Our goal is RIGHT FIRST TIME.

BioCurie’s patent-pending technology platform is the culmination of over 25 years of proprietary know-how developed by Dr. Braatz. The technology has been validated in laboratory and industrial settings showing tangible real-word benefits. Our pipeline includes the first AI-driven software module minimal viable product (MVP) for AAV gene therapy development and manufacturing. The AAV module includes first-in-class validated mechanistic models (algorithms) for AAV production in mammalian HEK293 and Sf9 insect cells, which are the prevailing systems for making gene therapy products, including all FDA-approved AAV gene therapies (the most expensive drugs on the planet). Our models have demonstrated a significant improvement in yield, quality, and time. For example, we have shown that the model can reduce the time to produce a batch by at least 8-fold. Given that an average batch requires approximately 5 weeks and $1.5M to produce enough product to treat 5 adults, our technology allows a biopharma company to generate 8-times as much product and revenue per bioreactor while significantly reducing the variable and fixed costs. Importantly, this means that 8 times as many patients will get access to lifesaving gene therapies. Our technology is continuously evolving and improving, which means this is just the tip of the iceberg.

Our mAI AAV™ module MVP will be launched in 2024 as the world’s first AI-driven software for gene therapy production. In addition to AAV, we have multiple modules in development that will feed into a modular, scalable software as a service (SaaS) architecture. Our versatile platform can keep pace with the science, expanding its applicability to a rapidly growing total addressable market. Our solution is deployable on a global scale to enable delivery of lifesaving therapies to patients around the world.

BioCurie’s AI-driven solution is addressing one of the main underlying causes of disparities in CGT access – the manufacturing challenge – to make these therapies faster, better, and cheaper. With the handful of gene therapies already on the market costing on average 30 times the median household income in the US per dose, there are growing concerns that not all patients will be able to afford these treatments, and this will exacerbate existing inequalities. The worry is that the commercialization of CGTs might further penalize disadvantaged communities and ethnic groups that, on average, have lower incomes and more restricted access to healthcare. Since the field is still fairly nascent, we have the opportunity to preempt this issue and help ensure equitable patient access from the outset.

AAV is the most common vector for gene therapy, as evidenced by more than 250 candidates currently in the clinic, most of which are for underserved rare disease patient populations. The initial focus of the BioCurie mAI Platform™ is on adeno-associated virus gene therapy (AAV-GT). mAI AAV™ – the world’s first AI-driven software for AAV production – can be applied to all stages of process development and manufacturing across the value chain, from preclinical development through commercial manufacturing. Moreover, it can be applied to all major AAV vectors, production cell lines, and bioreactors, which means it could in principle expedite all 250+ clinical stage AAV-GT candidates.

To date, five FDA-approved AAV-GTs are available in the US to treat devastating genetic diseases for the first time, including Novartis’ Zolgensma® to treat spinal muscular atrophy in infants and Sarepta’s Elevidys® to treat Duchenne muscular dystrophy in children. However, AAV-GTs are the most expensive drugs in the world, primarily due to the high COGs that reflect the complexity of current manufacturing. Despite the recognized unmet need and clinical efficacy of these therapies, several companies have recently discontinued development of promising AAV-GT candidates and European payers have rejected covering several approved therapies due to the prohibitive cost. Likewise, for diseases that predominantly affect minority populations such as sickle cell disease, companies without first-mover advantage have been dropping out due to concerns about profitability. By helping to bend the cost curve, our technology could make such candidates favorable for developers and payers in terms of cost-benefit, profitability, and affordability.

Beyond AAV-GT, we are applying our platform to other CGT modalities to maximize the impact of our technology in addressing unmet needs. In collaboration with major research hospitals (including the world’s largest children’s research hospital), we are applying our technology to datasets for cell therapies derived from hundreds of cancer patients, primarily infants and children with life-threatening rare solid tumors. In doing so, we will help our collaborators improve their processes and provide new insights, while at the same time expanding our AI platform to help many more patients in the future.

Our technology will help bring CGTs from niche to mainstream medicine and provide equitable access to all patients, particularly those in underserved populations.

BioCurie’s leadership team combines world-class scientific, clinical, business, and operational experience with proximity to biopharma, academia, and patients.

In 2021, Irene Rombel and Richard Braatz created BioCurie to revolutionize process development and manufacturing of cell and gene therapies (CGTs). Our mission is to provide access to these lifesaving therapies for all patients who would benefit. CEO Dr. Rombel (PhD, MBA) is an industry veteran and entrepreneur with 25+ years of experience in science and business, spanning biopharma, consulting, investing, and academia, and expertise in CGT. Prior to founding BioCurie, she held leadership roles at Spark Therapeutics and J&J, was involved in CGT development, and saw firsthand the great promise of CGT along with the challenges ahead that have indeed become reality for the whole industry. Chief Scientist Richard Braatz (PhD) is a leader in AI, ML, and process control for biomanufacturing. Professor Braatz is the Director of the MIT Center for Continuous mRNA Manufacturing, the Associate Faculty Director of the Center for Biomedical Innovation, and has worked with over 20 biopharmaceutical companies to help with their most challenging manufacturing problems. Over the past 5+ years, he has focused most of his research on CGT anticipating that this would become a major unmet need. Notably, he developed the first validated mechanistic models for AAV production, resulting in major improvements in yield, quality and speed. Notably, he has advised FDA on data modeling and advanced analytic since 2005, and is one of their advisors on AI/ML for biopharmaceutical manufacturing, including defining the term “AI” for the industry and regulators. Hannah Kennedy, our head project engineer with a Bachelor’s degree in biomedical engineering, works closely with our collaborators to understand the end-user needs for manufacturing CGTs. She acts as a mediator between end-users in R&D or commercial CGT manufacturing to create an intuitive product.

To build upon our unique combined expertise CGT and AI and expand our substantial network, we have assembled a world-class Board of Directors and Advisory Board of world-class industry leaders that bring tremendous experience and proximity to the communities we are serving, including biopharmaceutical companies and research hospitals that develop, produce, and deliver these therapies to patients.

To ensure that we are developing a commercially viable product that meets a major unmet need, we have been in dialog with 50+ biopharma companies, contract manufacturing, and research hospitals. This confirms the magnitude of the painpoint in CGT development and manufacturing across the industry, and the need for a transformative solution like the mAI Platform™.

We have collaborations with St. Jude’s Children’s Hospital and Children’s National Hospital, and are applying the mAI Platform™ to patient-specific cell therapy data for infants, children, and adults. Our near-term goal for these collaborations is to leverage our AI technology to develop optimal processes that result in faster, safer and more potent cell therapies for cancer patients. Importantly, these data are helping to improve and validate our AI platform, which will then be applied to CGTs for other underserved disease indications, both rare and common.

With the mAI BioCurie Platform™, we are pioneering a new product category: AI-driven software for decision making in CGT development and manufacturing.

The unique challenge of CGT production is a function of three layers of complexity: (1) the high biological complexity of each therapy, (2) the high degree of variation among CGTs even within the same class of therapeutic modality (e.g., AAV gene therapy), and (3) the high operational complexity of developing and manufacturing each therapy. This challenge is compounded by an industry-wide practical problem that is a deal-breaker for AL/ML: lack of CGT data, and the prohibitively high cost and time to generate such data. A problem of this magnitude calls for disruptive innovation, which inspired us to create the mAI BioCurie Platform™.

What is the status quo? Biopharmaceutical companies and contract manufacturers are relying on legacy processes and modeling approaches used for traditional biologics, which are relatively simple and homogenous. These approaches are woefully inadequate for CGTs. The current practice known as statistical design of experiments (DOE) requires a large number of experiments to build models, which means it is a costly, low throughput approach. Some companies and researchers are exploring data-driven ML, which will fail for an important practical reason: big process datasets do not exist for CGT and are prohibitively expensive and time-consuming to produce (see AI section).

How can our solution succeed where others have failed? We have developed an innovative proprietary AI-driven modeling platform that incorporates decades of knowledge spanning biology, chemistry, and physics in the form of mechanistic models for CGT production. This allows us to accurately predict the best manufacturing conditions beyond where data have been collected. Not only do we overcome the limitations of small, sparse data, we can make predictions that can extrapolate well beyond experimental conditions to enable major step changes in productivity. Components of our technology have been validated in research and industrial settings for many therapeutic modalities, including AAV gene therapy. Our models have demonstrated a significant improvement in yield, quality, and time.

How can BioCurie’s solution catalyze broader positive impacts from others, and change the market? The raison d’être of the mAI Platform is to empower developers in industry and academia to develop and manufacture CGTs by addressing major bottlenecks and painpoints. Our target customers fall into four main segments: Biopharma, contract manufacturers, research organizations, and tools companies. Customer benefits delivered by BioCurie’s solution – speed, quality, reproducibility, flexibility, and lower costs – translate to greater probability of success and higher NPV per product. Furthermore, by allowing companies to significantly drive down the COGS, we enable CGTs to be priced at a point that is both affordable for payers (and patients) and profitable for companies. This is essential for the financial viability and sustainability of the CGT sector, helping ensure the continued development of innovative CGT products for an increasing number of unmet medical needs.

CGTs are potentially “one and done,” meaning that a single dose or short course of treatment can be curative for a vast range of diseases. By enabling the fast, robust, scalable development and manufacture of CGTs, BioCurie’s mAI Platform™ addresses Targets 3.2 and 3.3 of UN Sustainable Development Goal 3.

Target 3.2: Our AI-driven solution addresses the preventable death of newborns (3.2.2) and children under 5 years of age (3.2.1). Rare genetic diseases afflict more than 200 million children worldwide, a third of whom will die before their 5th birthday. Most of these diseases are chronic and progressive, and many manifest at birth or within the first two years of life. Currently, only 5% of known rare diseases have an approved treatment. Fortunately, CGTs can bridge this gap with their unique ability to treat and cure many genetic diseases by directly addressing the underlying genetic cause. Of the ~4000 CGTs currently in preclinical or clinical development, about a third are treatments for rare genetic diseases. CGT data from our collaborators include cell therapy datasets for children aged 3–5 years for a variety of rare lethal cancers.

The FDA has approved only a handful of CGTs that can treat rare, life-threatening diseases in young children, including Zolgensma®, Elevidys®, Skysona®, and Zynteglo®. However, these products are expensive to make, resulting in price tags of $2.1M–$3.3M per patient, which makes them inaccessible for most patients. BioCurie’s solution will bend the cost curve to democratize these lifesaving therapies for all infants and children who could benefit.

Target 3.4.1: Our solution also addresses the premature mortality from non-communicable diseases (NCDs), such as cancer, diabetes, cardiovascular, and chronic respiratory disease. The human, societal, and economic impact of these diseases is profound and growing as populations age. Unfortunately, many disease indications within these major therapeutic areas cannot be addressed with current medicines, which is an unmet need that impacts hundreds of millions of patients globally.

CGTs have the potential to treat and cure many of these recalcitrant diseases. Of the ~4000 CGTs in development, over a third are for a broad range of cancers. Numerous CGTs are in preclinical and clinical development for diabetes, cardiovascular, and chronic respiratory disease, and the FDA recently approved the first cell therapy product for type I diabetes.

There are two major hurdles to overcome before CGTs can make a significant impact on these common NCDs: scalability and cost. First, the cumulative number of patients suffering from these diseases is much greater than rare genetic diseases, which creates a logistical challenge as current processes are not scalable. Supply cannot meet demand without technological innovation. Second, each CGT is expensive due to manufacturing issues. Bottom line: industry can’t produce enough CGT products to meet the unmet medical need - and even if it could, patients wouldn’t be able to afford them. BioCurie’s technology can play an important role in democratizing these remarkable therapies. Since these medicines are potentially curative, they would be pharmacoeconomically beneficial in addition to alleviating disease and suffering.

From the outset in 2021, we knew that solving the CGT manufacturing bottleneck in the biopharmaceutical industry would require harnessing AI in an unprecedented manner. AI/ML approaches driven purely on data, while effective for some tasks such as playing chess and Go, would not be effective in CGT manufacturing due to the limited quantity and quality of data and the high time and cost needed to collect such data.

The mAI BioCurie Platform™ for building models and making decisions integrates suites of components that can be mixed and matched for the particular therapy and user objective. One suite of components are fit-for-purpose data analytics and machine learning (DA/ML) methods for building models for CGT applications. The second suite of components build mechanistic models describing the individual steps in the manufacturing process; more precisely, the mechanistic models are based on information on the biology, physics, and chemistry that we have extracted and curated from the journal literature, patents, and other sources. These components mathematically describe processes that occur within cells, the transport of molecules into and out of cells, interactions between different cell populations, and the effects of fluid dynamics. 

The mAI Platform™ integrates and coordinates the mechanistic and DA/ML models to describe the entire production process, filling in with DA/ML modeling when appropriate. The various modeling components are implemented in a highly computationally efficient manner with GPU computing used to speed up the model building. A third suite of components employs the models to make decisions, with each component solving a particular objective, such as design of process operations, design of a real-time model-based control system to reduce the effects of cell-to-cell variations and disturbances, and real-time monitoring of process operations. The fourth suite of components is used to construct the graphical user interface for each modality. The last components are the database containing curated scientific and process data, and a software tool for identifying outliers which are then analyzed by a CGT expert.

Our platform is modular by design, allowing us to plug-and-play components as needed for each CGT modality. Multiple layers of security have been implemented with SaaS integration in mind from the start, so that our solution is deployable on a global scale to enable delivery of lifesaving therapies to patients around the world.

The mAI Platform™ leverages several decades of scientific and process data, which we scrape from the journal literature and patents. In addition, we leverage CGT process data from our collaborators, and over time data from our future customers will also feed into the platform for continuous improvement. (To incentivize data sharing, we will offer a discount on the software.) Before data are fed to the database, the data are sent to the software component that identifies likely outliers for a CGT expert to assess and decide whether to include in the database. The database has been designed to handle both numerical and textual data, including associated metadata which defines information on the data. The database can handle process, omics, imaging, and patient data.

The ethical and responsible application of BioCurie’s AI-driven platform to CGT process development lies at the heart of the technology and the company, as our goal is to bring lifesaving therapies to patients as quickly, safely and cost-effectively as possible. BioCurie’s Chief Scientist, Dr. Richard Braatz, is a trusted thought leader in AI as it applies to biopharmaceutical process development manufacturing and has advised FDA, the White House, and USPTO on this important topic. In September 2023, Dr. Braatz was a keynote speaker at the FDA workshop (FDA/PQRI Workshop on the Regulatory Framework for Utilization of Artificial Intelligence in Pharmaceutical Manufacturing) that is informing the FDA guidance on AI for Biopharmaceutical Manufacturing for regulators and the entire biopharmaceutical industry.

The biggest potential risk for BioCurie pertains to security of the mAI BioCurie Platform™, the proprietary models and databases that we have developed, and the datasets themselves. The security of datasets from customers and collaborators is of paramount importance as these pertain to proprietary processes and CGT candidates, especially those that are patient-derived. We treat the datasets from collaborators and users with the upmost care and security. Data from our collaborators are anonymized and kept in a secure location. For our future users, we have implemented a secure database on our server to store the data, with multiple layers of security.

To minimize regulatory barriers through the evolution of BioCurie’s platform, we requested advice from CBER Advanced Technology Team (CATT), a group within the FDA that provides guidance to companies with novel, innovative technologies for improving human health. We have a meeting scheduled in November to discuss important topics including relevant regulatory guidances and considerations to keep in mind to ensure that we are following best practices for ensuring safety, security, and compliance.

BioCurie’s mission is to have a transformational impact by revolutionizing CGT development and manufacturing. Building a powerful, AI-driven software solution that could potentially be applied to most, if not all, CGTs, is an audacious goal, and the impact for patients, families, and healthcare systems would be profound. Our combined 50+ years of experience in technology innovation and business gives us a pragmatic ability to focus, prioritize, and execute in a disciplined manner. This guides our strategy to ensure we meet our objectives and have a meaningful impact on people’s lives in the near- to medium-term, as well as the long-term.

2024 will be a pivotal year for BioCurie, as we deliver on important objectives and milestones:

• Completing, beta-testing, and launching the mAI AAV™ software product for gene therapy production.
• Developing, validating, and applying ML models for cell therapies to our collaborators’ processes to enable them to efficiently make safer, more potent therapies.
• Building out the scalable mAI BioCurie Platform™ for CGT production.
• Securing strategic collaborations and early customers to test and validate our software product; therefore, enabling further traction in the CGT field.
• Collaborating with stakeholders such as the Greater Philadelphia Precision Medicine Tech Hub and National Institute of Innovation in Biopharmaceutical Manufacturing (NIIMBL), where our software can be leveraged to advance innovation to accelerate the delivery of CGTs to patients.
• Providing training, mentoring, and work experience through internships, particularly students from non-traditional backgrounds, to empower them to pursue exciting careers in AI, CGT, and advanced manufacturing.

2025 to 2029 will be an exciting time when the value of our disruptive technology will be significant in scope and scale, translating to a meaningful impact for patients. To achieve this, we will deliver on key technical commercial milestones:

• Completing, beta-testing, and launching the scalable mAI BioCurie Platform™ for CGT production in 2025.
• Ramping our customer base by utilizing our ever-growing network to reach more patients with lifesaving therapies, with the conservative goal of capturing 5% market share by 2028 (which translates to 150 unique CGT products, each of which represents a novel lifesaving therapy).
• Improving further traction and influence in the CGT field by showing measurable improvement in time, quality, and cost as customers leverage our software for CGT products and processes.
• Substantially increasing the probability of clinical, regulatory, and commercial success for CGT developers, which translates to more innovative therapies for patients, more revenue for our customers, and a better outlook for the sector (where “a rising tide lifts all boats”).
• Expanding our network of collaborators, especially research hospitals, to catalyze innovation while staying close to the patient.
• Adding new modules for additional CGT modalities (such as different viral vectors and cell types) to expand the utility of the platform and its reach to help more patients.

To meet these milestones, we have detailed 2-year and 5-year plans spanning R&D, product development, hiring, and commercialization. Within the next 5 years, we expect to be delivering on our mission to empower biopharma and manufacturers to make CGTs faster, better, and cheaper.

Full-Time: 2

• Irene Rombel, PhD, MBA: Chief Executive Officer
• Hannah Kennedy: Head Project Engineer

Part-Time: 6

• Richard Braatz, PhD: Chief Scientist
• Min Jae Yoo: Chief of Staff
• 4 Computer Science/Engineer Interns

Contractors/Consultants: 3

• Ronald Goldstein: Finance and Accounting
• Kate Shay, Duane Morris: Legal
• Christina McDonough, Fish & Richardson: IP

Board of Directors and Advisory Board: 7

• Rosemary Mazanet, MD, PhD
• Patrick Callahan, JD
• Georgia Keresty, PhD, MPH
• Chris Mason, MD, PhD
• Basant Sharma, PhD

Driven by the major and escalating unmet need in CGT development and manufacturing, BioCurie was conceived by Founders Irene Rombel and Richard Braatz, established and incorporated in 2021. For the past two years, BioCurie has been building the mAI BioCurie Platform™, developing the mAI AAV™ module MVP for gene therapy production, and filed a foundational non-provisional patent application. BioCurie is the culmination of over 25 years of proprietary know-how and expertise and leverages 5 years of Dr. Braatz’ research in AI/ML and AAV modeling prior to BioCurie’s formation.

Irene Rombel is the CEO, President, Chairman, and Co-Founder of BioCurie. Since inception in May 2021, Dr. Rombel is the full-time leader, key decision-maker, and majority shareholder of the Company. Throughout her career spanning academia, investing, consulting, big biopharma, and biotech, Dr. Rombel has succeeded in male-dominated industries through consistently high performance, delivery, and leadership. Her unique background distinguishes her as a leader who can successfully execute as well as inspire other women to pursue leadership roles in STEM industries that are critical to the future of healthcare. To position the company for success, BioCurie has formed a world-class Board of Directors and Advisory Board that is highly diverse and includes C-suite women leaders who are on the Boards of publicly traded companies. BioCurie’s first full-time technical employee and Head of Project Engineering, Hannah Kennedy, is an outstanding biomedical engineering and team leader.

Co-Founders Irene Rombel and Richard Braatz created BioCurie to revolutionize CGT production to bring these lifesaving therapies to all patients that would benefit. To achieve this audacious goal, they realized the need to build a diverse team of enthusiastic, talented people who share the vision, values, and passion for innovation and doing good. Drs. Rombel and Braatz are in a unique position to recognize the value of DEI, as both were born to working class immigrants and were first in their families to go to college. As “outsiders,” they were able to succeed through hard work, academic aptitude, and people who believed in them and took the time to provide guidance and mentoring. This does not mean lowering the bar for excellence, which is patronizing and does not help team members or the company to succeed. Rather, it means recognizing the potential of individuals and giving them the opportunity, support, and encouragement to succeed. To achieve this, BioCurie works closely with the University of Delaware (UD)and DelTech (a local community college) to mentor and teach cutting-edge skills to budding computer scientists and engineers, many of whom come from non-traditional backgrounds (like Irene and Richard). Of the 12 interns who have worked or are currently working at BioCurie, more than half are women and/or persons of color. Importantly, each individual was selected based on merit and a passion to learn and apply new skills to an important problem. This is a win-win for BioCurie and our team members who gain experience in working with a world leader in AI and contributing to a transformative technology platform.

BioCurie continues to work closely with UD and DelTech, with Dr. Rombel regularly participating on career panels and meeting with a diverse pool of students interested in pursuing careers in STEM and the life science industry. BioCurie has been recognized as a “poster child” for innovation and diversity by the Senator Carper and the Delaware Department of State, and was recently highlighted in October in honor of Women’s Small Business month.

To build a company that could revolutionize CGT manufacturing, we focused on the team and key stakeholders from the outset. After creating a company built on the technology and know-how of the world leader in AI for biomanufacturing (Dr. Braatz), we leveraged our network to bring on board world-class industry leaders and entrepreneurs to form our BOD and Advisory Board. We also forged relationships with stakeholders that can provide connections, funding, and/or talent, including FDA, National Institute of Innovation in Manufacturing Biopharmaceuticals (NIIMBL), and local colleges. In 2023, we recruited and trained more than a dozen interns who have helped build our solution, including our Head of Product Engineering and Chief of Staff. We have detailed 2-year and 5-year hiring plans to build out the team, contingent on funding.

To confirm and refine our value proposition, we have met with dozens of companies and research organizations that represent our end-users and target customers. We have collaborations with leading research hospitals, and are in partnering discussions with innovative companies. These strategic collaborations will provide data, validation, and non-dilutive funding.

BioCurie has a two-phase Go-to-Market strategy that strikes a balance between generating near-term revenues and creating long-term value:

Phase 1 (2024–2025) is focused on (1) launching our mAI AAV™ MVP and (2) partnering with leading companies. This will provide validation, revenue, customer feedback, and data. Our beachhead market is biopharmaceutical companies with in-house CGT development and/or manufacturing. Initial BD efforts will focus on collaborating with innovative companies that have CGT process datasets, and understand the value of BioCurie’s technology for improving their processes and/or enabling new processes.

Phase 2 (2026 onwards) is the launch of the mAI BioCurie Platform™ and transition to the SaaS model (see below). Our proprietary pricing model has multiple revenue streams (annual license fee, setup fee, services, milestones). The scalable nature of our software platform creates high operating leverage with >90% gross margins at peak sales.

To create a highly scalable B2B business with global reach and high impact, we are leveraging the software-a-service (SaaS) business model. Our software will be licensed to companies that are developing and manufacturing CGTs via a subscription-based model. This generates multiple revenue streams per customer, with retention as the software will be integral to the manufacturing process. Our software can be applied at any stage of a product’s life cycle, from preclinical development through commercial manufacturing.

The SaaS architecture allows our software to be deployed across numerous customer sites around the world from a centralized location in an efficient, cost-effective manner, enabling high operating margins, rapid growth, and continuous innovation. The nature of the software and the end-markets is ideal for direct B2B sales to biopharma and contract manufacturers. Opportunistically, we could also leverage channel partners such as well-established, non-competitor software, and cloud-based companies that sell into our end-markets to broaden our geographic reach and market penetration.

By design, our scalable solution and business model enables rapid growth, continuous innovation, and the potential to help millions of patients around the world.

BioCurie’s strategy for achieving financial sustainability and profitability is built on a phased plan with multiple income streams from non-dilutive and dilutive funding sources, commensurate with the stage of the technology platform and commercial software products.

Phase 0 (2021–2023): BioCurie has been financed through an investment of $150k by the Founders and a $100k grant awarded in January 2023 by the State of Delaware. These cumulative funds have been used to

• Develop IP and file a non-provisional patent application
• Build most of the prototype commercial software MVP for AAV-gene therapy production (mAI AAV™)
• Build a significant part of the BioCurie mAITM platform
• Build a BioCurie website
• Hire a team of 8 interns, and the first full-time employee (in addition to the CEO, who does not receive any compensation) to head up product engineering
• Analyze data for our collaborators (STJ and CNH)
• Attend industry conferences to learn, build awareness, and forge collaborations
• Establish corporate legal documentation, including agreements with Founders, Board Members, and Advisory Board members

To secure non-dilutive funding, we are writing grant proposals (e.g., SBIR, ARPA-H) and in discussions with biopharmaceutical companies and CDMOs (contract development and manufacturing organizations) to secure strategic collaborations that would generate revenue.

We are also seeking an investment of $3M in seed financing, which would fund 18 months of operations and allow us to achieve major value-creating milestones, including building the mAI BioCurie Platform™ MVP. We have interest from VCs and Angels, but the timing is uncertain given the challenges and uncertainty in the market.

Phase 1 (2024–2025): This period will focus on technology development, launching our first MVP software, collaboration, and building the R&D team. To achieve this, we will generate income from grants, projects for strategic collaborators, and product sales from the mAI AAV™ software. We will seek Series A financing in the ~$20M range, which will allow us to launch the mAI PlatformTM MVP, and build out the BioCurie team, especially R&D and S&M.

Phase 2 (2026 onwards): The long-term goal is to transition from strategic projects and collaborations to the SaaS model, once the platform is ready for prime-time. The main source of income will be from SaaS revenues (multiple revenue streams per customer). The focus will be on customer acquisition and growing sales while continuing to invest in R&D to build new modules to further leverage the scalable platform and address new customer needs as CGTs evolve. In a Bear Market scenario, we expect to be profitable in Y5, generating >$400M in revenue in Y6 with an operating margin of 90%. In a Bull Market scenario, we would be profitable in Y3, generating >$600M in revenue with an operating margin of 93%.

For the past 24 months since incorporation, we have bootstrapped the company with $150k personal investment from BioCurie’s founders and $100k of grant funding, in addition to 100% and 20% of the CEO’s and Chief Scientist’s uncompensated time. This has enabled us to:

(1) Develop the strategy and scalable business model for monetizing the first AI-driven technology for CGT production.

(2) File a foundation patent application.

(3) Hire a team of engineers and computer scientists to help build the platform and AAV-gene therapy MVP.

(4) Develop the AAV-GT MVP (80% complete), and make substantial progress on the scalable SaaS platform (20% complete).

(5) Buy a server (refurbished).

(6) Build a website and a media presence to build awareness.

(7) Attend industry conferences to build collaborations and forge relationships that will evolve to strategic partnerships and future customers.

(8) Assemble a world-class leadership team.

To deliver on our goals for developing and commercializing the mAI BioCurie Platform™ and building the company, we have a detailed execution plan and associated operating costs. As a software platform company, our capex is low and most of our operating expenses in 2024–2025 are for hiring engineers and scientists with the requisite skills to help us build and deploy our solution.

We are seeking $3M seed financing in Q1 2024, which would give us a runway of 18 months. Seed financing will be combined with funding from grants and customer project revenue. This will allow us to deliver on the following milestones:

• Complete, beta-test, and launch two software module MVPs for AAV gene therapy production in the main two systems used for clinical and commercial manufacturing.
• Develop two new software modules for new CGT modalities (undisclosed)
• Collaborate with research hospital to access data, improve and validate. our AI-driven platform, and expand its application to new CGT modalities (e.g. different cell types).
• Design the scalable SaaS architecture, build the SaaS infrastructure, and beta-test the SaaS MVP, culminating in a launch-ready commercial MVP.
• Secure our pending patent application in US and other jurisdictions.

Our projected operating expenses are as follows, contingent on funding:

$3M cash burn over 18 months (assuming 1/1/24 to 6/30/25)

TOTAL OPERATING EXPENSE IN 2024: $1.62M:

(1) Salary expense (human capital) in 2024: $1.34M

• Team (current): CEO (FT), Chief Scientist (PT), Head of Product Engineering (FT), Chief of Staff (PT)
• Team (hire in 2024): CTO, 4 Engineers (process modeling, systems biology, cell modeling, data analytics)
• Contractors, Consultants: Accounting/finance, legal, technical (subject matter expertise as needed)
• Interns

(2) Non-salary expenses in 2024 (SG&A and R&D): $0.28M

• SG&A: IP, legal, rent, insurance, sales & marketing, travel, and other overhead
• R&D: Hardware, software, data storage, tech support

We request $100k in funding. This funding is critical and very timely as it builds upon an innovative MVP that is close to completion and would enable launch of the world’s first AI-driven software for gene therapy production. The execution risk is low as (1) we have a validated prototype, (2) we have an outstanding product engineer (Hannah Kennedy, a biomedical engineer) who has worked with BioCurie since April 2023, and (3) we have excellent computer scientists who worked with BioCurie as interns over the summer of 2023 and proved they can deliver.

Based on our track record, we have exceeded our set goals and have been very productive on a relatively modest budget. This is a consequence of our technical expertise, experience with leading teams, fiscal discipline, and a strict eye on meeting objectives and timelines.

We request $100k to fund

• Salary for a full-time product engineer: $72k
• Salary for a part-time computer scientist: $20k
• SG&A (IP, legal, accounting, conferences): $8k (this will partially offset operating expenses and indirect costs associated with the work detailed below)

This funding will allow us to execute on important value-creating milestones:

(1) Completion, beta-testing, and commercial launch of the mAI AAV™ software MVP in 2024, providing validation, customer feedback, and revenue.

(2) Analysis of CGT and patient data from our collaborators, providing data for training our platform, and validation that our technology can provide useful insights for CGT researchers and developers.

(3) Further development of the scalable mAI BioCurie Platform™ MVP.

BioCurie is at an exciting inflection point. The Cure Residency would be invaluable to the Company’s success as it comes at a critical time when BioCurie’s mAI AAV™ module MVP for gene therapy is close to completion and launch-readiness. Importantly, it will allow us to leverage our first-mover advantage and position us to become the category leader in AI-driven software for CGT manufacturing.

The Cure seed funding would allow us to retain our full-time Head of Project Engineering (Hannah Kennedy) and hire part-time computer scientist to enable us to achieve both objectives within the year-long residency. By enabling BioCurie to achieve these important milestones and value inflection points, the Company will be in a stronger position to secure investor financing and form collaborations. It will allow the company to launch the mAI AAV™ MVP to generate early customer feedback as well as revenue. In addition, the funding would allow us to continue our collaborations with leading non-profit research hospitals to analyze their precious CGT patient datasets, proving them with novel insights to produce safer and more potent therapies.

While the Cure seed funding is essential for moving the company and technology forward, mentoring from Cure’s Executive Advisory Board is the most exciting and strategically important aspect of the residency. BioCurie would greatly benefit from the depth and breadth of the Board, spanning entrepreneurs, investors, biopharma (our target customers), engineers, AI, and healthcare leaders. Also, the timing is ideal as BioCurie is at an important juncture and would get tremendous value from the Board’s advice, guidance, and connections that could lead to new investors, customers, and collaborators. Likewise, the access to Cure’s ecosystem would help us achieve timely visibility and networking opportunities.

The physical residency at Cure’s offices in NYC is also wonderful opportunity to work closely with the Cure team and fellow entrepreneurs. Since the BioCurie team in located in Delaware and Massachusetts, it is not financially feasible to relocate a team member to NYC. Fortunately, CEO Irene Rombel can readily commute between DE and NYC via Amtrak so it is possible to work one or more days per week at the Cure site. Dr. Rombel has strong ties to NYC, serving as a member of Columbia University Translational Therapeutics Accelerator Steering Committee since 2016, and the Columbia University Irving Cancer Drug Discovery Advisory Board since January 2023.