Juvena

Juvena Therapeutics is a biotech company on a mission to unlock the therapeutic potential of secreted proteins ​​through a computationally driven platform that enables the Company to mine proteins that are secreted by human stem cells and bring their therapeutic potential to light. Once identified, Juvena can translate them into biologics for a cure for multiple diseases.

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Dr. Hanadie Yousef, Co-Founder and CEO, focused on studying protein signaling and changes in protein signaling that occur systematically in blood circulation as well as locally in tissues. By understanding these changes that occur during the natural aging process, scientists can target those pathways to rejuvenate one’s own body’s stem cell functions and promote disease modifying phenotypes. Juvena can target those pathways to rejuvenate a patient's organ function and work towards the restoration of homeostasis. These ideas and discoveries laid the foundation of the platform and approach they are taking at Juvena in developing biologics for rare and chronic diseases.

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Dr. Jeremy O'Connell, Co-Founder and CSO, is a proteomics expert in addition to having expertise in machine learning. He received training using quantitative mass spectrometry-based proteomics to deconstruct complex protein mixtures and predict protein-on-protein interactions with machine learning. As she was building the business model, Hanadie was looking specifically for a technical co-founder that would compliment her expertise. With her background in systems biology, and an understanding of the underlying signaling changes in mechanisms to rejuvenate tissue function, someone who could understand and elucidate complex protein-on-protein interactions would allow them to build Juvena’s platform.

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Through a combination of advancements in human stem cells, computational drug discovery, and secreted protein research, Juvena’s goal is to quickly apply secreted proteins to restore cellular functions in various diseases. With this proprietary and efficient platform, Juvena is the clear leader in the secreted protein space and is positioned to disrupt multiple disease treatment standards, especially for rare and chronic diseases.

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Highlights

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* Secreted Proteins as a novel therapy for rare diseases: As first in market, with advanced science and technology, Juvena builds a proprietary platform and decodes stem cell secreted proteins to rejuvenate tissue and develop novel therapies for rare and chronic diseases, with multiple products in pipeline. 

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* Computationally Driven Drug Discovery Platform: Drug development has remained a laborious and time-intensive process, often taking years and hundreds of experiments for a drug to hit the market. There is a need for the implementation of technology that expedites identification of drug candidates while retaining highly predictable safety and efficacy. Juvena has developed a machine learning platform that predicts secreted proteins’ ability to modify a specific disease and ranks them in order of predicted disease efficacy.

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* Novel Restorative Secreted Protein Library: Juvena has discovered that proteins released by stem cells display unique restorative properties. The Company has developed a proprietary library profiling proteins secreted by human stem cells. This library has been built out to characterize over 1,000 proteins and is continuously expanding. This proprietary library is the foundation of Juvena’s computational platform.

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* Numerous Disease Applications: Juvena’s process results in a compounding effect for the computational platform by using screening data to featurize the library and retrain the model, leading to better predictions; as a result, the platform can be extended for many organs and diseases. Juvena is starting with neuromuscular diseases, expecting treatments to be directly administered via injection. The pipeline today also includes candidates for osteoarthritis, metabolic, hepatic and cardiovascular diseases.

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* World Class Scientific and Founding Team: Co-Founder and CEO Hanadie Yousef, PhD (UC Berkeley PhD, Stanford Post Doc), is a Stem Cell & Aging Biology expert; Co-Founder and CSO Jeremy O'Connell, PhD (Harvard Post Doc), is a Proteomics and Systems Biology expert. The Company also boasts a team of senior executives with decades of experience in pharma, drug discovery and development, as well as a growing R&D team, business advisors and scientific advisors from Berkeley and Stanford.

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* Large and Growing Market: The global rare disease market was estimated to be $161.4B in 2020, and is predicted to grow with a 13.1% CAGR. Juvena’s targeted therapeutics can seek expedited orphan drug approval by the FDA in these markets, shortening the cost and time to market for the Company. In addition, Juvena’s technology can be applied to protein discovery across organs. This allows the Company to quickly identify, create and test new therapeutics at the protein-level across diseases.

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* Strong and Prestigious Investors: Juvena has attracted a top tier group of deep pocketed investors globally, including Mubadala Capital, the sovereign wealth fund of Abu Dhabi, and Horizons Ventures, the private investment fund of Sir Li Ka-shing, Bison Ventures, Alumni Ventures, and Jeff Dean, the Head of Google AI, among others.

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Investment Opportunity:

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Juvena has completed a first close for their Series A of $30M at a pre-money valuation of $70M led by Mubadala Capital and Horizons Ventures. The Company is raising a $10M extension on the same terms in part to support the lead program's pre-IND study and pursue new disease areas for development. To date, the company has raised over $47M in combined venture capital and non-dilutive grant funding. The round is oversubscribed with a number of prestigious investors on the cap table, but through Plum Alley's diversity and relationship with the founders we have secured allocation for Plum Alley Investor Members. Please submit your commitments here early to secure your investment.

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The Company’s confidential and private financing documentation and other diligence files are available for review in Dropbox. Please request access to Dropbox materials on the left side panel. Please note all documents are PRIVATE, CONFIDENTIAL and NOT FOR DISTRIBUTION. If you are interested in learning more about investing in Juvena’s Series A, please email Ben Robbins.

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Product & Technology

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Background & Science Overview

Secreted proteins are released from inside the cell to the outside, extracellular space. Such proteins can enact various functions from cell growth to pH maintenance. Since secreted proteins exit the cell, they often bind to receptors on other nearby cells. The diagram below visualizes an example of this, with the secreted protein shown as the blue square, and binding to another cell.

Secreted proteins are natural communication signals in the body. They are responsible for activating the immune response to fight infection, initiating tissue repair processes, and ultimately enhancing and inducing stem cell activation. However, as the ability to generate human stem cells in a dish was recently discovered, proteins secreted by these stem cells represent a novel field of research. Dr. Hanadie Yousef is an early investigator in the field, and has published multiple papers detailing the capacity of secreted proteins to restore diseased human cells. This phenomenon occurs in multiple diseases, including Alzheimer’s, osteoarthritis, and muscle dystrophy. 

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Juvena began by creating a unique library of proteins secreted by human stem cells. The library is a database, and stores information about the features of each protein. Since building a protein library is an extensive process requiring the characterization of numerous traits, it is a time-intensive process even for experts in the field. However, using its proprietary computational platform, Juvena has built a library characterizing over 1,000 discrete stem cell secreted proteins in just a year and a half. The documented traits span receptor interactions, structural properties, and tissue expression, amongst others.

The Juvena team utilizes deep learning models, bioinformatics and computational techniques to in silico rank order and predict what proteins in their library are driving a given disease modifying genotype.The data is then used to retrain the models through an iterative process. Every round of screening enables the models to have a compounding effect because once they generate those hits, that information is used to featurize the library to retrain and results in better predictions. The model is getting smarter with each round of screening. The following image visualizes the library and algorithm’s integration.

Systematic Biologics Drug Discovery Platform

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Juvena’s proprietary library covers these proteins secreted by human stem cells that have been proven to have some therapeutic potential. From there, the Company establishes and screens these proteins for a given trait through human in vitro screening assays established for a given organ. The goal of this process is to identify key drivers of rejuvenation specific to that organ that can then be translated into protein-based therapies. Once the hits are generated in vitro, the Company does extensive preclinical validation in animal models. If these results are positive, Juvena moves to considering safety, manufacturability, and the mechanism of action. The Company uses this top-to-bottom, unbiased method to hone in on novel candidates and novel targets. Once a protein is selected, it is further engineered towards the target product profile. They are also now expanding into antibodies and biospecifics. Since secreted proteins are already produced by the human body and naturally exhibit restorative properties, they likely would not require additional modification to lower toxicity or degree of ionization. The five steps of Juvena’s platform are summarized below. 

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Juvena has been granted a patent protecting the use of purified secreted protein therapeutics. With an additional 14 patents pending, the Company seeks to cover numerous aspects of the process from the protein library to machine learning algorithm. Having used this platform to rank over 300 proteins in silico for neuromuscular and skeletal applications, screened 22 in vitro, and validated 8 in live animal models since its full operation in 2018, Juvena is poised to establish itself as a leader in restorative medicine.

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Juvena’s Pipeline Today

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Juvena has already built and validated its proprietary platform, identifying 22 hits across neuromuscular, skeletal, and metabolic diseases, and has three leads in optimization with one advanced lead candidate. This candidate is in the midst of doing pre-IND studies to bring it to market for a rare autosomal-dominant muscle wasting disease known as Myotonic Dystrophy 1 (DM1). Juvena has now expanded the platform to several different organs, therapeutic areas within neuromuscular skeletal, hepatic, metabolic, and inflammatory disease areas.

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DM1 and DMD are both rare diseases with no current cure. As such, Juvena’s therapeutics would likely be eligible for Orphan Drug designation and expedited approval from the FDA. 

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Myotonic Dystrophy Type I (DM1) - DM1 affects approximately 140,000 people in the U.S; however, a study published in 2021 found that DM1 prevalence was 5X higher than reported. DM1 is typically more severe than Myotonic Dystrophy Type 2. Current treatments for DM1 are primarily physical exercise and do not modify disease. Juvena’s therapeutic for DM1 improves muscle regeneration in human cells, and improves multiple aspects of muscle function in live mouse models of DM1. 

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Duchenne’s Muscular Dystrophy (DMD) - DMD affects approximately 17,000 people in the U.S. It is estimated that approximately 20,000 children are diagnosed with DMD globally each year. DMD is a fatal disease and most patients pass away from it in their 20’s but can live into their 30’s or 40’s with proper care. Current standard treatment for DMD consists of a combination of steroids, beta blockers, and BiPAP machines. Steroids can only slow disease progression by 2-3 years, and are accompanied by drastic side effects such as bone loss. 

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Juvena’s therapeutic candidate for DM1 also shows encouraging efficacy in DMD mouse models, increasing grip strength and treadmill endurance significantly. The potential for a multi-purpose candidate for both DM1 and DMD would prove an exciting opportunity for Juvena’s growth. 

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Market Opportunity & Competitive Landscape

Treatments for rare diseases often lag due to the costly and time-consuming nature of the traditional drug development process paired with smaller individual markets. However, the systemic neglect of rare diseases has created a ballooning market: in 2020, the global rare disease market was estimated to be $161.4B and is predicted to grow with a 13.1% CAGR. Since many rare diseases currently have no treatments, drugs targeting these patients can seek expedited orphan drug approval from the FDA. The ability to quickly churn out efficacious and safe drugs operating on the protein level has remained coveted by the space, and will only become more important as the testing of the boundaries of experimental gene targeting rolls out over the next few years. Importantly, Juvena’s platform is not restricted to rare diseases, as the machine learning algorithm can rank secreted proteins by predicted effect across all diseased organs.

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Juvena has demonstrated the validity of its computational platform in in vitro and in vivo animal model testing, and is currently in pursuit of IND approval for clinical trials. Juvena aims to possess the world’s largest and first disease-driven secreted protein library. This will enable Juvena to license out their platform as needed, and will provide significant leverage for partnerships with well-established pharmaceutical companies.  

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The market map below was created by Plum Alley to help visualize where Juvena fits into the biotech landscape. With the advent of CRISPR technology, the biotech sector is experiencing a growing divide defined by protein-based versus gene-based interventions. Moreover, computational biology has evolved enough to enable in silico components of drug development, which has spurred the rise of computational platforms for candidate identification and/or drug visualization. Juvena sits in a unique position primarily due to its niche focus on secreted proteins, and further differentiated by a machine learning-powered pipeline. As indicated by the market map, most biotech startups are concentrated in genomic or broad proteomic discovery whereas few are focusing on secreted proteins. The two companies that occupy the same category as Juvena are not U.S-based. For context, Serono has a secreted protein library but no computational pipeline; Serono thus formed a partnership with Xantos in 2004, which had computational capability. However, Serono was merged with Merck in 2006, and little has been published on the partnership since then. In 2017, Inpharmatica partnered with Serono to develop novel secreted protein therapeutics. Currently, Inpharmatica is Juvena’s most likely competitor. However, since 2001 Inpharmatica has discovered 200 novel protein sequences, which is a slower pace than Juvena. Thus, Juvena is optimally positioned to spearhead the rapid emergence of secreted proteins as a novel therapeutic across diseases. 

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Team

Key Leadership

Dr. Hanadie Yousef, Co-Founder & CEO - An experienced scientist with a PhD from UC-Berkeley, Hanadie spent 4 years at Stanford Medical School completing a postdoctoral fellowship in the Wyss-Coray lab. During this time, she published in multiple prestigious scientific journals including Nature Medicine and Cell Reports. Of particular note, Plum Alley portfolio company founder (Mammoth Biosciences) and Nobel Laureate Dr. Jennifer Doudna served on Hanadie’s PhD Committee at UC Berkeley. Hanadie has interned at Genentech and worked at Regeneron for over 5 years. In addition, she was a SPARK scholar at Stanford and earned awards at the Bay Area Aging Meeting, the Alzheimer’s Researchers’ Symposium, and the International Society for Stem Cell Research Conference.

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Dr. Jeremy O’Connell, Co-Founder & CSO - Jeremy completed his PhD in Biochemistry, Cellular, and Systems Biology at UT-Austin followed by two postdoctoral fellowships at Harvard University and Medical School. During his postdoctoral fellowships, Jeremy focused on computational mapping of protein-protein interactions and mass spectrometry characterization of proteins. Jeremy has published 13 papers in journals such as PNAS. 

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Dr. Edward Moler, Head of Data Science - Eddie earned his PhD in Chemistry from UC-Berkeley and has spent a combined 12 years at biotech companies including Novartis and Tethys Biosciences. Eddie has also managed analytics/bioinformatics departments at Phoenix Energy Technologies, Quest Diagnostics, GE Healthcare, and Spatial Genomics, Inc. In addition to his ample experience directing bioinformatics initiatives, Eddie also spent over 3 years at GE Healthcare beginning as an Analytics team leader and escalating to R&D Manager. 

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Dr. Jim Maguire, Head of Discovery - Jim obtained his PhD in Chemistry from University of Illinois Urbana-Champaign. After completing his postdoctoral fellowship, Jim honed R&D skills during 6 years as a manager at Ciphergen Biosciences and over 12 years at pharmaceutical company Novo Nordisk. In his spare time, Jim’s expertise was also utilized by Catalyst Biosciences as a consultant.

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Impact

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Altering the course of diseases and longevity 

Juvena is the first and only biotech company with the ability to systematically screen and debut stem cell secreted proteins as a novel therapeutic. Being able to screen in a rapid and disease-specific manner enabled by a computational platform contains high potential for revolutionizing current treatments for many underserved diseases. These diseases affect hundreds of thousands of patients globally, who currently have limited or no treatment options available to them. Juvena possesses the technology and expertise to identify, engineer and produce secreted proteins with outsized therapeutic potential to treat these orphan diseases, bringing relief to patients around the world. In addition, through the licensing potential of the Company’s proprietary protein library, the impact is multiplied through improving drug development processes for other therapeutic companies across disease categories.