Siren Biotechnology is a novel biotech company creating a universal Adeno-Associated Virus (AAV) Immuno-Gene Therapy platform.
Millions of people worldwide are affected by cancer. To meet the need for more robust and effective cancer-treating therapies, Siren Biotechnology has created a universal AAV immuno-gene therapy platform to enable gene therapies to be cheaper, easier and faster for all the patients who need them, starting with rare solid tumors in the brain and the eyes.
Siren Bio was founded by Nicole Paulk, PhD, an Assistant Professor at University of California, San Francisco and previously Postdoctoral Researcher at Stanford University. While at UCSF, Nicole’s lab focused on AAV applications and disruptive technologies that address the current challenges of this application. In 2021, Nicole left her academic position to commercialize this novel AAV technology and founded Siren Bio.
Siren’s innovative platform combines the promise of two transformative therapeutic technologies – AAV gene therapy and cytokine immunotherapy, allowing for efficient and effective drug delivery for tumor killing, significantly reducing the time and cost from earlier generations of AAV development and increasing the accessibility to patients.
AAV gene therapy uses AAV vectors to deliver therapeutic genes to target cells. An AAV vector is a bioengineered tool derived from adeno-associated virus (AAV) and is used to deliver genetic material into target cells for gene therapy applications. Cytokine immunotherapy involves using cytokines (small proteins important for cell signaling) to stimulate the immune system to fight cancer. This approach enhances the body's natural immune response against tumor cells, aiming to activate immune cells, increase inflammation in the tumor microenvironment, and promote anti-tumor responses.
AAV and Cytokine Immunotherapy are combined for super powers. By merging these two modalities, Siren Bio looks to overcome some limitations of each approach individually and create a more effective cancer treatment strategy.
* Massive and Growing Gene Therapy Market: The global gene therapy market has been experiencing substantial growth and is projected to continue expanding significantly, especially with AAV vectors. As of 2024, the market size is estimated to be around $7.3 billion and is expected to reach approximately $52.4 billion by 2033, with a compound annual growth rate (CAGR) of around 25% during the forecast period.
* Breakthrough and Next Generation AAV Platform: Siren Bio created the next generation of universal AAV by combining AAV gene therapy and cytokine immunotherapy to deliver off-the-shelf de-risked cytokines for efficient and effective tumor therapy. The universal platform is agnostic to tumor type with reduced risk and multiple layers of safety, which enables precision targeting and low-dose local administration.
* AI-Driven Robust Pipeline Development: Using AI/Natural Language Processing and big data to select high priority disease indications to apply the proprietary platform technology, Siren has developed a rare and orphan disease strategy with brain and eye cancers as a starting point, providing first-in-class opportunities. Siren Bio is positioned to target all cancer types and beyond.
* Strong and Experienced Team and Advisors: Siren Bio is founded and led by Nicole Paulk, Phd, a renowned scientist and global AAV leader. She is joined by Nathalie Clément, PhD, VP of Vector Development, who has deep experience in AAV drug product development, and Teilo Schaller, PhD, Director of Corporate Strategy and Business Development. Siren also has world class scientific and industry advisors from academic institutions and biopharma companies.
* Strong and Prestigious Investor Group: Siren Bio has attracted a diverse group of investors globally, including Tau Capital, a venture arm of a Sovereign Fund based in Abu Dhabi, Founders Fund, Lux Capital, Valor Equity Partners as well as funding and support from Endless Frontier Labs, California Institute for Regenerative Medicine(CIRM) and MilliporeSigma.
Siren Bio has completed a first close of $20M for the Series A of $30M at a pre-money valuation of $60M led by Tau Capital. The company is raising the remaining $10M for the second close to support the Investigational New Drug (IND) application, GMP vector production, pipeline development and technology innovations.
Virtual Company Presentation
Tuesday, July 2nd, 2024
12:00 pm ET // 9:00 am PT
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Final Investment Commitments Due
Friday, July 12th, 2024
We will take commitments on a rolling basis. Please submit final commitments here.
Funding & Documents Due
Friday, July 19th, 2024
At the end of the commitment period, you will receive details regarding closing documentation and wiring instructions via Carta.
The Company's confidential financing documents and diligence materials are available for review in the DropBox data room. Please request access to data room materials at the top session of the page. All documents are private & confidential, and not for further distribution. If you have specific questions or are interested in investing in Siren Bio, please contact us and submit your final investment amount via this link.
The global gene therapy market has been experiencing substantial growth and is projected to continue expanding significantly. The market size is estimated to be around $7.3 billion as of 2024 and is expected to reach approximately $52.4 billion by 2033. Several factors are driving this growth, including advances in gene-editing and vector technologies, and the rising number of gene therapy clinical trials. The market is dominated by applications in oncology, which represent the largest segment due to the high incidence of cancer and ongoing developments in cancer gene therapies. Other significant applications include treatments for rare genetic diseases, cardiovascular diseases, and neurological disorders. Continuous developments in bioengineering are anticipated to enhance the efficiency of gene therapy in the coming years.
Continuing Evolution of Gene Therapy and Advances in AAV
Gene therapy represents a groundbreaking approach for addressing genetic diseases, employing strategies to modify gene expression with target cells using non-viral or viral vehicles. Adeno-Associated Virus (AAV) has become a pivotal tool in clinical gene therapy for treating a wide range of diseases, due to its safety profile, the ability to enter cells efficiently and to establish long-term gene expression in different tissues. There are currently 238 clinical trials of AAV based gene therapies and they focus on major human diseases including ocular, neurological, metabolic, hematological, neuromuscular, cardiovascular, and oncogenic diseases. It is undoubtedly a technology with considerable promise, but also with a set of challenges still ahead. While there are concerns about the payload size, potential high dosing, immune responses and adverse effects with conventional AAV technologies, advances are being made to the sector. The increased demand also created challenges for the existing manufacturing methods. As more and more gene therapies have reached the clinic, it has become clear that these technological challenges need to be addressed to unlock the full potential of AAV vector gene therapy.
The foundation has been laid and the path for further advances is accelerating. AAV was discovered in 1965 and it took until 2017 for the first FDA approved AAV based gene therapy product, Luxturna, a medicine developed by Spark Therapeutics to treat vision loss due to a rare genetic disorder of the retina. The development of this drug originated from a study at University of Pennsylvania in 1992. Till today, six AAV vector-based gene therapies have been approved by the FDA. Just recently in April 2024, Pfizer announced the newest FDA approved AAV based BEQVEZ for adults with hemophilia B. Pfizer licensed BEQVEZ from Spark Therapeutics in December 2014, and it’s unclear when Spark first started the development of this therapy. Conventional AAV development typically takes about 10-15 years and $2-3 Billion to commercialize. Universal AAVs with a shorter developmental cycle are highly anticipated.
Siren Biotechnology
Siren Bio was founded in 2021 by Nicole Paulk, PhD, an Assistant Professor at University of California, San Francisco (UCSF) and previously a Postdoctoral Researcher at Stanford University. Nicole’s lab at UCSF focused on AAV applications and disruptive technologies that address the current challenges of this application. In 2021, she left her academic position to found Siren Bio to focus on commercializing this novel technology. Siren Bio is building a “universal” AAV platform which will enable gene therapies to be cheaper, easier and faster for patients, starting with rare solid tumors in the brain and the eyes. A major component of Siren’s approach is to be universal, meaning that the Company will use its AAV approach combined with cytokines to treat a full range of cancers and eventually other diseases as well.
“Unlike most ‘novel’ therapeutics in the biotech industry, Siren’s Universal AAV Immuno-Gene Therapy lives up the adjective. Not only is there breakthrough therapeutic potential but Siren’s universal design can shorten clinical development and manufacturing timelines, and finally unlocks the possibility of helping patient populations on a larger scale than ever before in AAV gene therapy.”
- Scott Nolan, Founders Fund
Siren Bio is providing a solution by combining the proprietary AAV platform with cytokine immunotherapy to deliver these engineered cytokines that address tumor-targeting and bioavailability challenges. Using AAV engineered with cytokines as payload to target tumors, such an approach enables long-term cytokines expression which is steady and durable. Cytokines would be produced directly in the tumor microenvironment and are self-limiting, so only low doses are needed, to ensure a safe therapy delivery.
Cytokines
Cytokines are a group of small proteins that play a crucial role in cell signaling. They are made by certain immune and non-immune cells and have an effect on the immune system. They are involved in a wide range of biological processes, including inflammation, immune responses, and the regulation of cell growth and differentiation. Cytokines can be classified into several categories based on their functions, including interleukins, interferons, tumor necrosis factors, chemokines, and growth factors. They can also be made in the laboratory and used to help the body fight cancer, infections, and other diseases.
Cytokines are known to be pleiotropic agents in our body that conduct basal cancer immunosurveillance. However, the traditional cytokine therapies are facing various challenges that limit its therapeutic potentials and effectiveness. They have profoundly short half-lives, which can be up to only a few hours. As a result, they usually fail to provide sustained clinical benefits. They lack specificity when targeting tumors, and often producing off-target effects that are undesirable. Due to these characteristics, high doses are usually needed but they could cause transient toxicity in patients.
Universal AAV Platform
Adeno-associated virus (AAV) is a versatile viral vector technology that can be engineered for very specific functionality in gene therapy applications.
Picture 2 below illustrates the delivery of AAVs expressing engineered cytokines, how it directs tumor cell lysis and activates a series of immune responses for efficient and effective tumor cell killing.
Siren Bio developed a universal AAV immuno-gene therapy platform based on the research from Nicole’s lab at UCSF, using the exquisitely designed AAV vectors that are best-in-class. The platform bypasses significant challenges of cytokine therapies to leverage their potent anti-tumor activities. The advantages of Siren’s platform include:
The safety characteristics of Siren’s platform has been one of the biggest differentiators and it sets Siren Bio apart from other AAV systems:
Siren Bio’s universal AAV system is optimized to drastically reduce the development time and capital needs for each therapy program. Siren Bio aims to make gene therapies cheaper, easier and faster for all patients.
IP Strategy
Siren Bio has developed a strong IP strategy and built a broad patent family to protect its proprietary platform technology, providing a clear path to market. The patent for the original technology that was developed at Nicole’s lab is optioned to Siren from UCSF. Since Nicole founded Siren Bio, the team has filed four new patents of its own for the new technologies with more underway, beyond the original technology. The Company also filed numerous trademark applications. Please see the data room for more information.
AI-Driven Indication Selection
A McKinsey’s report points out one main application for AI/ML in drug development is target selection, selecting the appropriate target to optimize the probability of therapeutic success. Siren Bio is developing a robust pipeline combining its universal AAVs and an AI-driven disease profiling, to enable the first ever iterative indication selection pipeline in gene therapy.
Powered by AI and natural language processing, utilizing big data, Siren Bio is able to select high priority indications for its next generation platform. Through running high throughput organoid testing as well as in vivo validation, the Company has identified the lead asset SRN-101 to target rare cancers of the brain and eye. The multiple indications are all orphan diseases and rare diseases, and such a strategy provides Siren Bio the opportunity to pursue various regulatory designations for accelerated approvals.
Siren Bio’s current priorities include initiating the vector production as well as to complete the IND submission. The Company recently secured a partnership with Catalent, a global leader in pharmaceutical manufacturing, to support the development and manufacturing of Siren Bio’s clinical scale AAV vector productions. Catelent offered a competitive pricing for the first year’s contract with Siren to ensure this exclusive opportunity to manufacture a breakthrough AAV vector. MilliporeSigma [Merck Group] just announced Siren Bio as the winner of its North American Advance Biotech Grant. With this corporate grant, Siren will receive products, technologies and contract testing services for its therapeutic development, as well as consultation and training from MilliporeSigma’s experts. These two strategic supporters will help provide strong and reliable logistics for Siren to launch and conduct clinical trials in Q3 2025.
Inducible Platform
Siren Bio is currently developing a new inducible platform, providing the option to activate payload protein expression with small molecules that are clinically validated through oral administration. There are outstanding benefits of such an inducible platform. The payload’s expression could be reversible, temporal and dose responsive. Such a system provides better control of the gene therapy for some special cases. There are many inducers available with existing safety data packages to leverage. These inducers can be administered orally and the modular is compatible with Siren’s payloads. Currently the engineered inducible payloads are being validated in intro and in vivo to prove the efficacy and feasibility of the inducible platform.
To date, the Company has been funded by $32.5M in total, including the $20M of funding with the first close of the Series A.
Prior to the A round funding:
The Company’s venture rounds have attracted prestigious and deep-pocketed investors:
Non-dilutive grant funding
Siren Bio was awarded a $4M non-dilutive translational research grant funding from the California Institute for Regenerative Medicine (CIRM) in November 2023 and will use this funding to support its pre-IND meeting with the FDA. The Advance Biotech Grant from MilliporeSigma will be in the form of products, technologies and services to support Siren’s development.
Current Raise
Siren Bio has completed a first close of $20M for the Series A of $30M at a pre-money valuation of $60M led by Tau Capital. The company is currently raising the remaining $10M for the second close. The use of proceeds will support the Investigational New Drug(IND) application, GMP production, pipeline development and technology innovations.The terms of the A round are presented below.
Series A Financing Terms:
Terms
Glossary Definitions
Series B Ext. Details
Financing Amount
Total $ raised in this financing round.
$30M Target
Lead Investors
A lead investor is one that invests a material portion of the financing round and outlines the terms for co-investors to participate.
Tau Capital
Post-Money Valuation
Valuation of the company that includes the capital raised in the current fundraising round. Typically calculated as pre-money valuation plus the investment but may vary depending on other factors, such as the conversion of prior round shares.
$60M
Price Per Share
Price set by the lead investor for the Series B Ext. shares. This share price determines the cost basis as well as the conversion price in the event of an exit, change of control, or liquidation.
$6.4097
The current delivery platforms for gene therapies can be primarily put into two categories: viral and non-viral-based. Viral-based gene therapy utilizes viruses as gene delivery vectors, including AAV, adenovirus, retrovirus and lentivirus etc. Non-viral-based gene therapy includes antisense oligonucleotides, siRNAs, and cell-based CRISPR genome editing.
Picture 5 below shows a timeline of currently approved gene therapy products and the delivery platform they utilize, with viral vectors or non-viral systems. Adeno-associated virus (AAV) (in red) vectors have emerged as the preferred delivery choice in clinical trials and FDA approved applications. Big pharmaceutical companies have been setting up their AAV infrastructure and partnering with biotech companies on this effort. There are companies such as Spark Therapeutics developing an AAV gene therapy platform, or working on other types of technological innovations, yet not any of them has developed the universal AAV for all disease types. Siren Bio has positioned itself as the first-in-class, true market leader to disrupt the gene therapy industry.
These are the AAV based gene therapy platforms, all of which have found substantial commercial success. Siren Bio, follows suit, while also being the only company on the market to develop universal AAV for all cancer types and beyond.
Siren Bio is led by a strong team with a group of world class scientific and industry advisors.
Nicole is the founder and CEO of Siren Biotechnology. She was an Assistant Professor at University of California San Francisco and completed her postdoctoral research at Stanford School of Medicine. Nicole is a global AAV leader and is on the scientific advisory board of Dyno Therapeutics, Metagenomi, Johns Hopkins Medicine and other organizations.
VP of Vector Development. Natalie oversees all vector manufacturing operations at Siren Bio. She has unparalleled experience in AAV drug product development, with research focused on improving viral vectors for a variety of gene therapy applications.
Chief of Staff. Akela ensures everyone at Siren is thriving, the lab and business operations are effective and efficient, and the strategic initiatives get from 0 to 1. She received her PhD in Developmental and Stem Cell Biology at UCSF and previously led the single-cell sequencing efforts for gene therapy screening at Gordian Biotechnology.
Siren Biotechnology provides an opportunity to capitalize on the novel AAV technology and the macro-environment trends in gene therapies that are driven by breakthroughs in biotechnology and broader machine learning applications in drug discoveries. It also provides an opportunity to capitalize on the real asset for rare and orphan diseases that Siren Bio has established in its proprietary pipeline.
Considerations with this opportunity include market and business execution risks:
Siren Biotechnology is the first in market biotech company with the ability to develop a next generation universal AAV platform combining cytokine immuno-gene therapy. The traditional gene therapies all take a long development cycle to eventually commercialize. Siren Bio’s novel platform could potentially shorten the development and commercialization timeline, to bring much needed therapeutic solutions to patients in a cheaper, easier and faster way. Especially for the rare and orphan cancers Siren’s lead asset is targeting, many lives in the world could be saved. Siren Bio is truly building a breakthrough biotech company that will disrupt the gene therapy market and the therapeutic industry.
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