– New strategic partnership leverages the power of the Dyno platform, enabling Roche to advance next-generation AAV gene therapies across multiple targets

– Dyno to receive US$50 million upfront cash with the potential to earn over US$1 billion in milestones plus royalty payments

WATERTOWN, Mass., October 24, 2024 — Dyno Therapeutics, Inc., a genetic technologies company applying artificial intelligence (AI) to enable in vivo gene delivery, today announced its second research collaboration with Roche (SIX: RO, ROG; OTCQX: RHHBY) to develop next-generation adeno-associated virus (AAV) vectors for gene therapies targeting neurological diseases. Dyno and Roche previously announced a research collaboration and license agreement for neurological diseases and liver-directed therapies in October 2020. Under the terms of this new collaboration, Dyno Therapeutics provides Roche further access to the company’s field-leading platform and sequence design technologies enabling in vivo gene delivery.

Existing gene therapies have primarily used a small number of naturally occurring AAV vectors limited by low delivery efficiency as well as problems with pre-existing immunity and manufacturability. To overcome these challenges, Dyno has pioneered the application of AI and high-throughput in vivo data collection to engineering AAV capsids for improved tissue targeting, immune-evasion and manufacturability. Dyno’s Low-Shot Efficient Accelerated Performance (LEAPSM) technology, paired with the capability to make billions of in vivo sequence-function measurements each month, enables optimization of capsids for therapeutic success at an accelerated rate. As a platform built to solve the most critical challenges facing gene therapy developers, Dyno’s industry-leading gene delivery solutions enable Dyno partners to create ever better gene therapies.

Under the terms of the new agreement, Dyno is responsible for the design and discovery of novel AAV capsids with improved functional properties. Roche in turn is responsible for conducting capsid validation studies and further preclinical, clinical, and commercialization activities for multiple neurological gene therapy product candidates leveraging novel Dyno capsids. Roche will pay Dyno US$50 million upfront, along with additional payments during the research phase of the collaboration, plus potential preclinical, clinical, and sales milestone payments totaling over US$1 billion, and royalties on net sales of commercial products.

“This new collaboration with Roche, focused on developing next-generation gene therapies for underserved patients with life-altering neurological diseases, is a testament to the outstanding progress made by Dyno’s platform and to the commitment we make to partners in all of our projects,” said Eric Kelsic, Ph.D., Founder and Chief Executive Officer of Dyno. “Our approach combines extensive in vivo data with the world’s most advanced AI models for sequence-function prediction, empowering Dyno capsid engineers with industry-leading capabilities for solving the longstanding challenge of therapeutic gene delivery. Dyno’s platform brings the entire field closer to realizing a future where all gene therapies are safe, effective, and widely accessible to all patients who need them.”

“We are very pleased to take our partnership with Dyno Therapeutics to the next level. Our combined knowledge and resources will allow us to explore new treatments for historically difficult-to-treat neurological diseases,” said Boris L. Zaïtra, Head of Roche Corporate Business Development. “We are dedicated to making significant advancements in this field, and part of this is partnering with companies like Dyno Therapeutics. Our previous collaboration with Dyno Therapeutics gives us great confidence to increase our investment in therapeutic gene delivery, to support our neurological disease portfolio.”

About Dyno Therapeutics:
Dyno Therapeutics is building high-performance genetic technologies to transform patient outcomes by overcoming the in vivo gene delivery challenge for therapeutic developers. Dyno’s platform integrates AI with high-throughput experimentation to accelerate the design of AAV capsids that significantly outperform existing gene delivery vectors. Just as exponential breakthroughs in computer chip technology powered the AI revolution, Dyno’s versatile platform is leveraging foundational advances in vivo multiplexing technologies and high-performance computing to address a broad range of therapeutic challenges. Dyno has empowered therapeutic innovation through partnerships with leading gene therapy developers, including Astellas, Roche, and Sarepta, and with technology companies including NVIDIA. Visit www.dynotx.com for additional information.

Media Contact:
Thermal for Dyno Therapeutics
dynotx@thermalpr.com

– Harnessing the convergence of exponential advances in AI, genome sequencing and DNA synthesis technologies, Dyno’s approach to enabling safe and highly efficient in vivo gene delivery accelerates the development of optimized gene therapies

– Dyno’s LEAP^SM technology achieves super-human design of capsids that perform dramatically better than all prior variants, supporting earlier in vivo validation of high-performance DNA delivery

WATERTOWN, Mass., May 9, 2024 – Dyno Therapeutics, Inc., a techbio company pioneering applications of artificial intelligence to engineer AAV capsids that expand the potential of genetic medicine, today hosted a Scientific Symposium at the 27th American Society of Gene & Cell Therapy (ASGCT) Annual Meeting being held in Baltimore, MD.

The Scientific Symposium showcased Dyno’s approach to applying artificial intelligence to engineering novel adeno-associated virus (AAV) capsids for optimized in vivo delivery. The Symposium, titled “AAV Capsid Design in the Era of AI,” covered Dyno’s approach to solving one of the most difficult challenges of gene therapy: safely and efficiently delivering therapeutic DNA to target organs within a patient’s body.

“The present AI revolution in biotech was prefaced by decades of exponential change in the tech industry which catalyzed the personal computer revolution by putting a computer on every desk in every home, then into every pocket and on every wrist. Now the convergence of exponential change in AI, genome sequencing, and DNA synthesis technologies is driving a similar trend, this time with respect to the cost of in vivo gene delivery,” said Eric Kelsic, Ph.D., Founder and Chief Executive Officer of Dyno Therapeutics.

“Today gene therapies can cost several millions of dollars per dose,” Kelsic continued. “Dyno is committed to reducing the cost of delivering therapeutic DNA down to zero, which will be key to making the next generation of transformative gene therapies even more affordable. Historical trends suggest that dramatic cost reductions will actually grow the overall gene therapy market, supporting a robust ecosystem of gene therapy developers and eventually enabling billions of patients to benefit from life-changing gene therapies.”

Using generative AI, Dyno recently increased the efficiency of capsid-mediated in vivo DNA delivery in the eye by 80-fold with the Dyno eCap™ 1 capsid, and to the brain by 100-fold with the Dyno bCap™ 1 capsid. Building on these initial successes, Kelsic shared how Dyno’s AI-powered methods achieved two breakthroughs, in Low-Shot Efficient Accelerated Performance (LEAP), and in the design of synthetic capsid serotypes:

• Capsids designed with LEAP dramatically outperformed capsids designed by humans without AI-assistance, improving in vivo delivery efficiency and potentially enabling lower manufacturing costs: Dyno developed LEAP technology to efficiently generate capsid sequences with enhanced performance beyond any of the capsids in the training data. LEAP now enables Dyno to rapidly advance better capsids into in vivo validation studies, resulting in faster engineering and more effective use of R&D resources. Vitally, LEAP also helps to bring down the cost of in vivo delivery by yielding capsids that more precisely deliver more therapeutic DNA per dollar of production cost.
• Applying AI to capsid diversification generated diverse synthetic serotypes, towards expansion of patient populations who can benefit from gene therapy: Pre-existing immunity to natural AAV capsids can make anywhere from 20-80% of gene therapy patients ineligible for treatment. Dyno’s AI-powered methods successfully designed synthetic capsids that differ substantially from natural capsid sequences while still remaining functional for production and transduction of human cell lines. These results demonstrate the potential of these AI methods to broaden the number of patients who can benefit from gene therapy using synthetic capsids for gene delivery. Growing the demand for gene therapies by increasing the size of the addressable patient population is one additional way to accelerate an exponential reduction in the cost of gene therapies, since higher product revenues enable more profits to be invested in innovation that further reduces costs, thereby enabling more patients to benefit from future therapies.

Kelsic added that these breakthroughs in applying AI to the design of high-performance biological sequences will benefit from Dyno’s collaboration with NVIDIA, announced earlier in the day. The work will help advance design capabilities for gene therapies and other sequence-based medicines with potential for transformative patient impact. The collaboration will focus on scaling Dyno’s pioneering “lab-in-the-loop” sequence design approach using NVIDIA’s optimized cloud and BioNeMo platforms.

About Dyno Therapeutics

Dyno Therapeutics is solving the in vivo gene delivery challenge while partnering with gene therapy developers to maximize patient impact. Dyno’s platform combines AI with high-throughput experimentation to accelerate the design of AAV capsids with properties that significantly outperform current in vivo gene delivery vectors, with the goal of expanding the range of diseases treatable with genetic medicines. Dyno has partnered with leading gene therapy developers, including Astellas, Novartis, Roche, and Sarepta, and is broadly open to partnering across therapeutic areas. Dyno was founded in 2018 and is located in Watertown, Massachusetts. Visit www.dynotx.com for additional information.

Media Contact:
Alice Tirard
Dyno Therapeutics
alice.tirard@dynotx.com

– The work will help advance design capabilities for gene therapies and other sequence-based medicines with potential for transformative patient impact

– The collaboration will focus on scaling Dyno’s pioneering “lab-in-the-loop” sequence design approach using NVIDIA’s optimized cloud and BioNeMo platforms

WATERTOWN, Mass., May 9, 2024 – Dyno Therapeutics today announced a collaboration with NVIDIA to leverage Dyno’s field-leading artificial intelligence (AI) and in vivo experimentation capabilities, along with the built-to-scale NVIDIA BioNeMo AI-powered drug design platform, to help advance biological sequence design.

Everything life does is controlled by biological sequences: DNA, RNA, and proteins. The capacity to design these sequences can drastically improve outcomes in healthcare and technology. Over the past decade, Dyno has pioneered an AI-powered approach to sequence design, creating some of the first in vivo-validated biologics using generative AI. Recently, Dyno’s proprietary generative AI methods yielded optimized capsid products that allow enhanced in vivo delivery of genetic therapies for Dyno’s partners, including the Dyno eCap™ 1 capsid in the eye and the Dyno bCap™ 1 capsid in the brain. Both have been validated through in vivo studies. Sequence-design algorithms become much more powerful when trained with appropriately large and diverse data sets and sufficiently fast and versatile computational resources. Dyno believes transformative sequence design capabilities can be brought within reach using its extensive proprietary datasets and the scale NVIDIA’s compute platform enables.

Dyno relies heavily on NVIDIA accelerated computing for its inference and design pipelines. NVIDIA will support the collaboration through its cloud infrastructure, software and the NVIDIA BioNeMo framework. These will enable Dyno to research and deploy advanced machine-learning models at a higher velocity for sequence design. Dyno’s machine learning scientists and engineers will work with NVIDIA AI experts to scale, enhance, and optimize Dyno’s AI-powered inference and search algorithms, serving them through NVIDIA NIM microservices and BioNeMo, both part of NVIDIA AI Enterprise.

“For billions of years, Darwinian evolution has been the world’s most powerful sequence design algorithm, but the resulting gene and genome sequences represent only a slim fraction of what we now know is possible to achieve. For decades, bioengineering progress has advanced primarily through mimicking this process in the lab. Dyno has demonstrated that a new route is possible by combining AI with high-throughput molecular experimentation in a self-reinforcing learning loop,” said Eric Kelsic, Ph.D., founder and Chief Executive Officer of Dyno Therapeutics. “Our work with NVIDIA will massively scale and improve this capability so that we can rapidly navigate sequence space at a pace matching revolutionary advances in modern computation, creating transformative medicines that help many more patients.”

“One of the greatest impacts of generative AI is its ability to revolutionize life sciences and healthcare,” said Rory Kelleher, Global Head of Business Development for Life Sciences at NVIDIA. “NVIDIA’s collaboration with Dyno will optimize and scale high-performance biological sequence design, helping to dramatically accelerate the pace of drug discovery and development.”

All patients can potentially benefit from the ability to design therapies based on biological sequences. As the diversity of life vividly displays the breadth of the sequence-based biological design space, improved sequence-design capabilities have the potential to create myriad new medicines with vast potential for life-changing impact. For this reason, Dyno was founded to apply advanced sequence design technologies to solve therapeutic challenges. Dyno’s team has been focused over the past decade on solving the challenge of in vivo delivery for genetic therapies by engineering optimized Adeno-associated virus (AAV) capsid sequences, and in doing so became a world leader in machine-guided sequence design and generative AI. The collaboration is made possible as a result of the insights and learnings generated by the Dyno team, including billions of in vivo sequence-function data points measured across millions of distinct capsid sequences, and the computational revolution being catalyzed by NVIDIA platforms.

Dyno’s team, accelerated by NVIDIA’s full-stack accelerated computing and AI expertise, will develop and apply AI models across numerous research areas including multi-property capsid optimization and design of novel AAV serotypes, while also generalizing these capabilities to a broader range of therapeutically relevant molecules. Dyno’s partners will benefit from the accelerated pace of Dyno’s research and development of new capsid products, as well as from computational capabilities that Dyno may offer to pharmaceutical partners through NVIDIA’s BioNeMo.

About Dyno Therapeutics

Dyno Therapeutics is solving the in vivo gene delivery challenge while partnering with gene therapy developers to maximize patient impact. Dyno’s platform combines AI with high-throughput experimentation to accelerate the design of AAV capsids with properties that significantly outperform current in vivo gene delivery vectors, with the goal of expanding the range of diseases treatable with genetic medicines. Dyno has partnered with leading gene therapy developers, including Astellas, Novartis, Roche, and Sarepta, and is broadly open to partnering across therapeutic areas in gene therapy and machine learning. Dyno was founded in 2018 and is located in Watertown, Massachusetts. Visit www.dynotx.com for additional information.

Media Contact:
Alice Tirard
Dyno Therapeutics
alice.tirard@dynotx.com

WATERTOWN, Mass., April 23, 2024 – Dyno Therapeutics, Inc., a techbio company pioneering applications of artificial intelligence to engineer AAV capsids that expand the potential of genetic medicine, today announced a Scientific Symposium and the presentation of three research abstracts, including one oral presentation, at the upcoming 27th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) being held May 7-11th, 2024 in Baltimore, Maryland. That same week Dyno Therapeutics will also be giving two talks on the theme of Machine Learning at SynBioBeta’s Global Synthetic Biology Conference held from May 6-9th, 2024 in San Jose, California.

From its inception, Dyno Therapeutics has been a leader in applying generative AI to advance the frontiers of AAV engineering. Through its AI-powered platform, the company has achieved improved gene delivery to a broad array of gene therapy targets, developing capsids to target the eye, muscle and brain. The company’s presence at both the ASGCT and SynBioBeta conferences will highlight recent successes from applying machine learning to capsid design, and explore what these applications mean for gene therapy in an era of rapid AI development.

Dyno’s ASGCT Scientific Symposium will showcase how artificial intelligence enables the design of novel capsids optimized across multiple in vivo delivery properties, and furthermore makes it possible to create synthetic capsids with high-edit distances from natural serotypes, thereby potentially allowing more patients to benefit from gene therapies. At SynBioBeta, Dyno engineers will delve into the reality of ML-driven approaches, highlighting both the promise and challenges that arise when solving real-world problems like in vivo delivery for gene therapies via capsid design.

ASGCT Dyno Scientific Symposium

Title: “AAV Capsid Design in the Era of Artificial Intelligence”
Presenter: Eric Kelsic, Ph.D., Founder and CEO, Dyno Therapeutics
Date and Time: May 9th 12:15 – 13:15 EDT
Location: Baltimore Convention Center, Room 309-310

ASGCT Research Abstracts

Oral Presentation: Applying Artificial Intelligence to Multi-Property Optimization of AAV Capsids for Neuronal Gene Delivery
Date and Time: May 10th, 2024 17:00 – 17:15 EDT
Location: Baltimore Convention Center, Ballroom 4
Abstract: #301

Poster Presentation: Non-Human Primate Evaluation of an Engineered AAV Capsid for Retinal Cell-Specific and Biofactory-Based Ocular Gene Therapies
Date and Time: May 8th, 2024 12:00 – 19:00 EDT
Abstract: #516

Poster Presentation: Expanding the Serotype Frontier: Design of Synthetic AAV Capsids with Artificial Intelligence
Date and Time: May 10th, 2024 12:00 – 19:00 EDT
Abstract: #1465

SynBioBeta Global Synthetic Biology Conference

Oral Presentation: AI-Designed Capsids: Powering a New Age of Genetic Medicine
Date and Time: May 8th, 2024, 11:00 – 11:45 PDT
Location: San Jose Convention Center, Main Stage – Grand Ballroom 220A

Lunch & Learn: Generative AI is Not Enough: Bridging In-Silico to Impact—Where Hype Faces Reality
Date and Time: May 9th, 2024, 12:15 – 13:00 PDT
Location: San Jose Convention Center, Meeting Room 212B

About Dyno Therapeutics

Dyno Therapeutics is solving the in vivo gene delivery challenge while partnering with gene therapy developers towards maximizing patient impact. Dyno’s platform combines AI with high-throughput experimentation to accelerate the design of AAV capsids with properties that significantly outperform current in vivo gene delivery vectors, with the goal of expanding the range of diseases treatable with genetic medicines. Dyno has partnered with leading gene therapy developers, including Astellas, Novartis, Roche, and Sarepta, and is broadly open to partnering across therapeutic areas. Dyno was founded in 2018 and is located in Watertown, Massachusetts. Visit www.dynotx.com for additional information.

Media Contact:
Alice Tirard
Dyno Therapeutics
alice.tirard@dynotx.com

– 80x improvement vs. AAV2 in delivery to the retina seen in non-human primate (NHP) –

– Head-to-head against other retina-IVT capsids, Dyno eCap 1 capsid significantly outperforms in delivery to all major cell types in the retina –

– Dyno eCap 1 product and other proprietary capsids for IVT delivery are available for licensing to partners developing optimized gene therapies –

WATERTOWN, Mass., Oct 25, 2023 – Dyno Therapeutics, Inc., a techbio company pioneering applications of artificial intelligence to engineer AAV capsids that can expand the potential of genetic medicine, today announced the launch of its Dyno eCap 1™ capsid product, a leading eye AAV gene delivery vector with best-in-class potential, in a keynote address at the company’s Scientific Symposium at the 30th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT). The Dyno eCap 1 vector provides significantly improved delivery to the eye compared to other externally engineered capsids, including transduction throughout multiple layers of the retina.

“Enabling effective delivery to all cells in the eye, and in particular across the entire retina, is crucial to enable gene therapies to treat ocular diseases such as wet age-related macular degeneration (wAMD), geographic atrophy, and retinitis pigmentosa,” said Adrian Veres, M.D., Ph.D., Chief Scientific Officer and Co-founder of Dyno. “The Dyno eCap 1 vector is accelerating the next generation of ocular gene therapies for both genetic and non-genetic diseases, joining our growing suite of leading-edge capsids ready to help our partners bring the world’s best gene therapies into the clinic to help more patients.”

Dyno creates highly optimized delivery vectors by deploying a pioneering machine-guided approach. This approach combines state-of-the-art methods in machine learning and generative artificial intelligence (AI) for protein sequence design, in combination with large, internally collected in vivo datasets that provide high-resolution insights into numerous relevant capsid delivery properties. To engineer its state-of-the-art capsids for ocular gene delivery, Dyno conducted robust measurement of transduction as well as spatial localization across hundreds of thousands of capsid sequences, mapping the multi-modal properties of the ocular capsid sequence space from which the Dyno eCap 1 vector could be identified. This field-leading capsid displays consistent high performance for retinal transduction across retinal layers and cell types when delivered via intravitreal injection, a common non-surgical route of administration.

Key Data on Dyno eCap 1 Technology

• The Dyno eCap 1 vector exhibits 80-fold better transduction to the retina compared to the commonly used AAV2 capsid.
• The Dyno eCap 1 vector transduces the retina better than a cohort of external engineered IVT capsids, supporting a field-leading profile.
• The Dyno eCap 1 vector consistently transduces cell types broadly across retinal layers, including rod cel, bipolar cells and retinal ganglion cells.
• The Dyno eCap 1 vector was validated in cynomolgus monkey (Macaca fascicularis), the most relevant NHP model for predicting translatability to human clinical trials. Improved performance is highly consistent across bulk RNA-seq, single-cell RNA-seq and histology.

“At Dyno, we are dedicated to realizing the full potential of gene therapy by helping our partners solve the challenge of delivering genes to every cell, every organ and every patient,” said Dyno Chief Executive Officer and Co-founder Eric Kelsic, Ph.D. “The trailblazing performance of our AI-designed capsids, as demonstrated by Dyno eCap 1 technology, continues to draw leading gene therapy developers to Dyno, so they can succeed in bringing transformative gene therapies to patients who await better treatments.”

About Dyno Therapeutics

Dyno Therapeutics is solving the in vivo gene delivery challenge while broadly partnering with gene therapy developers towards maximizing patient impact. Dyno’s platform combines AI with high-throughput experimentation to accelerate the design of AAV capsids with properties that significantly outperform current in vivo gene delivery vectors, with the goal of expanding the range of diseases treatable with genetic medicines. Dyno’s platform has attracted partnerships with leading gene therapy developers, including Astellas, Novartis, Roche, and Sarepta, and Dyno continues to be broadly open to partnering across all therapeutic areas. Dyno was founded in 2018 and is located in Watertown, Massachusetts. Visit www.dynotx.com for additional information.

Media Contact:
Lisa Raffensperger
Ten Bridge Communications
lisa@tenbridgecommunications.com

WATERTOWN, Mass., October 11, 2023 – Dyno Therapeutics, Inc., a techbio company pioneering applications of artificial intelligence to engineering AAV capsids that expand the potential of genetic medicine, today announced a Dyno Scientific Symposium and the presentation of three research abstracts at the upcoming 30^th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT) being held October 24-27, 2023 in Brussels, Belgium.

Dyno Scientific Symposium:

Title: “Dyno Therapeutics: NHP-Validated Capsids for Best-in-Class Ocular and CNS Gene Delivery”
Presenter: Eric Kelsic, Ph.D., Co-founder and CEO, Dyno Therapeutics
Date and Time: Wednesday, October 25 from 13:25 to 14:25 CET
Location: Maison de la Poste

Dyno’s scientific symposium will showcase in vivo NHP data on field-leading capsids across the eye and CNS. Dyno’s AI-designed capsids significantly advance gene delivery capabilities, towards unlocking the full potential of genetic medicine.

Research abstracts showcasing Dyno’s capsids:

Title: “Dyno eCap 1 capsid: Cell-Type Resolved Validation of AAV capsids Optimized for Intravitreal Delivery to the Non-Human Primate Retina”
Date and Time: Wednesday, October 25 from 18:15 to 19:30 and Thursday, October 26 from 19:30 to 20:30 CET
Poster/Abstract Number: #P038

Title: “Dyno bCap 1 capsid: Single-Cell Characterization of CNS Transduction by Intravenously Administered AAV Capsids in Non-Human Primates”
Date and Time: Wednesday, October 25 from 18:15 to 19:30 and Thursday, October 26 from 19:30 to 20:30 CET
Poster/Abstract Number: #P012

Research abstracts featuring Dyno’s platform capabilities:

Title: “VAEprop: A Generative Machine Learning Approach for Designing High-Performing AAV Capsids for the Non-Human Primate Brain”
Date and Time: Wednesday, October 25 from 18:15 to 19:30 and Thursday, October 26 from 19:30 to 20:30 CET
Poster/Abstract Number: #P076

About Dyno Therapeutics
Dyno Therapeutics is solving the in vivo gene delivery challenge while partnering with gene therapy developers towards maximizing patient impact. Dyno’s platform combines AI with high-throughput experimentation to accelerate the design of AAV capsids with properties that significantly outperform current in vivo gene delivery vectors, with the goal of expanding the range of diseases treatable with genetic medicines. Dyno has partnered with leading gene therapy developers, including Astellas, Novartis, Roche, and Sarepta, and is broadly open to partnering across therapeutic areas. Dyno was founded in 2018 and is located in Watertown, Massachusetts. Visit www.dynotx.com for additional information.

Media Contact:
Rhiannon Jeselonis
Ten Bridge Communications
rhiannon@tenbrigecommunications.com

– Dyno bCap 1 exhibits 100x improvement versus AAV9 in delivery to the central nervous system (CNS) and 10x detargeting of liver after intravenous (IV) dosing, as characterized across multiple non-human primate (NHP) species –

– Compared head-to-head with other capsids engineered for CNS-IV delivery, Dyno bCap 1 performs significantly better overall in delivery to the CNS, liver detargeting, and production efficiency –

– The Dyno bCap 1 product and other proprietary capsids for CNS-IV delivery are available for immediate licensing to partners developing optimized gene therapies –

WATERTOWN, Mass., May 19, 2023 – Dyno Therapeutics, Inc., a techbio company pioneering applications of artificial intelligence to engineer AAV capsids that can expand the potential of genetic medicine, today announced the launch of its Dyno bCap 1™ capsid product, a breakthrough CNS-targeted AAV gene delivery vector with best-in-class potential, in a keynote address at the company’s Scientific Symposium at the American Society of Gene & Cell Therapy (ASGCT) 26^th Annual Meeting. The Dyno bCap 1 vector provides dramatically improved CNS delivery and liver detargeting compared to leading natural capsids and stronger all-around characteristics relative to other engineered CNS-IV capsids.

“Safe and effective gene delivery to the brain is a primary factor limiting the treatment of CNS diseases with gene therapy today. We believe effective delivery to all cells throughout the brain will unlock the potential to treat patients affected by a variety of genetic diseases, including amyotrophic lateral sclerosis, Angelman syndrome, Parkinson’s disease and Alzheimer’s disease,” said Adrian Veres, M.D., Ph.D., CSO and Co-founder of Dyno. “We look forward to further exploring the transformative potential of Dyno bCap 1, as well as our growing line of capsid products, by partnering with leading developers of gene therapies.”

To create high-performing capsids, Dyno has pioneered the application of state-of-the-art methods in deep learning and generative artificial intelligence (AI) to protein sequence design, while also leveraging large, internally collected in vivo datasets that provide high-resolution insights into the many therapeutically relevant capsid delivery properties. By combining AI and high-throughput biology, Dyno’s platform is capable of more fully exploring the AAV capsid sequence space in search of capsids that are optimized across multiple dimensions, such as CNS targeting, liver detargeting, and production efficiency. As a result, the protein sequence for the Dyno bCap 1 product is highly novel, with a pattern of sequence changes that would not occur using methods most typically used for engineering AAV capsids, such as random mutation or insertion of short peptides in the capsid protein sequence. After AI-driven design of the capsid sequence, Dyno extensively characterized the in vivo delivery properties of Dyno bCap 1 across species in NHPs, the most relevant animal models for translation to humans.

Key Data on Dyno bCap 1 Technology

• Relative to the commonly used AAV9 capsid, Dyno bCap1 exhibits 100-fold better pan-brain CNS transduction upon crossing of the blood-brain barrier and 10-fold better liver detargeting.
• Dyno bCap1 improvements in transduction and targeting specificity are conserved across NHP species in both cynomolgus monkey (Macaca fascicularis) and African green monkey (Chlorocebus sabaeus), increasing confidence that the breakthrough CNS delivery capabilities of Dyno bCap 1 could be relevant for applications in human therapeutics.
• Whereas naturally-derived capsids such as AAV9 transduce only a small fraction of brain cells in NHPs, with a low IV injected dose of 1e13vg/kg, payloads delivered by the Dyno bCap 1 capsid transduced between 4-14% of cells in the brain, and 5-20% of neurons across pan-brain regions and the spinal cord, potentially broadening the diseases which can be successfully treated with gene therapy.
• Compared in library format head-to-head against an external engineered AAV capsid reported to have improved brain transduction relative to other CNS-IV capsids, Dyno bCap 1 demonstrated consistent brain transduction across animals, with comparable or improved transduction relative to the external capsid, and dramatically better production efficiency, demonstrating the transformative potential of Dyno bCap 1 for CNS-IV delivery.

Licensing Dyno bCap 1 Technology
Dyno Therapeutics is making Dyno bCap 1 technology and additional proprietary capsids with improved CNS delivery properties available immediately for licensing to gene therapy developers across academia and industry.

“Dyno’s business is partnership-centric: We partner with gene therapy developers, providing them with the very best capsids so that they can invest their efforts at the leading edge of genetic medicine,” said Dyno CEO and Co-founder, Eric Kelsic, Ph.D. “With the Dyno bCap1 launch, we are delivering on this promise for our partners, both existing and to come. We’re ready to build new partnering relationships in the CNS and beyond that will enable our industry to realize the potential of genetic medicines to help patients in need all around the world.”

About Dyno Therapeutics
Dyno Therapeutics is solving the in vivo gene delivery challenge while broadly partnering with gene therapy developers towards maximizing patient impact. Dyno’s platform combines AI with high-throughput experimentation to accelerate the design of AAV capsids with properties that significantly outperform current in vivo gene delivery vectors, with the goal of expanding the range of diseases treatable with genetic medicines. Dyno has partnered with leading gene therapy developers, including Astellas, Novartis, Roche, and Sarepta, and is broadly open to partnering across therapeutic areas. Dyno was founded in 2018 and is located in Watertown, Massachusetts. Visit www.dynotx.com for additional information.

Media Contact:
Rhiannon Jeselonis
Ten Bridge Communications
rhiannon@tenbridgecommunications.com

 

WATERTOWN, Mass., May 2, 2023 – Dyno Therapeutics, Inc., a techbio company pioneering applications of artificial intelligence to engineering AAV capsids that can expand the potential of genetic medicine, today announced a Dyno Scientific Symposium and the presentation of four research abstracts at the upcoming 26^th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) being held May 16-20, 2023 in Los Angeles, Calif.

Among the results to be presented is a breakthrough in CNS delivery: Dyno’s AI-guided design and subsequent in vivo characterization of a novel AAV capsid that delivers genetic payloads to a significant and potentially therapeutically relevant fraction of neurons across the central nervous system (CNS), including deep brain structures, via IV administration in non-human primates.

Dyno Scientific Symposium
Title: “The Capsids You Need: AI-Guided Design and In Vivo Validation of AAV Capsids for Better Delivery to Muscle, Eye and CNS”
Date and Time: Friday, May 19 from 12:00-1:30 p.m. PT
Location: Petree Hall C

Dyno’s scientific symposium will describe the transformative properties of Dyno’s license-ready capsids across therapeutic areas, including a breakthrough in CNS delivery aided by generative AI.

Dyno is leveraging its platform to additionally design optimized capsids for muscle and eye delivery, towards significantly expanding the potential of genetic medicine.

Symposium speakers:
Eric Kelsic, Ph.D., CEO and Co-founder
Adrian Veres, Ph.D., CSO and Co-founder
Jamie Kwasknieski, Ph.D., Head of Platform
Yvette Leung, MBA, Head of Corporate Development

Research abstracts showcasing Dyno’s capsids:
Title: “Crossing the Non-Human Primate Blood Brain Barrier with Machine-Guided AAV Capsid Design”
Date and Time: Wednesday, May 17 at 12:00 p.m. PT
Poster/Abstract Number: 382

Title: “Optimizing Intravitreal Delivery to the Non-Human Primate Retina with Machine-Guided AAV Capsid Design”
Date and Time: Friday, May 19 at 12:00 p.m. PT
Poster/Abstract Number: 1284

Research abstracts featuring Dyno’s platform capabilities:
Title: “A Robust Machine Learning Algorithm for Improving AAV Capsid Performance”
Date and Time: Wednesday, May 17 at 12:00 p.m. PT
Poster/Abstract Number: 467

Title: “Automated Micro-TFF System Streamlines Purification and Operator Time in a Lean rAAV Manufacturing Operation”
Date and Time: Thursday, May 18 at 12:00 p.m. PT
Poster/Abstract Number: 887

Pre-meeting workshop and panel discussion:
Title: “Building the team that’s right for your startup”
Speaker: Eric Kelsic, PhD, CEO and Co-founder
Date and Time: Tuesday May 16, at 9:40 a.m PT, Concourse Hall 150 & 151
Session: The Magic Year – Founders tips for what to do in your last six months of academia and first six months in industry

About Dyno Therapeutics
Dyno Therapeutics is solving the in vivo gene delivery challenge while broadly partnering with gene therapy developers towards maximizing patient impact. Dyno’s platform combines artificial intelligence (AI) with high-throughput experimentation to accelerate the design of AAV capsids with properties that significantly outperform current in vivo gene delivery vectors, towards expanding the range of diseases treatable with genetic medicines. To date, Dyno has partnered with leading gene therapy developers, including Astellas, Novartis, Roche, Sarepta and is broadly open to partnering across therapeutic areas. Dyno was founded in 2018 and is located in Watertown, Massachusetts. Visit www.dynotx.com for additional information.

Media Contact:
Rhiannon Jeselonis
Ten Bridge Communications
rhiannon@tenbrigecommunications.com

BOSTON, MA — March 11, 2022— Dyno Therapeutics is pleased to announce it has been recognized on the Forbes list of America’s Best Startup Employers 2022. This prestigious award is presented by Forbes and Statista Inc., the world-leading statistics portal and industry ranking provider, to the top 500 companies in the U.S.

America’s Best Startup Employers were selected by evaluating:

• Employee satisfaction
• Employer reputation
• Company growth

Dyno is looking for dynamic and driven high-potential problem-solvers to support the optimization of AAV gene therapies to transform patient lives with cutting-edge science. Interested in becoming an AAViator and joining our team? Visit www.dynotx.com/careers to see all open positions.

 

About Dyno Therapeutics

Dyno Therapeutics is a pioneer in applying artificial intelligence (AI) and quantitative in vivo experiments to gene therapy. The company’s proprietary CapsidMap™ platform rapidly discovers and systematically optimizes Adeno-Associated Virus (AAV) capsid vectors that significantly outperform current approaches for in vivo gene delivery, thereby expanding the range of diseases treatable with gene therapies. Dyno was founded in 2018 by experienced biotech entrepreneurs and leading scientists in the fields of gene therapy and machine learning. The company is located in Cambridge, Massachusetts. Visit www.dynotx.com for additional information.

Presentations describe use of in vivo screening and machine learning to accelerate the analysis, design, and validation of improved AAV vectors.

Cambridge, MA – May 11, 2021 – Dyno Therapeutics, a biotechnology company applying artificial intelligence (AI) to gene therapy, will describe ongoing enhancements to its machine learning platform in three oral presentations at the 24^th annual meeting of the American Society of Gene and Cell Therapy (ASGCT), taking place virtually from May 11-14, 2021.

Dyno’s presentations, summarized below, highlight advancements of the company’s CapsidMap™ platform that enable increased capsid design efficiency, optimized experiments for in vivo capsid validation, and improved quality of in vivo measurements.

 

Efficient design of optimized AAV capsids using multi-property machine learning models trained across cells, organs and species, Tuesday May 11, 2021 at 5:45-6:00pm EST

Machine learning models improve AAV capsid design efficiency, defined as the probability that a designed variant will have improved function. We synthesized and barcoded capsid libraries containing 803,041 designed sequence variants of three natural AAV serotypes and measured their properties as delivery vectors both in vitro and in vivo.  Single-property machine learning models trained on these data can improve the efficiency of library design by at least several hundred-fold. Furthermore, models trained on multiple properties help overcome data sparsity and measurement error, thereby improving model accuracy, and providing a more reliable interpretation of experimental results.

 

Risk-Adjusted Selection for Validation of Sequences in AAV Design Using Composite Sampling, Tuesday May 11, 2021 at 6:00-6:15pm EST

Using our machine learning models, billions of promising AAV variants can be designed and scored computationally for predicted fitness. Accurate high-throughput experimental testing is practically limited, however, to hundreds of thousands of variants. From these high-throughput measurements we must then choose on the order of hundreds of variants for more extensive experimental validation, to identify the best possible individual capsid variants.

To address this question of which capsid variants should be tested experimentally, we developed a novel optimization algorithm called Composite Sampling (CS). This algorithm reduces a pool of hundreds of thousands of variants in a way that maximizes the chances of including the best candidates in the validation set. We show the value of the method through two datasets, demonstrating that Composite Sampling is consistently better than conventional approaches for selecting high performing sequences for the validation set.

 

AAV Capsid Property Estimation Is Improved by Combining Single-Molecule ID Tags and Hierarchical Bayesian Modeling of Experimental Processes May 13, 2021 at 6:15-6:30pm EST

Data-driven capsid engineering can only be as good as the quality of the data. While our high-throughput barcoded approach to measuring capsid properties allows generation of large datasets needed to train machine learning models, measuring many capsids at once introduces biases and noise in the data. To remove these biases and noise from in vivo measurements, we built a probabilistic model of AAV packaging and transduction to allow inference of the distributions for the underlying properties being measured. This presentation will describe validation of improved property value estimates from the model in comparison to naive estimates using experimental controls.

 

More information on our presentations may be found in the ASGCT program

 

About Dyno Therapeutics

Dyno Therapeutics is a pioneer in applying artificial intelligence (AI) and quantitative in vivo experiments to gene therapy. The company’s proprietary CapsidMap™ platform rapidly discovers and systematically optimizes Adeno-Associated Virus (AAV) capsid vectors that significantly outperform current approaches for in vivo gene delivery, thereby expanding the range of diseases treatable with gene therapies. Dyno was founded in 2018 by experienced biotech entrepreneurs and leading scientists in the fields of gene therapy and machine learning. The company is located in Cambridge, Massachusetts. Visit www.dynotx.com for additional information.