At Dyno, we are empowering a diverse team of the best problem-solvers to drive cutting-edge science toward improving patient health.

This is easy to say but impossible to do without innovating on how biotech companies approach work. At Dyno, we believe that by nurturing a healthy work experience that promotes courage, openness, respect, focus, and commitment our employees, or AAViators, will improve patient health in a state of joy. Today, as a 50-employee company, we work in a Scrum-inspired Agile framework, which we will scale as we grow to 150 employees in the next few years.

We seek to improve patient health by optimizing gene vectors (e.g., capsids) so our partners can deliver safer and more efficacious gene therapies. We do this through a closed-loop process which combines machine learning with in vivo & in vitro experimentation: With each iteration we get closer to capsids that move the needle on what is possible in gene therapy.

While it would be nice to simply dream success into reality, in practice, it requires effective teamwork. The typical biotech approach is to use traditional project management, a sequential process of initiation, planning, execution, monitoring & controlling, and finally, project closure. This approach requires having done similar work in the past so one can anticipate most of what is needed to be successful, as well as having stable technology one can rely on. While this works really well in manufacturing and construction, it often falls short in high-tech industries.

Starting in the 1980s, the pitfalls of traditional project management began to be examined as described in The New New Product Development Game. What followed was the slow adoption of Agile work practices across a growing set of industries involved in complex work. Complex means the work you are undertaking likely hasn’t been done before, everything you need to do to be successful isn’t known, and you still need to develop technology which doesn’t currently exist. Agile, practiced through a light-weight framework called Scrum, overcomes complexity by guiding teams to approach work with an empirical, incremental, and lean mindset. As teams routinely apply what they learn, and prioritize what to do next, they are able to minimize wasted effort, quickly take advantage of new learnings, and complete projects which have never been done before.

Since our work at Dyno is highly complex, traditional project management, although more familiar, just doesn’t fit the nature of our work or our AAViators expectations. By the time a project manager finishes drafting one detailed plan, the team will have learned something which significantly alters the said plan. What’s worse is the psychological toll continuous change has on a team when using traditional project management—which aims to minimize the occurrence of change! The result is that change begins to feel like failure, so much that it’s tempting to try to prevent change, ultimately leading to poorer outcomes.

Next, I’ll highlight our approach with its key roles and responsibilities.

We plan, execute, and learn in two-week increments called Sprints, which begin with planning … But before we focus on planning the next two weeks, we take a step back and refine our roadmap together. This roadmap acts to visualize how we think we can achieve our company goals over the next 12-18 months. We find it important to understand where our efforts today will take us and to have confidence we are balancing our desire for success with a sustainable experience. After we commit to our revised roadmap, every team, across both R&D and corporate, does Sprint Planning together. We are open about the goals we are committing ourselves to accomplish over the next two weeks, while accounting for known constraints like taking time to vacation or develop ourselves. We make these commitments extremely clear by documenting  “Definitions of Done”, or brief statements of what it means for each deliverable to be officially completed.

We execute … Every workday during the Sprint, each team meets for 15 minutes to see how the Sprint is progressing and adapts it as needed; at the end of each day, all team leads meet for another 15 minutes and discuss any crossteam impacts which need to be raised and resolved so that Sprint goals can be achieved. Individuals and teams have significant flexibility over the course of the Sprint to accomplish what they committed to during planning.

We learn … At the end of the Sprint, every team conducts a Sprint Review to determine what was done, what was not done and why, and to decide what they should do next. This reinforces accountability in a healthy way. The Sprint Review is followed by a Sprint Retrospective where each team inspects how they are working as a team and commits to doing something to improve teamwork in the next Sprint. A Review and Retrospective is also conducted at the Company level to ensure broad transparency and commitment to evolving how Scrum is used at Dyno.

Of course, our approach would never work without the focused involvement of three key roles: The Team who collectively determines the work that needs to be done, the Product Owner who leads the team and prioritizes work, and the Agile Captain who facilitates the framework while promoting teamwork. The Agile Captain is a volunteer from the team, some stick with the role, other teams go through a role rotation, either way the role is vital for team success in our Agile framework.

Our approach requires even the most involved AAViators to spend less than 10% of their time within the framework events, which is an important metric we respect as we look for ways to improve how we work together. We constantly ask ourselves: How can we make our framework better while keeping the time required under 10%? Additionally, when teams have unsuccessful Sprints it’s psychologically nice for them to know that they can start afresh in the next Sprint, now with the added benefit of their learnings. Finally, each Sprint presents an opportunity to pause, take stock of the current situation, and refocus the teams’ and company’s efforts on the most important priorities. We get 24 opportunities a year to do this; that far exceeds what you could expect within a traditional project management framework.  

Since our first Sprint, our framework has continually evolved to achieve our desired outcomes. We do not expect the way we work today to enable success in a company with 150 employees; however, we have absolute confidence that we can evolve our framework and maintain a healthy work experience which promotes courage, openness, respect, focus, and commitment.

We’re excited about the progress we’ve made thus far, and enthusiastically welcome others to join us on our awesome journey! Come learn more at the upcoming 8 June 2021 webinar, Biotech and Scrum: Rethinking How Biotech Innovates in the 21st Century.

Scientific leaders bring deep expertise in machine learning and AAV gene therapy

Cambridge, MA – April 26, 2021 – Dyno Therapeutics, a biotech company applying artificial intelligence (AI) to gene therapy, today announced the expansion of the company’s Scientific Advisory Board (SAB) with the addition of Debora Marks, Ph.D., of Harvard Medical School and the Broad Institute, and Nicole Paulk, Ph.D., of the University of California San Francisco. 

 

Dr. Marks and Dr. Paulk will play an instrumental role in providing scientific insight and expert guidance, complementing the company’s diverse and interdisciplinary team that is focused on applying machine learning to Adeno-Associated Virus (AAV) capsid engineering for improved gene therapy delivery. They join existing members of Dyno’s SAB, George Church, Ph.D., Robert Winthrop Professor of Genetics at Harvard Medical School and a Core Faculty member at Harvard’s Wyss Institute for Biologically Inspired Engineering, and Tomas Bjorklund, Ph.D., Associate Professor of Neuroscience at Lund University. 

 

“We are honored and delighted to welcome Professors Debora Marks and Nicole Paulk to Dyno’s SAB. These preeminent scientists bring world-leading expertise in the areas of machine learning and AAV gene therapy which will accelerate Dyno’s design of best-in-class capsids that solve unmet medical needs,” said Eric Kelsic, Ph.D., co-founder and CEO of Dyno Therapeutics. “Debora offers unique insights based on her pioneering work applying machine learning to protein structure and design. Nicole’s deep scientific expertise in AAV gene therapy research, development and manufacturing will be invaluable for guiding our platform to generate products that help millions of patients.”

Dr. Debbie Marks, PhD

Dr. Debbie Marks, PhD

Debora S. Marks, Ph.D. is an Associate Professor of Systems Biology at Harvard Medical School, and an Associate Member of the Broad Institute of Harvard and MIT. Dr. Marks has led a distinguished career in academia and industry, and is an expert in the application of machine learning algorithms for protein design and engineering. She earned her B.Sc. in Mathematics from the University of Manchester, U.K., and her Ph.D. in Mathematical Biology from Humboldt University, Germany. 

 

Dr. Debora Marks commented, “I’m very excited to start working with Dyno’s world-class team and I’m particularly impressed by Dyno’s use of machine learning as a systematic approach to solving gene therapy’s biggest challenge: efficient, safe and precise gene delivery to target tissues.”

 

Dr. Nicole Paulk, PhD

Dr. Nicole Paulk, PhD

Nicole Paulk, Ph.D. is an Assistant Professor of AAV Gene Therapy at the University of California San Francisco Department of Biochemistry & Biophysics. She is a pioneer in next-generation AAV gene delivery and gene editing platforms. She has developed therapies for gene repair and gene transfer for numerous rare diseases, and has applied high-throughput comparative proteomic and epigenomic approaches to address challenges in fundamental AAV biology. She earned her B.S. in Medical Microbiology from Central Washington University, and her Ph.D. in Viral Gene Therapy from Oregon Health & Science University.

 

Dr. Nicole Paulk said, “I am eager to contribute my expertise to Dyno’s efforts to design novel AAV vectors that overcome the limitations of current vectors, ultimately to expand the opportunities for gene therapy to help more patients.”

 

About Dyno Therapeutics

 

Dyno Therapeutics is a pioneer in applying artificial intelligence (AI) and quantitative high-throughput 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.

Cambridge, MA – February 11, 2020 – Dyno Therapeutics, a biotech company applying artificial intelligence (AI) to gene therapy, today announced a publication in Nature Biotechnology that demonstrates the use of artificial intelligence to generate an unprecedented diversity of adeno-associated virus (AAV) capsids towards identifying functional variants capable of evading the immune system, a factor that is critical to enabling all patients to benefit from gene therapies. The research was conducted in collaboration with Google Research, Harvard’s Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School laboratory of George M. Church, Ph.D., a Dyno scientific co-founder. The publication is entitled “Deep diversification of an AAV capsid protein by machine learning.”

 

It is estimated that up to 50-70% of the human population have pre-existing immunity to natural forms of the AAV vectors currently being using to deliver gene therapies. This immunity renders a large portion of patients ineligible to receive gene therapies which rely upon these capsids as the vector for delivery. Overcoming the challenge of pre-existing immunity to AAV vectors is therefore a major goal for the gene therapy field.

 

“The approach described in the Nature Biotechnology paper opens a radically new frontier in capsid design. Our study clearly demonstrates the potential of machine learning to guide the design of diverse and functional sequence variants, far beyond what exists in nature,” said Eric Kelsic, Ph.D., Dyno’s CEO and co-founder.  “We continue to expand and apply the power of artificial intelligence to design vectors that can not only overcome the problem of pre-existing immunity but also address the need for more effective and selective tissue targeting. At Dyno, we are making rapid progress to design novel AAV vectors that overcome the limitations of current vectors, improving treatments for more patients and expanding the number of diseases treatable with gene therapies.”

 

The Nature Biotechnology paper describes the rapid production of a large library of distinct AAV capsid variants designed by machine learning models. Nearly 60% of the variants produced were determined to be viable, a significant increase over the typical yield of <1% using random mutagenesis, a standard method of generating diversity.

 

“The more we change the AAV vector from how it looks naturally, the more likely we are to overcome the problem of pre-existing immunity,” added Sam Sinai, Ph.D., Dyno co-founder and Machine Learning Team Lead. “Key to solving this problem, however, is also ensuring that capsid variants remain viable for packaging the DNA payload. With conventional methods, this diversification is time- and resource-intensive, and results in a very low yield of viable capsids. In contrast, our approach allows us to rapidly unlock the full potential diversity of AAV capsids to develop improved gene therapies for a much larger number of patients.

 

This research builds upon previous work published in Science in which a complete landscape of single mutations around the AAV2 capsid was generated followed by evaluation of the functional properties important for in vivo delivery. In parallel with these works, Dyno has established collaborations with leading gene therapy companies Novartis, Sarepta Therapeutics, Roche and Spark Therapeutics to develop next-generation AAV gene therapy vectors with a goal of expanding the utility of gene therapies for ophthalmic, muscle, central nervous system (CNS) and liver diseases.

 

About CapsidMap™ for Designing Optimized AAV Gene Therapies

By designing capsids that confer improved functional properties to Adeno-Associated Virus (AAV) vectors, Dyno’s proprietary CapsidMap™ platform overcomes the limitations of today’s gene therapies on the market and in development. Today’s treatments are primarily confined to a small number of naturally occurring AAV vectors that are limited by delivery efficiency, immunity, payload size, and manufacturing challenges. CapsidMap uses artificial intelligence (AI) technology to engineer capsids, the cell-targeting protein shell of viral vectors. The CapsidMap platform applies leading-edge DNA library synthesis and next generation DNA sequencing to measure in vivo gene delivery properties in high throughput. At the core of CapsidMap are advanced search algorithms leveraging machine learning and Dyno’s massive quantities of experimental data, that together build a comprehensive map of sequence space and thereby accelerate the design of novel capsids optimized for gene therapy.

About Dyno Therapeutics

Dyno Therapeutics is a pioneer in applying artificial intelligence (AI) and quantitative high-throughput 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.

Collaboration combines Dyno’s AI-powered AAV vector capabilities with Roche and Spark Therapeutics’ leading-edge gene therapy capabilities
Dyno is eligible to receive milestone payments that may exceed $1.8 billion

Cambridge, MA – October 14, 2020 – Dyno Therapeutics, a biotech company applying artificial intelligence (AI) to gene therapy, today announced a collaboration and license agreement with Roche (SIX: RO, ROG; OTCQX: RHHBY) to apply Dyno’s CapsidMap™ platform for the development of next-generation adeno-associated virus (AAV) vectors for gene therapies for central nervous system (CNS) diseases and liver-directed therapies for the portfolio of both Roche and Spark Therapeutics, a member of the Roche Group.

Dyno’s proprietary CapsidMap™ platform represents a transformative approach to the identification of novel AAV capsids – the cell-targeting protein shell of viral vectors – optimizing tissue targeting and immune-evading properties, in addition to improving packaging capacity and manufacturability.

Under the terms of the agreement, Dyno will be responsible for the design of novel AAV capsids with improved functional properties for gene therapy, while Roche and Spark Therapeutics will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the novel capsids. Dyno will receive an undisclosed upfront payment and if successful, is eligible to receive additional payments during the research phase of the collaboration as well as clinical and sales milestone payments and royalties for any resulting products. The aggregate potential value of future milestone payments to Dyno may exceed $1.8 billion.

“This new partnership represents Dyno’s largest collaboration to date, and we are excited to work with Roche and Spark Therapeutics to expand the frontier of gene therapies for the central nervous system and liver. The Dyno, Roche and Spark teams share a bold vision for gene therapy and believe that enhancing vectors that deliver these therapies is key to developing new treatments for patients in need,” stated Dyno’s CEO and co-founder Eric Kelsic, Ph.D. “Partnering is a fundamental element of Dyno’s business strategy, and the continuing interest by leading gene therapy developers is accelerating our growth plans and positive impact on patients.”

“We strongly believe in the potential of gene therapy and are excited to bring together experts from Roche, Spark and Dyno to develop next-generation gene therapies. Dyno’s innovative AI-powered approach to designing optimized AAV vectors will further complement and build on our progress in gene therapy. We look forward to leveraging Dyno’s technology to develop new, innovative treatments for patients across CNS and liver-directed therapies,” said James Sabry, Head of Roche Pharma Partnering.

About CapsidMap™ for Designing AAV Gene Therapies

By designing capsids that confer improved functional properties to Adeno-Associated Virus (AAV) vectors, Dyno’s proprietary CapsidMap™ platform overcomes the limitations of today’s gene therapies on the market and in development. Today’s treatments are primarily confined to a small number of naturally occurring AAV vectors that are limited by delivery, immunity, packaging size, and manufacturing challenges. CapsidMap uses artificial intelligence (AI) technology for the design of novel capsids, the cell-targeting protein shell of viral vectors. The CapsidMap platform applies leading-edge DNA library synthesis and next generation DNA sequencing to measure in vivo gene delivery properties in high throughput. At the core of CapsidMap are advanced search algorithms leveraging machine learning and Dyno’s massive quantities of experimental data, that together build a comprehensive map of sequence space and thereby accelerate the discovery and optimization of synthetic AAV capsids.

About Dyno Therapeutics

Dyno Therapeutics is a pioneer in applying artificial intelligence (AI) and quantitative high-throughput 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.

Xconomy Startup of the - Year Zoom Call

Dyno Therapeutics has been named Startup of the Year by Xconomy, an award that recognizes the most innovative new company with a focus on those advancing creative solutions to the challenges of biology, to break onto the scene this year.

“We are incredibly honored to be selected as Xconomy’s Startup of the Year and recognized for our pioneering approach to gene therapy,” said Eric Kelsic, PhD, chief executive officer of Dyno Therapeutics. “Key to Dyno’s rapid ascent has been our systematic focus on solving gene therapy’s biggest challenge, the efficient, safe and precise gene delivery to target tissues. Just as essential to our success is our diverse team of the best problem solvers who are driving cutting-edge science toward improving patient health.”

Dyno Therapeutics is a pioneer in applying artificial intelligence (AI) and quantitative high-throughput 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 recently came out of stealth and earlier this year, signed deals valued in excess of $2 billion with gene therapy leaders Novartis and Sarepta.

Since 2017, the mission of Xconomy’s annual awards programs has been to provide the industry a moment to pause, recognize, and honor the very best the life sciences has to offer – the people, companies, and organizations that challenge the status quo and never accept what works as good enough.

 

 

 

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