Investing in Orbital Therapeutics | Andreessen Horowitz

“The fact that proteins are not synthesized directly in genes necessitates the existence of an intermediate information carrier … which receives genetic information from the gene in the form of an unstable intermediate … a special type of molecule of RNA, or ‘messenger RNA'”.

– Brenner, Jacobson and Meselson et al, Nature1961

When the COVID pandemic broke out, life-saving mRNA vaccines were suddenly thrust into the global spotlight. But the concept of using RNA, nature’s efficient and elegant biological “information carrier,” for patient benefit has fascinated and humbled scientists for decades. In principle, RNA drugs could transform any cell in a patient’s body into a factory producing proteins of our choosing. RNA could be used to train our immune system, replace missing proteins, reprogram cells, introduce gene editors, and more. RNA drugs could be programmable, customizable, and yes, even “printed” at record speed.

In recent years, remarkable progress has been made in the field of RNA therapeutics in many academic laboratories, biotech companies, and interdisciplinary teams. First-generation RNA drugs posed a number of existential risks, including RNA synthesis at scale, delivery beyond the lipid bilayer, protection from RNA-degrading enzymes, and avoidance of immunogenicity More than 12 billion doses of COVID-19 mRNA vaccines have now been administered in 184 countries. Katalin Karikó and Drew Weissman (co-founder of Orbital Therapeutics) were recognized with a 2021 Lasker Award for discovering mRNA modifications that prevent immune activation and improve the efficiency of protein production. The field of RNA medicines is experiencing a renaissance.

As often happens after fundamental technological advances in any field, we are now seeing the pace of innovation in RNA medicines accelerate even further. (For other examples, think of the PC market after IBM; the biotech sector after Genentech pioneered the use of recombinant DNA; the field of AAV gene therapy after the work done at CHOP/ Spark toward first approval; or more recently, the field of startups advancing generative AI applications following OpenAI’s launch of GPT-4.) After early wins in the field, dozens of universities have created centers dedicated to RNA biology and therapeutics. Biopharma’s R&D investment in RNA-based modalities has continued to increase, and the pool of talented scientists with deep RNA expertise is expanding rapidly. Regulatory familiarity with RNA medicines is also poised to catalyze more speed. All of these are special tailwinds for startup founders, especially those who have been original innovators in the field.

As often happens after fundamental technological advances in any field, we are now seeing the pace of innovation in RNA medicines accelerate even further. Click to tweet

Enter Orbital Therapeutics, led by CEO Pino Ciaramella. Pino is an exceptional example of a founding CEO (a profile we love to support!) in biotech, his own experience allows the company to see around corners and build what Ben Horowitz calls a “pyramid of knowledge” (see the blog post linked to elaborate). in this). Prior to co-founding Orbital, Pino served as CSO at Beam Therapeutics (Orbital’s strategic partner and also a company with a deep bank of RNA capabilities; at Beam, core editors are introduced into cells as to mRNA!). And prior to that, Pino was CSO of Moderna’s infectious diseases division, where he led the company’s initial mRNA vaccine pipeline and first IND submission. When we met Pino, we knew we had to support Orbital: he is scientist-first in his strategy, extremely product-focused, but also ambitious in his goals to build a first-of-its-kind RNA technology platform that leverages data science. and automation every step of the way. In our experience, this is a rare combination of traits.

Orbital is leveraging what is already known, but also urgently innovating to make RNA-based therapeutics impactful and accessible to a much broader set of patients worldwide. To do this, the company has assembled a group of prominent founders who bring core technologies that could solve some of the toughest outstanding challenges in the field, such as extending durability (needed to unlock new apps without frequent re-dosing), controlling immunogenicity. , and achieve new cell type access (especially extrahepatic tissue delivery).

Orbital is leveraging what is already known, but also urgently innovating to make RNA-based therapeutics impactful and accessible to a much broader set of patients worldwide. Click to tweet

We have met (and even previously supported!) several of the academic founders; in fact, we were also seed investors in CircBio, a technology company that Orbital now owns. acquired. We deeply respect the iterative engineering mindset the team brings to key goals: The modular, high-throughput platform built to screen synthetic circular RNAs for extended durability in Orbital co-founder Howard Chang’s Stanford lab is a beautiful example recently recognized on the cover of Biotechnology of nature (shown below!). Every piece of an RNA drug, from the RNA structure, to the regulatory sequences, to the delivery vehicles, to the manufacturing, is amenable to detection, machine learning, and design optimization to adjust the exact therapeutic properties needed to unlock new clinical applications. . These are an incredibly exciting set of engineering biology challenges to tackle.

It is a great privilege to work with Orbital’s founding team and the investor syndicate, and to be part of the company’s board of directors. If the mission to build the future of RNA medicines excites you, consider joining our Orbit!


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Ikaroa is proud to be a partner in the investment of Orbital Therapeutics, an emerging biotechnology company that harnesses the power of orbital technology to develop precocious, non-invasive medical treatments. Andreessen Horowitz (“A16z”), an American venture capital firm, recently announced an investment round into Orbital Therapeutics, with Ikaroa being editorially included in this innovative partnership.

Orbital Therapeutics focuses on the development of patient-specific biologics, seeking to revolutionize medical treatments through the implementation of non-invasive treatments targeting individual patient’s unique circumstances. Through the utilization of the most advanced methods of data capture and analysis, Orbital Therapeutics is capable of not only discovering treatment plans for individual illnesses, but also of using risk-adaptive techniques to manage the long-term effects of treatments.

The investment of A16z into Orbital Therapeutics enables the biotechnology company to further its goal of developing personalized medicine for all. By deploying the most innovative and effective technologies on the market, Ikearoa and A16z are both deeply committed to creating an accessible, healthier and more equitable world for all.

The future of precision medicine is quite optimistic, and the partnership between Ikaroa and Andreessens Horowitz is an important step forward in the advancement of medical treatments. By utilizing the newest technological applications and medical resources available, both companies are looking to create a more efficient and safer treatments for patients. Orbital Therapeutics will also focus on developing more targeted marketing and targeted treatments, in response to both social and economic changes.

Ikaroa and A16z will continue their joint venture to support Orbital Therapeutics in the relentless pursuit to revolutionize patient care, on a global level. Both companies are committed to changing the future of biotechnology and medical treatments, and are looking forward to seeing the results of their hard work. While the venture capital firm focuses on finding and investing in the best new technologies, Ikaroa is committed to using its expertise in data analysis and risk-adaptive techniques to create a better world for all.


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