In 1998, American scientists Andrew Fire, Craig Mello and colleagues described a mechanism that can degrade mRNA from a specific gene. This mechanism, RNA interference (RNAi), is activated when RNA molecules occur as double-stranded pairs in the cell. Fire and Mello’s work on the use of RNAi for targeted silencing of disease-causing genes won the Nobel prize in 2006. And while the FDA has approved four RNAi drugs, beginning with ONPATTRO® (patisiran) in 2018, the main challenge in turning RNAi into medicine has been tissue delivery.
Headquartered in Boston, Atalanta Therapeutics is developing new treatment options for neurodegenerative diseases and other central nervous system (CNS) disorders by utilizing its proprietary RNAi platform, branched siRNA, to target the brain and spinal cord. The initial areas of therapeutic focus include Huntington’s disease, Parkinson’s disease and Alzheimer’s disease, alongside ongoing preclinical research work on other CNS disorders.
Named after the mythological Greek heroine and fierce huntress, Atalanta was founded in 2018 by Anastasia Khvorova, PhD, Craig Mello, PhD, and Neil Aronin, MD, of the RNA Therapeutics Institute at the University of Massachusetts Chan Medical School (UMMS). With Series A funding led exclusively by F-Prime Capital and strategic collaborations with Biogen and Genentech, the company successfully emerged from stealth in January 2021 with $110 million.
GEN Edge chatted with CEO Alicia Secor about the founding of Atalanta and executing a company launch during the COVID-19 pandemic.
GEN Edge: What is Atalanta’s origin story?
Alicia Secor: The origins of Atalanta can be traced back to pioneering work by Anastasia Khvorova and her colleagues at the UMass Chan Medical School to crack RNAi distribution in the CNS. Oligonucleotide therapeutics have made their way into the forefront of the biotech armamentarium. Still, the application of RNAi to CNS has had persistent limitations, primarily in getting broad distribution and reaching deep brain structures.
In talking with her colleague Neil Aronin, internationally recognized as a leading Huntington’s disease researcher, he challenged Anastasia to look for chemistry innovations that could allow RNAi to treat CNS diseases like Huntington’s. Collaborating with Anastasia and Neil was our third founder, Craig Mello, who shared the Nobel Prize in 2006 for his discovery of RNAi.
Anastasia embraced a mission to solve the problem of RNAi distribution in the CNS. She did it by working with an incredible team of scientists to explore innovations in chemistry. The result was the discovery of the new siRNA construct that underpins Atalanta’s platform. It’s a branched construct: two siRNA duplexes joined by a linker.
Anastasia’s work in mice, rats, sheep, and non-human primates demonstrated that she could achieve broad CNS distribution with a six-month duration and deep brain penetration. Unlike other modalities or RNAi approaches, we don’t use conjugation; our siRNA is delivered as a naked molecule. It was fascinating that these studies showed significant target knockdown in the striatum, which is relevant for Huntington’s disease.
In April 2019, the seminal publication came out in Nature Biotechnology, which set the field on fire with significant excitement for the preclinical data that Anastasia generated. The technology generated a lot of interest from big pharma. F-Prime was on the leading edge of interest in Anastasia’s work, and they exclusively provided the initial Series A funding.
In the past three years, we have since innovated, and we’re probably now working on the second and third generations of the chemistry, outperforming the initial first-generation chemistry coming out of UMMS and described in that Nature Biotechnology paper.
Today we have about 40,000 square feet at our headquarters in Boston’s Seaport District. More than 20,000 of that is dedicated to lab space. We wanted to ensure that we established key capabilities, including in vitro and in vivo testing and chemical synthesis. We have assembled an impressive team with industry vets with backgrounds in neuroscience and oligonucleotides, and we’re aiming to be at 70 employees reasonably soon.
GEN Edge: How was the launch affected by the COVID-19 pandemic?
Secor: We began the company build in June 2019, started hiring people, and then COVID hit. Still, we were able to attract top talent. Even during COVID, we established our in vitro, in vivo, and oligo synthesis capabilities. And the only thing that caused us delay was ordering equipment and having vendors help install it.
But in terms of getting the work done, our collaborators at Biogen and Genentech remain incredibly impressed by all the data we’ve generated, and we have accomplished a lot in the last three years.
GEN Edge: Why did you decide to partner so early?
Secor: There are a lot of different strategic considerations and many variables we considered. We believe our platform truly represents a disruption in the application of RNAi to the brain. It was in high demand. It has incredibly broad applicability. If there’s a CNS target where therapeutic benefit can be achieved by knocking down the protein, then that disease is potentially addressable with our technology. There are more targets than we could ever pursue independently as a brand-new startup company.
The non-dilutive cash was a consideration but not the only driver. Access to the scientific and development expertise of companies like Genentech and Biogen has accelerated our learning. These collaborations also enable the build of a much broader pipeline and have the potential to accelerate the translation of the technology to help patients.
We’re two years into those research collaborations. The execution has practically been flawless, and we have now generated compelling data across multiple targets and species. We believe that on a preclinical basis, the technology is validated.
GEN Edge: What is Atalanta’s mission, and where are you at with progress toward that mission?
Secor: Our mission is to translate this platform into medicines that can fulfill unmet needs in CNS, not just neurodegeneration.
Things are going full force ahead, and we are focusing now on developing a wholly-owned pipeline that will deliver an essential part of the value equation for future investors. We have embarked on a rigorous year-long process to identify the most compelling CNS targets. Our Board of Directors has blessed this initial set of targets, and we are pursuing in vitro work on multiple targets in parallel between now and the end of the year, which will inform how we prioritize in vivo studies next year.
We have not yet disclosed what the in-house targets are. But some guiding principles are that we follow biology and genetics to understand disease-relevant targets where knockdown is safest and yet will have a significant effect on disease. We’re looking for diseases where preclinical models can recapitulate human disease because we’re looking for quick go/no-go decision points. We’re looking for validated clinical endpoints. What do we measure? How can we win? The targets we’ve selected for screening this year span rare and prevalent diseases. The overarching goal is to create a balanced pipeline to advance two to three programs into clinical development in the near term.
GEN Edge: Does Atalanta manufacture RNAi medicines?
Secor: We’re still a preclinical-stage company. When you launch a company based on just a license or technology out of academia, you need to work hard to establish independence and do your own validation work. So, we were building and validating all during that initial phase of the pandemic. And now, after executing the partnerships, we probably have ongoing work on between eight and ten different targets. A lot of that is discovery, but much is now in the preclinical stages of development. We manufacture in-house all our oligos for preclinical non-GLP work. But ultimately, when it comes to GLP manufacturing and commercial manufacturing, we will probably be outsourcing that.
GEN Edge: What key milestones are in Atalanta’s sights?
Secor: There are multiple potential milestones and future royalties we could realize over the coming years within our existing collaborations. Near-term milestones will be based on pre-clinical achievements as well as potential ‘limited’ new target nominations that were reserved in the contracts.
In parallel, we’re advancing our internal, wholly-owned pipeline, and the key initial milestones there are showing in vivo success and generating IND filings.
GEN Edge: Do you have plans for raising additional financing in the near future?
Secor: With our sizeable Series A and collaboration up-fronts, $110 million, we are well capitalized with ample runway. We are also fortunate to have a high-quality investor in F-Prime. With our existing collaborators, we have the potential to achieve multiple near-term milestones to extend our runway further. That’s a strong position to be in. I empathize with many of my CEO colleagues and other companies struggling in these challenging market conditions. We have not declared the timing for our next financing round as there is no current need. That said, we have a lot of inbound interest from additional high-quality investors and are building relationships for the future.
GEN Edge: Why was the company named Atalanta?
Secor: The name Atalanta is derived from Greek mythology. Atalanta was a fierce huntress and the only woman to sail with the Argonauts in the quest for the golden fleece. If you know about RNAi, you know the importance of AGO2, a protein in the Argonaute family. And our company was built and is now led by remarkable women, chief among them Anastasia and Aimee Jackson, our CSO. All these themes run together, making it a perfect name.
