Q&A with Michael Hodges, CEO of 1Strand and Partner at Claris Ventures

I sat down to talk with Dr. Michael Hodges , CEO of not for profit 1strand about the booming RNA therapeutics scene here in San Diego. Michael is a highly experienced and successful pharmaceutical industry veteran who has worked on multiple drug development programs in big PHARMA and biotech as the team leader/team member. He has deep RNA therapeutics drug development expertise and is currently supporting a number of Biotechnology companies and VCs in the role of scientific advisor and/or board director.?

The mission of 1STRAND is to showcase San Diego County as the premier location for RNA Research and Development (R&D), and to be a forum for continual education to highlight the positive impact of RNA medicines on public health. 1strand’s board of directors facilitate the dissemination of RNA education for those who are seeking to learn more about the RNA drug development. San Diego county is recognized as a biotechnology hub with more than 1,700 life science establishments, and within this figure, close to 30 companies are focused on RNA drug development. The aim is to present San Diego as the place where existing companies can grow, and new ventures can begin.

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How did 1Strand find its home in San Diego and how did San Diego become the hotbed for RNA therapeutics?

RNA therapeutics can be traced all the way back to Ionis pharmaceuticals who at the time was known as Isis pharmaceuticals. Ionis was the first RNA based therapeutics biotech in San Diego and was followed by the next generation of RNA companies such as Arcturus and Arrowhead therapeutics. In parallel to these burgeoning biotechnology companies, academia was also strong. Gene Yeo, (Professor of Cellular and Molecular Medicine at the UCSD), has founded multiple companies spun out of UCSD.?

If you want to start an RNA company, especially on the West coast, you have to look to San Diego. Of course, if you just focus on market cap, then the biggest RNA hub is Boston. However, if you examine the number of biotech startups and innovation, I think that San Diego may be ahead of our East Coast colleagues. We have had multiple good news over the last 6-months book ended by Novartis purchase of DTx pharma to last more recently the large capital raise by Capstan therapeutics.?

In addition to our great weather, San Diego has the infrastructure and the RNA experienced people, a lot of whom are veterans of Ionis or one of their spin outs, like I was. Most of 1strand’s BOD have some past or present connection with Ionis.?

What led to the discovery of RNA therapeutics and what do RNA therapeutics actually do?

RNA therapeutics are drug interventions that modify the functionality of RNA transcripts, like mRNA or microRNA. RNA are the intermediaries between the Host genome (DNA) and proteins. Through this modification the functionality of proteins can be controlled. Proteins are the essential building blocks within the body’s cells and are responsible for multiple key functions. When the synthesis of proteins goes awry then diseases occur. RNA therapeutics are designed to correct the expression of malfunctioning proteins, through their effects on the intermediary RNA molecules, and thus successfully treat diseases.?

What was the first ever RNA therapeutic to be discovered?

Fomiversen was the first RNA medicine to be approved by the FDA in 1998 for the treatment of CMV retinitis in patients with HIV/AIDS. Whilst better antiviral drugs superseded Fomiversen, this initial development and approval of this antisense oligonucleotide opened up the field for others to follow, e.g. Alnylam, Dicerna, Moderna and BioNTech.

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What is the biggest challenge RNA therapies face??

The biggest challenges in the development of successful RNA medicines are three fold : duration of the effect on mRNA; safety and toleration; and delivery to specific cell types. RNA therapeutics can successfully modulate RNA but sometimes the duration of the effect is not long enough. If the amount of RNA drug that is given needs to be high, in order to increase the duration of the effect, then safety and toleration issues can occur. Lastly, RNA drug delivery to liver cells is very good and not so good to other cells, for example the brain. At the moment, successful RNA drugs are mostly limited to liver disease, because only small amounts can be given safely and are all that is required for efficacy (for liver targets).?

How does RNA therapy differ from DNA therapy?

RNA therapy are drugs that modify the functionality of RNA and the downstream expression of proteins. This modification tends to be transient, hence duration of effect can short, which as stated above can be a downside. However, DNA therapy, if we are referring to DNA gene editing, makes permanent changes to the genome (DNA). Whilst gene editing has the opportunity of providing long lasting efficacy, should safety and toleration issues occur, they may lead to irreversible toxicity(ies). If RNA therapy causes issues with safety and toleration, these negative effects are more likely than gene editing to be temporary..

Which areas of RNA therapeutics have seen the most funding from VCs?

Over the last year there has been a serious lack of funding in many therapeutic areas. However, RNA drug development has continued to be well funded, as we saw from the recent large raise from Capstan therapeutics. As mentioned above, the goal is to move RNA out of the liver and into organs and tissues that have been historically hard to deliver RNA drugs. Several RNA companies are targeting non-liver e.g. Arcturus the lung, DTx Pharma the peripheral nerves and Jaan Biotherapeutics the heart.

What does the future of RNA therapeutics look like in SD

RNA drug development will remain a hot space in biotech and in the investment community, both here in San Diego and indeed at the other RNA hubs in the US (Boston, San Francisco) as well as in Europe (Copenhagen DK, Leiden NL and London UK). Researchers in the RNA space are opening up more and more doors, metaphorically speaking, that we can deliver RNA drugs to more tissues and more cells in the body, enabling a wider array of disease targets. I have no doubt that the RNA space here in San Diego and the other RNA hubs will continue to grow and thrive.?

What is the goal of 1Strand and what is the most exciting aspect of the organization?

The mission of 1STRAND is to showcase San Diego County as the premier location for RNA therapeutics, Research and Development (R&D), and to be a forum for continual education to highlight the potential positive impact of RNA medicines on public health.?

San Diego county is recognized as a biotechnology hub with more than 1,700 life science establishments, and within this figure, close to 30 RNA focused companies. We aim to present San Diego as the place where existing companies can grow, and new ventures can begin. Currently there is a high talent pool of professionals in San Diego and with highlighting San Diego as a top center, we hope to attract additional qualified individuals to San Diego County.

Along with the high number of RNA biotechnology companies, San Diego is also known for having the top prestigious educational and academic centers in the world, including some carrying out RNA research. 1STRAND aspires to enable the sharing of RNA information between these institutions, the local industry companies, and the public. In light of the COVID-19 pandemic, 1STRAND has recognized the importance of not only science industry professionals to have access to the latest information and scientific developments happening in and around San Diego County, and far beyond, but also for the general public in the San Diego County region to have access to local, reliable resources for this information as well.

Who is 1Strand geared towards and what is the best way to get involved with the organization?

1strand is looking to engage with people who are working in the RNA drug development space here in San Diego, as well as in other RNA hubs.?

Any advice to biotechs trying to break into the RNA space?

We at 1strand would be happy to provide help (gratis) to any RNA NwCo thinking about setting up in San Diego county.?