Following the release of Clarivate’s report ‘RNA Technology Companies to Watch’, DDW’s Diana Spencer speaks to Strand Therapeutics’ Jacob Becraft and HAYA Therapeutics’ Samir Ounzain to find out how this technology could revolutionise disease treatment.
Therapies that act upon or incorporate RNA to fight disease have gained traction over the last decade and were pushed into the spotlight further with the regulatory approvals of mRNA vaccines during the global Covid-19 pandemic.
Success with rare diseases, which typically do not respond well to traditional approaches, is setting RNA therapies apart. Demonstrating benefits such as fewer side effects and lower cost to enhanced efficacy and accessibility, this emerging therapeutic modality is giving hope to patients and clinicians.
The momentum of RNA technologies is apparent in the significant increase in scientific knowledge, IP and deal-making value over recent years. From 2010 to 2020, the number of patents filed globally increased by 52%, and the number of RNA-related research publications jumped by 160% between 2012 and 2021.
Clarivate has identified seven recently created innovative RNA technology companies that are developing solutions to tackle currently undruggable targets.
Aro Biotherapeutics
A company pioneering the development of tissue-targeted genetic medicines with a patented platform technology, Centyrin, positioned to precisely target diverse therapeutics to specific cells of interest. Lead programmes include Centyrin-oligonucleotide conjugate therapies meant to provide targeted delivery of oligonucleotides to extra-hepatic tissues and Centryrin-small interfering (siRNA) conjugate therapies for oncology targets.
Cargene Biopharma
A company developing highly specific, stable, potent, siRNA-based oligonucleotide therapeutics via the company’s OSCAR algorithm and SMoP pharmacophore design platform. The company aims to address a broad range of diseases, with an initial focus on liver and ophthalmic disorders.
DTx Pharma
A company that has developed a proprietary platform technology called FALCON (Fatty Acid Ligand Conjugated OligoNucleotide). The FALCON platform has the potential to address multiple therapeutic areas, including CNS, cardiovascular, immunology and oncology.
HAYA Therapeutics
A precision therapeutics company that has developed a proprietary drug discovery engine, DiscoverHAYA, enabling a pipeline of lead, long non-coding RNA (lncRNA)-targeting, anti-fibrotic candidates for many tissues including lung, kidney, liver and the solid tumour microenvironment. The company’s lead development candidate (HTX-001) is a modified ASO targeting the lncRNA Wisper, a cardiac myofibroblast-enriched driver of fibrosis.
Laronde
A company whose platform, Endless RNA (eRNA), involves novel, closed-loop, programmable, persistent, non-immunogenic RNA constructs to express therapeutic proteins inside the body.
Replicate Bioscience
A company designing self-replicating (srRNA) immunotherapies with a primary focus on drug resistance in oncology and new treatments for autoimmune and inflammatory disorders. Lead candidates include RBI-1000 for breast cancer, RBI-2000 for solid tumors, RBI-3000 for lung cancer and RBI-8000 for inflammatory/autoimmune disease.
Strand Therapeutics
An emerging company developing next-generation, programmable, long-acting mRNA therapeutics capable of delivering precise, multi-functional, potentially curative treatments with a single dose for cancer immunotherapy and other diseases.
Jacob Becraft, CEO and co-founder, Strand Therapeutics
DS: Why do you think your company was chosen?
JB: Strand was founded in 2018, and our programmable mRNA technology has broad applicability across a variety of diseases. Our initial focus is to develop mRNA therapies that act through multiple immune mediated mechanisms to deliver potentially curative treatments in oncology. In solid tumours, Strand’s mRNA approach has the potential to significantly improve response rates to checkpoint inhibitor therapy. In haematological tumors, Strand’s early work may have the potential to revolutionise CAR-T therapy and massively simplify supply chains.
Strand’s mRNA therapeutics enable precise control of the location, timing, intensity and duration of therapeutic protein expression for improved efficacy and lower toxicity. Our team has been focused on engineering mRNA so that it’s only used to express cargo protein in certain cells regardless of where the molecule ends up in the body. In that sense, it doesn’t matter where the mRNA is delivered, but ultimately where it is expressed. Our strategy relies on microRNAs, which are tiny molecules that latch onto messenger RNA and cause it to be degraded. There are more than 2,000 microRNAs coded for in the human genome, and different tissues express them at different levels.
DS: How will your work ultimately impact disease treatment?
JB: Our programmable mRNA, or as some people in the industry have called “mRNA 2.0,” will enable mRNA to be used beyond just vaccines, and in broader disease areas such as oncology. As a result, we are programing mRNA with more precision and control in cell behavior, which allows for multiple mechanisms to be modulated and timed, enabling drug development in a wider diversity disease and therapeutic areas.
DS: What will 2023 hold for your company?
JB: We plan to first evaluate our mRNA therapy in an initial clinical trial as a treatment for solid tumours. Our engineered mRNA could also be used for in vivo/in situ cell therapies, which reach and reprogramme specific cells, without removing them from a patient’s body.
Samir Ounzain, CEO and co-founder, HAYA Therapeutics
DS: What’s unique about your research?
SO: Our mission is to create novel, differentiated drug candidates for treating fibrotic and other severe diseases by decoding and reprogramming the dark genomes’ source code to target disease-driving cell states. Through our platform, we can gain foundational knowledge into the biology of long non-coding RNAs (lncRNAs). By focusing on the dark genome, we can create RNA-guided, cell-state modifying drug candidates with the potential for improved efficacy, safety and accessibility than currently available therapeutics.
HTX-001 targets the lncRNA Wisper, which is known to play an essential role in heart failure, with an initial indication focus of non-obstructive hypertrophic cardiomyopathy. We believe our approach can bring significant hope to these patients and change the treatment paradigm for heart failure management and therapeutic intervention.
DS: What’s next on the horizon for HAYA?
SO: By early 2023 we plan to close our series A financing, which will help us advance our DiscoverHAYA drug discovery engine, expanding our pipeline and accelerating our lead compound into clinical testing. Additionally, the HAYA team has been working on several other proprietary platforms which complement DiscoverHAYA. These platform modules will allow us to dive deeper into the biology of the dark genome and its role in ageing-related chronic diseases, enabling novel insights to identify, track and drug lncRNA targets.
To that end, our platform has tremendous potential in other diseases beyond cardiovascular diseases, such as cancer, as demonstrated by our recent collaboration with Univeristy Hospital in Lausanne to develop a next-generation oncology therapy targeting the tumour microenvironment in solid tumours.
DS: Why is RNA technology such a game-changer?
SO: As seen with the Covid-19 pandemic, RNA-based medicines can significantly impact the healthcare industry and have transformational potential to change the drug development paradigm. Companies are now advancing novel technologies that can tap into the potential of RNA – from delivery to target identification – and create new ways to treat patients that were previously unimaginable. As the field continues to grow and mature, we remain optimistic that RNA technology will revolutionise how we treat all patients – from those individuals with rare diseases to patients with more common and chronic conditions.
Read Clarivate’s full report ‘RNA Technology Companies to Watch’.
