Investing in new innovative RNA technologies can lead to rapid value creation, and Europe is a fertile ground to hunt for them. The discovery of DNA and the gene underlies much of modern medical therapy, and with the recent advent of successful gene therapies, is undergoing a renaissance. Only in the last couple of decades, however, has the translator of DNA—RNA, gained appreciation as a potential inroad for new therapies and led to the creation of several multibillion-dollar companies. While the field of RNA therapy has started to blossom recently, it, much like biotechnology companies in Europe, has underappreciated potential. The main purpose of RNA, known as messenger RNA or mRNA, is to convert (or translate) the genetic information of DNA into proteins. There are many other forms of RNA now recognized, and each a potential target for therapies to combat disease and illness in ways considered ‘undruggable’ until now. A short list would include the protein synthesis RNAs: messenger RNA (mRNA, Moderna- Covid-19 Vaccine), transfer RNA (tRNA), ribosomal RNA (rRNA), and small nuclear RNAs (snRNA), and regulatory RNAs: micro RNA (miRNA) and short interfering RNA (siRNA). The applications of these RNA ‘species’ is for therapeutics for various treatment applications, including cancer, cardiovascular disease, kidney disease, infectious disease, metabolic disease and more.

Examples of RNA therapies already approved include: Macugen (approved 2004; Pfizer) for the treatment of AMD, Exondys 51 (approved 2016; Sarepta Therapeutics Inc) for the treatment of Duchenne muscular dystrophy; Spinraza (December 2016; Biogen) approved for the treatment of spinal muscular atrophy in children and adults, and Onpattro (August 2018; Alnylam Pharmaceuticals) approved for the treatment of hATTR in adults.

Investing in new innovative RNA technologies can lead to rapid value creation, and Europe is a fertile ground to hunt for them. The discovery of DNA and the gene underlies much of modern medical therapy, and with the recent advent of successful gene therapies, is undergoing a renaissance. Only in the last couple of decades, however, has the translator of DNA—RNA, gained appreciation as a potential inroad for new therapies and led to the creation of several multibillion-dollar companies. While the field of RNA therapy has started to blossom recently, it, much like biotechnology companies in Europe, has underappreciated potential. The main purpose of RNA, known as messenger RNA or mRNA, is to convert (or translate) the genetic information of DNA into proteins. There are many other forms of RNA now recognized, and each a potential target for therapies to combat disease and illness in ways considered ‘undruggable’ until now. A short list would include the protein synthesis RNAs: messenger RNA (mRNA, Moderna- Covid-19 Vaccine), transfer RNA (tRNA), ribosomal RNA (rRNA), and small nuclear RNAs (snRNA), and regulatory RNAs: micro RNA (miRNA) and short interfering RNA (siRNA). The applications of these RNA ‘species’ is for therapeutics for various treatment applications, including cancer, cardiovascular disease, kidney disease, infectious disease, metabolic disease and more.

Examples of RNA therapies already approved include: Macugen (approved 2004; Pfizer) for the treatment of AMD, Exondys 51 (approved 2016; Sarepta Therapeutics Inc) for the treatment of Duchenne muscular dystrophy; Spinraza (December 2016; Biogen) approved for the treatment of spinal muscular atrophy in children and adults, and Onpattro (August 2018; Alnylam Pharmaceuticals) approved for the treatment of hATTR in adults.

The patient’s view

When was the last time you noticed the intimidating list of side effects before taking a medicine your physician prescribed you? You may have even thought to yourself, “is it worth it?” Well, you’re not the only one. As investors in a HealthTech venture capital fund, “patients don’t like taking pills” is a common phrase we hear in diligence calls we conduct with numerous physicians. We’ve also heard during diligence processes that “approximately 50% of patients with a chronic disease do not take their medications as prescribed”. A key reason is that patients are hesitant when it comes to taking a medication that might lead to side effects and potential long-term implications.

Traditionally, patients have been treated with oral drugs, or injectable biologics, for various acute and chronic indications. Pharmaceutical developments have had a dramatic impact on our lives and improved healthcare outcomes for hundreds of millions of people around the world. Drugs, as the mainstay of medical therapy, are here to stay.  Nonetheless, we are beginning to see new alternatives to pharmaceutical therapy emerge, which offer patients a new way of taking control over their healthcare decisions.

Could devices be an alternative to traditional drugs?

The accelerating convergence of technology and healthcare has led to a surge of research into next-gen devices, which are intriguing for both patients and physicians. As an illustrative example, a survey among 514 patients that was published in The Journal of Headache and Pain revealed that 67% of patients with acute headache preferred to be treated with an external neurostimulation device rather than a pill.

The question is then, what qualities and characteristics should these new devices, which could potentially replace traditional pharmaceuticals, have? These new solutions need to provide a tangible series of benefits to patients. First and foremost, they must demonstrate strong efficacy at least as good as the standard of care if not more, as well as superior safety profile, and be held to the highest regulatory standards (such as an FDA approval).  Also, to drive adoption they must be able to address reimbursement, and, for connected devices, have an engaging user interface while adhering to the strictest data privacy regulations.

The migraine space as an example

While 14.7% of the global population suffers from migraines, the need for alternative treatment solutions remains strong. A survey among 2,444 patients demonstrated that 66% of patients had low compliance to traditional pharmaceutical therapy due to concerns about side effects.  An even higher number, 79%, sought out a novel product with similar efficacy but with less adverse events.

Theranica’s Nerivio was developed to address these exact efficacy and safety concerns of both patients and physicians. At the onset of a migraine, the device is placed on the upper arm and managed via a smartphone app. But not only that it’s a user friendly connected device, it also went through a rigorous pivotal study of 252 patients that demonstrated efficacy similar to (if not higher than) triptans, and with minimal side effects. Based on the above, Nerivio was recognized by Time magazine as one of the best inventions of 2019. It recently received FDA approval (de novo clearance) for the acute treatment of migraines and was launched in the US as an intriguing alternative to pharmaceuticals.

Are we at the beginning of a revolution?

Patients are increasingly becoming better informed and eager to learn about new options that will allow them to take control of their healthcare decisions. Nerivio is one example, which has the potential to challenge the way physicians and patients think about treating certain medical conditions.  In fact, some devices have already penetrated the market in cases where traditional drugs have failed to demonstrate sufficient efficacy. For example, severe Alzheimer patients benefit from implantable neurostimulators that ease the disease burden.

Various other indications are being targeted by such disruptive devices, giving hope to millions of patients around the world: Chronic pain (e.g., Proclaim by Abbott), sinus pain (e.g., ClearUp by Tivic Health), autoimmune diseases (e.g., SetPoint Medical), essential tremor (e.g., Cala Trio by Cala Health), overactive bladder (e.g., Renova by BlueWind Medical), Obesity and diabetes (e.g., Epitomee), and many others. This trend towards medical devices as high-quality treatment solutions in segments of high unmet need is gaining traction. The sky is the limit.

A bright future for healthcare

So, what does it mean for big pharma and medical device companies? Some have started taking an interest in these innovative products, believing they might benefit commercially and financially from bringing these products into their portfolios. Such products provide an attractive value proposition in terms of efficacy and safety. Connected devices also represent an additional value to patients – an opportunity to leverage data for more accurate and personalized treatment, enhance data sharing and connectivity within social networks, and even increase compliance. Furthermore, aggregated and deidentified big data could contribute to the development of new personalized treatments.

Pharma and biopharma are here to stay, and will continue to advance care, but devices expect to provide additional high-quality treatment options and would jointly serve the world’s population towards better health.