Rapid whole genome sequencing. Gene editing. RNAi. CAR-T. The list goes on.
The pace of innovation in genomic medicine is staggering. The application of genomic technologies across medicine runs the gamut from disease discovery, to diagnosis, to drug development, to disease model development, and out to personalization of therapies.
Combine this with the fact that over 80 percent of rare diseases are genetic diseases; the vast majority of which lack treatments and have crippling often life threatening, unaddressed medical needs. Unsurprisingly, given these dynamics, the field of rare diseases has seen rapid implementation of genomic technologies – leading to the development of genetically targeted therapies to address these unmet medical needs.
Convergence of technologies
Individually these technologies are game changing for specific aspects of disease diagnosis or management. However, when integrated, the effects are synergistic. Take, for example, a new privately held biotech in San Francisco, Perlara. Its tagline is “no disease left behind”; its business model is focusing on discovering treatments for incredibly rare conditions.
The company advances an entirely new model of drug development that combines the wide availability of gene sequencing of ultra-rare genetic disorders with gene editing technology (CRISPR-Cas9). This complementary approach allows them to rapidly develop new genetic models of disease that are specific to a given patient’s genotype. Phenotypic drug screening against rapidly created disease models can quickly generate new lead compounds or identify compounds for drug repurposing. Using this model, they can partner with biotechs and patient advocacy groups to produce potential drug candidates quickly, allowing them to efficiently address even the smallest populations with newly discovered genetic disease.
Perlara is tapping partnerships with Big Pharma companies and niche rare disease patient advocacy groups to accelerate the treatment of novel drugs. Indeed, they recently announced partnership with Novartis to advance new candidate molecules for the treatment of lysosomal storage disorders. They also partner directly with ultra-orphan patient advocacy groups to advance drug development in diseases traditional biotechs and pharmas would consider too rare to merit investment. One of the company’s first patient advocacy partnerships is to identify re-purposable drugs for the ultra-rare, recently discovered, NGLY1 syndrome; the story of this disease discovery is itself fairly amazing and was covered by The New Yorker Magazine.
Clinically mature technology platforms
The market has recently experienced an incredible simultaneous maturation of both discovery platforms, such as rapid, low cost, gene sequencing and gene editing, as well as targeting and delivery systems, including clinically effective gene therapy vectors, targeted and stabilized oligonucleotides, and RNAi technology.
Take for example, the recent approval of nusinersen for the treatment of an ultra-rare genetic condition, spinal muscular atrophy (SMA). Due to a defect in the SMN1 gene, patients with SMA do not produce enough survival motor neuron (SMN) protein, an essential protein in the maintenance of motor neurons. Nusinersen is an RNAi therapeutic that specifically targets the causative protein of neurodegeneration in SMA – SMN.
For decades RNAi has been widely used in the laboratory to rapidly and quickly validate the roles of individual proteins and map how these proteins affect cellular- and organism- level pathology. Previously, targeting and delivery issues impaired clinical development and prevented this approach from yielding many, new drug approvals. However, with next generation modified RNA oligonucleotide technology, nusinersen is able to, quite effectively, circumvent these limitations and directly affect SMN protein production. Thanks to these clinically relevant innovations, the drug received a recent approval in the treatment of patients with SMA.
The future of genetic therapies
Both Perlara and nusinersen are excellent examples of cases where the advancement of multiple genetic technologies to the point of convergence in either drug discovery or drug development are powering new genetically-driven approaches. Each new drug approval, like nusinersen, is the clinical validation and promise of an entire genetic technology platform. Viewed from this lens the future of drug development in genetic therapeutics has never been more positive.
About the Author
Samuel Falsetti is the Head of Medical Strategy and Product Innovation at Cambridge Biomarketing, the leader in rare disease consulting and marketing services.
Filed Under: Drug Discovery