Therapeutics
Number of companies working on RNA therapeutics in clinical development
RNA-based aptamers or decoys have entered clini- cal development (Table 1).
mRNA Antisense RNA miRNA siRNA RNA aptamer
Graph 1:Companies developing RNA-based therapeutics in the clinic (as of July 2018). Data provided by GlobalData Plc
Number of clinical trials by RNA therapeutic class
Emerging technologies New technologies and modalities to target RNA include the application of the CRISPR-Cas9 genome editing technology, DNA-directed RNA interference (ddRNAi) technology, and the devel- opment of selective small-molecule modulators of RNA or RNA-modifying enzymes14. For example, CAL-1, Calimmune’s lead therapeutic candidate, represents an RNA-based gene therapy using ddRNAi to silence the CCR5 gene to control HIV infection and to protect individuals with HIV from developing AIDS. Several companies that focus on the development of small-molecule RNA modula- tors have been established in recent years. For example, Expansion Therapeutics Inc (San Diego, California, USA) has developed a platform to iden- tify small molecules interacting with RNA (SMiRNA™), including mRNA and various non- coding RNAs, across multiple therapeutic areas. In addition, STORM Therapeutics (Cambridge, UK) specialises in RNA epigenetics, and the develop- ment of small-molecule inhibitors of RNA-modify- ing enzymes for the treatment of cancer. Targeting splice-variant control sequences within
mRNA Antisense RNA miRNA siRNA RNA aptamer
Graph 2:Number of RNA-based therapeutics in clinical trials (as of July 2018). Data provided by GlobalData Plc
Forecast drug sales
introns (non-coding regions of an RNA transcript or DNA sequence within a gene) or exons (coding regions) offers further opportunities to develop therapeutics. For example, Skyhawk Therapeutics Inc (Waltham, Massachusetts, USA), was founded this year with a platform to identify selective small- molecule modulators of the RNA spliceosome complex that target RNA mis-splicing (exon skip- ping), which drives multiple diseases including neu- rological conditions and cancer. These emerging technologies offer great opportunities to develop alternative strategies to target RNA for drug devel- opment.
Marketplace The first notable success for RNA-based therapeu- tics was the FDA approval of the RNA aptamer, Macugen
(Pfizer/Valeant
Pharmaceuticals
Graph 3: Forecasted global sales for RNA-based therapeutics from 2016-24. Revenue is given in US$m. Data provided by GlobalData Plc
22
International Inc), for the treatment of AMD in December 2004. Since then, two antisense RNAs and one siRNA have gained FDA approval: Exondys 51 (approved in September 2016; Sarepta Therapeutics Inc) is used to treat Duchenne muscu- lar dystrophy; Spinraza (December 2016; Biogen Inc) represents the first approved drug for the treatment of spinal muscular atrophy in children and adults; Onpattro (August 2018; Alnylam Pharmaceuticals Inc) represents the first FDA
Drug Discovery World Fall 2018
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72
