Biotech Values

[drbio45]

From: Josh Schimmer <[e-mail]<mailto:[e-mail]>>
Date: June 18, 2018 at 4:30:21 PM EDT

Subject: Emerging SMA programs
Reply-To: Josh Schimmer <[e-mail]<mailto:[e-mail]>>


For our tidbit today, we wanted to highlight emerging therapies in Type 1 spinal muscular atrophy (SMA) given the risdiplam (PTCT/Roche) data this weekend. Risdiplam’s early CHOP intend results at 6 months seems fairly strong and comparable to AVXS-101 and Spinraza (IONS/BIIB), causing the negative IONS/BIIB stock reaction. However, we do caution the sample size is still fairly small (n=11 who have reached 6 mo). The oral delivery of risdiplam is a clear cost and convenience advantage relative to the intrathecal administration of Spinraza. A detailed chart comparing SMA Type 1 trials is highlight at the end.

We also wanted to highlight Exicure’s novel approach to targeting SMA using spherical nucleic acids (SNA). Key advantages of SNA include increased cell uptake, extra-hepatic delivery, and increased half-life. In pre-clinical SMA mice models, SNA has shown 4x increased survival compared to Spinraza (nusinersen) as well as highly increased SMN2 full length mRNA. Data shown below.

Risdiplam (PTCT/Roche) CHOP-INTEND scores

[https://evercore.na.bdvision.ipreo.com/NSightWeb_v2.00/Downloads/Files/31251a48-1949-4a64- a51d-6ab36ffb869e.jpg]

Source: PTCT/Roche Presentation



Spinraza (IONS/BIIB) CHOP-INTEND scores in ENDEAR/SHINE



[https://evercore.na.bdvision.ipreo.com/NSightWeb_v2.00/Downloads/Files/770ac0c9-fa5c-4a63- be39-16bec7c4c562.jpg]

Source: IONS/BIIB Presentation



AVXS-101 CHOP-INTEND scores



[https://evercore.na.bdvision.ipreo.com/NSightWeb_v2.00/Downloads/Files/5b979dbb-7ed8-4a4b- 9ccc-f40ab0772750.jpg]

Source: NVS Poster

Exicure Pre-clinical SMA Program

[https://evercore.na.bdvision.ipreo.com/NSightWeb_v2.00/Downloads/Files/e567edda-6a17-405b- b9d9-57196083c21e.jpg]


[https://evercore.na.bdvision.ipreo.com/NSightWeb_v2.00/Downloads/Files/ebc6da19-f0d2-4109- bf15-a09dd0aad125.jpg]


[https://evercore.na.bdvision.ipreo.com/NSightWeb_v2.00/Downloads/Files/4af7c9f3-7895-4e88- 800a-c61c6756b114.jpg]

Source: Exicure Presentation



Detailed Comparison between Spinraza, AVXS-101, and Risdiplam

[https://evercore.na.bdvision.ipreo.com/NSightWeb_v2.00/Downloads/Files/6b451280-4866-447f- 8908-b5c9e11886e1.png]

Source: Spinraza, AVXS-101, Risdiplam Publications and Presentations