Ann: Update - Notification of buy-back - NEU, page-91

I agree that it would be somewhat unlikely, but there certainly has been precedence. Drugs like Vitrakvi (Larotrectinib) and Spinraza (Nusinersen) received breakthrough designation with similar targeted approaches and compelling Phase 2 data, with small phase 2 sizes.
. Vitrakvi (Larotrectinib)Developer: Bayer and Loxo Oncology.Indication: Treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion.Approval Pathway:Breakthrough Therapy Designation: Received due to strong preliminary Phase 1/2 data showing high response rates in patients with NTRK fusion-positive cancers, regardless of tumor type.Accelerated Approval: Approved in 2018 under the FDA's tumor-agnostic pathway.Phase 2 Data:Trial Size: Pooled from 55 patients across three studies (two Phase 1 trials and one Phase 2 trial).Efficacy: Demonstrated an overall response rate (ORR) of 75% with durable responses in multiple cancer types.Safety: Mild to moderate adverse events, manageable within oncology settings.Impact:Vitrakvi was a breakthrough for precision oncology, focusing on NTRK gene fusions independent of tumor location.

2. Spinraza (Nusinersen)Developer: Biogen and Ionis Pharmaceuticals.Indication: Treatment for spinal muscular atrophy (SMA), a rare genetic neuromuscular disorder.Approval Pathway:Breakthrough Therapy Designation: Received due to strong early efficacy data in treating SMA Type 1 (the most severe form).Accelerated Approval: Approved in 2016.Phase 2 Data:Trial Size: Focused trials included ~20-25 patients for early studies, such as ENDEAR and NURTURE trials.Efficacy: Significant improvements in motor function, survival rates, and the ability to achieve developmental milestones not typically observed in SMA patients.Safety: Generally well-tolerated with manageable side effects, including mild headache and injection site pain.Impact:Spinraza became the first FDA-approved therapy for SMA.