Ascendis Pharma（ASND）：Navepegritide的优先审评重申12个月数据可能足以获批

PlaceboVoxzogoPlacebo-adjPlacebon/a15 ug/kg QDn/a6.0 (37% <5yo)8.49.152%52%54%-5.21 (0.93)-5.13-5.14Week 52Week 52Placebo-adjWeek 52Month 6Month 12Month 184.415.61 (1.05)-3.94 (1.07)6.896.026.013.754.26 (1.53)4.06 (1.20)3.513.513.510.010.240.240---n/aNon/an/a---11%5%-2%7%0%0%0%15%48%-25%73%n/an/an/a27Voxzogo/vosorotide (BMRN)Infigratinib (BBIO)Ph3 NCT01603095Ph2 PROPEL2 Cohort 5Savarirayan et al., Lancet 2020BBIO Presentation 03/26/2023 and 06/04/2024Infigratinib0.25 mg/kg QD5-18 yo4.9-11.3yo606142%1211 (responder dropped out due to study siteclosure. 91% respose rate, one patient withbaseline AGV >6cm/yr did not respond atany of the time points).7.24 (58% 5 - <8 yo, 8% <5yo)0.52(5-11yo)1.71*1.57** (p<0.0001)0.13*NS1.980%98%Most were grade 1/not assessed as related to infigratinib. Mostcommon AE was nasopharyngitis (40.3%)3.382.512.50-0.03 (NS)2.011.95 (-0.07 frombaseline)1.95 (-0.07 frombaseline)1.88 (-0.14 from baseline,p = 0.001)96%98% Kelly Shi, Ph.D. * | Equity Analyst(212) 336-6937 | kshi@jefferies.comJose Lora, Ph.D. * | Equity Associate+1 (332) 236-6815 | jlora@jefferies.comYifan Xu, Ph.D. * | Equity Associate+1 (212) 778-8057 | yxu4@jefferies.comClara Dong, Ph.D. * | Equity Analyst+1 (212) 284-2432 | ydong1@jefferies.comHangfei Fu, Ph.D. * | Equity Associate(212) 323-7562 | hfu@jefferies.com Exhibit 2 - Cross-Trial Comparison of TransCon CNP vs. Voxzogo in Children Aged < 5yo.Source: Jefferies research; published dataOur KOL Dr. Ron Rosenfeld Highlighted QW Dosing as an Attractive for New Patient Starts andExpects a 60/40 Split Between Voxzogo (~$2B peak cons)/Navepegritide Initially; We ThinkAdditional Benefits from Skytrofa Addition in Ph2 COACH Could Help Tip the Balance TowardNavepegritide.Our KOL highlighted Navepegritide’s QW dosing as a potential attractive advantagevs Voxzogo that would be preferred especially in a pediatric population. On the adoption front, hecommented that Voxzogo has first-to-market advantage and longer-term data validating BMRN'sclaim that growth rate appears to be sustained. He initially expects a 60/40 (50/50 possible) uptakefor new patient starts. For patients already on Voxzogo, he thinks they will likely stay on Voxzogountil there’s more experience with Navepegritide. On AVG as the primary efficacy endpoint, henoted that emerging therapies are likely to gain approval based on their effect on this measure andthat AVG's potential as a surrogate marker for long-term effects on achondroplasia-associated co-morbidities, though uncertain, remains important. He also commented that treating at the earliestage possible is important since some co-morbidities disproportionately affect infants.This quarter, we look to Ph2 COACH data of Skytrofa+Navepegritide combo, which we think couldbe a driver of Navepegritide's adoption if additive benefits are observed, potentially providing anew treatment paradigm for children with achondroplasia. At a recent investor event, mgmt guidedPh2 COACH will compare one arm of patients who've had Navepegritide for at least one year withbaseline AGV of ~5.5 to 6cm vs treatment naive patients who were directly started on the comboregimen.Please see important disclosure information on pages 3 - 9 of this report.This report is intended for Jefferies clients only. Unauthorized distribution is prohibited. Company DescriptionAscendis PharmaAscendis Pharma A/S is a biopharmaceutical company specializing on its TransCon technologies to create prodrugs that provide for the predictableand sustained release of an unmodified parent drug. The company was founded by Jan Moller Mikkelsen, Dirk Vetter, and Harald Rau in September2006 and is headquartered in Hellerup, Denmark.Company Valuation/RisksAscendis PharmaOur $229 price target is DCF-based (a WACC of 10% and terminal growth rate of 0%). Risks include clinical, regulatory, manufacturing, commercial,financing, and competition.BioMarin Pharmaceutical Inc.We derive our price target based on NPV analysis of BMRN products. Risks include commercial disappointment and key pipeline delays/failure.BridgeBio Pharma, Inc.Our $33 price target is based on selected products approved or in development, including ~$21/sh for acoramidis in ATTR-CM (85% probability-adjusted), ~$6/sh for infigratinib in achondroplasia (85% probability-adjusted), ~$5/sh for encaleret in ADH1 (85% probability-adjusted), ~$1/sh forBBP-418 in LGMD2i (75% probability-adjusted) at a ~13% annual discount rate. Risks associated with BBIO include: (1) clinical/regulatory/commercialrisks; (2) competition; and (3) general drug industry risks (e.g., pricing/reimbursement).Analyst Certification:I, Kelly Shi, Ph.D., certify that all of the views expressed in this research report accurately reflect my personal views about the subject security(ies) and subjectcompany(ies). I also certify that no part of my compensation was, is, or will be, directly or indirectly, related to the specific recommendations or views expressedin this research report.I, Jose L