世代生物（GBIO）：第一季度专注于主要RNAi靶点和2025年年中自身免疫适应症披露

USA | BiotechnologyGeneration Bio 1Q: Focus On Lead RNAi Target & AutoimmuneIndication Disclosure In Mid'25 1Q was incremental w/ GBIO continuing to advance their program on cell-targeted LNP (ctLNP) to selectively deliver siRNA to modulate T cellsin vivo.Focus is on siRNA target(s) and T cell-driven autoimmune disease indication(s)they aim to disclose in mid'25, as well as supporting preclin data in upcomingquarters for IND submission in 2H26. $158M cash runway to 2H27. Stock is down –63% YTD (vs XBI –14%) following their platform reprioritization, likely due to lackof catalysts, and broader macro environment.But, we think the stock could rebound once investorsget a better sense of the indication they plan to pursue in T-cell autoimmune diseases, as well as w/supporting preclin data to give investors confidence in their strategy. Plus, a defined timeline to enterclin along w/ a potential streamlined path to registration should help make the stock work this yr. GBIO aims to deliver siRNA only to T cells w/o adversely impacting the broader immune system--IND in 2H26.RNAi as a modality has garnered increasing attention, but site-specific delivery ex-liver remains a major bottleneck. GBIO has the unique capability of targeting T cells w/ ctLNPs.Plus, there is clear white space w/ no one else developing siRNA therapeutics for T cell-drivenautoimmune diseases. GBIO's corporate deck outlines several potential T-cell driven diseases, and we believe theycould pursue 1 or more of these.These include: skin (alopecia, vitiligo, atopic derm), blood vessels(Giant Cell Arteritis Polymyalgia Rheumatica), IBD (UC, Crohn's), and liver (AIH, PBC). Each of theindications has a prominent role in T-cell pathology, leaving plenty of oppty to improve upon theSOC with respect to safety & efficacy.Apart from indication, the siRNA tgt(s) are also undisclosed--we expect to learn more in GBIO's mid'25 update. GBIO's ctLNP-siRNA allows more durable and controllable target inhibition.Recall, co has shownthat T cell-selective LNPs containing an unoptimized siRNA achieved efficient delivery and ~98%KD of the B2M protein in human T cells in bothin vitroand mouse studies, which provide someinsights into their platform. Financials:Cash $158M runway into 2H27. OpEx $25.3M (vs $17.3M est) due to one-timerestructuring costs.Model changes: adj expenses,PT$4 (prior $5). Farzin Haque, Ph.D. * | Equity Analyst+1 (212) 778-8349 | fhaque@jefferies.com Maury Raycroft, Ph.D. * | Equity Analyst(212) 323-3990 | mraycroft@jefferies.com James Stamos, Ph.D. * | Equity Associate(212) 323-7644 | jstamos@jefferies.com Amin Makarem, Ph.D. * | Equity Associate+1 (332) 236-6822 | amakarem@jefferies.com Amy Qian, Ph.D. * | Equity Associate+1 (212) 707-6465 | aqian@jefferies.com The Long View: Generation Bio Investment Thesis / Where We Differ GBIO is a preclinical-stage genetic medicine company developing potentiallytransformative non-viral gene therapies. Three core elements of its proprietaryplatform are:1)iqDNA for durable expression of large genetic payloads,2)ctLNP for redosable delivery to multiple targets, and3)viral capsid-free manufacturing for scalability to millions of pts. GBIO's current leadtherapeutic focus isin vivoHSC programs SCD & β-thal and then in the liver,hemophilia A, while working on extra-hepatic programs. Although very early,strong proof-of-concept data in NHP in lead programs could drive GBIO'svaluation higher, given the potential of its broadly applicable platform. Upside Scenario,$6.00, +1,438% Downside Scenario,$0.25, -36% Base Case,$4.00, +925% •Faster timeline to clin for lead programs•MRNA collaboration program targeting T cellsadvances•RapidlyexpandctLNPmodulardeliveryplatform to selectively reach many other celltypes and therapeutic areas•BD deals expanding pipeline•PT $6using a blend of DCF and EPS multiples •Strong proof-of-concept data in T-cell drivenautoimmune indications w/ siRNA delivery•Current cash sufficient into 2H27 (per GBIO)•PT $4using a blend of DCF and EPS multiples •Further delays or failure to show strong proof-of-concept data in non-human primates•Competitors develop similar technologies fornon-viral gene tx•Competitive landscape in selected indicationsset a high bar for GBIO to beat•PT$0.25usingablendofDCFandEPSmultiples Sustainability Matters Catalysts •Top material issue(s):1) Employee Engagement, Diversity & Inclusion.GBIO has programs tocultivate DEI & consistently provide competitive compensation and benefits designed to meet thediverse needs of its employees, and promote their well-being.2) Human Rights & CommunityRelations.GBIO is involved with nonprofit organizations that seek to increase representation ofunderrepresented minority/disadvantaged individuals in the scientific and medical community.3)Access & Affordability.GBIO has a vision to deliver differentiated genetic therapies to address geneticdiseases. •Mid'25– disclose siRNA tgts and T cell-drivenautoimmune disease indic