RTW Investments

# Signal Note: RTW Investments Initiates $1.2B Position in MDGL RTW's substantial new stake signals confidence in Madrigal's resmetirom (MGL3196), a THR-β agonist for non-alcoholic steatohepatitis (NASH), likely ahead of near-term clinical catalysts. The $1.2B position size (representing ~9-10% of market cap) indicates conviction that current valuation doesn't reflect pipeline value, particularly if Phase 2b data demonstrates hepatic fat reduction with acceptable safety margins. Key near-term catalyst: regulatory feedback on resmetirom's development pathway and potential expedited review designation.

# Signal Note: RTW Investments New $843M Position in INSM RTW's substantial entry into Insmed signals conviction in INSM's core pulmonary NTM franchise, likely driven by upcoming clinical/commercial inflection points for brensocatib (seribantumab) as a foundational NTM therapy with potential label expansion. The position size (~5% stake) suggests confidence in near-term catalysts, possibly tied to regulatory decisions or Phase 3 data readouts that could materially expand the addressable market beyond current NTM indications. This contrarian move by a data-driven investor may reflect undervaluation relative to pipeline probability-adjusted NPV.

# Signal Note: RTW Initiates $588M Position in PTC Therapeutics RTW's substantial entry into PTCT likely reflects conviction in the company's pipeline depth across rare genetic disorders, particularly selatogene meptacopan (FABHALTA) for PNH/C3GN—which generated $109M in 2023 revenue—and phase 3 readouts expected in 2024-2025 for additional indications. The ~7.7M share position (roughly 8-9% of outstanding) suggests confidence in near-term catalysts and valuation following recent market volatility, positioning for potential label expansions or positive efficacy data that could substantially de-risk the rare disease franchise.

# Signal Note: RTW Initiates $566M Position in argenx RTW's substantial entry into ARGX suggests conviction in efgartigimod's commercial trajectory, likely driven by recent FDA approvals in generalized myasthenia gravis (approved Dec 2023) and expanding pipeline potential in IgG-related disorders. The $566M position size indicates confidence in near-term revenue inflection from MG market penetration and upcoming readouts in conditions like IgA nephropathy and pemphigus vulgaris.

**Signal Note: RTW Investments enters PTGX with $442M position** RTW's substantial new stake signals confidence in PTGX's lead program PN-943, a selective antagonist for intestinal P2X7 receptors currently in Phase 2 for ulcerative colitis—a validated mechanism with potential differentiation versus conventional immunosuppressants. The timing suggests conviction ahead of near-term UC data readouts or upcoming clinical milestones that could de-risk the inflammatory bowel disease franchise.

# Signal Note: RTW Investments Initiates $343.6M Position in Natera (NTRA) RTW's substantial entry suggests conviction in Natera's core non-invasive prenatal testing (NIPT) franchise and expanding oncology liquid biopsy portfolio, particularly Signatera for minimal residual disease (MRD) detection across solid tumors. The timing may reflect anticipated reimbursement decisions or clinical readouts in 2024-2025 that could validate MRD as a standard-of-care biomarker, driving volume and margin expansion beyond current prenatal diagnostics revenues.

**RadNet Signal Note:** RTW Investments' $281M entry into RDNT (imaging services provider) appears driven by operational leverage potential in diagnostic imaging rather than a pipeline catalyst. The position size suggests conviction in RadNet's AI-enabled workflow optimization and margin expansion as utilization recovers post-COVID, though this is a services play without direct drug/indication exposure.

# Signal Note: RTW Initiates $273M Position in TARS RTW's substantial entry into Tarsus signals confidence in the company's core asset, topical iota-carrageenan (FzeldenAlexandru), which is in Phase 3 development for dry eye disease (DED). The timing suggests conviction ahead of potential Phase 3 readouts expected in 2024-2025, a binary catalyst that could validate the topical antiviral approach in a large, underserved market where current therapies remain limited to symptom management.

# Signal Note: RTW Investments Initiates $270M Position in COGT RTW's substantial entry suggests conviction in Cogent's pipeline, likely driven by upcoming catalysts around seribantumab (a MET inhibitor) in non-small cell lung cancer and gastric cancer indications, where clinical data readouts could unlock valuation. The ~7.6M share purchase represents a meaningful conviction bet, typical of RTW's thesis-driven approach, though near-term binary events and commercial execution risk remain key variables to monitor.

# Signal Note: RTW Investments Initiates $269M Position in Penumbra (PEN) Wong's data-driven team is betting on Penumbra's neurointerventional and aspiration thrombectomy platforms, likely motivated by strong Q3 revenue growth (26% YoY) and expanding TAM in acute ischemic stroke treatment. The $269M stake signals confidence in sustained margin expansion and international market penetration, particularly in the high-growth EMEA region where Penumbra has accelerated adoption.

**Signal Note: RTW Investments $205M APGE Entry** RTW's substantial new position in Apogee likely reflects conviction in its late-stage dermatology pipeline, particularly bBelay (imsidumab), a monoclonal antibody targeting IL-13 in atopic dermatitis and pruritus. The timing suggests positioning ahead of anticipated Phase 2b/3 data readouts expected in 2024-2025, where efficacy in moderate-to-severe AD could validate differentiation versus existing IL-4Rα and JAK inhibitors in a crowded market.

**Signal Note: RTW Investments Initiates $192.6M Position in APLS** Wong's new 7.7M share stake suggests conviction in Apellis' complement pipeline, likely driven by near-term catalysts around pegcetacoplan (APL-2) label expansions or geographic approvals—the drug generated ~$300M+ in 2023 FPF revenue but faces competitive pressure from newer C3 inhibitors. The position size ($192.6M) represents material conviction and warrants monitoring commercial execution and Phase 3 readouts in geographic indications (e.g., nIgA nephropathy, c3GN) over the next 12-24 months.

**Signal Note: RTW Investments Initiates $190.8M ACADIA Position** RTW's new 7.1M share stake signals conviction in ACADIA's commercial turnaround, likely driven by psilocybin-assisted therapy program COMP360 for treatment-resistant depression (TRD), which faces a resubmission decision in 2025 after initial CRL. The 5.2% stake positions RTW for potential upside on regulatory clarity and commercial execution in the nascent psychedelic-assisted therapy market, though binary regulatory risk remains material.

# Signal Note: RTW Investments Initiates $176M Position in STOK RTW's substantial entry into Stoke Therapeutics signals conviction in the company's lead program, STK-001 (an antisense oligonucleotide for Dravet syndrome), which is progressing through Phase 2b trials with potential catalysts in 2024-2025. The $176M position size (~5.5M shares) represents meaningful allocation for a data-driven fund and suggests confidence in either upcoming trial readouts or commercial potential in rare genetic seizure disorders with limited treatment options.

# RTW Investments Initiates $174M RGEN Position Wong's significant new stake in Repligen signals confidence in the company's bioprocess solutions portfolio, which benefits from sustained demand in cell and gene therapy manufacturing—a secular tailwind as more advanced therapies move toward commercialization. The entry size (1.06M shares, ~3.4% of outstanding) suggests conviction in RGEN's recurring revenue model and margin expansion potential, particularly as its chromatography and filtration platforms become standard manufacturing infrastructure across the biopharma industry.