Rare and Orphan Disease Therapeutics Sector Outlook — September 2026

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HEALTH CARE › PHARMACEUTICALS, BIOTECHNOLOGY AND LIFE SCIENCES › RARE AND ORPHAN DISEASE THERAPEUTICS

Rare Disease: Forward Revenue Pricing Splits Wide

The report shows how pipeline durability, commercial execution and transaction evidence separate the sector.

September 2026 · Prepared by NeuraCap AI · Confidential

Market data as of 2026-09-28 · primary valuation basis EV / Revenue (CY2027E)

Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice

Sources & methodology

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1. 01

   HEALTH CARE › PHARMACEUTICALS, BIOTECHNOLOGY AND LIFE SCIENCES › RARE AND ORPHAN DISEASE THERAPEUTICS

   This is the cover slide introducing the Rare and Orphan Disease Therapeutics sector outlook.

   We're opening our view on rare and orphan disease therapeutics as of September 2026, built on EV/Revenue for CY2027E as the primary valuation lens. This sets up the split we'll walk through between pipeline-stage companies and commercial orphan franchises.

   Everything on this page

   HEALTH CARE › PHARMACEUTICALS, BIOTECHNOLOGY AND LIFE SCIENCES › RARE AND ORPHAN DISEASE THERAPEUTICS Rare Disease: Forward Revenue Pricing Splits Wide The report shows how pipeline durability, commercial execution and transaction evidence separate the sector. September 2026 · Prepared by NeuraCap AI · Confidential Market data as of 2026-09-28 · primary valuation basis EV / Revenue (CY2027E) Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 1

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   CONTENTS

   What This Report Covers

   This slide lists the five sections and appendix that structure the report.

   We've organized this so the bottom line comes first — five sections covering the landscape, valuation, precedent deals and strategic implications, plus a full appendix. If you only have time for one section, section 01 carries the complete story, so everything after it is optional depth.

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   CONTENTS What This Report Covers 01 The Bottom Line Rare Disease Valuations Separate Durable Franchises from Concentrated Pipeline Risk 02 The Landscape Pipeline Companies Dominate the Set, but Commercial Execution Changes the Valuation Read 03 Valuation & Situations The Premium End Holds a Wide Lead on Forward Revenue 04 Precedent Transactions Higher Transaction Multiples Sit Alongside Commercial Orphan Franchises 05 Strategic Implications Stronger Standing Starts with Durable Revenue and a Repeatable Patient-Finding Engine 06 Appendix Comparables Detail, Methodology, Sources and Assumptions Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 2

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   01 · THE BOTTOM LINE

   Rare and Orphan Disease Therapeutics Split Between Pipelines and Orphan Commercialization

   This slide summarizes the sector's central finding: a wide valuation split between pipeline and commercial orphan models.

   The headline here is that premium names trade at 19.8x forward EV/Revenue while the discount end sits at 1.7x, with a 4.7x sector median across 28 of 38 rated companies. Because this is a forward multiple, the gap persists even after the market has already priced in forecast growth. That tells us the remaining spread reflects differences in how durable investors judge each franchise's revenue to be, so the operating question becomes what supports that durability.

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   01 · THE BOTTOM LINE Rare and Orphan Disease Therapeutics Split Between Pipelines and Orphan Commercialization The full story on one page · figures on EV / Revenue (CY2027E), market data as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. Primary valuation basis: EV / Revenue on CY2027E consensus (28 of 38 companies eligible; multiples failing the platform's plausibility gates are excluded, never plotted). Practitioners price this industry on EV / Revenue rather than EV / EBITDA; validated coverage supports the industry standard (28 of 38 companies), so this report follows it. Qualitative characterisations are NeuraCap views. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 3 1 The Valuation Gap Survives a Forward Revenue Test The premium end sits at 19.8x forward EV / Revenue, compared with 1.7x at the discount end. A forward multiple already credits forecast growth, so the remaining gap sits alongside different views of durability. 2 Revenue Is the Practical Lens for an Uneven Profit Base The middle of the range is 4.7x across the 28 names with a forward revenue estimate among 38 approved companies. Revenue is the cleaner comparison because most of the set is not consistently profitable while still funding pipelines. 3 Faster Growth Travels with Only a Modest Pricing Step Across the 24 names in the growth split, the faster-growing group sits at 4.2x and the slower-growing group at 3.5x. The observed spread suggests forecast growth alone does not separate the two ends of the range. 4 Patient Conversion and Durability Remain the Operating Test Patient finding, reimbursed starts and persistence shape the quality of orphan revenue. Pipeline breadth, exclusivity runway and confirmatory obligations further distinguish durable franchises from concentrated-asset exposure. 4.7x Sector median EV/Revenue CY2027E consensus · EV/Revenue is the lens because practitioners price this growth set on revenue and 6 of 38 names are… 19.8x Premium end EV/Revenue vs 1.7x at the discount end top quartile (n=7) against bottom quartile (n=7) on EV/Revenue — the spread the report explains 42 Transactions with disclosed terms 118 recorded in this tier · 3 told as case studies, the full list in the appendix

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   SECTION 02

   02

   This divider introduces the landscape section covering pipeline and commercial business models.

   We're moving into the landscape next — most companies here carry clinical-stage risk, while a smaller group runs a distinct specialty orphan commercial model. That distinction is what drives the valuation differences we'll unpack in the following pages.

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   SECTION 02 02 THE LANDSCAPE Pipeline Companies Dominate the Set, but Commercial Execution Changes the Valuation Read Most companies carry clinical risk, while specialty orphan commercialization offers a distinct operating model. 02 of 06 Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 4

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   02 · MARKET MAP

   One Dominant Pipeline Model Sits Beside a Distinct Commercial Orphan Model

   This slide groups the approved companies by business segment and shows median EV/Revenue per group.

   We've grouped the approved universe by business model, and one pipeline-stage segment dominates the set numerically while a smaller commercial orphan segment sits apart. The median multiples by group show this isn't just a headcount story — the two models are priced differently. That's the foundation for the valuation work we do next.

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   02 · MARKET MAP One Dominant Pipeline Model Sits Beside a Distinct Commercial Orphan Model 38 approved companies grouped by business segment · median EV / Revenue (CY2027E) per group · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. Segment grouping follows the platform's classification; group medians on rated names only. "Why it matters" lines are NeuraCap views. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 5 CLINICAL-STAGE RARE DISEASE PIPELINES 37 cos median 4.7x Vertex (VRTX) Alnylam (ALNY) United (UTHR) BridgeBio Pharma (BBIO) BioMarin (BMRN) Protagonist (PTGX) Rhythm (RYTM) Travere (TVTX) Mirum (MIRM) PTC Therapeutics (PTCT) Edgewise (EWTX) Sarepta (SRPT) BioCryst (BCRX) Ultragenyx (RARE) Dyne Therapeutics (DYN) Harmony (HRMY) Pharvaris N.V. (PHVS) Palvella (PVLA) Septerna (SEPN) Agios (AGIO) Savara (SVRA) Rigel (RIGL) Pharming Group (PHAR) Gyre Therapeutics (GYRE) Design (DSGN) Rezolute (RZLT) Crescent Biopharma (CBIO) Wave Life Sciences (WVE) +9 more This group represents 97% of the set and carries the widest mix of clinical, regulatory and commercialization risk. SPECIALTY ORPHAN PRODUCT COMMERCIALIZATION 1 cos 7.4x · 1 rated Eton (ETON) This model turns concentrated prescriber access, payer execution and patient support into a more directly observable commercial test.

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   02 · LANDSCAPE

   Commercial Maturity Changes What Forward Revenue Means

   This slide explains how commercial maturity changes the meaning of forward revenue across segments.

   Forward revenue means something different depending on where a company sits commercially — an early pipeline forecast carries more uncertainty than a revenue line from an already-launched orphan product. We break down what each segment does and why that matters for how we should read its multiple. Full company-level detail sits in the appendix for anyone who wants to trace a specific name.

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   02 · LANDSCAPE Commercial Maturity Changes What Forward Revenue Means Segment view of the approved universe · EV / Revenue (CY2027E) medians on rated names · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. "What they do / why it matters" is a NeuraCap view. Full company-level detail in the appendix and companion tables. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 6 Segment n Share of universe Median EV/Revenue Names to know What they do — and why it matters Clinical-stage rare disease pipelines 37 97% 4.7x Vertex Pharmaceuticals Incorporated (VRTX) · Alnylam Pharmaceuticals, Inc. (ALNY) · +35 more Pipeline depth shapes the range. The group sits at 4.7x across 27 names with a forward revenue estimate. Program-level risk, patient finding, exclusivity and funding needs can make similar revenue forecasts carry different durability. Specialty orphan product commercialization 1 3% 7.4x n=1 Eton Pharmaceuticals, Inc. (ETON) Commercial execution is visible. The single specialty orphan commercialization name sits at 7.4x. Reimbursed starts, net price, persistence and center penetration provide a direct operating read on franchise quality.

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   SECTION 03

   03

   This divider introduces the valuation section focused on the gap between premium and discount names.

   Next we go inside the valuation itself. The premium end holds a wide lead on forward revenue, and that gap survives even after forecast growth is already built into the multiple — which is the puzzle this section works through.

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   SECTION 03 03 VALUATION & SITUATIONS The Premium End Holds a Wide Lead on Forward Revenue The gap persists after forecast revenue is already reflected in the valuation lens. 03 of 06 Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 7

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   03 · PUBLIC MARKET VALUATION

   Forward Revenue Pricing Leaves a Wide Gap Between the Two Ends

   This slide ranks the rated companies by EV/Revenue (CY2027E) and shows the sector median.

   Across the rated companies, EV/Revenue (CY2027E) spans from the premium end down to the discount end, with a sector median of 4.7x. We use revenue rather than EBITDA here because a meaningful share of the 38 names are loss-making on forward EBITDA, so revenue is the lens that keeps the comparison meaningful. The tier zones on this page split the rated set at its own quartiles, giving us a consistent way to talk about where any given name sits.

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   03 · PUBLIC MARKET VALUATION Forward Revenue Pricing Leaves a Wide Gap Between the Two Ends EV / Revenue (CY2027E) · all 28 rated companies, sorted descending · sector median 4.7x · EV/Revenue is the lens because practitioners price this growth set on revenue and 6 of 38 names are loss-making on forward EBITDA · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. Primary valuation basis: EV / Revenue on CY2027E consensus (28 of 38 companies eligible; multiples failing the platform's plausibility gates are excluded, never plotted). Practitioners price this industry on EV / Revenue rather than EV / EBITDA; validated coverage supports the industry standard (28 of 38 companies), so this report follows it. Tier zones are NeuraCap groupings cut at the rated set's quartiles; every multiple quoted on this page is a median on the same EV / Revenue (CY2027E) basis. Panel commentary is a NeuraCap view. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 8 PREMIUM · median 19.8x CORE · median 4.7x DISCOUNT · median 1.7x Sector median 4.7x WHAT SEPARATES THE TWO ENDS The endpoints remain far apart. The premium end sits at 19.8x forward EV / Revenue, compared with 1.7x at the discount end. Forward forecasts raise the bar. Because forecast revenue is already in the denominator, sustained premium pricing requires confidence beyond a near-term revenue step. Asset risk still matters. Exclusivity runway, competitive entry, confirmatory obligations and concentrated-asset exposure shape how durable that forecast appears.

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   03 · VALUATION DRIVERS

   Profitability Separates the Two Ends: Names Above the 28% Margin Line Carry 4.1x Against 2.8x Below It

   This slide splits the rated companies by revenue growth and by EBITDA margin to test what drives the valuation gap.

   When we cut the set by profitability, names above the 28% margin line carry 4.1x against 2.8x below it — a meaningful split. Growth tells a smaller story: faster growers sit at 4.2x against 3.5x for slower growers, which doesn't close the gap on its own. That association, not causation, points our attention toward margin discipline as one of the stronger threads behind the valuation gap.

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   03 · VALUATION DRIVERS Profitability Separates the Two Ends: Names Above the 28% Margin Line Carry 4.1x Against 2.8x Below It Median EV / Revenue (CY2027E) by revenue-growth cohort and by EBITDA-margin cohort (each split at its covered median) · rated names with estimates · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. Cohort medians on rated names with the required estimates (faster n=12; slower n=12; higher-margin n=6; lower-margin n=6). Driver readings are NeuraCap views on the supplied data — association, not causation. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 9 EV/Revenue, median per cohort · growth split at 19% · EBITDA-margin split at 28% The Growth Split Shows a Narrow Valuation Step Above 19% growth, 12 names sit at 4.2x; below that mark, 12 names sit at 3.5x. The observed difference is modest relative to the full valuation range. Patient Finding Remains the Commercial Proof Point Diagnosed patients become durable revenue only when testing, referral, reimbursement and treatment initiation work as one operating system. Durability Extends Beyond the Revenue Forecast Orphan exclusivity, patent runway, persistence and confirmatory obligations shape the risk around revenue already credited by a forward multiple.

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    03 · SITUATION MAP

    Valuation Support and Growth Create Four Different Operating Agendas

    This slide maps rated companies into four quadrants by valuation versus the sector median and growth versus the covered median.

    Plotting valuation against growth gives us four distinct situations rather than one continuous story, cut at the sector median of 4.7x and the covered growth median. This is a way to characterize where a company sits today, not a signal to buy or sell anything. Each quadrant implies a different operating agenda, which is exactly what we turn to next.

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    03 · SITUATION MAP Valuation Support and Growth Create Four Different Operating Agendas Cut on EV / Revenue vs the sector median (4.7x) (rows) and revenue growth vs the covered median (19%) (columns) · 4 rated names without the second measure are not mapped · observations, not recommendations Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. Situation boundaries are the cohort's own medians (Directional, NeuraCap view). This page characterises situations; it does not recommend buying or selling any security. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 10 Growth with Valuation Support Above-median multiple · above-median revenue growth 5 names BridgeBio Pharma, Inc. (BBIO) · Rhythm Pharmaceuticals, Inc. (RYTM) · Travere Therapeutics, Inc. (TVTX) · +2 more Five names sit above both the valuation and growth reference lines. Their operating test is whether patient conversion and persistence can sustain expectations already embedded in the price. Valuation Ahead of Growth Above-median multiple · below-median revenue growth 5 names Vertex Pharmaceuticals Incorporated (VRTX) · United Therapeutics Corporation (UTHR) · Mirum Pharmaceuticals, Inc. (MIRM) · +2 more Five names carry above-reference valuations with below-reference growth. Durability, margin quality and exclusivity become central when near-term growth offers less support. Growth Awaiting Recognition Below-median multiple · above-median revenue growth 7 names Alnylam Pharmaceuticals, Inc. (ALNY) · Ultragenyx Pharmaceutical Inc. (RARE) · Agios Pharmaceuticals, Inc. (AGIO) · +4 more Seven names show above-reference growth but below-reference valuations. The gap sits alongside questions about revenue quality, asset concentration, funding needs or the durability of the forecast. Growth and Valuation Pressure Below-median multiple · below-median revenue growth 7 names BioMarin Pharmaceutical Inc. (BMRN) · PTC Therapeutics, Inc. (PTCT) · Sarepta Therapeutics, Inc. (SRPT) · +4 more Seven names sit below both reference lines. Their operating agenda centers on patient finding, portfolio focus, cost structure and the path to a more durable revenue base.

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    03 · GROWTH VS PROFITABILITY

    Few Names Clear Both the Growth and Margin Bars

    This slide plots revenue growth against EBITDA margin and shows median EV/Revenue per quadrant.

    Among the companies with both growth and margin estimates, very few clear both bars at once — most sit strong on one dimension and weak on the other. The quadrant medians show that combining growth and margin, even in a small group, still commands a distinct valuation read. That scarcity is itself a signal about where the real execution risk sits.

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    03 · GROWTH VS PROFITABILITY Few Names Clear Both the Growth and Margin Bars Revenue growth (CY2027E, x-axis) vs EBITDA margin (CY2026E, y-axis) · 12 companies with both estimates · cuts at the covered medians (11% growth, 28% margin) · median EV/Revenue per quadrant · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. Quadrant cuts are the covered set's medians. Quadrant medians on names with a meaningful EV/Revenue (balanced n=2; margin-only n=4; growth-only n=4; neither n=2). Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 11 -20% 0% 20% 40% 10% 20% 30% 40% 50% MARGIN ONLY median 4.1x BALANCED median 3.4x NEITHER median 2.4x GROWTH ONLY median 3.5x SRPT BCRX PHAR UTHR PTCT VRTX HRMY BMRN RIGL ALNY ETON TVTX x: revenue growth (CY2027E) · y: EBITDA margin (CY2026E) HOW TO READ THIS Across the 12 names with both growth and margin data, 2 clear the 11% growth bar and the 28% margin bar. Four clear only the margin bar, while four clear only the growth bar. Two clear neither bar, showing that balanced operating performance is uncommon within this measured set. The balanced median rests on 2 names and is lifted by TVTX at 5.3x. Rule of 40 (revenue growth + EBITDA margin ≥ 40%): 8 of 12 names clear it.

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    03 · THE AGENDA

    Choose the Operating Path That Matches the Company’s Current Position

    This slide frames the operating questions an owner or acquirer should resolve based on where a company sits.

    Based on the situations we just mapped, we lay out the questions each type of company should be answering right now — not a recommendation, but a starting point for the conversation. Where a company sits on growth and valuation should shape what it prioritizes operationally over the next stretch. This sets up the transaction evidence we look at next.

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    03 · THE AGENDA Choose the Operating Path That Matches the Company’s Current Position NeuraCap view · framed as the questions an owner or acquirer should resolve · observations, not recommendations Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. All content on this page is Directional — NeuraCap advisory judgment grounded in the cohort data shown earlier. It does not constitute investment advice. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 12 Deepen the Patient-Finding Engine Test whether genetic testing, registry referral and center penetration can expand reimbursed starts within the reachable patient pool. What changes the answer: The answer changes when diagnosed patients are not converting into treated patients. Broaden Beyond Concentrated-Asset Risk Assess whether capital belongs behind adjacent indications, reusable platform chemistry or a more balanced mix of commercial and clinical assets. What changes the answer: The answer changes when one program carries most of the clinical or funding exposure. Defend Franchise Durability Examine exclusivity runway, competitive entry, persistence and confirmatory obligations together rather than treating forecast revenue as equally durable. What changes the answer: The answer changes as protection shortens or genotype-targeted competition approaches. Test Build Versus Buy Compare internal development with acquiring products, programs or commercial capabilities that fit the existing prescriber and patient-finding footprint. What changes the answer: The answer changes when external assets can use infrastructure already in place.

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    SECTION 04

    04

    This divider introduces the precedent transactions section.

    We now turn to the deal record. Higher transaction multiples sit alongside commercial orphan franchises, and the disclosed terms span everything from clinical pipelines to already-marketed products at different stages of maturity.

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    SECTION 04 04 PRECEDENT TRANSACTIONS Higher Transaction Multiples Sit Alongside Commercial Orphan Franchises Disclosed terms span clinical pipelines, marketed products and different stages of operating maturity. 04 of 06 Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 13

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    04 · DEAL CASE STUDIES

    The Transaction Record Spans Clinical Pipelines and Commercial Franchises

    This slide walks through case studies drawn from the transactions with disclosed terms.

    We've selected a small set of transactions with disclosed terms to illustrate how the market has actually paid for pipeline and commercial assets, using LTM multiples at announcement. These are not directly comparable to the CY2027E public basis we use elsewhere, so we're not claiming a spread between the two. The complete transaction list, including names without disclosed terms, sits in the appendix for full traceability.

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    04 · DEAL CASE STUDIES The Transaction Record Spans Clinical Pipelines and Commercial Franchises 3 of 42 transactions with disclosed terms, told as case studies · multiples on LTM financials at announcement where disclosed · the complete list is in the appendix · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. 148 precedent record(s) carry data-quality flags (deal value unit unresolved; divestiture roles reassigned; duplicate filings collapsed); figures are shown as recorded in the filing. 76 recorded transactions with neither a disclosed value nor a multiple are omitted from the precedent list and the case studies (kept in the companion workbook). Deal multiples are LTM at announcement (Definitive, from filings); they are not directly comparable to the CY2027E public basis and no spread is claimed. "Why the deal happened" is a NeuraCap read of the recorded evidence. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 14 Jun-2025 $9.1B Sanofi acquires Blueprint Medicines Corporation EV / LTM revenue 4.5x EV / LTM EBITDA n/a WHY THE DEAL HAPPENED The strategic fit is assessed through the target's patient franchise, development risk and overlap with an acquirer's rare disease capabilities. In this sector, those factors shape whether ownership adds commercial reach or program depth. HOW THE TARGET WAS VALUED The relevant benchmark is a program-level risk-adjusted NPV cross-checked against forward revenue and peak-sales potential. Consideration structure also matters where clinical or regulatory milestones remain. Feb-2021 $6.7B Jazz Pharmaceuticals Public Limited Company acquires GW Pharmaceuticals plc EV / LTM revenue 3.4x EV / LTM EBITDA n/a WHY THE DEAL HAPPENED The transaction suggests a fit that should be tested against patient-finding infrastructure, prescriber access and pipeline adjacency. Those capabilities can matter as much as broad commercial scale in concentrated orphan markets. HOW THE TARGET WAS VALUED The valuation read should separate marketed revenue from pipeline value and apply risk-adjusted NPV by program. Exclusivity, payer access and remaining development obligations frame the comparison. Mar-2026 $5.2B Biogen Inc. acquires Apellis Pharmaceuticals, Inc. EV / LTM revenue 5.0x EV / LTM EBITDA n/a WHY THE DEAL HAPPENED The strategic fit should be read through the target's stage, patient pool and need for specialist commercialization. The transaction structure can bridge different views of clinical, regulatory and launch risk. HOW THE TARGET WAS VALUED The useful comparison is the value assigned to approved products and development programs separately. Forward revenue, peak-sales potential and milestone structure provide supporting reference points.

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    SECTION 05

    05

    This divider introduces the strategic implications section.

    From here we move to what this means operationally. Stronger standing starts with durable revenue and a repeatable way of finding patients — and owners can test their own product mix, commercial reach and capital needs against the valuation evidence we've just shown.

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    SECTION 05 05 STRATEGIC IMPLICATIONS Stronger Standing Starts with Durable Revenue and a Repeatable Patient-Finding Engine Owners can test product mix, commercial reach and capital needs against the valuation evidence. 05 of 06 Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 15

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    05 · STRATEGIC IMPLICATIONS

    Durable Revenue Requires Clinical Focus and Commercial Precision

    This slide lays out the operating questions the data raises for owners, management teams and boards.

    Durable revenue in this sector depends on clinical focus paired with commercial precision — capital needs to follow patient economics that can sustain a multi-year revenue stream. For management teams, that means concentrating on testing, referral, reimbursed starts and persistence rather than broad awareness alone. For boards, it's about balancing pipeline ambition against what the company can actually fund itself.

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    05 · STRATEGIC IMPLICATIONS Durable Revenue Requires Clinical Focus and Commercial Precision NeuraCap view · the questions this data puts on the table for the next twelve months Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. This page is Directional — NeuraCap views drawn from the analysis in this report. Observations, not recommendations. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 16 FOR OWNERS Align Capital with Durable Patient Economics Prioritize programs where patient finding, reimbursement, persistence and exclusivity support a credible multi-year revenue stream. FOR MANAGEMENT TEAMS Convert the Reachable Patient Pool Focus operating resources on testing, referral, reimbursed starts and treatment persistence rather than broad awareness without measurable conversion. FOR BOARDS Match Portfolio Breadth to Funding Capacity Balance pipeline ambition against commercial self-funding, concentrated readout risk and the cost of maintaining multiple registrational paths.

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    SECTION 06

    06

    This divider introduces the appendix covering the full company universe, methodology and sources.

    The final section is the reference material — the full comparable set behind every figure in the body, the valuation basis we used, and where each underlying disclosure can be traced.

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    SECTION 06 06 APPENDIX The Full Universe, Methodology and Sources Comparables detail behind every figure in the body, the valuation basis, and where each underlying disclosure lives. 06 of 06 Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 17

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    06 · PUBLIC COMPARABLES (1 OF 2)

    Public Comparables on EV / Revenue (CY2027E), Grouped by Valuation Tier

    This slide lists public comparables on EV/Revenue (CY2027E), grouped by valuation tier, for the first half of the rated set.

    This page carries the rated companies behind every chart in the body, shaded by whether each sits above or below the 4.7x sector median. Not every company in the universe carries an eligible multiple, which is why the rated set here is a subset of the full universe. Every ticker links back to its underlying source, so any figure in this report can be traced to where it came from.

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    06 · PUBLIC COMPARABLES (1 OF 2) Public Comparables on EV / Revenue (CY2027E), Grouped by Valuation Tier Teal shading marks a EV/Revenue above the sector median (4.7x); amber marks below · 28 rated companies; 10 not rated (no eligible EV/Revenue) · tickers link to the underlying source · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. All 28 rated rows are in this appendix and in the companion workbook, which carries the complete field set. Names without an eligible multiple are listed in the companion workbook. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 18 Company Ticker Segment EV EV/Revenue (CY2027E) Rev growth EBITDA margin Rule of 40 PREMIUM — ≥8.5x · median 19.8x · 7 companies Crescent Biopharma, Inc. CBIO Clinical-stage rare disease pipelines $217M 45.3x n/a n/a n/a Protagonist Therapeutics, Inc. PTGX Clinical-stage rare disease pipelines $8.6B 44.7x n/a n/a n/a Aardvark Therapeutics, Inc. Common Stock AARD Clinical-stage rare disease pipelines $24M 23.5x n/a n/a n/a Septerna Inc SEPN Clinical-stage rare disease pipelines $1.5B 19.8x -23% n/a n/a PepGen Inc. PEPG Clinical-stage rare disease pipelines $63M 13.8x -88% n/a n/a Rhythm Pharmaceuticals, Inc. RYTM Clinical-stage rare disease pipelines $6.6B 12.0x 78% n/a n/a Vertex Pharmaceuticals Incorporated VRTX Clinical-stage rare disease pipelines $129B 8.8x 10% 44% 54 CORE — 2.4x–8.5x · median 4.7x · 14 companies Sionna Therapeutics, Inc. SION Clinical-stage rare disease pipelines $23M 8.4x n/a n/a n/a BridgeBio Pharma, Inc. BBIO Clinical-stage rare disease pipelines $12.7B 7.5x 65% n/a 77 Eton Pharmaceuticals, Inc. ETON Specialty orphan product commercialization $1.6B 7.4x 47% 21% n/a Mirum Pharmaceuticals, Inc. MIRM Clinical-stage rare disease pipelines $5.3B 6.5x 17% n/a n/a United Therapeutics Corporation UTHR Clinical-stage rare disease pipelines $18.3B 5.3x 9% 42% 47 Travere Therapeutics, Inc. TVTX Clinical-stage rare disease pipelines $5.8B 5.3x 49% 51% 119 Gyre Therapeutics, Inc. GYRE Clinical-stage rare disease pipelines $671M 4.8x 27% n/a n/a Alnylam Pharmaceuticals, Inc. ALNY Clinical-stage rare disease pipelines $32.3B 4.7x 27% 27% 56

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    06 · PUBLIC COMPARABLES (2 OF 2)

    Public Comparables on EV / Revenue (CY2027E), Grouped by Valuation Tier

    This slide continues the public comparables table on EV/Revenue (CY2027E), grouped by valuation tier.

    This is the second half of the rated comparable set, using the same tiering and the same 4.7x median reference as the prior page. Together, the two pages give a complete, traceable view of the rated names behind the analysis. Names without an eligible multiple are held in the companion workbook rather than plotted here.

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    06 · PUBLIC COMPARABLES (2 OF 2) Public Comparables on EV / Revenue (CY2027E), Grouped by Valuation Tier Teal shading marks a EV/Revenue above the sector median (4.7x); amber marks below · 28 rated companies; 10 not rated (no eligible EV/Revenue) · tickers link to the underlying source · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. All 28 rated rows are in this appendix and in the companion workbook, which carries the complete field set. Names without an eligible multiple are listed in the companion workbook. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 19 Company Ticker Segment EV EV/Revenue (CY2027E) Rev growth EBITDA margin Rule of 40 CORE — CONTINUED — 2.4x–8.5x · median 4.7x · 14 companies Wave Life Sciences Ltd. WVE Clinical-stage rare disease pipelines $177M 3.9x -12% n/a n/a Agios Pharmaceuticals, Inc. AGIO Clinical-stage rare disease pipelines $1.3B 3.7x 93% n/a n/a BioCryst Pharmaceuticals, Inc. BCRX Clinical-stage rare disease pipelines $2.3B 3.1x 5% 21% n/a PTC Therapeutics, Inc. PTCT Clinical-stage rare disease pipelines $4.0B 2.9x 9% 32% 47 Design Therapeutics, Inc. DSGN Clinical-stage rare disease pipelines $552M 2.7x 75% n/a n/a BioMarin Pharmaceutical Inc. BMRN Clinical-stage rare disease pipelines $10.7B 2.4x 14% 23% 40 DISCOUNT — <2.4x · median 1.7x · 7 companies Ultragenyx Pharmaceutical Inc. RARE Clinical-stage rare disease pipelines $2.2B 2.3x 30% n/a n/a Rigel Pharmaceuticals, Inc. RIGL Clinical-stage rare disease pipelines $812M 2.2x 22% 28% 59 Entrada Therapeutics, Inc. TRDA Clinical-stage rare disease pipelines $36M 1.8x 88% n/a n/a Sarepta Therapeutics, Inc. SRPT Clinical-stage rare disease pipelines $2.4B 1.7x -23% 29% 0 Pharming Group N.V. PHAR Clinical-stage rare disease pipelines $683M 1.6x 9% 8% 21 Harmony Biosciences Holdings, Inc. HRMY Clinical-stage rare disease pipelines $1.8B 1.6x 13% 31% 42 Vanda Pharmaceuticals Inc. VNDA Clinical-stage rare disease pipelines $118M 0.4x 36% n/a n/a

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    06 · PRECEDENT TRANSACTIONS (1 OF 2)

    All Precedent Transactions with Disclosed Terms, Newest First

    This slide lists precedent transactions with disclosed terms, newest first, for the first part of the list.

    A meaningful share of recorded transactions carry disclosed terms, and we list those here newest first with LTM multiples at announcement where available. Deal values link back to the underlying filing for anyone who wants to verify a specific transaction. Transactions without a disclosed value or multiple sit in the companion workbook rather than in this list.

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    06 · PRECEDENT TRANSACTIONS (1 OF 2) All Precedent Transactions with Disclosed Terms, Newest First 42 transactions with disclosed terms in this tier (118 recorded) · multiples on LTM financials at announcement where disclosed · deal values link to the underlying filing · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. 148 precedent record(s) carry data-quality flags (deal value unit unresolved; divestiture roles reassigned; duplicate filings collapsed); figures are shown as recorded in the filing. 76 recorded transactions with neither a disclosed value nor a multiple are omitted from the precedent list and the case studies (kept in the companion workbook). Deal multiples are LTM at announcement (Definitive, from filings); they are not directly comparable to the CY2027E public basis and no spread is claimed. 18 of 42 transactions shown; the rest are in the companion workbook. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 20 Date Transaction EV EV/LTM Rev EV/LTM EBITDA Why it matters Aug-2026 State Street Corporation → Slate Medicines, Inc. n/a n/a 14.4x The announced transaction carries a disclosed 14.4x EBITDA multiple. It adds a financial acquirer to a record otherwise led by sector participants. Aug-2026 Fulcrum Therapeutics, Inc. → Slate Medicines, Inc. $245M n/a n/a The announced transaction carries a disclosed value of $245M. It places the target within a broader pattern of active interest in rare disease assets. Jul-2026 Vertex Pharmaceuticals Incorporated → Crinetics Pharmaceuticals, Inc. $7.9B n/a n/a The pending transaction carries a disclosed value of $7.9B. Its scale shows that major sector participants remain active around substantial clinical-stage platforms. Jun-2026 Servier Pharmaceuticals LLC → Edgewise Therapeutics, Inc. $1.5B n/a n/a The announced transaction carries a disclosed value of $1.5B. The combination pairs a pharmaceutical acquirer with a clinical-stage rare disease target. May-2026 Angelini Pharma S.p.A. → Catalyst Pharmaceuticals, Inc. $3.1B 5.3x 15.4x The announced transaction carries a disclosed value of $3.1B, with 5.3x EV / Revenue and 15.4x EBITDA benchmarks. It provides both revenue and profit reference points for a commercial franchise. Apr-2026 Chiesi Farmaceutici S.p.A. → KalVista Pharmaceuticals, Inc. $2.0B 2.0x n/a The completed transaction carries a disclosed value of $2.0B and a 2.0x EV / Revenue benchmark. The terms provide a reference for a rare disease pipeline moving toward commercialization. Apr-2026 Neurocrine Biosciences, Inc. → Soleno Therapeutics, Inc. $2.8B 9.7x n/a The completed transaction carries a disclosed value of $2.8B and a 9.7x EV / Revenue benchmark. The multiple sits alongside a target with a focused rare disease franchise. Apr-2026 n/a → Agios Pharmaceuticals, Inc. n/a 2.0x n/a The announced transaction is recorded at 2.0x EV / Revenue. It offers a direct revenue reference without requiring a profit-based comparison. Apr-2026 n/a → Travere Therapeutics, Inc. n/a 2.3x n/a The announced transaction is recorded at 2.3x EV / Revenue. It broadens the observed range for rare disease assets with revenue benchmarks.

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    06 · PRECEDENT TRANSACTIONS (2 OF 2)

    All Precedent Transactions with Disclosed Terms, Newest First

    This slide continues the list of precedent transactions with disclosed terms, newest first.

    This page completes the disclosed-terms transaction list, carrying the remaining names in the same newest-first order. As on public comparables, these multiples sit on their own LTM basis and aren't a direct read-across to the forward public multiples used elsewhere in the report. The full set, including transactions outside this tier, is available in the companion workbook.

    Everything on this page

    06 · PRECEDENT TRANSACTIONS (2 OF 2) All Precedent Transactions with Disclosed Terms, Newest First 42 transactions with disclosed terms in this tier (118 recorded) · multiples on LTM financials at announcement where disclosed · deal values link to the underlying filing · as of 2026-09-28 Source: NeuraCap analytics platform; market data and consensus estimates as of 2026-09-28; company disclosures via SEC EDGAR where linked. 148 precedent record(s) carry data-quality flags (deal value unit unresolved; divestiture roles reassigned; duplicate filings collapsed); figures are shown as recorded in the filing. 76 recorded transactions with neither a disclosed value nor a multiple are omitted from the precedent list and the case studies (kept in the companion workbook). Deal multiples are LTM at announcement (Definitive, from filings); they are not directly comparable to the CY2027E public basis and no spread is claimed. 18 of 42 transactions shown; the rest are in the companion workbook. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 21 Date Transaction EV EV/LTM Rev EV/LTM EBITDA Why it matters Mar-2026 Eli Lilly and Company → Centessa Pharmaceuticals plc $5.1B n/a n/a Value shown as recorded in the filing; deal value unit unresolved. Mar-2026 Biogen Inc. → Apellis Pharmaceuticals, Inc. $5.2B 5.0x n/a Value shown as recorded in the filing; deal value unit unresolved. Dec-2025 BioMarin Pharmaceutical Inc. → Amicus Therapeutics, Inc. $4.7B 7.9x 79.9x Value shown as recorded in the filing; deal value unit unresolved. Oct-2025 Novartis AG → Avidity Biosciences, Inc. $11.0B n/a n/a Value shown as recorded in the filing; deal value unit unresolved. Oct-2025 Alkermes plc → Avadel Pharmaceuticals plc $1.8B 4.1x 113.6x Value shown as recorded in the filing; deal value unit unresolved. Oct-2025 BioCryst Pharmaceuticals, Inc. → Astria Therapeutics, Inc. $645M n/a n/a Value shown as recorded in the filing; deal value unit unresolved. Jun-2025 Sanofi → Blueprint Medicines Corporation $9.1B 4.5x n/a Value shown as recorded in the filing; deal value unit unresolved. May-2025 BioMarin Pharmaceutical Inc. → Inozyme Pharma, Inc. $278M n/a n/a Value shown as recorded in the filing; deal value unit unresolved. Oct-2024 Sanofi → Fulcrum Therapeutics, Inc. $156M 1.9x n/a Value shown as recorded in the filing; deal value unit unresolved.

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    06 · METHODOLOGY

    Sources, Assumptions and Data Quality

    This slide explains the sources, assumptions and data-quality treatment behind the analysis.

    We built this analysis on market data and consensus estimates as of September 2026, using EV/Revenue on CY2027E as the primary basis and company filings for underlying disclosures. Every figure in this report links to the record it came from, and where a link isn't available, the appendix names the source and the basis on which it was read. That traceability is what lets you verify any single figure in this deck rather than take it on faith.

    Everything on this page

    06 · METHODOLOGY Sources, Assumptions and Data Quality How this report was built, what was excluded, and where every underlying disclosure lives · as of 2026-09-28 Every figure in this report links to the record it was taken from. Where a figure has no link, the appendix names its source and the basis on which it was read. Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice 22 VALUATION BASIS Primary valuation basis: EV / Revenue on CY2027E consensus (28 of 38 companies eligible; multiples failing the platform's plausibility gates are excluded, never plotted). Practitioners price this industry on EV / Revenue rather than EV / EBITDA; validated coverage supports the industry standard (28 of 38 companies), so this report follows it. EV / Revenue on CY2027E is the lead convention: it is the sector-appropriate prior for Rare and Orphan Disease Therapeutics and it clears the coverage gate with 28 of 38 companies (74%). P / E is carried as a cross-check. A revenue lens is used rather than a profit multiple because the set is not consistently profitable on a forward basis (11 of 38 names with a meaningful EBITDA). DATA QUALITY & EXCLUSIONS 158 records were excluded or quarantined by the platform's validation gates (unit errors, implausible ratios, ineligible securities and classification failures); the full ledger ships in the companion tables and never feeds a statistic in this report. DEFINITIVE VS DIRECTIONAL Definitive content is disclosed or consensus data passed through stated arithmetic. Directional content — tier boundaries, situation cuts, "why it matters" commentary, the agenda pages — is NeuraCap analyst judgment and is labeled as such where it appears. WHAT THIS REPORT IS NOT This report characterises a sector. It does not recommend buying, selling or holding any security, and no statement in it should be read as investment advice or a price target. WHERE THE DATA LIVES 1055 registered source documents stand behind the figures in this report. Metric hyperlinks throughout the deck open the specific filing or data record; by publisher: sec.gov (1054) · home.treasury.gov (1). The companion workbook beside this deck carries the complete source index.

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    The Widest Valuation Gap Remains Between the Premium and Discount Ends.

    This is the closing slide reiterating that the widest valuation gap sits between the premium and discount ends.

    The widest valuation gap in this sector remains between the premium and discount ends, and that's the split worth testing against your own portfolio or targets. The companion tables carry the full universe, the exclusion ledger and the complete source index for any figure here you'd like to trace further.

    Everything on this page

    The Widest Valuation Gap Remains Between the Premium and Discount Ends. NeuraCap AI — Rare and Orphan Disease Therapeutics Coverage September 2026 · Prepared by NeuraCap AI · Confidential Rare and Orphan Disease Therapeutics Coverage | September 2026 | Confidential | Not investment advice Sources & methodology 23

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