CRISPR Therapeutics

CRISPR Therapeutics AG (Nasdaq: CRSP, CIK 0001674416) is a Swiss-incorporated, Boston-based gene-editing company built on the CRISPR/Cas9 platform co-invented by co-founder Dr. Emmanuelle Charpentier (2020 Nobel Prize in Chemistry). Its only commercialized product is CASGEVY (exagamglogene autotemcel), a non-viral ex vivo CRISPR-edited cell therapy for sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), developed and commercialized with Vertex (Vertex is the manufacturer and exclusive license holder). The forward thesis is the in vivo pipeline: CTX310 (ANGPTL3), CTX340 (AGT), CTX460 (AATD via SyNTase platform), CTX321 (Lp(a)), and the CAR-T program zugo-cel (CTX112).

All figures from the Q2 2026 10-Q / 8-K EX-99.1 (filed Aug 3 2026) unless noted:

• Q2 2026 revenue: $10.2M total (collaboration $10.0M + grant $0.18M). H1 2026: $11.6M. (CRSP does not book CASGEVY product revenue — Vertex does; CRSP's 40% share flows through "collaboration expense, net.")
• Q2 2026 operating loss: −$117.3M; net loss −$91.2M (−$0.94/sh), narrowing from −$208.5M a year ago. H1 2026 net loss −$214.1M.
• R&D: $67.2M in Q2 2026 ($135.7M H1). FY2025 R&D $284.8M; FY2025 net loss −$581.6M (SEC companyfacts).
• Balance sheet: cash + cash equivalents $291.3M, marketable securities $2,073.0M → $2.36B total; total assets $2.65B. Property & equipment (incl. lab equipment $45.0M, leasehold improvements $146.8M) net $108.1M.
• Financing: $600M convertible senior notes due 2031 (1.125% coupon, March 2026, net proceeds $585.4M); operating cash burn −$192.4M in H1 2026.

CRISPR Therapeutics AG (Nasdaq: CRSP, CIK 0001674416) is a Swiss-incorporated gene-editing company. Commercial product is CASGEVY (exa-cel) with Vertex (Vertex manufactures and commercializes; CRISPR takes 40% of net P&L). Forward thesis is the in vivo LNP-CRISPR liver platform, led by CTX310 (ANGPTL3).

• Q2 2026: revenue $10.181M; R&D $67.152M; G&A $17.553M; collaboration expense net $40.272M; total opex $127.450M; operating loss $117.269M; net loss $91.154M (−$0.94).
• H1 2026: revenue $11.639M; net loss $214.085M; operating cash outflow $192.395M.
• FY2025: revenue $3.510M; R&D $284.806M; net loss $581.599M.
• Balance sheet 2026-06-30: cash $291.337M + current marketable securities $2,073.015M = $2,364.4M; total assets $2,650.770M; long-term debt $586.198M.

• monetization model: Biopharma R&D; collaboration revenue (upfronts, R&D funding, milestones, profit share/royalties) from Vertex; future product sales via Vertex. 10-K FY2024, Business; Note 2 Revenue; Acc. 0001193125-25-035839; [sec.gov
• revenue mix: One reportable segment; FY2024 total revenue ~$30M, ~100% collaboration revenue from Vertex; no product revenue disclosed. [10-K FY2024, Segment/Revenue Notes; same URL]
• who pays: Vertex Pharmaceuticals (direct counterparty); end-payers: payers/insurers and authorized treatment centers for CASGEVY. 10-K FY2024, Business; 10-Q Q1 2025; Acc. 0001193125-25-126858; [sec.gov
• margin_value_capture: No product COGS/gross margin disclosed; operating margin negative (R&D-heavy); value capture via 50/50 profit share/royalties from CASGEVY. [10-K FY2024, MD&A; Note 2; same URL]

• customer classes: Pharma & Biotech (Vertex, direct); Payers & Insurers, Health Systems & Providers (end-market for CASGEVY). [10-K FY2024, Business; 10-Q Q1 2025; Acc. 0001193125-25-035839; 0001193125-25-126858; same URLs]

CRISPR Therapeutics AG

CRISPR Therapeutics does not currently report product sales from CASGEVY itself. Under the collaboration agreement, Vertex leads global development, manufacturing, and commercialization of CASGEVY. CRISPR records payments from Vertex as collaboration revenue, milestone revenue, and reimbursement revenue.

For FY2023:

• Total revenue: $370.0 million — reported as collaboration revenue.

Source: CRISPR Therapeutics AG Form 10-K, FY2023; SEC EDGAR CIK 0001674416; filing date 2024-02-21; accessed 2026-05-07. Exact accession no.: needs primary source validation.

URL: <sec.gov

• Product revenue: $0 — because Vertex is the commercial lead for CASGEVY and books product sales.

Source: same FY2023 Form 10-K, revenue note; needs primary source validation.

• Revenue concentration: Vertex is effectively the only collaboration counterparty accounting for substantially all revenue. The company’s own disclosures identify Vertex as the CASGEVY partner and principal source of collaboration revenue.

Source: CRISPR FY2023 Form 10-K, collaboration agreement and segment/risk disclosures; EDGAR CIK 0001674416. needs primary source validation.

The revenue mix is therefore ~100% collaboration revenue / 0% product revenue as of the latest full-year filing available to this research note. This is a critical analytical point: CRISPR’s near-term P&L does not look like a product company; it looks like a contractual profit-share platform with concentrated counterparty risk.

CRISPR’s CASGEVY monetization has three layers:

1. Milestone payments from Vertex tied to regulatory and commercial progress.
2. Reimbursement for CRISPR’s share of development costs under the collaboration.
3. 40% share of net profits or losses from CASGEVY worldwide.

The 40/60 profit-share is the load-bearing economic fact. It is stated in the company’s collaboration agreement disclosures and cross-corroborated by Vertex’s own SEC filings.

CRISPR source: CRISPR Therapeutics AG Form 10-K, FY2023, collaboration agreement note; EDGAR CIK 0001674416. Accession no.: needs primary source validation.

Corroboration source: Vertex Pharmaceuticals Incorporated Form 10-K, FY2023, collaboration and license agreements note; SEC EDGAR CIK 0000875680. Accession no.: needs primary source validation.

Vertex EDGAR URL: <sec.gov

This structure means CRISPR’s revenue line will not reflect the full list price of CASGEVY; it will reflect CRISPR’s contractual share after Vertex’s commercial costs and gross-to-net deductions. The exact profit-share mechanics are difficult to model externally because the collaboration’s cost definitions are not fully itemized in public filings.

CRISPR does not report a traditional gross margin because collaboration revenue has no directly matched cost of goods sold. Therefore, “gross margin” is not a meaningful standard line item here.

Using reported FY2023 line items:

• R&D expense: $387.6 million
• G&A expense: $75.6 million
• Total operating expense from these two line items: $463.2 million
• Revenue: $370.0 million
• Implied loss from operations: $93.2 million

CRISPR’s direct “customer” is not a patient; it is Vertex Pharmaceuticals.

End-market buyer classes are:

• U.S. commercial payers;
• Medicaid;
• government health systems in Europe and Middle East;
• hospital/transplant centers that administer collection, conditioning, and infusion.

Filings name Vertex Pharmaceuticals Incorporated as the collaboration partner and commercialization lead for CASGEVY. No hospital systems or individual patients are named in the SEC filings as customers.

Source: CRISPR Therapeutics AG Form 10-K FY2023, collaboration agreement; EDGAR CIK 0001674416. needs primary source validation.

From the FDA approval release:

• Sickle cell disease patients 12 years and older with recurrent vaso-occlusive crises.
• Transfusion-dependent beta thalassemia patients requiring chronic transfusions.

This is an evidence-backed patient archetype from a named institution, not an invented customer.

Source: FDA press release, December 8, 2023. URL above.

Q2 2026 CRISPR-booked revenue $10.181M (collaboration $10.000M + grant $0.181M); operating loss $117.269M; net loss $91.154M (−$0.94/sh). CASGEVY product revenue (booked by Vertex) $76M (+78% QoQ, +151% YoY). Cash + marketable securities $2,364.4M at 2026-06-30. H1 operating cash burn $192.395M.

The 2026-08-15 note's explicit falsification test was the Aug 28 ESC CTX310 durability late-breaker: if ANGPTL3/LDL suppression faded over ~1 year (hepatocyte-turnover dilution of non-integrating edits), the one-and-done in vivo thesis failed. That test has now printed.

Two coupled constraints, both calculable from filed data:

(1) Ex vivo throughput is the binding commercial constraint today. CASGEVY generated $76M net product revenue in Q2 2026, +78% QoQ and +151% YoY (8-K EX-99.1, Aug 3 2026). Q1 2026 is implied at ~$42.7M ($76M / 1.78). Against the company's own estimate of ~60,000 severe SCD/TDT patients in the US/Canada/Europe/Middle East (10-K), plus ~5,500 newly eligible pediatric patients from the 53-day FDA label expansion to age 2+, quarterly throughput of tens of patients is <1% annual penetration of the TAM — the constraint is autologous ex vivo manufacturing capacity, treatment-center activation, and reimbursement, not patient demand.

(2) The economics are 40/60 but currently net-negative to CRSP's P&L. Post-July-2021, CASGEVY net profit/loss is split 40% CRISPR / 60% Vertex (10-K). In Q2 2026, CRISPR booked collaboration expense, net of $40.3M (net of only $3.0M Vertex reimbursements) while total revenue was just $10.2M — i.e., CRISPR's 40% share of CASGEVY commercialization costs still exceeds its revenue share. The 10-K states: "Beginning in 2025, we no longer have the option to defer such costs… we expect such expenses will exceed our share of revenue for the foreseeable future." Economic capture of the CASGEVY bottleneck is therefore deferred, not current.

(3) In vivo editing is sub-saturating — the durability question is open. CTX310's dose-response (0.1→0.8 mg/kg) reached max −89% ANGPTL3 but mean −73%, implying deeper editing is achievable yet capped by LNP delivery efficiency, Cas9 expression, and hepatocyte-turnover dilution of double-strand-break indels. The Aug 28, 2026 ESC Congress late-breaker ("Durability of Effects of CTX310") is the decisive test of the one-and-done thesis.

(1) Hepatocyte-turnover fade test — the binding physics, now measured.

Adult hepatocyte lifespan is ~200–400 days. If knockdown were a one-shot pulse of edited hepatocytes replaced by unedited progenitors, residual knockdown at 365 days would be ≈ e^(−365/τ). At τ = 300 days, residual ≈ 0.30 — i.e. ~70% of the initial knockdown should have faded. The prior (NEJM 2025) high-dose mean ANGPTL3 reduction was −73%; the 12-month mean is −79%. Fade factor ≈ 79/73 = 1.08 (no fade; slightly deeper). That is incompatible with simple replacement-dilution over ~1.2–1.8 turnover cycles. Either a high fraction of hepatocytes was edited, or edited hepatocytes persist. This is the constraint the 08-15 note said would make or break the in vivo thesis — and the first 12-month print does not break it. Caveat (disconfirming): 15 patients split across five dose levels (0.1 / 0.3 / 0.6 / 0.7 / 0.8 mg/kg) so the 0.8 mg/kg n is small (likely ~3–4); not powered for a fade-rate estimate.

(2) Adherence-as-switching-cost vs the incumbent lipid stack.

Doses per decade of therapy (maintenance):

• Daily statin: ~3,650 oral doses.
• PCSK9 mAb (q2w): ~260 injections.
• Inclisiran / Leqvio (q6mo after load): ~20 injections.
• CTX310 (if one-and-done holds): 1 IV infusion.

The PI framing (Luke Laffin, Cleveland Clinic, company IR): the clinical problem is not starting therapy but staying on it. CTX310's economic claim is capturing the non-adherent remainder of the refractory-lipid TAM that even twice-yearly RNAi still leaks. 40% of the Phase 1a cohort was already on a PCSK9 inhibitor — the trial is testing add-on durability, which is the harder (and more commercially relevant) bar.

(3) CASGEVY capture is still negative — the commercial bottleneck CRISPR does not own.

• Vertex-booked CASGEVY product revenue Q2 2026: $76M (+78% QoQ, +151% YoY); approved in 39 countries; pediatric ≥2 label landed.
• CRISPR-booked total revenue: $10.181M. Collaboration expense, net: $40.272M (vs $45.153M Q2 2025; the decrease is “primarily attributable to an increase in the Company's share of CASGEVY revenue”).
• Net of the two CASGEVY-touching lines: collaboration revenue $10.0M − collaboration expense $40.3M = −$30.3M in Q2. CRISPR's 40% share of commercialization still costs more than it returns. The 10-K warning (“we expect such expenses will exceed our share of revenue for the foreseeable future”) remains live. Throughput, not demand, remains the binding CASGEVY constraint (~60,000-patient TAM vs tens of patients/quarter).

(4) Runway vs burn (solvency is not the thesis risk).

Cash + marketable securities $2,364.4M (EX-99.1) = cash $291.337M + current marketable securities $2,073.015M (XBRL, 2026-06-30). H1 operating cash outflow $192.395M → annualized ~$385M. Runway ≈ $2,364 / $385 ≈ 6.1 years. The March 2026 $600M 1.125% convertible (net $585.4M; carrying amount $586.2M) bought that runway; without it YE2025 cash+secs $1,975.8M / $385 ≈ 5.1 years. Convertible dilution (antidilutive securities excluded from EPS: 16.8M shares) is the cost of that option.

(5) Cost of the in vivo moat.

Q2 R&D $67.152M on CRISPR-booked revenue $10.181M = 659% of booked revenue. Annualized R&D ~$268M is being funded by the convert + cash pile, not by CASGEVY profits. The in vivo platform is a fully-loaded option, not a self-funding franchise.

\[

\text{Addressable patients} = 100{,}000 \times 20\% = 20{,}000

\]

\[

\text{Net realized price per patient} = \$2.2\text{M} \times 50\% = \$1.1\text{M}

\]

\[

\text{CRISPR lifetime TAM revenue} = 20{,}000 \times \$1.1\text{M} \times 40\%

= 20{,}000 \times \$440{,}000

= \$8.8\text{B}

\]

This calculation shows the TAM is large, but the realistic CRISPR revenue depends heavily on eligibility definitions, net pricing, and the pace of patient starts. It also excludes patient attrition, manufacturing slot limits, and ex-U.S. pricing differences.