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Affini-T Financial Model

• Platform: TCR (T cell receptor) discovery + lentiviral engineering of patient T cells; proprietary Fas-41BB survival switch converts tumor death signal to survival signal
• Coordinated CD4+/CD8+ T cell response - CD4 helper cells prevent CD8 exhaustion and sustain anti-tumor activity in immunosuppressive TME
• Targets oncogenic driver mutations present in every cancer cell (KRAS G12V, KRAS G12D, Mutant P53, MCPyV) - mutations cannot be easily lost, minimising escape mechanisms
• Differentiator vs. approved KRAS inhibitors (e.g., LUMAKRAS/sotorasib): covers G12V and G12D subtypes where no approved therapies exist; avoids tumour escape via cell-intrinsic mechanism
• Pipeline architecture: 1st-Gen (lentiviral + switch) → 2nd-Gen (gene edits) → 3rd-Gen (synthetic bio) → 4th-Gen (allo, in situ)

Three primary oncology markets cited, 2021 global figures:

Combined addressable market (3 indications): ~$21.6B+

Annual incidence (US + EU + China, newly diagnosed, 2021):

• KRAS G12V: Pancreatic ~74K, Colorectal ~98K, Lung ~40K
• KRAS G12D: Pancreatic ~92K, Colorectal ~128K, Lung ~30K
• Global bubble chart incidence nodes: 60K, 106K, 149K, 235K, 370K, 393K, 555K, 124K, 815K (geographic distribution, tumour types not all individually labelled)

Non-dilutive partnerships cited as a future Series A/B milestone.

No revenue. Preclinical traction only:

• Multiple KRAS candidates advanced
• Manufacturing process established
• Gene editing strategy developed
• Facilities contracted
• Dozen-plus T cell therapeutic candidates advanced through Fred Hutch co-founders' prior work
• Published peer-reviewed data: WT1 TCR gene therapy (Chapuis et al., Nat Med 2019); PDAC T cell therapy (Stromnes et al., Cancer Cell 2015); Fas-41BB switch survival data (Oda et al., JEM 2020)
• Seed investors: VIDA Ventures, Leaps by Bayer, Humboldt, Agent Capital, Alexandria

• LUMAKRAS (sotorasib) approved only for KRAS G12C - Affini-T targets G12V and G12D where no approved therapies exist
• Scientific moat: Fred Hutch co-founders (Phil Greenberg MD, Aude Chapuis MD, Tom Schmitt PhD) with >12 T cell clinical programs; SAB includes Jim Allison PhD (Nobel laureate), Pam Sharma MD/PhD, Rafi Ahmed PhD, David Kranz PhD, Susan Kaech PhD
• Platform differentiation: proprietary TCR discovery + Fas-41BB switch + CD4/CD8 coordination - multi-layer vs. single-modality competitors
• Prior institutional relationships: Juno Therapeutics, NIH NCI, Fred Hutch, Bluebirdbio

Management:

• Jak Knowles MD - CEO (ex-CytoSen, Century, Exonics, Bayer)
• Loïc Vincent PhD - CSO (ex-Takeda, Sanofi, Endotis Pharma, Adaptate)
• Kim Nguyen PhD - CTO (ex-Precision, Vitalant, Terumo)
• Kathy Yi MBA - COO/CFO (ex-Cerevel, Sangamo, Novartis)

Funding ask: Not explicitly stated in deck (J.P. Morgan conference format - Series A implied as next round)

Use of funds (inferred from roadmap milestones, Series A/B phase):

• KRAS G12V + G12D: First-in-human safety studies
• Clinical readout for MCC (Merkel Cell Carcinoma) and KRAS
• p53 and PIK3CA clinical candidates
• Automated TCR discovery engine
• Non-viral manufacturing + next-gen synthetic biology
• Non-dilutive partnerships

Infrastructure: 95,000 sq.ft. Boston cGMP clinical and commercial manufacturing facility contracted

• Archetype + why: Clinical-stage biotech R&D burn / pipeline NPV model. Affini-T is pre-IND, pre-revenue, with multiple programs across discovery and preclinical stages. The appropriate model is a program-by-program R&D spend and milestone timeline model, with a probability-weighted NPV (rNPV) overlay for each pipeline asset as a terminal value proxy. This is the standard VC/biotech framework - no revenue forecasting until Phase 2 readout assumptions.

• Forecast horizon & granularity:
• Near-term operating model: 2022–2026 (annual), quarterly detail for 2022–2023
• Pipeline NPV: per-program horizon to peak sales (2030–2035), discounted at biotech-standard 10–15% WACC
• Milestone timeline driven by slide 23 roadmap: Seed (2021 complete) → Series A/B (2022–2023) → Clinical POC (2023+)

• Key drivers & assumptions:

*Burn / operating cost drivers:*

• Headcount ramp: ~30–50 FTEs at Seed; double to ~80–120 at Series A close, driven by bi-coastal build-out
• Avg. fully-loaded cost per FTE: ~$200K–$250K/yr (Boston biotech market)
• R&D spend per program per year in preclinical: ~$3M–$8M (cell therapy process dev + manufacturing costs)
• IND-enabling / Phase 1 per program: ~$10M–$25M (autologous cell therapy trials are cost-intensive; patient leukapheresis, manufacturing, clinical sites)
• cGMP facility build-out: 95,000 sq.ft.; capex ~$50M–$100M (phased; typical for cGMP cell therapy)
• Manufacturing COGS per patient dose (autologous): ~$150K–$350K (analogous to CAR-T; Affini-T proprietary Lentiviral + Switch process may differ)

*Pipeline program timing (from roadmap):*

• KRAS G12V (HLA-A11): Lead program, furthest in discovery → preclinical; FIH in 2022–2023
• KRAS G12D (HLA-A11): Discovery/preclinical stage
• Mutant P53 (HLA-A2): Early discovery
• MCPyV (Viral driver, HLA-A2): Discovery → clinical stage implied

*Revenue assumptions (if modelling peak sales for NPV):*

• Therapy price per patient: ~$400K–$500K per infusion (consistent with approved CAR-T pricing: Kymriah $475K, Yescarta $373K)
• Addressable patients per program per year (US+EU+China): KRAS G12V pancreatic ~74K total incidence; apply ~2–5% treatment penetration in early years
• Probability of success (PoS) per stage: Discovery→Preclinical 60%; Preclinical→Phase 1 50%; Phase 1→Phase 2 40%; Phase 2→Approval 30% (cell therapy oncology historical benchmarks)
• Royalty / partnership split: 10–20% royalty on ex-US sales if non-dilutive partnership executed

*Market size validation:*

• Pancreatic: $2.6B+ market, 7.5% CAGR
• Colorectal: $12.1B+ market, 4.9% CAGR
• Lung: $6.9B+ market, 6.7% CAGR

• Scenarios (Base / Bull / Bear - which variables flex):
• Bear: KRAS G12V Phase 1 safety signal delays; 2nd program (G12D) pushed 2 years; cGMP cost overruns +30%; PoS halved vs. base; requires Bridge/Series B extension
• Base: KRAS G12V achieves FIH 2023; G12D Phase 1 by 2024; Series A raises ~$80–120M; clinical POC 2025–2026; peak sales KRAS G12V ~$600M–$1B (US+EU)
• Bull: Accelerated IND filing; multiple FIH readouts 2023–2024; non-dilutive partnership deal (upfront + milestones $50–200M); allo/in situ platform unlocks broader market; KRAS peak sales >$1.5B

• Required sheets / outputs:

1. Assumptions - all drivers in one input sheet (toggle switches by scenario)
2. Headcount & Opex - department-level burn by quarter (R&D, G&A, Clinical Ops, Manufacturing)
3. Pipeline Timeline - Gantt-style program progression by asset with IND/Phase 1/2 dates
4. Cash Runway - cumulative burn vs. available capital; breakeven/next raise trigger
5. rNPV per Program - probability-weighted peak sales NPV per asset (KRAS G12V, G12D, p53, MCPyV)
6. Portfolio NPV Summary - sum of rNPVs; sensitivity to discount rate and PoS
7. Financing Schedule - Seed (complete), Series A (2022), Series B (2023–2024), IPO / partnering (2025+)
8. Scenario Dashboard - Bear/Base/Bull NPV and runway side-by-side