Biotechnology Industry Terminology

non-pathogenic viral vector used for in vivo gene delivery; limited cargo (~4.7 kb); distinct serotypes for tissue tropism; manufacturing in HEK293 or Sf9 systems; immunogenicity considerations; Selecting AAV9 for CNS tropism in a neurodegenerative program; Our AAV capsid engineering aims to evade pre-existing antibodies; Comparing HEK293 vs baculovirus-Sf9 systems for AAV manufacturing scale-up

interim analyses and adaptations pre-specified to preserve Type I error; includes response-adaptive randomization, sample size re-estimation, arm dropping, enrichment, and seamless Phase 2/3 designs; We plan a futility interim to drop underperforming arms; The DMC will guide sample size re-estimation per the adaptive protocol; Our seamless Phase 2/3 may transition without halting enrollment

Absorption, Distribution, Metabolism, Excretion; central to PK profiling and DMPK strategy; assessed via in silico, in vitro, and in vivo studies; informs dose selection and safety; We need a full CYP induction/inhibition panel for ADME risks; Poor solubility is limiting absorption; consider enabling formulation; High volume of distribution suggests tissue binding

US marketing application for biologics under the Public Health Service Act; includes CMC, nonclinical, clinical, labeling; PDUFA review timelines, potential advisory committee; Our BLA submission is targeted for Q4 after process validation; FDA accepted the BLA and set a PDUFA date in October; We converted from an NDA to a BLA given the product is a mAb

large, complex molecules or living therapies (mAbs, proteins, vaccines, cell/gene therapies); manufactured in living systems; cold chain and immunogenicity concerns; biosimilars after LOE; Our biologic requires cold chain and strict GMP controls; The biosimilar landscape intensifies after LOE; Manufacturing variability can affect glycosylation profiles

predictive, prognostic, diagnostic, pharmacodynamic, or surrogate markers; can be molecular, imaging, or clinical readouts; enable patient selection and dose optimization; We’ll use an EGFR mutation biomarker to select patients; pCR will serve as a surrogate endpoint for early efficacy; Our PD biomarker is receptor occupancy on T cells

stirred-tank, perfusion, or single-use systems; controls pH, DO, temperature, and feed; key to upstream scale-up and process intensification; We’re scaling from 2 L to 2000 L single-use bioreactors; Perfusion intensified our upstream to boost cell-specific productivity; Tight DO control improved glycan profiles

autologous or allogeneic engineered T cells targeting antigens like CD19 or BCMA; risks include CRS and neurotoxicity; vein-to-vein time is critical; We saw Grade 2 CRS managed with tocilizumab; An allogeneic CAR-T could shorten manufacturing lead times; Antigen escape drives our plan for dual-targeting CARs

outsourced process development and GMP manufacturing; tech transfer, scale-up, validation; MSAs and quality agreements govern responsibilities; We’re tech-transferring our DS process to a second CDMO; The quality agreement defines deviation and CAPA ownership; Parallel CDMOs mitigate single-source risk

therapeutic use of living cells (e.g., CAR-T, NK, MSC); autologous vs allogeneic sourcing; stringent sterility and release testing; classified as ATMPs in the EU; Our autologous cell therapy needs just-in-time logistics; Allogeneic cells can lower cost and improve scalability; Release testing includes sterility and potency assays

Chinese Hamster Ovary cells dominate recombinant protein production; enable human-like glycosylation; used in fed-batch and perfusion; We selected a high-producing CHO clone via limiting dilution; Glycoengineering CHO lines improved ADCC; Fed-batch in CHO reached 8 g/L titer

covers DS/DP description, process controls, specs, stability; defines CQAs, CPPs, and control strategy; central to IND/BLA/NDA quality; Defining CQAs guided our purification steps; We established a control strategy linking CPPs to CQAs; Stability-indicating methods support shelf-life claims

test essential for safe and effective use of a therapy; often requires PMA in the US; co-developed and referenced in labeling; The CDx detects NTRK fusions for therapy eligibility; FDA requested PMA for the companion assay; Labeling ties treatment to a validated CDx result

includes raw materials, disposables, labor, QC, overhead; biologics COGS impacted by titer, yields, and DSP throughput; affects pricing and gross margin; Intensified upstream lowered COGS per gram; COGS modeling supports long-term pricing strategy; High Protein A resin costs are a DSP bottleneck

outsourcing clinical operations, monitoring, biostatistics, and data management; selection via RFP; vendor oversight is critical; We’ll outsource Phase 2 to a global CRO network; The CRO will handle site initiation and monitoring; KPIs and governance ensure CRO performance

gene editing using Cas nucleases, base or prime editors; delivery via LNPs or viral vectors; off-target effects and IP are key considerations; ABE8e improved specificity vs wild-type Cas9; LNP delivery targets hepatocytes for in vivo editing; We licensed CRISPR IP to ensure freedom to operate

values programs by risk-adjusted free cash flows (rNPV); sensitive to WACC, probability of success, pricing; triangulated with comps; Our rNPV increased after positive Phase 2 data; WACC and peak sales assumptions drive DCF outcomes; DCF triangulates with comps and precedent deals

ownership percentage decreases after new equity round or option pool increase; pre/post-money valuation sets dilution; anti-dilution provisions in down rounds; The Series A caused 20% dilution to common holders; Expanding the option pool increased founder dilution; Our term sheet includes weighted-average anti-dilution

harvest, clarification, chromatography (Protein A, ion exchange), virus clearance, UF/DF; often the capacity bottleneck for mAbs; Protein A capture followed by polishing improved purity; UF/DF set final concentration and buffer; Viral clearance validation met regulatory expectations

oversees centralized approvals (MAA) in the EU; CHMP and CAT provide scientific opinions; PRIME expedites development; We’ll file a centralized MAA to EMA; CHMP adopted a positive opinion for our product; PRIME designation supports accelerated EU development

enables rolling review and more frequent FDA interactions; for serious conditions with unmet need; may complement Priority Review or Breakthrough; Fast Track will let us submit the CMC section early; We’ll leverage frequent FDA touchpoints to de-risk Phase 3; Fast Track plus Priority Review could shorten timelines

SAD/MAD design; sentinel dosing for safety; MABEL-based starting dose; may use microdosing or healthy volunteers depending on risk; Our FIH uses sentinel dosing for the first cohort; MABEL informed the conservative starting dose; The SAD/MAD study includes exploratory PD markers

ICH E6(R2/R3) standards for ethics and data integrity; informed consent, monitoring, and documentation; ALCOA+ principles; An audit flagged consent form deviations under GCP; We’ll enhance data integrity per ALCOA+; The monitoring plan aligns with ICH GCP guidelines

in vivo vs ex vivo approaches; integrating vs episomal vectors; durability and long-term follow-up; safety concerns like insertional mutagenesis; Our in vivo therapy aims for a functional cure; Integration risks inform our vector choice; A 5–15 year follow-up plan is part of the safety strategy

applies to nonclinical safety studies; requires SOPs, QA oversight, and archival of records; essential for IND-enabling tox; The tox study was audited for GLP compliance; QA inspected deviations and corrective actions; All raw data will be archived per GLP requirements

ensures products are consistently produced and controlled; requires validated processes, batch records, deviations/CAPA, and lot release; Annex 1 for aseptic; We executed PPQ runs to validate the process; A deviation led to a CAPA and retraining; Annex 1 updates drove aseptic upgrades in fill/finish

evidence review for clinical and cost effectiveness; informs reimbursement decisions by agencies like NICE, HAS, G-BA; may result in price negotiations; NICE requested additional comparative evidence; Our G-BA dossier supported added benefit vs SOC; HTA feedback shaped our real-world evidence plan

cost per QALY gained vs comparator; sensitivity to utilities, costs, and time horizon; not to be confused with the US organization ICER; The ICER of $120k/QALY fell below the threshold; We ran one-way sensitivity on utility weights; Shorter time horizons worsened the ICER outcome

US authorization to begin clinical trials; includes CMC, nonclinical, and clinical protocols; 30-day safety review; requires safety reporting; Our IND-enabling tox studies are nearly complete; FDA’s 30-day review starts upon IND receipt; We’ll submit a protocol amendment for the dose expansion

patents and trade secrets; composition-of-matter, method-of-use, and formulation claims; patent term extensions (PTE/SPC); freedom-to-operate analysis; We filed a composition-of-matter patent pre-IND; An SPC could extend EU exclusivity post-approval; FTO analysis cleared key CRISPR claims

influential clinicians/scientists guiding development; engage via advisory boards; can accelerate trial enrollment and credibility; Our KOLs preferred PFS as the primary endpoint; KOL feedback refined inclusion/exclusion criteria; A KOL-led registry will support RWE generation

patent or data exclusivity expiry enabling generics/biosimilars; triggers price erosion; lifecycle management strategies mitigate impact; We expect biosimilar entry two years post-LOE; A new SC formulation extends the franchise; Contracting strategy will cushion LOE erosion

payers, HTA, and pricing strategy to secure reimbursement; launch sequencing and evidence plans; contracting and patient support; US-first launch enables earlier revenue despite payer hurdles; Our value story is anchored in QALYs and RWE; Early payer advisory boards shaped our evidence plan

biological pathway and target engagement; differentiates from competitors; informs biomarker and dosing strategy; On-target cytopenias align with the MOA; Our MOA supports tumor-agnostic development; We animated the MOA for investor education

IgG subclasses with effector functions; engineered formats (bispecifics, ADCs); produced in CHO with glyco control; An IgG1 backbone enables ADCC; Our bispecific mAb targets two checkpoints; The ADC couples a mAb to a cytotoxic payload

US marketing application for small molecules (and some biologics historically under CDER); 505(b)(1) or 505(b)(2) pathways; labeling negotiations and potential CRL; We’re pursuing a 505(b)(2) leveraging literature; Priority Review shortened our NDA timeline; We addressed a CRL with additional CMC data

for rare diseases (≤200,000 prevalence in US); benefits include tax credits, fee waivers, and 7–10 years exclusivity; protocol assistance in EU; Orphan status de-risks our rare pediatric program; EU orphan designation supports 10-year exclusivity; We’ll leverage the tax credit for clinical costs

sets user fees and review goals; PDUFA date signals expected FDA action; current framework is PDUFA VII; The PDUFA date is October 15; PDUFA VII updates include new review goals; We’re preparing for a potential advisory committee pre-PDUFA

relationship between concentration and effect; EC50/Emax models; PD biomarkers and exposure-response inform dose; Receptor occupancy correlates with clinical benefit; PK/PD modeling supports the Phase 2 dose; IL-6 reduction serves as a PD biomarker

concentration-time behavior (Cmax, AUC, t1/2); bioavailability and distribution; noncompartmental and population PK analyses; Exposure increased dose-proportionally up to 600 mg; Food-effect altered Cmax but not AUC; PopPK identified weight as a covariate

detection and management of adverse events; safety databases, signal detection, RMP; PSUR/DSUR reporting; REMS when needed; Signal detection in FAERS triggered label updates; Our RMP adds a pregnancy registry; DSUR submission summarized annual safety data

reusable technology enabling multiple assets; economies of scope; partnered programs and out-licensing; multiple shots on goal; Our LNP platform supports five liver targets; We out-licensed the platform to a big pharma for CNS; The platform thesis underpins portfolio diversification

combines quantity and quality of life via utility weights (0–1); used in cost-effectiveness analysis; informs payer decisions; The therapy adds 1.8 incremental QALYs vs SOC; Utility mapping came from EQ-5D data; HTA bodies rely on QALYs to compare therapies

derived from RWD (EHRs, claims, registries, devices); supports label expansion, external controls, and HTA submissions; requires robust causal inference; An external control from a registry supported our filing; We’re integrating claims and EHRs for RWE; RWE will underpin our post-launch outcomes study

net gain relative to investment; applied to programs, BD deals, or commercialization; complements rNPV in portfolio decisions; The BD deal cleared our ROI hurdle rate; Marketing ROI improved after payer segmentation; ROI plus strategic fit drove the go/no-go decision

months of cash remaining at current burn; extended via financing, cost controls, or partnerships; central to operating plans and milestones; We have 18 months of runway post-Series A; A partnership milestone extends runway into 2027; Cost containment adds three months of runway

first significant institutional round; sets valuation and key terms; funds to clinical POC or key technical de-risking; The Series A targets $25M to complete Phase 1; The lead investor proposed a term sheet with pro rata rights; Use of proceeds focuses on IND and FIH

market sizing for strategy and fundraising; TAM total universe, SAM served by model, SOM realistically captured; built top-down and bottom-up; TAM is $5B; SAM $1.2B; SOM $250M at year 3; A patient-based bottom-up model supports SOM; Investors challenged our TAM assumptions during diligence

concentration of product in culture (g/L); key driver of COGS and facility throughput; improved via media, feeds, and cell-line engineering; We achieved 8 g/L in fed-batch CHO; Perfusion increased space-time yield; Titer gains allowed smaller chromatography columns

AAV, lentivirus, adenovirus platforms; selection based on tropism, cargo size, immunogenicity; manufacturing and QC complexity; We chose lentivirus for ex vivo CAR-T transduction; Adenovirus enables high expression for vaccines; Suspension culture simplified vector scale-up