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70 pagesSDDS 2026 21 pagesPHGDH RNA-Binding Domain: Comprehensive Biological 18 pagesPHGDH ACT Domain: Lead Optimization 13 pagesPHGDH Allosteric RBD Binder 6 pagesDisease2Target: Pancreatic Cancer KRAS-Combination 6 pagesDisease to Target: Alzheimer's GET Score 5 pagesPHGDH RNA-Binding Domain Small Molecule Ranking

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ComparisonCAR-T Generations: From Zeta-Only to Composable ArchitecturesSide-by-side analysis of CAR-T receptor designs discussed at SDDS 2026. Each generation addresses a specific failure mode of the prior one.ConceptAI in Drug DiscoveryA cross-cutting theme across SDDS 2026: where AI is already load-bearing, where it’s hype, and what constrains its impact.DiseaseAlzheimer's DiseaseNeurodegenerative disease. Major topic across Nobel panels — Session IV and Session XII. The Amyloid Paradox Antibodies (lecanemab) can make brains essentially plaque-free — yet cognitive…DrugBimekizumab (Bimzelx)A dual-specificity antibody targeting both IL-17A and IL-17F, developed by UCB. Presented by Alistair Henry at Session I.TargetGLP-1 ReceptorThe glucagon-like peptide 1 receptor — a Class B GPCR that is the primary target of the incretin therapeutic revolution. Central to Session VII.PersonAlistair HenryDrug discovery leader at UCB. Presented at Session I on drug discovery by design — listening to human pathobiology and back-translating from approved molecules.SessionSession I — Drug Discovery I: The Productivity Paradox, the Dynamic Proteome, and What Molecules Teach UsThe Productivity Paradox, the Dynamic Proteome, and What Molecules Teach Us Three R&D leaders — Mike Quigley (Sanofi), Karen Akinsanya (Schrödinger), and Alistair Henry (UCB) — circle a…ResearchPHGDH Project DashboardAuto-regenerated by project_dashboard.py at 2026-09-25 17:05:05. Cells are color-coded by Achievement score (1-9 reverse-NIH, 9 best): green ≥5 yellow 4 red ≤3 Table 1 — PLEASER ×…OrganizationGenentechBiotech pioneer, now part of Roche. Represented by Aviv Regev at Session II. Strategy: Lab in the Loop Four iterative loops spanning targets, indications, medicines, and patients…ComparisonElimination Therapies: Modalities Converging on a Single GoalThe defining therapeutic ambition of SDDS 2026: don’t manage disease — eliminate its cellular root causes.ConceptCAR-T TherapyChimeric Antigen Receptor T-cell therapy — engineered T cells that recognize and kill target cells. A central theme across SDDS 2026, covered extensively in Session V (Rosenberg), Session V…DiseaseGlioblastomaAn aggressive brain cancer. One of the first solid tumors where CAR-T is showing real responses. Discussed extensively by Carl June at Session V.DrugMaritideAn antibody-peptide conjugate developed by Amgen. Presented by Jay Bradner at Session VII. Mechanism: The Geometry Is the Drug Three components working in concert: Antibody that antagonizes…TargetIL-17 PathwayThe interleukin-17 family of cytokines — central to chronic inflammation and autoimmunity. Discussed extensively by Alistair Henry at Session I in the context of bimekizumab.PersonAndy PlumpHead of R&D at Takeda for twelve years. Presented at Session II on learning from failure. Key Arguments Drug discovery’s funnel slide is an average — biology lacks calculus Failure is…SessionSession II — Drug Discovery II: Closing the Loop on BiologyClosing the Loop on Biology Four leaders — Aviv Regev (Genentech), Jonathan Cohen (NVIDIA), Andy Plump (Takeda), and John Reed (J&J) — converge on a single thesis: drug discovery is…ResearchDiscussion and Conclusion — Disease2Target Pancreatic KRAS-Combination Validationstudy, the app gave the target-level evidence for all seven genes in one place, in minutes, where gathering it by hand means visiting six or more databases.OrganizationJohnson & Johnson (J&J)Diversified healthcare company with pharma-plus-medtech footprint. Represented by John Reed at Session II.ComparisonIncretin Landscape: The GLP-1 Revolution and BeyondSide-by-side analysis of the incretin-class drugs discussed at SDDS 2026. Each generation outmodes the last primarily by efficacy — technological obsolescence, not patent cliffs.ConceptChina StrategyA recurring theme across SDDS 2026: China as simultaneously competitor, source of in-licensable assets, and clinical-trial accelerator. Discussed most extensively at Session III.DiseaseLupus (Systemic Lupus Erythematosus)A systemic autoimmune disease. Central case study for the immune reset paradigm at SDDS 2026. CAR-T for Lupus Georg Schett & Fabian Müller (Erlangen): refractory SLE patients treated with…DrugRetatrutideA GIP/GLP-1/glucagon triple agonist developed by Lilly. Presented by Kenneth Custer at Session VII. Why Add Glucagon? Adding glucagon to the GIP/GLP-1 backbone is counterintuitive …TargetIL-23Interleukin-23, a heterodimeric cytokine involved in chronic inflammation. Discussed at Session I in relation to the IL-17 pathway.PersonAviv RegevHead of Research & Early Development at Genentech. Presented at Session II on the lab-in-the-loop architecture.SessionSession III — VC Perspectives: Investing in Early-Stage InnovationInvesting in Early-Stage Innovation Panel Discussion Moderated by Joe Jimenez (former Novartis CEO), facilitated by Mark Mercola (Stanford).ResearchMethods — Disease2Target Pancreatic KRAS-Combination Validation(target.smartdrugdiscovery.org/). ParameterValueDatasetpancreatic adenocarcinoma (MONDO_0006047)Snapshot#143, version 9Snapshot created15 September 2026Candidate genes6,000Evidence…OrganizationSanofiGlobal pharmaceutical company. Represented by Mike Quigley at Session I. Strategy at SDDS 2026 Constellation view: maps biologies across therapeutic areas (not within them), with…ComparisonPharma AI Strategies: Who Is Doing What and WhyA cross-company comparison of AI approaches discussed at SDDS 2026. Every major company has an AI strategy — but they differ in where they place the bet, how they integrate it, and what…ConceptDynamic ProteomeThe thesis that static structural snapshots of proteins are necessary but insufficient for drug discovery — the next leap requires modeling proteins as dynamic machines operating on…DiseaseMultiple MyelomaA blood cancer of plasma cells. One of the most dramatic drug discovery success stories — average life expectancy has gone from 2 years to nearly 20.DrugSGR-1505A physics-discovered small molecule developed by Schrödinger. Presented by Karen Akinsanya at Session I. Key Data Asset to clinic-ready in 10 months 100% response rate in Waldenström’s…TargetLRRK2Leucine-rich repeat kinase 2 — the brightest near-term target for Parkinson’s disease. Discussed at Session IV.PersonBrian KobilkaHelene Irwin Fagan Chair of Cardiology, Stanford University. Nobel Prize in Chemistry, 2012 — for studies of G-protein-coupled receptors (GPCRs). Panelist at Session XII.SessionSession IV — Nobel Laureate Panel Discussion I: Breakthroughs Don't Travel in Straight LinesBreakthroughs Don’t Travel in Straight Lines Three Nobel laureates — Carolyn Bertozzi (Chemistry 2022), Randy Schekman (Physiology/Medicine 2013), and Thomas Südhof (Physiology/Medicine…ResearchReferences — Disease2Target Pancreatic KRAS-Combination ValidationJY, et al. Drug Discovery at the Speed of AI (presentation), slides 25–40 and 67. SPARC, UAB. Chen JY, Saghapour E, Kurmachalam N, Oishe G, Sembay Z.OrganizationSchrödingerSits at the seam between healthcare and software — computational drug discovery platform. Represented by Karen Akinsanya at Session I.ConceptHuman PathobiologyThe principle that drug discovery should be grounded in human disease biology rather than animal model biology. A central theme of Session I, championed especially by Alistair Henry (UCB).DiseaseObesity~100 million Americans; ~2 billion globally. Fewer than 1 in 10 eligible Americans currently using modern obesity medicines.TargetSARM1Sterile alpha and TIR motif containing 1 — an NAD hydrolase implicated in axonal degeneration. Case study presented by Karen Akinsanya (Schrödinger) at Session I, published with BMS in J.PersonCarl JuneRichard W. Vague Professor in Immunotherapy at Penn; director of the Parker Institute for Cancer Immunotherapy at UPenn.SessionSession IX — Drug Discovery IV: The Elimination ImperativeThe Elimination Imperative: From Pathogenic Cells to Durable Remission Three leaders — Robert Plenge (BMS), Flavius Martin (Gilead), and Kendra Rose (Bayer) — converge on a thesis: the…ResearchResults — Disease2Target Pancreatic KRAS-Combination Validationclaims: 8 supported, 3 partly supported, 2 not testable in the app, and 1 missed by the co-pilot. Sources: manuscript Supplemental Data §S5…OrganizationTakedaJapanese pharmaceutical company, founded 1781. Represented by Andy Plump at Session II. Transformation Under Plump ~15K → ~50K employees; ~10B → ~30B revenue Japan from ~50% to ~10% of both…ConceptImmune ResetThe concept that deep B-cell depletion via CAR-T or T-cell engagers can “reboot” the immune system — producing drug-free remissions in autoimmune diseases.DiseaseParkinson's DiseaseA neurodegenerative disease. Major focus of Randy Schekman and Thomas Südhof at Session IV. ASAP — Aligning Science Across Parkinson’s Founded after Schekman’s wife’s death from PD…TargetTIE2 PathwayAn endothelial receptor tyrosine kinase that maintains vascular integrity. Long considered “undruggable.” Discussed by Anthony Adamis at Session VII.PersonCarolyn BertozziBaker Family Director of Sarafan ChEM-H at Stanford. Nobel Prize in Chemistry, 2022 — for the development of bioorthogonal chemistry. Panelist at Session IV.SessionSession V — Lifetime Achievement: Carl JuneBeyond CD19 — Engineering the Next Decade of Cell Therapy Carl June (Penn) fast-forwards through what his group is building on top of CD19 CAR-T: armored cells, dual-targeted CARs for…ResearchSupporting Data Inventory — Disease2Target Pancreatic KRAS-Combination ValidationBox, not in this repo. Each row below links straight to the file. Access. The figures are held in Box under lab access control, not republished here.OrganizationUCBBiopharmaceutical company. Represented by Alistair Henry at Session I. Key Programs Discussed Bimekizumab (Bimzelx) — the headliner; dual F specificity designed at the atom level…ConceptLab in the LoopThe iterative architecture where data, AI, and experimental biology form a continuous cycle: experiment → model → predict → repeat. Articulated by Aviv Regev (Genentech) at Session II.TargetVEGFCentral target in retinal disease — necessary and sufficient for both vessel leakage and neovascularization. Career-defining work of Anthony Adamis and Napoleon Ferrara (Genentech).PersonDavid BakerHenrietta and Aubrey Davis Endowed Professor of Biochemistry, University of Washington; Director, Institute for Protein Design.SessionSession V — Lifetime Achievement: Panel DiscussionOrigin Stories from the CAR-T Pioneers Sadelain and June on how CD19 CAR-T actually got built, what nearly killed it, and what comes next. Was CD19 CAR an Obvious Bet? No.ConceptNeoantigen-Targeted Cell TherapyThe strategy of targeting tumor-specific mutations (neoantigens) with engineered T cells — the leading approach for bringing cell therapy to solid epithelial cancers.PersonJohn ReedHead of R&D at Johnson & Johnson. Presented at Session II on J&J’s “disease-area strongholds” model and persistence-driven pipeline.SessionSession V — Lifetime Achievement: Steven RosenbergForty Years of Teaching the Immune System to Kill Cancer Steven Rosenberg (Chief of Surgery Branch, NCI since 1974) traces the arc from IL-2 to TIL to the first human gene transfer to…ConceptNew Approach Methods (NAMs)Non-animal model systems for drug discovery and development — including organoids, microphysiological systems (MPS), tissue explants, patient-derived material, iPSCs, and humanized…PersonJonathan CohenBiology computing leader at NVIDIA. Presented at Session II on the compute stack coming for biology. Key Arguments Biology is accelerated computing’s next killer app Each layer …SessionSession V — Lifetime Achievement: Michel SadelainFrom a CAR Molecule to an Evolving Therapeutic Platform Michel Sadelain traces CAR-T evolution from the 1991 zeta-chain fusions through CD19 to three new designs — 1XX, HIT, and pre-TCR …ConceptProductivity ParadoxThe observation that despite unprecedented advances in science, technology, and investment, pharma R&D productivity has not improved — and may have declined.PersonKaren AkinsanyaLeader at Schrödinger. Presented at Session I on the dynamic proteome and the ceiling of structure-based drug design.SessionSession VI — Lifetime Philanthropy Award: Joan & Sandy WeillJoan & Sandy Weill: Philanthropy as a Force Multiplier in Biomedical Research Inaugural Lifetime Philanthropy Award.ConceptTranslation CliffThe persistent failure of preclinical biology to predict human outcomes — the single most common reason promising drugs die.PersonMichel SadelainFounding director of the Columbia Initiative in Cell Engineering and Therapy (CICET), previously Center for Cell Engineering at Memorial Sloan Kettering.SessionSession VII — Drug Discovery III: Repair Pathways, Receptor Engineering, and the Incretin CenturyWhen Biology Becomes the Drug: Repair, Receptor Engineering, and the Incretin Century Three architects — Anthony Adamis (Merck), Jay Bradner (Amgen), and Kenneth Custer (Lilly) — on retinal…PersonMike QuigleyR&D leader at Sanofi. Presented at Session I on the productivity paradox and decision systems for scalable discovery.SessionSession VIII — CEO Perspectives Panel DiscussionThe Industry Is At a Crossroads Three CEOs — Ashley Magargee (Genentech), Brett Monia (Ionis), Bob Bradway (Amgen) — on policy threats, healthcare costs, and industry advocacy.PersonRandy SchekmanProfessor of Molecular and Cell Biology, UC Berkeley; HHMI Investigator. Nobel Prize in Physiology or Medicine, 2013 (with James Rothman and Thomas Südhof) — for discoveries of machinery…SessionSession X — Investment Banking Perspectives: Funding Continued SuccessThe Market Is Warm, Not Hot — and That’s Exactly the Point Three senior investment bankers — Sonia Gupta (Goldman Sachs), Jerry Lee (J.P.PersonSteven RosenbergChief of the Surgery Branch at the National Cancer Institute since 1974 — still operating and still running trials. Father of cancer immunotherapy.SessionSession XI — Federal Perspectives and Washington UpdatesThe FDA Is Moving Faster Than You Think — and NIH Is Rewriting How Science Gets Done Five senior federal officials on structural shifts in the regulatory and funding environment.PersonThomas SüdhofAvram Goldstein Professor of Neurosurgery and Professor of Molecular & Cellular Physiology at Stanford. Nobel Prize in Physiology or Medicine, 2013 (with James Rothman and Randy Schekman) …SessionSession XII — Nobel Laureate Panel Discussion II: When the Molecules Don't BehaveWhen the Molecules Don’t Behave Three laureates — Thomas Südhof (2013), Brian Kobilka (2012), and David Baker (2024) — on the A-beta paradox, allosteric GPCR modulators, and de novo protein…

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