Senti Biosciences Holdings, Inc. · NASDAQ:SNTI
Senti Biosciences — SPAC Merger (December 2021)
52 slides from Senti Biosciences's SPAC merger presentation, Dec 20, 2021
Slide 1: Outsmarting Complex Diseases with Intelligent Medicines: Corporate Overview
Exhibit 99.2 ™ Outsmarting Complex Diseases with Intelligent Medicines Corporate Overview December 2021
Slide 2: Disclaimer
Disclaimer This presentation (“Presentation”) is for informational purposes only to assist interested parties in making their own evaluation with respect to the proposed business combination (the “Business Combination”) between Dynamics Special Purpose Corp. (“Dynamics”) and Senti Biosciences, Inc.
Slide 3: Senti Bio
SENTI BIO Proprietary gene circuit technology platform enables the development of “smart” next-gen cell and gene therapies with enhanced efficacy, safety and control Multiple therapeutic modalities (e.g. NK cells, T cells, iPSCs, gene therapy, mRNA, etc.) offering vast opportunities Potential to add
Slide 4: Senti's Founding Team
SENTI’S FOUNDING TEAM Senti is Founded and Led by Pioneers in Synthetic Biology and Cell Technologies FOUNDING TEAM Wilson Wong, Ph.D. Tim Lu, M.D., Ph.D. Philip Lee, Ph.D. Jim Collins, Ph.D. SCIENTIFIC ADVISOR CEO CTO SCIENTIFIC ADVISOR SENTI FOUNDERS’ AFFILIATIONS WORLD-CLASS COMPANY FOUNDERS REPR
Slide 5: Biology's Challenges
BIOLOGY’S CHALLENGES Today’s Cell and Gene Therapies Cannot Resolve Fundamental Disease Challenges …AND CANNOT OVERCOME FUNDAMENTAL CURRENT CELL AND GENE THERAPIES ARE SIMPLISTIC… DISEASE CHALLENGES Unable to precisely distinguish TARGET HETEROGENEITY diseased versus healthy cells CAR-NK CAR-T Unabl
Slide 6: Gene Circuit Platform Technology
GENE CIRCUIT PLATFORM TECHNOLOGY Senti’s Gene Circuits Use Biological Computation to Solve Biological Problems Genetic Parts Gene Circuits Gene Networks Transcription factor Evolution has Evolution has selected for selected for natural natural genetic circuits. genetic circuits Target gene and bindi
Slide 7: Senti's Design-Build-Test-Learn (DBTL) Process
SENTI’S DESIGN-BUILD-TEST-LEARN (DBTL) PROCESS Powerful and Scalable Engine Optimizes Gene Circuits to Enable Creation of Intelligent Medicines SENTI’S DESIGN-BUILD-TEST-LEARN ENGINE LEARN Central Knowledge Database Biological Data Optimized DESIGN BUILD TEST Gene Circuits Disease Indication Teams,
Slide 8: Senti's Gene Circuit Solutions
SENTI’S GENE CIRCUIT SOLUTIONS Senti’s Gene Circuit Platform is Designed to Overcome Fundamental Disease Challenges FUNDAMENTAL DISEASE CHALLENGES… …ARE TACKLED THROUGH INTELLIGENT GENETIC PROGRAMMING Integrates multiple targets to pinpoint diseased cells and spare TARGET HETEROGENEITY LOGIC GATING
Slide 9: Gene Circuits Software Platform Is Broadly Applicable
WE BELIEVE THAT OUR GENE CIRCUITS SOFTWARE PLATFORM IS BROADLY APPLICABLE Gene Circuits Could Potentially Power Multiple Cell and Gene Therapy Modalities for Broad Therapeutic Potential Diverse Modalities CAR OR CAR NOT Logic Gate Gate Gating NK Cells T Cells AAVs Combo Calibrated Multi Effector Rel
Slide 10: Logic Gating Enables Highly Specific Therapies
SENTI’S GENE CIRCUITS Logic Gating Enables Highly Specific Therapies by Recognizing Multiple Antigens Toolbox of TUMOR-ASSOCIATED ANTIGENS (TAA) SAFETY ANTIGEN ENGAGEMENT Gene Circuits ENGAGEMENT TRIGGERS CANCER CELL KILLING ENABLES PROTECTION OF HEALTHY CELLS SENTI NOT-GATE CANCER CELL SENTI NOT-GA
Slide 11: NOT Logic Gate Functions In Vivo to Kill Cancer Cells
SENTI’S GENE CIRCUITS NOT Logic Gate Functions In Vivo to Specifically Kill Cancer Cells and Spare Healthy Cells Toolbox of NOT-GATED CAR-NK CELLS REDUCE RESULTING IN ENRICHMENT Gene Circuits NOT-Logic-Gated Healthy Cancer 50:50 KILLING OF HEALTHY CELLS OF HEALTHY CELLS CAR-NK Cells Cells Cells Canc
Slide 12: Multi-Arming Circuits Enable All-in-One Combination Therapies
SENTI’S GENE CIRCUITS Multi-Arming Circuits Enable All-in-One Combination Cell and Gene Therapies Toolbox of Multiple Immune Gene Circuits Stimulators: Central Knowledge LEARN Database Logic IL15 Gating IL21 IL7 Biological Data IL18 Multi Optimized Arming IL12 Gene DESIGN BUILD TEST Circuits [….] Di
Slide 13: Multi-Armed CAR-NK Cells Improve Killing of Cancer Cells
SENTI’S GENE CIRCUITS Multi-Armed CAR-NK Cells Exhibit Significantly Improved Killing of Cancer Cells TUMOR CELL KILLING Toolbox of IN VITRO TUMOR CELL KILLING (INCUCYTE) (day 5 post co-culture, 2:1 ratio) Gene Circuits Tumor cells alone CAR-NK (no cytokines) CAR-NK + cytokine 1 CAR-NK + cytokine 2
Slide 14: Regulator Dial Circuit Controls Cell Therapies Using FDA-Approved Drugs
SENTI’S GENE CIRCUITS Regulator Dial Circuit Potentially Enables Control of Cell Therapies Using FDA- Approved Drugs Toolbox of OFF MULTIPLE DRUG ON Gene Circuits SWITCHES: Logic • HCV protease inhibitors Gating • IMiDs Little/no immune Multi • Tamoxifen Arming effectors secreted in absence of small
Slide 15: Regulator Dial Enables ~90-fold ON/OFF Control of IL-12 Secretion
SENTI’S GENE CIRCUITS Regulator Dial Enables ~90-fold ON/OFF Control of IL-12 Secretion In Vivo STUDY DESIGN Toolbox of Immune deficient NSG mice Gene Circuits ± Logic GRZ 75 mg/kg Vehicle or dGR oseZ Dosed dose No Vehicle or GRZ Dosed 1/2 dose dose dose Gating or vehicle Day -2 -1 0 1 2 3 4 8 Rando
Slide 16: Smart Sensors Enable Precise Recognition of Diseased Cells
SENTI’S GENE CIRCUITS Smart Sensors Enable Precise and Dynamic Recognition of Diseased Cells Toolbox of CURRENT GENE THERAPIES LACK SPECIFICITY FOR SPECIFIC DISEASED CELL TYPES Gene Circuits ON-target cells OFF-target cells Logic Gating Differential transcription factor profiles between cell types M
Slide 17: Smart Sensor Promoters Enable up to 1,000-fold Selectivity
SENTI’S GENE CIRCUITS Smart Sensor Promoters Enable up to 1,000-fold Selectivity for Diseased Cells SIGNALS SUCH AS GENE THERAPY WITH TRANSGENE EXPRESSION Toolbox of TRANSCRIPTION FACTOR(S) UP TO ~1,000X CELL TYPE SELECTIVITY Gene Circuits Logic Gating 100,000x * * 10,000x Multi 1,000x Arming 100x 1
Slide 18: Gene Circuit Enabled Pipeline
PIPELINE Gene Circuit Enabled Pipeline With Additional Collaboration Opportunities Modality Gene Circuit Name Indication Discovery Preclinical Phase 1 Phase 2 Phase 3 Rights Acute Myeloid SENTI-202 Leukemia SENTI-401 Colorectal Cancer Logic Gating SENTI-411 Solid Tumors Allogeneic SENTI-421 Solid/Li
Slide 19: Why NK Cells?
WHY NK CELLS? Natural Killer (NK) Cells are an Ideal Modality for Gene-Circuit Enhanced Cancer Cell Therapy Innate Killing Immune Activation Favorable Safety Broad Access Clinical Validation ü Natural ability to ü Proinflammatory ü Low/no incidence ü Does not require ü MD Anderson CD19 kill tumor ce
Slide 20: Proprietary Calibrated Release IL-15
PROPRIETARY CALIBRATED RELEASE IL-15 Senti’s Proprietary Calibrated Release IL-15 (crIL-15) Enhances NK Cell Persistence and Tumor Killing crIL-15 ENABLES BOTH AUTOCRINE AND PARACRINE SIGNALING crIL-15 IMPROVES NK PERSISTENCE AND SERIAL KILLING Tumor cells alone Unengineered NK cells Un-engineered N
Slide 21: SENTI-202: Logic-Gated CAR-NK Cells for AML
SENTI-202: LOGIC-GATED CAR-NK CELLS FOR PRECISION TARGETING OF AML SENTI-202: Designed to Address Unmet Needs in the Treatment of Acute Myeloid Leukemia (AML) Toolbox of SENTI’S LOGIC GATES SOLVE KEY DISEASE CHALLENGES IN AML UNMET NEED IN AML Gene Circuits CHALLENGES SENTI GENE CIRCUIT SOLUTIONS 1
Slide 22: SENTI-202 Summary
SENTI-202 SUMMARY SENTI-202: Potential to Develop a Cure With No Bone Marrow Transplant Needed PRODUCT SCHEMATIC FLT3 OR CD33 EMCN CAR OR CAR NOT Logic aCAR iCAR Gate Gate Gating Combo Calibrated Multi Effector Release crIL-15 Arming Gene Circuit SM-regulated Promoter Regulator Dial Cell-type Cell-s
Slide 23: SENTI-202 OR/NOT Logic Gating
SENTI-202 OR/NOT LOGIC GATING SENTI-202 OR/NOT Logic Gating: Deep Clearance of AML Blasts and AML LSCs While Sparing Healthy Hematopoietic Stem Cells (HSCs) FLT3 OR CD33 ENGAGEMENT TRIGGERS EMCN ENGAGEMENT ENABLES KILLING OF HETEROGENEOUS AML CANCER CELLS PROTECTION OF HEALTHY HSCs SENTI-202 CAR- AM
Slide 24: OR Gate: FLT3 OR CD33 CAR-NK Cells Suppressed Tumor Growth
OR GATE: CAR-MEDIATED NK CELL KILLING FLT3 OR CD33 CAR-NK Cells Significantly Suppressed Tumor Growth, Reduced Tumor Burden and Improved Survival Day 30 p-values MV4-11-BASED AML Moderate Significant No Cancer (3) vs (2): p < 0.05 XENOTRANSPLANTATION MODEL Tumor Load Tumor Load (3) vs (1): p < 0.01
Slide 25: NOT Gate Discrimination Study: FLT3 Cancerous vs EMCN+ Healthy Cells
NOT GATE DISCRIMINATION STUDY: FLT3 CANCEROUS CELLS VS EMCN+ HEALTHY CELLS EMCN iCAR Constructs Demonstrate Functional NOT GATE Protection of Model Healthy Cells KEY TAKEAWAYS CAR-NK cells without an EMCN- specific NOT GATE kill both FLT3+ 1:2 (E:T) ratio; 18hrs FLT3+ FLT3+ EMCN+ and FLT3+EMCN+ cell
Slide 26: NOT Gate Discrimination Study: AML Cells vs Primary Healthy Blood Stem Cells
NOT GATE DISCRIMINATION STUDY: AML CANCER CELLS VS PRIMARY HEALTHY BLOOD STEM CELLS SENTI-202 Product Candidate Protects Primary Donor HSCs While Maintaining On- Target Killing of Cancer Cells EMCN NOT-GATE CAR-NK CELLS EFFECTIVELY KILL EMCN NOT-GATE CAR-NK CELLS PROTECT AML CANCER CELLS HEALTHY HSC
Slide 27: SENTI-301: CAR-NK Cells for Treatment of HCC
SENTI-301: CAR-NK CELLS WITH MULTI ARMING AND REGULATOR DIAL CIRCUITS FOR ENHANCED TREATMENT OF HCC SENTI-301: Addressing Unmet Needs in the Treatment of Hepatocellular Carcinoma (HCC) SENTI’S MULTI-ARMING AND REGULATOR DIAL Toolbox of GENE CIRCUITS SOLVE KEY DISEASE CHALLENGES IN HCC UNMET NEED IN
Slide 28: SENTI-301 Summary
SENTI-301 SUMMARY SENTI-301 Aims to Safely Overcome the Immunosuppressive Tumor Micro-Environment for Patients with R/R HCC PRODUCT SCHEMATIC GPC3 CAR-NK + Regulated, Multi Arming CAR OR CAR NOT Logic Regulated Gate Gate Gating Payload IL-12 Expression for Safety & Control Combo Calibrated Multi Eff
Slide 29: SENTI-301 Regulated, Multi-Arming Gene Circuit
SENTI-301: ADDRESSING UNMET NEEDS WITH REGULATED, MULTI-ARMING GENE CIRCUIT SENTI-301 Multi-Arming Approach is Designed to Attack Cancer in Multiple Complementary Ways IMPROVE CAR-NK PERSISTENCE AND EFFECTOR FUNCTIONS WITH OPTIMIZED IMMUNE CELL RECRUITMENT AND DIRECT KILLING crIL-15 SIGNALING TUMOR
Slide 30: SENTI-301 Cancer Killing and Preclinical Confirmation
SENTI-301: ADDRESSING UNMET NEEDS WITH REGULATED, MULTI-ARMING GENE CIRCUIT SENTI-301 Cancer Killing Demonstrates Multi-Arming and Regulator Dial Approaches Confirmed with Preclinical Studies IMPROVE CAR-NK PERSISTENCE AND EFFECTOR FUNCTIONS WITH OPTIMIZED IMMUNE CELL RECRUITMENT AND DIRECT KILLING
Slide 31: CAR-NK Manufacturing
CAR-NK MANUFACTURING Senti’s Allogeneic Manufacturing Designed to Enable Widespread Distribution Senti Anticipates Scalable ~21 Day Process to Manufacture NK Cell Product With Off-the-Shelf Availability for Patients 1 2 3 4 5 6 Starting Cells Gene Modification Expansion Freezing & Prescription Infus
Slide 32: NK Manufacturing Strategy
NK MANUFACTURING Strategy to Build, Control, and Scale In-House GMP Allogeneic Cell Manufacturing Pivotal/Commercial Clinical Expansion of manufacturing Flexible cell facility for GMP manufacturing, product testing, and Development therapy suites to commercial support Phase 1/2 storage (~92,000 sf)
Slide 33: Manufacturing Collaboration
MANUFACTURING COLLABORATION Senti May Seek to Leverage its GMP Facility to Expand Synthetic Biology Enabled Biomanufacturing Through a Partnership ILLUSTRATIVE BIOMANUFACTURING DEAL STRUCTURE Senti Gets: Therapeutic Applications o Operational control of part of the GMP facility for its use o Expansi
Slide 34: Current Cell Therapies Inadequately Address Cancer Challenges
CURRENT CELL THERAPIES INADEQUATELY ADDRESS FUNDAMENTAL CHALLENGES IN CANCER Today’s Cell Therapies Cannot Resolve Key Cancer Challenges CURRENT AUTO CURRENT ALLO SENTI’S GENE CIRCUIT CURRENT ALLO CAPABILITIES T CELLS NK CELLS ENHANCED ALLO NK CELLS T CELLS POTENTIAL FOR OFF-THE-SHELF ADMINISTRATION
Slide 35: Spark Collaboration
SPARK COLLABORATION Spark Therapeutics Collaboration Will Leverage Smart Sensor Gene Circuit Technology to Develop Potential Next-Generation Precision Gene Therapies ILLUSTRATIVE PRODUCT SCHEMATIC DEAL SUMMARY AAV Gene Therapy with Cell Type-Specific Smart Sensor o Collaboration & option: Senti will
Slide 36: BlueRock Collaboration
BLUEROCK COLLABORATION Senti Entered Into a Collaboration with BlueRock Therapeutics to Develop Potential Next-Generation Regenerative Medicines ILLUSTRATIVE PRODUCT SCHEMATIC DEAL SUMMARY Gene Circuit-Engineered “Smart” Regenerative Medicines = Collaboration & Option: Senti will design, build, and
Slide 37: Use of Proceeds
USE OF PROCEEDS Over $290mm of Gross Proceeds in Combined SPAC and PIPE Financing Multiple Key Milestones Expected to be Achievable Into 2025 Pro Forma Cash of $326M Provides Runway o Present SENTI-301, SENTI-202, and SENTI-401 IND-enabling Into 2025 pharmacological data at key scientific conference
Slide 38: Progress & Upcoming Milestones
PROGRESS & UPCOMING MILESTONES YTD Progress Sets The Stage For Upcoming Value Driving Milestones 2021 YTD Achievements Anticipated 2022 Milestones Anticipated 2023 Milestones Data readouts: Present SENTI-301 and SENTI-202 IND-enabling File INDs for SENTI-301 and Presented pre-clinical POC data at AA
Slide 39: Management Team
MANAGEMENT TEAM Industry-leading Management with Top-tier Board, Scientific Advisors and Investors 1 EXECUTIVE TEAM Tim Lu, M.D., Ph.D. Philip Lee, Ph.D. Jose Iglesias, M.D. Curt Herberts, M.B.S. Deb Knobelman, Ph.D. CTO & CO-FOUNDER CEO & CO-FOUNDER CHIEF MEDICAL ADVISOR COO CFO BOARD OF DIRECTORS
Slide 40: SPAC Team
SPAC TEAM Dynamics is Led by an Experienced Team with a Track Record of Success Executive Experience Background o Founder, Chair, and CEO of Seer in 2017, advancing a transformative proteomics platform Omid Farokhzad o Previously co-founded Selecta Biosciences, Tarveda Therapeutics, and BIND Therape
Slide 41: Transaction Overview
TRANSACTION OVERVIEW A Compelling Transaction for All Stakeholders → Exposure to new class of biotech with a novel modality-agnostic drug development platform backed by groundbreaking science → SPAC + PIPE firepower enables multi-year runway through clinical POC 1 Sources and Uses ($mm) Pro-forma Va
Slide 42: Closing Remarks
SENTI BIO Closing Remarks Senti is the pioneer in therapeutic synthetic biology Our gene circuits are biological software that are designed to power next-gen cell and gene therapies Senti’s deep differentiated allogeneic CAR-NK pipeline has the potential to address key unmet needs in cancer, includi
Slide 43: Appendix
SENTI BIO Appendix
Slide 44: Scientific Advisory Board (SAB)
SCIENTIFIC ADVISORY BOARD (SAB) Senti is Founded by a World Class Team and Supported by an Advisory Board of Pioneers in Cell and Gene Therapy SENTI “SYNTHETIC BIOLOGY” ADVISORS SENTI “CLINICAL AND COMMERCIAL” ADVISORS Michael Varney, PhD Jim Collins, Ph.D. CHAIR OF R&D, SAB MEMBER AND PROFESSOR, MI
Slide 45: Starting Cells
STARTING CELLS Multiple Potential NK Cell Sources Are Available for Clinical Application Cell Source iPSC Cord Blood Peripheral Blood Multiple clinical networks for Requires generation of GMP iPSC A few established cord blood banks Supply Chain qualified donors with extensive use in bank(s) from qua
Slide 46: CAR-NK Cell Manufacturing Process
CAR-NK CELL MANUFACTURING PROCESS Robust Manufacturing Process Designed to Support All Internal Programs with 1 GMP Production of Allogeneic CAR-NK Cells Engineered with Proprietary crIL-15 EXPANSION CRYOPRESERVATION PERSISTENCE Greater than 6,000-fold expansion Pre-freeze and post-thaw cells have i
Slide 47: Tumor-Associated Antigen and Safety Antigen Paired Discovery Platform
TUMOR-ASSOCIATED ANTIGEN AND SAFETY ANTIGEN PARIED DISCOVERY PLATFORM Senti Developed a Powerful Tumor-Associated Antigen and Safety Antigen Paired Discovery Platform to Generate Targets for New Logic-Gated CAR-NK Candidates Tumor-Associated Antigen discovery Expression in Healthy tissue tumor cells
Slide 48: SENTI-202 NOT Gate Safety Antigen Candidates
TUMOR-ASSOCIATED ANTIGEN AND SAFETY ANTIGEN PARIED DISCOVERY PLATFORM SENTI-202 NOT GATE Safety Antigen Candidates Were Identified Through Senti’s Bioinformatics Approach SHORT LIST OF TARGET SAFETY ANTIGENS 1. Antigen 1 2. Antigen 2 20,216 3. Antigen 3 Protein 7,860 115 15 Coding 20,216 Genes Prote
Slide 49: Flow Cytometry for Healthy HSCs and AML LSCs: EMCN+ and EMCN-
FLOW CYTOMETRY FOR HEALTHY HSCs AND AML LSCs: EMCN+ AND EMCN- Senti Identified a NOT GATE Safety Antigen Called EMCN That Distinguishes AML LSCs From Healthy HSCs HEALTHY HSCs (FROM HEALTHY DONOR) AML LSCs (FROM AML PATIENT) KEY TAKEAWAYS • The ‘NOT GATE’ uses EMCN as a Safety Antigen input to diffe
Slide 50: SENTI-401: Logic-Gated and Multi-Armed CAR-NK Cells for CRC
SENTI-401: LOGIC-GATED AND MULTI-ARMED CAR-NK CELLS FOR PRECISION CRC TREATMENT SENTI-401: Addressing Unmet Needs in the Treatment of Colorectal Cancer (CRC) Toolbox of SENTI’S LOGIC GATES SOLVE KEY DISEASE CHALLENGES IN CRC UNMET NEED IN CRC Gene Circuits Previous CEA therapies Challenges Senti Gen
Slide 51: SENTI-401: CEA aCAR Anti-Tumor Activity
SENTI-401: CEA aCAR ANTI-TUMOR ACTIVITY + SENTI CAR-NK Cells Efficiently Kill CEA CRC cells CEA-CAR EXPRESSION CRC CANCER CELL KILLING 100 Tumor cells alone 500K 80 84.7% Unengineered NK 400K Cells SENTI CAR-NK 60 300K 200K 40 100K 20 0K 5 0 10 0 CAR expression 0 20 40 60 80 100 120 140 Elapsed time
Slide 52: SENTI-401: VSIG2 as Safety Antigen for CEA CAR-NK
SENTI-401: VSIG2 AS SAFETY ANTIGEN FOR CEA CAR-NK Senti Discovered VSIG2 as a Safety Antigen that is Highly Expressed in Healthy Epithelial Cells, but not in CRC Tumor Cells TUMOR-ASSOCIATED ANTIGEN: CEA SAFETY ANTIGEN: VSIG2 HEALTHY COLON COLORECTAL TUMOR 52 Source: Internal data Exhibit 99.3 Dynam