UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): September 30, 2022
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(Exact name of registrant as specified in its charter)
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(State or other jurisdiction of incorporation) | (Commission File Number) | (IRS Employer Identification No.) | ||||||||||||
(Address of principal executive offices including zip code)
Registrant’s telephone number, including area code: (650 ) 382-3281
N/A
(Former name or former address, if changed since last report)
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | |||||
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | |||||
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | |||||
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) | |||||
Securities registered pursuant to Section 12(b) of the Act:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒
Item 7.01 Regulation FD Disclosure.
Beginning on October 3, 2022, Senti Biosciences, Inc. (the “Company”) will participate in conferences with investors. A copy of the Company’s presentation slide deck that will be presented is being furnished as Exhibit 99.1 to this report on Form 8-K and has been posted to the Company’s website at https://investors.sentibio.com/events-presentations.
Limitation of Incorporation by Reference
In accordance with General Instruction B.2. of Form 8-K, the information in this report, including the Exhibit, is furnished pursuant to Item 7.01 and shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section. The information in this Item 7.01 of this Current Report on Form 8-K will not be deemed an admission as to the materiality of any information that is required to be disclosed solely by Regulation FD.
Cautionary Statements
This filing and the presentation include “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Important factors that may cause actual results to differ materially from those described in the forward-looking statements are disclosed in the “Risk Factors” contained in the Company’s Form S-1 filed with the Securities and Exchange Commission on September 12, 2022. All forward-looking statements are expressly qualified in their entirety by such factors. We do not undertake any duty to update any forward-looking statement except as required by law.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit No. | Description | |||||||
| 99.1 | ||||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |||||||
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| SENTI BIOSCIENCES, INC. | |||||||||||||||||
| Date: | September 30, 2022 | By: | /s/ Tim Lu | ||||||||||||||
| Name: | Tim Lu | ||||||||||||||||
| Title: | President and Chief Executive Officer | ||||||||||||||||
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Corporate Presentation 1 October 2022 ™
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 2 Disclaimer Forward Looking Statements This presentation contains forward-looking statements. Statements we make in this presentation may include statements which are not historical facts and are considered forward- looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are usually identified by the use of words such as “anticipates,” “believes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements relating to the preclinical, clinical and therapeutic potential of our gene circuit platform and our product candidates, including our plans to submit INDs for our product candidates, the market opportunity for our product candidates, if approved, the progress and success of our existing collaborations and our ability to enter into new collaborations, our manufacturing capabilities and our plans to begin operating our cGMP facility, our cash position and runway, and the timing of these items, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, uncertainty in the timing and results of our preclinical and clinical development activities, the risk that our product candidates may result in toxicities or adverse events that delay or preclude their further development, changes in the regulatory or competitive landscape for our product candidates and platform technology, our inability to maintain our existing collaborations or secure new partnerships, and changes in overall market conditions as well as those set forth in the section titled “Risk Factors” in our Registration Statement on Form S-1 (File No. 333-267390) filed with the Securities and Exchange Commission (the “SEC”) on September 12, 2022, and our subsequent SEC filings. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Trademarks This document contains references to trademarks, trade names and service marks belonging to other entities. Solely for convenience, trademarks, trade names and service marks referred to in this presentation may appear without the ® or TM symbols, but such references are not intended to indicate, in any way, that the applicable owner will not assert, to the fullest extent under applicable law, its rights to these trademarks and trade names. We do not intend our use or display of other entities’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other entities.
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Pipeline of CAR-NK Cell Therapies Diseases: blood cancers and solid tumors Gene Circuit advantages: Multi-Arming, selectivity and control Manufacturing: off-the-shelf, scalable with outpatient potential Platform Collaborations Precise gene therapy for eye, CNS and liver applications Targeted and controllable iPSC cell therapies for regenerative medicine 3 Pioneering Smarter Next Generation Cell and Gene Therapies Gene Circuits Multi-Arming Logic Gating (OR and NOT GATEs) Regulator Dial Smart Sensor to reprogram cells to sense, compute, and respond to disease Founded 2016 | Public June 2022 | Anticipated Cash Runway into 2024 | Headquartered South San Francisco, CA CNS: Central Nervous System
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 4 Industry-Leading Management With Top-Tier Board and Scientific Advisors Executive Team James Collins, PhD Scientific Co-Founder, MIT Wilson Wong, PhD Scientific Co-Founder, Boston University Ahmad (Mo) Khalil, PhD Boston University Martin Fussenegger, PhD ETH Zurich Scientific Advisors Michael Varney, PhD Erasca, Genentech Michael Kalos, PhD Arsenal, Janssen, Lilly Lawrence Fong, PhD UCSF Michael Andreeff, MD, PhD MD Anderson Cancer Center Robin Taylor, PhD, MBA SeaGen, Genentech Board of Directors David R. Epstein Former CEO of Novartis Pharma Omid Farokhzad, MD Seer Inc. Brenda Cooperstone, MD Pfizer Rare Disease James Collins, PhD Scientific Co-Founder, MIT Susan Berland Senior Financial Executive Ed Mathers NEA Tim Lu MD, PhD CEO & Co-Founder Tim Lu, MD, PhD CEO & Co-Founder Philip Lee, PhD CTO & Co-Founder Kanya Rajangam, MD, PhD CMDO Deb Knobelman, PhD CFO
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S CAR-NK Cell Therapy Pipeline 5
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 6 Gene Circuits Designed to Solve for Key Cell Therapy Challenges Senti’s Gene Circuit Solutions Cancer Cell Therapy Challenges Lack of NK cell expansion and persistence Antigen escape and tumor heterogeneity Dirty targets (on-target, off-tumor toxicity) Immunosuppressive tumor microenvironment Multi-Arming Autocrine and paracrine activation with proprietary Calibrated Release IL-15 and other cytokines Bivalent activating CAR with OR Logic Gate Inhibitory CAR protects healthy cells with NOT Logic Gate Pulsed Calibrated Release IL-12 with small molecule- controlled Regulator Dial Logic Gating Logic Gating Regulator Dial
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Extensive clinical experience with allogeneic donor-derived unengineered NK cells1 • Nearly 600 patients treated across 30+ single center academic trials • Well-tolerated o No (or minimal) CRS, neurotoxicity, GvHD • Anti-tumor activity observed in AML o 19% CR in 105 R/R AML patients aggregated from multiple trials Key limitations of unengineered NK cells Limited activity beyond AML, persistence, durability, donor variability and select single clinical center usage 7 NK Cells Have Compared Favorably to Current Approved T Cell Therapies In Clinical Trials Senti’s Gene Circuit technology, donor selection and scalable manufacturing address these limitations 1 Velluchamy 2017, Bachier 2021 Capabilities Current Auto T Cells Off-the-shelf potential with broad patient accessibility Designed with Logic Gates to achieve enhanced selectivity and safety Engineered with enhanced persistence ✓ ✓ ✓ Senti’s CAR-NK Cells Engineered to stimulate the patient immune system ✓
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 0 2,000 4,000 6,000 sIL-15 CAR-NK crIL-15 CAR-NK Pa ra cr in e A ct iv it y (p ST AT 5 M FI ) 8 Calibrated Release IL-15 (crIL-15) Increased Persistence and Activation of Both CAR-NK and Immune Cells in Tumor Milieu Phospho STAT5 levels increased in T cells exposed to supernatant from either crIL-15 or sIL-15 CAR-NK cell culture crIL-15: IL-15 released by local proteases → autocrine and paracrine effects crIL-15 CAR-NK Cells Unengineered NK Cells crIL-15 has paracrine activity and activates resting immune cells crIL-15 increases persistence of CAR- NK cells 0 0.2 0.4 0.6 0.8 1 0 5 10 15 20 25 V ia b le C el ls ( e6 ) Days in Culture crIL-15 increases CAR-NK serial killing compared to secreted IL-15 sIL-15: secreted wild-type IL-15 0 1 2 3 4 5 0 10 22 30 42 54 66 78 90 102 114 126 138 150 162 172 186 198 210 Tu m o r C el l A b u n d an ce Days Vehicle Unengineered NK Cells crIL-15 CAR-NK Cells sIL-15 CAR-NK Cells Cancer cells added Cancer cells added Cancer cells added
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Program Target Indications Discovery IND enabling Phase 1 Gene Circuits SENTI-202 CD33, FLT3 bivalent AML, MDS and other blood cancers ✓ Multi-Arming: designed for enhanced efficacy ✓ crIL-15: autocrine and paracrine activation ✓ OR GATE: bivalent activation ✓ NOT GATE selectivity: healthy cell protection SENTI-301 GPC3 HCC and other solid tumors ✓ Multi-Arming: designed for enhanced efficacy ✓ crIL-15: autocrine and paracrine activation ✓ Control: Regulator Dial crIL-12 SENTI-401 CEA CRC and other solid tumors ✓ Multi-Arming: designed for enhanced efficacy ✓ crIL-15: autocrine and paracrine activation ✓ NOT GATE selectivity: healthy cell protection ✓ Undisclosed: combo immune effectors Additional Programs Undisclosed Other tumors Undisclosed 2023 IND 2024 IND 9 Senti’s Next Generation CAR-NK Cell Therapy Pipeline Tackles Hard to Treat Cancers 2023 IND
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Manufacturing 10
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 11 Scalable Manufacturing to Support Off-The-Shelf Products Lentivi rus Outpatient use potential Patient Isolate from selected donors Thaw and infuse Scalable ~21 Day Process NK Cells Selected Donor Gene Circuit Engineered CAR-NK cells Engineer CryopreserveExpand Off-The-Shelf Gene Circuits 1 2 3 4 5 Easy to thaw vials Final product harvested and cryopreserved >100 doses per batch NK cells isolated from peripheral blood of selected donors NK cells efficiently engineered with Gene Circuits High post-thaw potency
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 12 Senti Selects NK Cell Donors to Support Robust Cell Expansion Senti screens and selects GMP donors using NK cell expansion and other functional attributes to minimize variability 1.E+08 1.E+09 1.E+10 1.E+11 1.E+12 1.E+13 1.E+14 1.E+15 0 10 20 30 40 To ta l N K C el ls f ro m S el ec te d S in gl e D o n o r Culture Time (Days) Senti process can potentially generate over 100 trillion NK cells from a single donor collection Preferred Donors 0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 A B C D E F G H I J K L Fo ld E xp an si o n ( 2 1 D ay s) Donors
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 13 Senti’s Cryopreservation Process Retains High Potency of CAR-NK Products Supporting Multi-Country and Multi-Site Clinical Evaluation 0 10 20 30 40 50 60 70 80 90 100 Pre-Freeze Post-Thaw % V ia b le C el ls CAR-NK cell viability retained post-thaw in vitro Vehicle Cryopreserved CAR-NK Cells In vivo activity with cryopreserved CAR NK cells in MOLM13 AML NSG mouse model (10 days after single dose)
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Pipeline Products 14
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 15 SENTI-202 for CD33 and/or FLT3 Expressing Blood Cancers Multi-Armed, off-the-shelf, selective CAR-NK • OR GATE: bivalent CD33 and/or FLT3 activation → potential for deep and durable responses in acute myeloid leukemia (AML) and other blood cancers • NOT GATE: inhibition by endomucin (EMCN) protective antigen selectively expressed on healthy cells → potential for improved safety and increased therapeutic window • crIL-15 → potential for increased persistence, autocrine and paracrine immune cell activation On track for IND in 2023 LSCs: Leukemic Stem Cells
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 16 SENTI-202 Shows Robust Preclinical Activity Broad in vitro killing of primary AML and MDS tumor cells In vivo suppression of tumor and increased mouse survival in MV4-11 AML NSG mouse model AML #1 0 10 20 30 40 50 60 70 80 90 100 Blasts LSCs Blasts LSCs Blasts LSCs Blasts % A M L/ M D S C el l K ill in g Unengineered NK Cells SENTI-202 CAR-NK Cells AML #2 AML #3 MDS 0 20 40 60 80 100 0 20 40 60 80 100 P ro b ab ili ty o f Su rv iv al Days Post Tumor Implantation Vehicle Unengineered NK Cells SENTI-202 CAR-NK Cells Group Vehicle Unengineered NK Cells SENTI-202 CAR-NK Cells Median Survival 49 55 81.5 Vehicle Unengineered NK Cells SENTI-202 CAR-NK Cells Day: 7 28 34
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 17 SENTI-202 Preclinical Selectivity via Inhibitory CAR Binding Endomucin on Healthy Primary Human Hematopoietic Stem Cells (HSCs) In vitro protection of healthy primary human HSC fraction expressing EMCN In vivo protection of EMCN+ model healthy cells Endomucin was identified and validated by bioinformatics, flow cytometry, and functional assays, and is expressed on up to 76% of HSCs, but not on leukemic stem cells or blasts CD33 and/or FLT3 CAR-NK Cells SENTI-202 CAR-NK Cells Enrichment of EMCN+ cells in NSG mouse model 3 weeks after injecting 1:1 EMCN-/+ cells with CAR-NK cells 0 10 20 30 40 50 60 CD33 and/or FLT3 CAR-NK Cells SENTI-202 CAR-NK Cells % K ill in g (L eu ke m ia ) 0 5 10 15 20 25 30 35 40 45 50 CD33 and/or FLT3 CAR-NK Cells SENTI-202 CAR-NK Cells % K ill in g (E M C N + H SC s)
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 18 Proposed Phase 1 Study in R/R CD33+ and/or FLT3+ Malignancies With Focus on AML Proposed Phase 1 study anticipated to enroll R/R CD33+ and/or FLT3+ heme malignancies • Received at least 1 prior treatment including targeted agents if FLT3, IDH1/2 mutation+ • 2 of 3 patients at each dose level with AML • Disease specific expansion cohorts for AML and MDS Planned study endpoints • Safety, DLT, identify recommended Phase 2 dose • Efficacy using standard ELN 2022 criteria for AML and other disease specific consensus criteria • PK, pharmacodynamics including endomucin protection, immunogenicity Lymphodepletion Fludarabine Cyclophosphamide SENTI-202 2-3 dose levels of cells Efficacy Additional cycles+ -5 to -3 0 7 14 28Days Planned Study Treatment/ Cycle Planned data-driven seamless Phase 1 to pivotal design 1 Seer 2020; 2 Brandwein 2020 High unmet need in patients with AML • 30.5% 5-year survival1 • 5 months median overall survival at relapse2
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 19 SENTI-301 for GPC3 Expressing Solid Tumors Multi-Armed, off-the-shelf, Regulator Dial controlled CAR-NK • GPC3 activating CAR → hepatocellular carcinoma (HCC) and other solid tumors • crIL-15 → potential for increased persistence, autocrine and paracrine immune cell activation • Pulsed crIL-12 controlled by FDA-approved drug via Regulator Dial → potential to remodel tumor micro-environment and increase anti-tumor immune responses with improved safety On track for IND in 2023
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 0 20 40 60 80 100 0 20 40 60 80 100P ro b ab ili ty o f Su rv iv al Days Post Tumor Implantation Vehicle Unengineered NK Cells crIL-15 GPC3 CAR-NK Cells 20 crIL-15 GPC3 CAR-NK Cells Preclinical Anti-Cancer Activity Group Tumor Cells Unengineered NK Cells crIL-15 GPC3 CAR-NK Cells Median Survival 48 49.5 Not reached Effective in vitro serial killing of HepG2 HCC cell line 0 1 2 3 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 Tu m o r C el l A b u n d an ce Days Vehicle Unengineered NK Cells crIL-15 GPC3 CAR-NK Cells Cancer cells added Cancer cells added Cancer cells added Proposed Phase 1 study anticipated to enroll an advanced metastatic GPC3 solid tumor population • Must have received standard of care • Advanced solid tumors with focus on HCC (70- 90% GPC3+) during dose finding • Disease specific expansion cohorts of advanced HCC and other solid tumors (29-54%2 GPC3+) including lung cancer Planned study treatment • Multi-dose and multi-cycle following conditioning • Small molecule administered as needed • 2-3 cell dose levels High unmet need in patients with liver cancer • 20.8% 5-year survival rate1 1 Seer 2020 (liver and intrahepatic bile duct cancer combined); 2 Moek 2018 Increased survival in HepG2 HCC NSG mouse model
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 21 1 10 100 1,000 10,000 100,000 0 mg/kg 50 mg/kg 100 mg/kg 0 mg/kg 50 mg/kg 100 mg/kg 0 mg/kg 50 mg/kg 100 mg/kg cr IL -1 2 ( p g /m L) Day 2 (GRZ ON) Day 9 (GRZ OFF) Day 11 (GRZ ON) Drug Drug Drug 1 Leonard 1997 crIL-12 release controlled by small molecule drug administered 2 days prior to sampling in a dose-dependent manner in vivo Vehicle GRZ 50 mg/kg GRZ 100 mg/kg Senti’s Regulator Dial Enables On-Demand Production of crIL-12 Controlled via FDA-Approved Small Molecule Drug IL-12 is a potent pro-inflammatory type 1 cytokine • Increases NK and T cell activation • Inhibits immunosuppressive cells such as tumor-associated macrophages • Responses noted with systemic administration of IL-121 IL-12 clinical use has been limited by toxicities • Narrow therapeutic window with systemic IL-12 Senti’s proprietary Regulator Dial is controlled by FDA-approved small molecule releasing crIL-12
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 22 SENTI-401 for CEA Expressing Solid Tumors Multi-Armed, off-the-shelf, selective CAR-NK • CEACAM5 (CEA) activating CAR → colorectal cancer (CRC) and other solid tumors • NOT GATE: inhibition by VSIG2 antigen on healthy epithelial cells → potential for improved safety, increased therapeutic window and reduced on- target, off-tumor toxicity • crIL-15 → potential for increased persistence and autocrine and paracrine immune cell activation • Undisclosed 4th arming → construct to further potentiate persistence, efficacy of CAR-NK cells and stimulate endogenous immune cells
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 23 Senti’s Approach to Select Paired Target and Protective Antigens Translates to Rapid Preclinical Proof of Principle 0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 Tu m o r C el l A b u n d an ce Days Vehicle Unengineered NK Cells crIL-15 CEA CAR-NK Cells Cancer cells added Cancer cells added Cancer cells added Effective in vitro serial killing of LOVO cell line by Multi-Armed CEA CAR Colorectal cancer CEACAM5 VSIG2 CEACAM5: 85-90% of CRC and 40-60% of other solid tumors including lung cancer1 VSIG2 was identified by bioinformatics using single cell RNA sequencing and validated as protective antigen with immunohistochemistry Decreased cell killing of VSIG2 expressing cells with addition of inhibitory CAR construct 1 Goldstein 2005 Healthy colon epithelium 0 10 20 30 40 50 60 70 80 90 CEA CAR-NK Cells CEA NOT VSIG2 CAR-NK Cells % T u m o r C el ls K ill ed CEA+ Cells CEA+ VSIG2+ Cells
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Platform Collaborations 24
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Program Indications Gene Circuit Discovery IND enabling Phase 1 Rights Gene Therapies for Tissue-Directed Targets GC-1001/GC-1002 Eye Smart Sensor GC-1003/GC-1004 CNS Smart Sensor GC-1005 Liver Smart Sensor Cell Therapies for Regenerative Medicine GC-1101 Regenerative Medicine Regulator Dial GC-1102 Regenerative Medicine Regulator Dial GC-1103 Regenerative Medicine Smart Sensor 25 Multiple Platform Collaborations Extend Utility of Gene Circuits
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 26 Two Collaborations to Develop Next Generation Cell and Gene Therapies AAV Gene Therapy with Cell Type-Specific Smart Sensor AAV Capsid Therapeutic Payload Low payload expression in OFF Target cell type(s) Compact promoter size to accommodate therapeutic payload transgene within ~4.5 kb AAV vector Synthetic Promoter Performance Profile: High payload expression in ON Target cell type AAV Gene Therapy with Cell Type-Specific Smart Sensor Collaboration for gene therapies Example Gene Circuits Gene Circuit-Engineered “Smart” Regenerative Medicines Senti Synthetic Promoter iPSC- derived Disease-Specific Smart Sensor1 Therapeutic Payload 2 Regulator Dial + Therapeutic Payload Oral drugOFF ON Senti’s Synthetic Promoter Collaboration for cell therapies
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 27 Smart Sensor Promoters Are Designed to Address Key Challenges in Gene Therapy Constitutive control promoter >100% strength of CAG ~10,000-fold specificity Iterative performance optimization Sp e ci fi ci ty (r at io O N :O FF t ar ge t ce ll lin es ) Strength (fraction of CAG, an industry standard constitutive promoter) Smart Sensor Promoter Data Senti’s Gene Circuit Solutions Gene Therapy Challenges Off-target tissue toxicity Sub-optimal therapeutic performance Enhance target tissue specificity and limit off-target tissue toxicity Improve expression and increase potency Smart Sensor Smart Sensor Smart Sensor Promoters designed to enable next- generation gene therapy by enhancing specificity to target tissue(s) (and thus limiting off-target tissue toxicities) and increasing strength, potentially enabling more efficacious therapies
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 28 Senti’s Gene Circuit Technology Has Broad Potential Across Modalities and Therapeutic Areas Wholly-Owned Programs with Opportunities for Future Development Opportunities for Future Development and Additional Partnering Multi-Arming Logic Gating Regulator Dial Smart Sensor Blood cancers Solid tumors Regenerative medicine Blood cancers Solid tumors Immunology Blood cancers Solid tumors Liver diseases Eye diseases CNS NK cells T cells in vivo Gene Therapy iPSCs
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Program 2022 Anticipated Milestones 2023 Anticipated Milestones SENTI-202 CD33, FLT3 bivalent AML, MDS and other blood cancers SENTI-301 GPC3 HCC and other solid tumors SENTI-401 CEA CRC and other solid tumors Present data at key scientific conferences Additional Programs Other tumors Manufacturing 29 Upcoming Value Driving Milestones Present data at key scientific conferences in 2H 2022 (e.g., ASH) File IND application in 2023 Present data at key scientific conferences in 2H 2022 (e.g., SITC) File IND application in 2023 Present dat t key scie tifi nferences Initiate preclinical work on additional CAR-NK pipeline programs Pre-clinical PoCs for additional pipeline candidates Startup of manufacturing by YE 2022 Present data at key conferences
O C T O B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Thank you! 30