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SENTI-202 Initial Clinical Data December 2024 Disclaimer 2 Forward Looking Statements This presentation contains forward-looking statements of Senti Biosciences, Inc. ("we," "us," "our") within the meaning of the Private

Key Takeaway: Senti Biosciences, Inc. has provided updates regarding its investigational product SENTI-202, a potential NK cell therapy for acute myeloid leukemia (AML). Initial clinical data indicates promising efficacy, with some patients achieving complete remission. However, the company also highlights risks related to ongoing clinical trials and external economic factors that may impact development. Financing has been secured to further pursue SENTI-202's clinical development milestones, with initial data expected by year-end 2024.

Market Sentiment Analysis

POSITIVE FACTORS

  • SENTI-202 shows potential as a first-in-class NK cell therapy for blood cancers.
  • Initial clinical data indicates promising results, including complete remission in some patients.
  • The company has secured financing to support further development of SENTI-202.

CONCERNS & RISKS

  • Results from ongoing and future studies may not replicate the initial findings.
  • Clinical development could be delayed due to regulatory or manufacturing challenges.
  • The impact of macroeconomic factors and geopolitical events could affect operations.

Full Press Release Details

SENTI-202 Initial Clinical Data December 2024
Disclaimer 2 Forward Looking Statements This presentation contains
forward-looking statements of Senti Biosciences, Inc. ("we," "us," "our") within the meaning of the Private Securities Litigation Reform Act of 1995. 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," "future," "objective," "opportunity," "potential," "proposed," "targets," "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 regarding attributes and benefits of our technology platform and of our product candidates, including their therapeutic potential; our
clinical trials, including trial design and endpoints, our ability to achieve such endpoints, our plans to transition our Phase 1 clinical trial of SNTI-202 to a pivotal study, the timing of initial clinical efficacy data and durability data from
our ongoing clinical trial; our manufacturing process and its potential benefits; our current and anticipated cash runway; the potential use of proceeds; and, 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. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on as a
guarantee, an assurance, a prediction or a definitive statement of fact or probability. 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. Many actual events and circumstances are difficult or impossible to predict, are beyond our control and will differ from
assumptions. 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, the risk that
results observed in studies of our product candidates, including preclinical studies and future clinical trials of any of our product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk that
we may cease or delay clinical development of any of our product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, the amount and type of
data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current and planned clinical trials, difficulties in manufacturing or supplying our product candidates for
preclinical and clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), our ability to obtain, maintain and protect our intellectual property, our dependence on third
parties for development and manufacture of product candidates, our ability to manage expenses and to obtain additional funding when needed to support our business activities and establish and maintain strategic business alliances and new business
initiatives, the impacts of macroeconomic and geopolitical events, the hostilities in Ukraine and Gaza, increasing rates of inflation and rising interest rates on business operations and expenses, and the risks that our product candidates may not
produce therapeutic benefits or may cause other unanticipated adverse effects, as well as those set forth in the section titled "Risk Factors" of Senti Bio's most recently filed periodic report, and other documents filed by Senti Bio from time to
time with the SEC. 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. This presentation includes statistical and other
industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties as well as our own estimates of potential market opportunities. All of the market data used involves a number of
assumptions and limitations, and you are cautioned not to give undue weight to such data. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be
reliable, although they do not guarantee the accuracy or completeness of such information. Our estimates of the potential market opportunities for our product candidates include several key assumptions based on our industry knowledge, industry
publications, third-party research and other surveys, which may be based on a small sample size and may fail to accurately reflect market opportunities. While we believe that our internal assumptions are reasonable, and management is responsible
for the accuracy of such assumptions and data, no independent source has verified such assumptions. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of
these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.
SENTI-202 Initial Clinical Data Corporate and Clinical Results Overview Tim Lu,
MD, PhD CEO and Co-Founder, Senti Biosciences 3
Senti's Gene Circuits Designed to Enhance Precision, Control, and Activity of Cell
& Gene Therapies NK: Natural Killer; TME: Tumor Microenvironment 4 Multi-Arming Regulator Dial Smart Sensor Logic Gating Sense diseased vs healthy cells (e.g., SENTI-202) Stimulate immune cells, overcome TME, promote NK cell
function (e.g., SENTI-301A) Dial payload expression up/down (e.g., BlueRock collaboration programs) Cell/disease-specific promoters (e.g., Spark collaboration programs) Therapeutic transgene expressed Gene Circuits
Internal Focus on Oncology, Partnering to Support Non-Oncology Indications AML:
Acute Myeloid Leukemia; CNS: Central Nervous System; HCC: Hepatocellular Carcinoma; MDS: Myelodysplastic Syndrome 1 Collaboration with Celest for clinical development to treat solid tumors in China, with an option to expand to Hong Kong, Macau,
and Taiwan 5 Programs Target Application Preclinical Early Stage Clinical Late Stage Clinical Collaborator SENTI-202 CD33 and/or FLT3 AML, MDS and other blood cancers SENTI-301A1 GPC3 HCC and other solid tumors Multiple Gene
Therapy Programs Undisclosed Eye, CNS and liver diseases Multiple iPSC Cell Therapy Programs Undisclosed Regenerative medicine
SENTI-202 Is a Potentially First-In-Class Selective Off-the-Shelf Investigational NK
Cell Therapy for Blood Cancers 6 Logic Gating to overcome AML heterogeneity via clinically validated CD33 and FLT3 targets Logic Gating also to spare healthy cells via EMCN target, which is selectively expressed on HSCs SENTI-202 is designed
to integrate validated mechanisms into one solution,engineered to solve key outstanding problems in AML Completion of private placement financing will allow us to continue SENTI-202 clinical development, and obtain additional efficacy and
durability data SENTI-202 Approach First patient dosed in 2Q 2024 Initial clinical data year-end 2024 2 of 3 R/R AML patients with MRD negative CR at first dose level 2024 Accomplishments CR: Complete Remission; EMCN: Endomucin; HSC:
Hematopoietic Stem Cell; LSC: Leukemic Stem Cell; MRD: Measurable Residual Disease
SENTI-202 Initial Clinical Data Unmet Need in Acute Myeloid Leukemia (AML) Stephen
A. Strickland, MD, MSCI Director of Leukemia Research, Sarah Cannon Research Institute 7
AML Is an Aggressive Leukemia with Poor Prognosis Rapidly progressing blood cell
cancer with clonal proliferation of leukemic blasts from myeloid lineage Initial treatment includes intensive chemotherapy followed by HCT for younger, fit patients and venetoclax/ HMA based therapy for older, unfit patients Most patients will
eventually relapse even with intensive therapy1,2 At relapse, ~20-30% CR with full hematologic recovery is reported with targeted agents in patients with FLT3/IDH1/2 mutations1 or with salvage chemotherapy2 Diseased bone marrow Median survival
of 5.3 months2 5-year survival rate is 12.6%2 R/R AML patient outcome AML: Acute Myeloid Leukemia; CR: Complete Remission; HCT: Hematopoietic Cell Transplantation; HMA: Hypomethylating Agents; R/R: Relapsed/Refractory 1 Dohner Blood 2022;
2 Brandwein AJBR 2020 8
There are Multiple Challenges to Developing Effective AML Therapies 1 Hansen Cancer
Drug Resistance 2022 9 Durability of response is limited due to: Leukemic cell clonal heterogeneity which requires use of multi- targeted and combination therapies Leukemia stem cells (LSCs), a small population with stem cell features such as
being undifferentiated, drug resistant and with capacity to self-renew are held to be responsible for relapse initiation even with bulk AML blast clearance1 Treatment tolerability limitations due to: Healthy hematopoietic cell toxicity from
limitations with AML targets that are often present on healthy hematopoietic stem cells (HSC)1 Overlapping toxicity profiles of approved AML therapies including bone marrow toxicity limits combination and sequential use of therapy Major
treatment challenges: Disease heterogeneity/ lack of LSC targeting 1 Limits response duration/ survival 2 Off-tumor/ On-target healthy cell toxicity 3 Limits treatment tolerability and dosing 4
Achieving Deep Responses and Blood Count Recovery in AML Correlates with Longer
Survival 1 Dohner Blood 2022; 2 Innes Blood 2018 10 Detection of measurable residual disease (MRD) in patients with CR by conventional methods correlates with shorter remissions and poorer survival1 Measurement of MRD is not standardized
across care centers currently with common methods used including multi-parametric flow cytometry, next generation sequencing (NGS), PCR in AML with specific mutations Achieving MRD negative status correlates with longer remissions and increased
survival Achievement of CR with full count recovery correlates with better prognosis compared to CR with incomplete or no count recovery2 CR includes bone marrow blasts <5% along with neutrophils 1.0 x 109/L (normal range 2.5-7.5 x 109/L)
and platelets 100 x 109/L (normal range 150-400 x 109/L) Effective AML Therapies: Achieve deep/MRD negative CR 1 Leads to durable remissions/ longer survival 2 Selectively kill AML blasts 3 Robust blood count recovery 4
SENTI-202 Initial Clinical Data Clinical Trial Data Kanya Rajangam, MD, PhD
President, Head of R&D and CMO, Senti Biosciences 11
Cancer cellkilling Blast cell LSC FLT3 CD33 SENTI-202 Is a Potentially
First-In-Class Selective Off-the-Shelf Investigational NK Cell Therapy for Blood Cancers 12 Activating CAR "kill" signal Bivalent CD33 and/or FLT3 CAR targets validated AML targets Potential for deep and durable responses in AML and other
blood cancers Inhibitory CAR "protect" signal Inhibition by endomucin (EMCN) protective antigen EMCN selectively expressed on healthy hematopoietic stem cells (HSCs) for potentially improved safety and increased therapeutic window Calibrated
release IL-15 Cell expansion, persistence, and tumor killing Designed to address key AML therapeutic challenges Bivalent CD33 and/or FLT3 activating CAR FLT3 EMCN CD33 Healthy cell protection Calibrated release IL-15 Endomucin inhibitory
CAR to protect healthy cells Persistence, activation of CAR-NK and immune cells Healthy NK cells from selected adult donors
SENTI-202 Phase 1 Trial (SENTI-202-101) Design1High starting dose based on NK
tolerability profile designed to enable early efficacy signal detection DLT: Dose Limiting Toxicity; R/R: Relapsed Refractory 1 NCT06325748; 2 1-2 prior for MDS 13 Adult patients R/R CD33 and/or FLT3 expressing heme malignancies 2 of 3
patients at each dose level with AML Received 1-32 prior AML treatments including targeted agents if FLT3, IDH1/2 mutation+ Patient Population "3+3" study design Dose escalation followed by disease-specific expansion cohorts for AML and
MDS Starting dose 1x109 CAR+ NK cells and target dose 1.5x109 CAR+ NK cells Plans to transition from Phase 1 to pivotal study Study Design Safety, DLT, identify recommended Phase 2 dose Efficacy, including bone marrow recovery and
MRD Pharmacokinetics (PK), pharmacodynamics (PD), biomarkers to supplement efficacy and immunogenicity Planned Endpoints 28 Day -7 -3 0 7 14 SENTI-202 2 dose levels Efficacy Additional cycles+ Multi-Dose
Cycle Lymphodepletion Flu/Ara-C
SENTI-202-101 Clinical Study Program OverviewEarly efficacy signals noted at the
first dose level 14 Enrollment Dose Level 1 (1 billion CAR+ NK cells/dose) cleared: 3 R/R AML patients enrolled Dose Level 2 (1.5 billion CAR+ NK cells / dose) cohort actively enrolling Safety Data SENTI-202 is well tolerated with a
tolerability profile consistent with other investigational NK cell therapies, and patients with underlying AML receiving lymphodepleting chemotherapy Efficacy Data 2/3 patients Mutation Neg/ MRD Neg CR (including 1 with adverse risk
genetics) 1/3 patient no response/ progressive disease PK SENTI-202 transgene consistently detected in the periphery in all 3 of the 1 billion CAR+ NK cells / dose patients Data from an open clinical database of an ongoing study and PI/ site
communication as of 19Sep2024
SENTI-202-101 Time on StudyEarly efficacy signals noted at the first dose level,
both CR patients continue in CR at 1+ month 15 NGS: Next-generation sequencing; MRD: measurable residual disease Data from an open clinical database of an ongoing study and PI/ site communication as of 19Sep2024
SENTI-202-101 Patient 1First Patient with CR after 2 cycles and clearance of all
AML mutations by NGS Data from an open clinical database of an ongoing study and PI/ site communication 16 Blast reduction <5% for CR ANC: Absolute Neutrophil Count; PLT: Platelet Count Data from an open clinical database of an ongoing
study and PI/ site communication as of 19Sep2024 26F with adverse-risk R/R AML (MDS related gene mutations) relapsed after intensive chemotherapy and prior HCT SENTI-202 well tolerated with no DLT/ AEI AEs include G4 hematologic toxicity
consistent with lymphodepletion that resolved with AML response, and G3 infections Patient continues in CR with ~ 2 months follow up Cycle 1 Cycle 2 Normocellular Marrow (60%) Hypocellular Marrow (10%) Normocellular marrow (80%) with
trilineage hematopoiesis ANC/PLT recovery threshold for CR
SENTI-202-101 Patient 2Second Patient with MRD- CR by MRD flow cytometry after 1
cycle 17 72M with FLT3 mutated (intermediate risk) R/R AML that relapsed after intensive chemotherapy and FLT3 inhibitor SENTI-202 well tolerated with no DLT/ SAEs AEs include G4 hematologic toxicity consistent with lymphodepletion that
resolved with AML response, and G2 fever (CRS) that resolved with supportive care Patient is currently receiving a second cycle as consolidation therapy Cycle 1 ANC: Absolute Neutrophil Count; PLT: Platelet Count Data from an open clinical
database of an ongoing study and PI/ site communication as of 19Sep2024 Blast reduction <5% for CR ANC/PLT recovery threshold for CR Hypercellular Marrow (80%) Hypercellular marrow (80%), no increase in blasts
SENTI-202 Initial Correlative DataSENTI-202 is detected in the peripheral blood
across all patients 18 Copies/ g DNA Time (Days) LLOQ Copies/ g DNA SENTI-202 doses SENTI-202 pharmacokinetics across 3 patients Interim data as of 19 Sep2024 Nominal value of 1 assigned for timepoints with non-measurable transgene LLOQ
extrapolated from copies/ reaction and is the lower limit of quantitation Patient 1 Cycle 1 Patient 1 Cycle 2 Patient 2 Cycle 1 Patient 3 Cycle 1
SENTI-202 Mechanism of Action and Early Clinical Results are Promising Indicators of
a Differentiated Clinical Profile 19 Durability data in 2025 SENTI-202 is designed to integrate validated mechanisms into one solution,engineered to solve key outstanding problems in AML Anticipated Clinical Catalysts First patient dosed in
2Q 2024 Initial clinical efficacy data by year-end 2024 2024 Accomplishments Generally well-tolerated at first dose level of 1 billion CAR+ NK cells / dose Second dose level of 1.5 billion CAR+ NK cells / dose is actively enrolling Early
clinical responses in two of three R/R AML patients along with robust count recovery are promising SENTI-202 PK generally consistent with allogenic CAR NK therapy with peaks detected post infusion at the first dose level
Executing Towards Bringing Gene Circuit Medicines to Patients 20 T
cells AAVs IPSCs & Other Modalities NK cells Gene Circuit SENTI-202 is a potential first-in-class logic gated CAR-NK program for AML Initial cohort data demonstrates evidence of efficacy and safety SENTI-301A first patient expected to
be enrolled in China in 4Q 2024 Experienced management team with track record of executing on timelines and accelerating innovative therapies Gene Circuit technology has been validated in NK cell, T cell, AAV, and iPSC
applications Multi-Arming Regulator Dial Smart Sensor Logic Gating Technology
SENTI-202 Initial Clinical Data Q&A 21

Frequently Asked Questions

What is the focus of SENTI-202?

SENTI-202 targets blood cancers like Acute Myeloid Leukemia (AML) using innovative NK cell therapy.

When was the first patient dosed for SENTI-202?

The first patient for SENTI-202 was dosed in the second quarter of 2024.

What are the initial results for SENTI-202?

Initial results include 2 out of 3 AML patients achieving measurable residual disease-negative complete remission.

What technology does SENTI-202 utilize?

SENTI-202 employs logic gating to target diseased cells while sparing healthy cells.

What is Senti Biosciences' future plan for SENTI-202?

Senti aims to transition SENTI-202 to a pivotal study based on upcoming clinical data.

Last updated: Dec 3, 2024