SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): November 10, 2022
SENTI BIOSCIENCES, INC.
(Exact name of registrant as specified in its charter)
|Delaware|| ||001-40440|| ||86-2437900|
(State or other jurisdiction
2 Corporate Drive, First Floor
South San Francisco, California 94080
(Address of principal executive offices including zip code)
Registrant’s telephone number, including area code: (650) 382-3281
(Former name or former address, if changed since last report)
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:
|Title of each class|| |
Name of each exchange
on which registered
|Common Stock, par value $0.0001 per share|| ||SNTI|| ||The Nasdaq Global Market|
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 2.02 Results of Operations and Financial Condition.
On November 10, 2022, Senti Biosciences, Inc. (the “Company”) issued a press release announcing its financial results for the quarter ended September 30, 2022.
The information in this Item 2.02 of Form 8-K and Exhibit 99.1 attached hereto is furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 (the “Securities Act”), as amended.
Item 7.01 Regulation FD Disclosure.
Reference is made to the disclosure set forth above in Item 2.02 of this Current Report on Form 8-K which is incorporated herein by reference.
Beginning on November 10, 2022, 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 99.2 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 Current Report on Form 8-K, including the exhibits, is intended to be furnished and shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934, or otherwise subject to the liabilities of that section and shall not be deemed to be incorporated by reference into any filing of the Company under the Securities Act or the Exchange Act. 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.
This filing and the presentation include “forward-looking statements” within the meaning of Section 27A of the Securities Act, and Section 21E of 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 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 (the “Commission”) on September 12, 2022 and other filings we make with the Commission. 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.
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:||November 10, 2022||By:|| ||/s/ Timothy Lu|
|Name:|| ||Timothy Lu, M.D., Ph.D.|
|Title:|| ||Chief Executive Officer & President|
Senti Bio Reports Third Quarter Financial Results and Pipeline Updates
- SENTI-202 on track for IND filing in 2023; clinical plans for SENTI-202 expand beyond AML to CD33
and/or FLT3 expressing hematologic malignancies including MDS -
- Selected development candidate for program to treat GPC3-expressing solid tumors including HCC, SENTI-301A; expected IND filing in 2023 -
- Preclinical data from two solid tumor CAR-NK programs highlighted at SITC -
- Cash position of $114.9 million as of September 30, 2022; maintain expectation of cash runway into 2024 -
SOUTH SAN FRANCISCO, Calif., November 10, 2022 — Senti Biosciences, Inc. (Nasdaq: SNTI) (“Senti Bio”), a biotechnology company innovating next-generation cell and gene therapies using its proprietary gene circuit platform, today reported financial results for the third quarter ended September 30, 2022, and highlighted recent pipeline advances, including an outline for its proposed Phase 1 clinical trial plans for SENTI-202, to include patients with CD33 and/or FLT3 expressing hematologic malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Senti Bio also selected SENTI-301A as the development candidate from its GPC3 targeting solid tumor program. SENTI-301A is a Multi-Armed off-the-shelf chimeric antigen receptor natural killer (CAR-NK) cell therapy candidate designed for the treatment of GPC3 expressing tumors including hepatocellular carcinoma (HCC), the most common form of liver cancer in adults.
In addition, Senti Bio’s data presentation at the Society for Immunotherapy of Cancer (SITC) Annual Meeting outlined continued progress with the solid tumor CAR-NK product candidate SENTI-301A and the SENTI-401 program. Both programs use Senti Bio’s proprietary gene circuit technology to potentially enhance activity against solid tumors by incorporating potent activating CARs and multifunctional cytokines to influence the tumor milieu as well as support enhanced CAR-NK activity. Specifically, SENTI-401 targets carcinoembryonic antigen (CEA) cell adhesion molecule 5 expressing solid tumors, including colorectal cancer (CRC), and also includes a NOT Logic Gate gene circuit to protect CEA expressing healthy cells from potential “on target, off tumor” killing. This Logic Gating strategy is designed to enable selective cytotoxicity of CAR-NK cells against tumor cells while protecting healthy cells.
“I am proud of our continued progress toward the clinic with our CAR-NK cell therapy oncology programs for both hematologic malignancies and solid tumors. With SENTI-202, we believe that we have generated compelling preclinical data demonstrating the killing of primary AML and MDS tumor cells, while maintaining protection of healthy hematopoietic stem cells, to support a clinical trial aimed at both cancer types, and we remain on track to file an IND in 2023,” said Timothy Lu, MD, PhD, Chief Executive Officer and Co-Founder of Senti Bio. “In addition, we recently selected our development candidate, SENTI-301A, which is designed to treat GPC3 positive tumors including HCC, and are on track to file an IND in 2023.”
Lu added, “Our scientists continue to generate exciting data across our pipeline; data from SENTI-301A and SENTI-401 are being highlighted today at the SITC Annual Meeting, and we are extremely excited to preview new data on SENTI-202 at the American Society of Hematology meeting next month. We remain steadfast in our vision of developing smarter medicines based on truly innovative advancements with our gene circuit technology platform.”
RECENT PIPELINE HIGHLIGHTS
CAR-NK Cell Oncology Pipeline and Gene Circuit Platform Highlights:
SENTI-202: A Logic Gated off-the-shelf CAR-NK cell therapy development candidate designed to selectively target and eliminate CD33 and/or FLT3 expressing hematologic malignancies, such as AML and MDS, while sparing the healthy bone marrow.
•Announced the acceptance of an abstract for presentation at the American Society of Hematology (ASH) meeting in December 2022; preclinical data to highlight the use of Logic Gating gene circuits to target and eliminate AML cells while sparing healthy hematopoietic stem cells.
•Outlined plans for a proposed Phase 1 clinical trial, including a dose-finding phase in patients with relapsed and/or refractory CD33 and/or FLT3 expressing hematologic malignancies. Disease-specific expansion cohorts would include relapsed and/or refractory AML. Multiple doses of SENTI-202 administration following standard fludarabine/cyclophosphamide (Flu/Cy) lymphodepleting chemotherapy is planned along with a potential to receive multiple cycles. Clinical trial endpoints would evaluate safety and identification of a recommended Phase 2 dose of SENTI-202, as well as efficacy using standard disease-specific response criteria.
•Manufacturing efforts and GMP facility buildout remain on track towards enabling flexible clinical manufacturing of CAR-NK cells in 2023.
•An IND application for SENTI-202 is expected to be submitted to the U.S. Food and Drug Administration (FDA) in 2023.
SENTI-301A: A Multi-Armed off-the-shelf CAR-NK cell therapy development candidate designed for the treatment of GPC3 expressing tumors, including HCC.
•Selected a development candidate, SENTI-301A, based on extensive optimization using Senti Bio’s proprietary screening platform for off-the-shelf CAR-NK cells with potent anti-tumor activity. SENTI-301A uses the following components:
◦Engineered NK cells that target glypican 3 (GPC3), which is highly expressed in 70% to 90% of HCCs and has low or no expression on normal adult tissues.
◦Calibrated release interleukin-15 (crIL-15), a multi-functional immuno-stimulatory payload designed to simultaneously stimulate surrounding immune cells and promote CAR-NK cell expansion, persistence and tumor killing.
•Preclinical data presented today at the SITC Annual Meeting demonstrates the use of gene circuits to improve the cytotoxicity and persistence of GPC3 targeting CAR-NK cells in treating HCC. Senti Bio’s novel GPC3 targeting activating CAR combined with crIL-15 technology provide the CAR-NK cells multi-arming to enhance persistence and killing activity of the NK cells, and to leverage the endogenous immune system for increased anti-tumor activity. The data presents evidence of robust in vitro and in vivo killing of relevant tumor cells with SENTI-301A.
•An IND application for SENTI-301A is expected to be submitted to the FDA in 2023
The presentation at the SITC Annual Meeting also includes data from ongoing development of Regulator Dial gene circuits that control expression of crIL-12 in response to FDA-approved small molecules. These data indicate that the Company’s Regulatory Dial gene circuits may be used with an expanded number
of FDA-approved drugs to modulate crIL-12 expression, including tamoxifen and grazoprevir, among others. These data give the Regulator Dial the potential for broader applicability beyond GPC3 expressing cancers and thus, the Company is actively exploring the continued development of this gene circuit for product opportunities across a wide range of additional solid tumors.
SENTI-401: A Logic Gated, Multi-Armed off-the-shelf selective CAR-NK cell therapy development program designed to precisely target CEA positive solid tumors (e.g., colorectal, pancreatic and lung cancers) while sparing healthy cells using the NOT Logic Gate.
•Presented preclinical proof-of-concept data at the SITC Annual Meeting that demonstrates the robust anti-cancer functionality of Logic Gated, Multi-Armed CAR-NK cells against a variety of colorectal cancer models:
◦Evaluated ways to enhance NK cell persistence and function using a combination of crIL-15 and IL-21, a previously undisclosed Multi-Arming combination, resulting in significantly enhanced and durable killing of CEA positive target cells in vitro and in vivo.
◦Long-term anti-tumor responses: a single dose of CEA targeting CAR-NK cells armed with crIL-15+IL-21 resulted in durable anti-tumor activity in human CRC xenograft models that express CEA, including complete tumor regressions.
◦CAR-NK cells equipped with an optimized inhibitory CAR (iCAR) suppressed activating CAR (aCAR)-mediated killing of healthy cells that co-expressed VSIG2-and CEA without diminishing aCAR-mediated anti-tumor activity of CEA expressing tumor cells.
THIRD QUARTER 2022 FINANCIAL RESULTS
•Cash and Cash Equivalents: As of September 30, 2022, Senti Bio held cash and cash equivalents of $114.9 million, which the Company believes is sufficient to fund operations into 2024.
•R&D Expenses: Research & development expenses were $8.1 million for the quarter ended September 30, 2022, compared to $5.4 million for the same period in 2021. The increase includes an additional $0.5 million in non-cash stock-based compensation expense.
•G&A Expenses: General and administrative expenses were $10.8 million for the quarter ended September 30, 2022, compared to $7.1 million for the same period in 2021. The increase includes an additional $1.2 million in non-cash stock-based compensation expense.
•Net Loss: Net loss was $16.6 million, or $0.38 per basic and diluted share, for the quarter ended September 30, 2022.
•CapEx: Capital expenditures were $14.2 million for the quarter ended September 30, 2022, primarily driven by the GMP manufacturing facility buildout and related equipment purchases.
About Senti Bio
Our mission is to create a new generation of smarter medicines that outmaneuver complex diseases using novel and unprecedented approaches. To accomplish this, we are building a synthetic biology platform that may enable us to program next-generation cell and gene therapies with what we refer to as Gene Circuits. These novel and proprietary Gene Circuits are designed to reprogram cells with biological logic to sense inputs, compute decisions and respond to their cellular environments. We aim to design Gene Circuits to improve the intelligence of cell and gene therapies in order to enhance their therapeutic effectiveness, precision, and durability against a broad range of diseases that conventional medicines do not readily address.
Our synthetic biology platform utilizes off-the-shelf chimeric antigen receptor natural killer (CAR-NK) cells, outfitted with Gene Circuit technologies, to target particularly challenging liquid and solid tumor oncology indications. Our lead product candidate is SENTI-202 for the treatment of CD33 and/or FLT3 expressing hematologic malignancies, such as AML and MDS. We are developing an additional CAR-NK product candidate, SENTI-301A, for the treatment of hepatocellular carcinoma (HCC) and other GPC3 positive cancers. We also have a CAR-NK program for the treatment of colorectal cancer (CRC) and other CEA positive cancers, SENTI-401. We have also demonstrated the breadth of our Gene Circuits in other modalities and diseases outside of oncology and have executed partnerships with Spark Therapeutics and BlueRock Therapeutics to advance these capabilities.
This document contains certain statements that are not historical facts and are considered forward-looking statements 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. These forward-looking statements generally are identified by the words “believe,” “could,” “predict,” “continue,” “ongoing,” “project,” “expect,” “anticipate,” “explore,” “estimate,” “intend,” “strategy,” “future,” “opportunity,” “plan,” “may,” “should,” “will,” “would,” “will be,” “will continue,” “will likely result,” “forecast,” “seek,” “target” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations of Senti Bio’s management and assumptions, whether or not identified in this document, and, as a result, are subject to risks and uncertainties. Forward-looking statements include, but are not limited to, statements regarding estimates and forecasts of financial and cash runway and the sufficiency of such cash runway, Senti Bio’s ability to continue to advance its pipeline of preclinical programs and product candidates, Senti Bio’s research and development activities, the generation and release of additional preclinical data, commencement of IND-enabling studies and the timing of submission of IND filings, plans for a Phase 1 clinical trial, and GMP manufacturing start up activities, as well as statements about the potential attributes and benefits of Senti Bio’s product candidates and platform technology. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by any investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Senti Bio. Many factors could cause actual future events to differ materially from the forward-looking statements in this document, including but not limited to: (i) changes in domestic and foreign business, market, financial, political and legal conditions, (ii) changes in the competitive and highly regulated industries in which Senti Bio operates, variations in operating performance across competitors, changes in laws and regulations affecting Senti Bio’s business, (iii) the ability to implement business plans, forecasts and other expectations, (iv) the risk of downturns and a changing regulatory landscape in Senti Bio’s highly competitive industry, (v) risks relating to the uncertainty of any projected financial information with respect to Senti Bio, (vi) risks related to uncertainty in the timing or results of Senti Bio’s preclinical studies, IND filings, and GMP manufacturing startup activities, (vii) Senti Bio’s dependence on third parties in connection with preclinical and IND-enabling studies, IND filings, and GMP manufacturing buildout and startup activities, (viii) risks related to delays and other impacts from the COVID-19 pandemic, and (ix) the success of any future research and development efforts by Senti Bio. The foregoing list of factors is not exhaustive. You should carefully consider the foregoing factors and the other risks and uncertainties described in the “Risk Factors” section of Senti Bio’s registration statement on Form S-1 (File No. 333-267390), and other documents filed by Senti Bio from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements in
this document. There may be additional risks that Senti Bio does not presently know, or that Senti Bio currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements in this document. Forward-looking statements speak only as of the date they are made. Senti Bio anticipates that subsequent events and developments may cause Senti Bio’s assessments to change. Except as required by law, Senti Bio assumes no obligation to update publicly any forward-looking statements, whether as a result of new information, future events, or otherwise.
Availability of Other Information About Senti Bio
For more information, please visit the Senti Bio website at https://www.sentibio.com or follow Senti Bio on Twitter (@SentiBio) and LinkedIn (Senti Biosciences). Investors and others should note that we communicate with our investors and the public using our company website (www.sentibio.com), including, but not limited to, company disclosures, investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference call transcripts and webcast transcripts, as well as on Twitter and LinkedIn. The information that we post on our website or on Twitter or LinkedIn could be deemed to be material information. As a result, we encourage investors, the media and others interested to review the information that we post there on a regular basis. The contents of our website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended.
Senti Bio Contacts:
Find more information at sentibio.com
Follow us on Linkedin: Senti Biosciences
Follow us on Twitter: @SentiBio
Senti Biosciences, Inc.
Unaudited Selected Consolidated Balance Sheet Data
|September 30,||December 31,|
|Cash and cash equivalents||$||114,940 ||$||56,034 |
|Restricted cash||3,295 ||3,257 |
|Property and equipment, net||47,259 ||12,368 |
|Operating lease right-of-use assets||18,883 ||20,708 |
|Total assets||189,441 ||96,702 |
|Total liabilities||49,098 ||36,326 |
|Redeemable convertible preferred stock||— ||171,833 |
|Total stockholders’ equity (deficit)||140,343 ||(111,457)|
Senti Biosciences, Inc.
Unaudited Consolidated Statements of Operations
(in thousands, except share and per share data)
|Three Months Ended||Nine Months Ended|
|September 30,||September 30,|
|Total revenue||$||1,766 ||$||1,103 ||$||4,227 ||$||1,968 |
|Research and development||8,056 ||5,410 ||24,904 ||15,548 |
|General and administrative||10,795 ||7,116 ||29,936 ||15,981 |
|Total operating expenses||18,851 ||12,526 ||54,840 ||31,529 |
|Loss from operations||(17,085)||(11,423)||(50,613)||(29,561)|
|Total other income (expense), net||445 ||17 ||10,613 ||(14,854)|
|Net loss per share, basic and diluted||$||(0.38)||$||(3.90)||$||(1.99)||$||(15.33)|
|Weighted-average shares outstanding, basic and diluted||43,424,172 ||2,925,957 ||20,150,459 ||2,897,850 |
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Corporate Presentation November 2022 ™
N O V E M 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.
N O V E M 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
N O V E M 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 Chief Medical and Development Officer (CMDO) Deb Knobelman, PhD CFO
N O V E M 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
N O V E M 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 complementary cytokines (e.g., IL-21) 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
N O V E M 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 Compare Favorably to T Cell Based Therapies 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 NA ✓ ✓ ✓ Senti’s CAR-NK Cells Engineered to stimulate the patient immune system ✓
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 0 1 2 3 4 5 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 CAR-NK Cells sIL-15 CAR-NK Cells 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) Increases 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 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 Cancer cells added Cancer cells added Cancer cells added crIL-15 CAR-NK Cells Unengineered NK Cells
N O V E M 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-301A GPC3 HCC and other solid tumors ✓ Multi-Arming: designed for enhanced efficacy ✓ crIL-15: autocrine and paracrine activation 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 ✓ IL-21: sustained anti-tumor function Additional Programs Undisclosed Other tumors Program candidates integrate Multi-Arming, Logic Gating and/or Regulator Dial Gene Circuits 2023 IND 2024 IND 9 Senti’s Next Generation CAR-NK Cell Therapy Pipeline Tackles Hard to Treat Cancers 2023 IND
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Manufacturing 10
N O V E M 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 CAR-NK 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
N O V E M 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
N O V E M 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)
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Pipeline Products 14
N O V E M 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 hematopoietic stem cells (HSCs) → 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
N O V E M 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 Across Multiple AML / MDS Models 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 (Days) 49 55 81.5 Vehicle Unengineered NK Cells SENTI-202 CAR-NK Cells Day: 7 28 34
N O V E M 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 to Protect Healthy Primary Human 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. FLT3 and/or CD33 expressed on tumor cells in ~95% of AML patients 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)
N O V E M 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
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 19 SENTI-301A for GPC3 Expressing Solid Tumors Multi-Armed, off-the-shelf, selective CAR-NK • GPC3 activating CAR → hepatocellular carcinoma (HCC) and other solid tumors • crIL-15 → potential for increased persistence, autocrine and paracrine immune cell activation On track for IND in 2023
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 20 SENTI-301A Aims to Address Unmet Needs in GPC3 Expressing Solid Tumors With a Focus on HCC GPC3 is a validated cancer target • Glypican-3 (GPC3) is a membrane-bound protein normally expressed in fetal tissues such as liver and placenta. • After birth, GPC3 is not expressed in healthy liver tissue or other human organs but is overexpressed in different tumor types, notably in HCC (70-90% GPC3+)1 and other solid tumors (29-54%2 GPC3+) • Academic GPC3 CAR-T cell trials have shown promising activity but limited by CAR-T toxicities precluding multiple dosing and limited durability3 SENTI-301A is designed to target GPC3 expressing tumors • Aim to address unmet need in HCC as the initial focus given the lack of targeted therapies and lack of effective immunotherapies • Tackle multiple solid tumors with high GPC3 antigen expression via NKs multi-armed with GPC3 CAR and crIL-15 1 Zheng 2022, 2 Moek 2018, 3 Shi 2020 Squamous Cell Lung Carcinoma Hepatocellular Carcinoma Large Cell Lung Carcinoma Ovarian Clear Cell Carcinoma Differentiated Thyroid Cancer Common GPC3 expressing tumors
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 0 1 2 3 0 1 2 3 4 5 6 Tu m o r C el l A b u n d an ce Days Vehicle Unengineered NK Cells SENTI-301A CAR-NK Cells SENTI-301A Preclinical Anti-Cancer Activity and Proposed Phase 1 Study in Advanced Solid Tumors With Focus on HCC 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 during dose finding • Disease specific expansion cohorts of advanced HCC and other solid tumors including lung cancer Planned study treatment • Multi-dose and multi-cycle following conditioning • 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) Group Vehicle Unengineered NK Cells SENTI-301A CAR-NK Cells Median Survival (Days) 48 49.5 93.5 Effective in vitro serial killing of HepG2 cell line Increased survival and response in HepG2 mouse model 21 0 20 40 60 80 100 0 20 40 60 80 100 120 P ro b ab ili ty o f Su rv iv al Days Post Tumor Implantation Vehicle Unengineered NK Cells SENTI-301A Cancer cells added Cancer cells added Cancer cells added
N O V E M 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 • IL-21 → construct to further potentiate persistence and efficacy of CAR-NK cells and to stimulate endogenous immune cells
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 23 Robust Preclinical Activity With CEA CAR-NK Cells That Is Augmented by Multi- Arming With Both crIL-15 and IL-21 0 1 2 3 4 5 1 2 3 4 5 6 N o rm al iz ed T u m o r C el l A re a Days Vehicle CEA CAR-NK Cells CEA CAR-NK Cells + TGFβ crIL15 + IL21 CEA CAR-NK Cells + TGFβ Cancer cells added Cancer cells added Cancer cells added Sustained serial killing with CEA CAR-NK cells expressing crIL-15 and IL-21 in the presence of the immunosuppressive cytokine TGFb Arming CEA CARs with the combination of Senti’s proprietary crIL-15 and IL-21 results in improved anti-tumor activity of NK cells Vehicle crIL-15 CEA CAR-NK Cells crIL-15+IL21 CEA CAR-NK Cells Day: 7 28 60 Sacrificed 111 Sacrificed 0 20 40 60 80 100 0 20 40 60 80 100 120 140P ro b ab ili ty o f Su rv iv al Days Post Tumor Implantation Vehicle crIL-15 CEA CAR-NK Cells crIL-15+IL21 CEA CAR-NK Cells TGFb is an immunosuppressive tumor factor highly expressed in CRC, known to suppress immune activation and help tumor escape1 1 Nature 2018
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Senti’s Approach to Select Paired Target and Protective Antigens Translates to Rapid Preclinical Proof of Principle for SENTI-401 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 1 Goldstein 2005 Healthy colon epithelium Decreased cell killing of VSIG2 expressing cells with addition of inhibitory CAR construct 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 24
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 25 Senti’s Discovery Platform for Tumor-Associated Antigen and Protective Antigen to Generate Many Targets for New Logic Gated CAR-NK Candidates 52 31 Expression in tumor cells A B C 4 Healthy tissue expression of A Expression in tumor cells D E F 1 2 3 4 5 Healthy tissue expression of E RNA expression data Filter for cell surface expression Curation and experimental validation Tumor-Associated Antigen discovery Protective Antigen discovery TissuesPotential Tumor- Associated Antigens TissuesPotential Protective Antigens
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 26 Gene Circuits Can Vastly Expand the Universe of Cancer Targets and Tumors That Can Be Addressed With Cell Therapies Heme Malignancies Solid Tumors N ee d f o r H ea lt h y C el l P ro te ct io n FLT3* CD33* CEA* Target GPC3* OR GATE to enhance efficacy and deepen response Multi-Arming to overcome immunosuppressive TME NOT GATE enables expansion to dirty targets Logic Gating Multi-Arming Gene Circuit Technologies * Senti’s current CAR-NK programs Target Target Target Target TargetTarget Target Target Target Target Target Target Target Target Target Target Target CD19 BCMA Approved autologous CAR-T cell therapies
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 27 Senti’s Regulator Dial Enables On-Demand Production of crIL-12 Controlled via Multiple Distinct FDA-Approved Small Molecule Oral Drugs Dose-dependent, reversible crIL-12 controlled by GRZ Vehicle GRZ at 50 mg/kg GRZ at 100 mg/kg 1 10 100 1,000 10,000 100,000 0 mg/kg50 mg/kg100 mg/kg 0 mg/kg50 mg/kg100 mg/kg 0 mg/kg50 mg/kg100 mg/kg cr IL -1 2 ( p g /m L) Day 2 GRZ ON) Day 9 (GRZ OFF) Day 11 (GRZ ON) DrugDrug Concentration dependent crIL-12 production CAR-NK activity suppressed by M2 macrophages → Activity restored by GRZ induced crIL-12 via Regulator Dial0 20 40 60 80 1 G ra n zy m e B ( % ) 0 1 10 100 1,000 10,000 0 0.01 0.1 1 cr IL -1 2 p g /m L GRZ (uM) - + + + Cancer target cells - - + + M2 macrophages - - - + GRZ 0 1 10 100 1000 0 0.1 1 10 cr IL -1 2 p g /m L Endoxifen (uM) IL-12 is a well-known immuno- stimulatory cytokine • Increases NK and T cell activation and 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 • Regulator Dials control IL 12 production with FDA approved oral drugs such as grazoprevir (GRZ) and endoxifen (active metabolite of tamoxifen) • Opportunities for application across multiple solid tumor indications 1 Leonard 1997
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Platform and Collaboration Opportunities 28
N O V E M 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 29 Multiple Platform Collaborations Extend Utility of Gene Circuits
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 30 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
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 31 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 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
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S 32 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 Gene Circuit Technology
N O V E M 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-301A 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 33 Upcoming Value Driving Milestones Present data at key scientific conferences in 2H 2022 (accepted abstracts at ASH) File IND application in 2023 Present data at key scientific conferences in 2H 2022 (abstracts published at 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 Present data at key scientific conferences in 2H 2022 (abstracts published at SITC)
N O V E M B E R 2 0 2 2 | SE N T I B IO SC IE N C E S Thank you! 34