SEC Filing | Sensei Biotherapeutics, Inc

Sensei Biotherapeutics, Inc.

Date: June 27, 2023

/s/ Christopher W. Gerry

Christopher W. Gerry

General Counsel and Secretary

8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): June 27, 2023

Sensei Biotherapeutics, Inc.

(Exact Name of Registrant as Specified in its Charter)

Delaware

001-39980

83-1863385

(State or Other Jurisdiction

of Incorporation)

(Commission

File Number)

(IRS Employer

Identification No.)

1405 Research Blvd, Suite 125

Rockville, MD

20850

(Address of Principal Executive Offices)

(Zip Code)

Registrant’s telephone number, including area code: (240) 243-8000

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 Securities Exchange Act of 1934:


Title of each class	Trading symbol	Name of each exchange on which registered
Common Stock	SNSE	The Nasdaq Stock Market LLC
Series A Preferred Stock Purchase Rights		The Nasdaq Stock Market LLC

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.

On June 27, 2023, Sensei Biotherapeutics, Inc. will host a virtual key opinion leader event titled “A New Vista for Cancer Care: Exploring SNS-101’s Potential as a Transformative Treatment Option for Patients with Solid Tumors.” A copy of the presentation for this event is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

The information in Item 7.01 and the exhibit attached hereto are being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall they be deemed incorporated by reference into any filing under the Exchange Act or the Securities Act of 1933, as amended, whether filed before or after the date hereof and regardless of any general incorporation language in such filing.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits


Exhibit Number		Exhibit Description

99.1		Sensei Biotherapeutics, Inc. presentation, dated June 27, 2023

104		The cover page from this Current Report on Form 8-K, formatted in Inline XBRL

SIGNATURES

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.

June 27, 2023 A New Vista for Cancer Care: Exploring SNS-101’s Potential as a Transformative Treatment Option for Patients with Solid Tumors Sensei Presenters: John Celebi Chief Executive Officer Dr. Edward van der Horst Chief Scientific Officer Ron Weitzman Consulting Chief Medical Officer Guest Speaker: James Gulley, M.D., Ph.D., F.A.C.P. Co-Director, Center for Immuno-Oncology Clinical Director, National Cancer Institute, NIH James Gulley, M.D., Ph.D., is an internationally recognized expert in cancer immunotherapy with a strong interest in prostate cancer. Since 1998 he has authored and run a variety of clinical trials at the National Cancer Institute (NCI). These innovative, investigator-initiated studies involve the use of cancer immunotherapy to (a) initiate immune responses, (b) expand immune responses and/or (c) allow the immune responses to be effective within the tumor microenvironment. In addition to his role as the CIO Co-Director, Dr. James L. Gulley is the Acting Clinical Director, NCI. Exhibit 99.1

Disclaimer This presentation has been prepared by Sensei Biotherapeutics, Inc. (the “Company,” "we," "us") and is made for informational purposes only. The information set forth herein does not purport to be complete or to contain all of the information you may desire. Statements contained herein are made as of the date of this presentation unless stated otherwise, and neither the delivery of this presentation at any time, nor any sale of securities, shall under any circumstances create an implication that the information contained herein is correct as of any time after such date or that information will be updated or revised to reflect information that subsequently becomes available or changes occurring after the date hereof. This presentation contains estimates and other statistical data made by independent parties and by us relating to market shares and other data about our industry. This presentation also contains "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 that are based on our management's beliefs and assumptions and on information currently available to management. These forward-looking statements include, without limitation, expectations regarding the development of SNS-101; the potential safety profile of SNS-101; the potential efficacy and other benefits of SNS-101; and expected clinical development timelines for SNS-101. When used in this presentation, the words and phrases "designed to," "may," "believes," "intends," "seeks," "anticipates," "plans," "estimates," "expects," "should," "assumes," "continues," "could," "will," "future" and the negative of these or similar terms and phrases are intended to identify forward-looking statements. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the development of therapeutic product candidates, such as preclinical discovery and development, conduct of clinical trials and related regulatory requirements, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies, including the preclinical studies of SNS-101, will not be replicated or will not continue in ongoing or future studies or clinical trials involving SNS-101 or Sensei’s other product candidates, our reliance on third parties over which we may not always have full control, and other risk and uncertainties that are described in our Quarterly Report on Form 10-Q filed with the SEC on May 9, 2023 and our other Periodic Reports filed with the SEC. Forward-looking statements represent our management's beliefs and assumptions only as of the date of this presentation and include all matters that are not historical facts. Our actual future results may be materially different from what we expect. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Certain information contained in this presentation relates to, or is based on, studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source.

Agenda WELCOME John Celebi President & Chief Executive Officer, Sensei Biotherapeutics Improving treatment for patients with cancer James Gulley, M.D., Ph.D., F.A.C.P. Co-Director, Center for Immuno-Oncology, Clinical Director, National Cancer Institute, NIH SNS-101 PHASE 1/2 CLINICAL TRIAL OVERVIEW Edward van der Horst, Ph.D. Chief Scientific Officer, Sensei Biotherapeutics Ron Weitzman, M.D. Consulting Chief Medical Officer, Sensei Biotherapeutics Q&A

Lack of Tumor Targeting is a Major Obstacle to CI Innovation Industry Problem Sensei’s Solution Conventional antibodies target immune checkpoints that are highly expressed in normal tissues, resulting in: Dose-limiting toxicities due to on-target/off-tumor action Pharmacological sink effect requires higher and more frequent dosing Suboptimal activity due to poor PK and dose-limiting toxicities Conditionally active antibodies are selectively targeted to the tumor microenvironment, potentially providing: Little or no toxicity due to selective on-target/on-tumor action Lower and less frequent doses by avoiding normal tissue binding Powerful activity selectively focused on the tumor microenvironment Only one new checkpoint inhibitor has been approved since the original CTLA-4 and PD-1/PD-L1 group Ipilimumab (anti-CTLA-4) Pembrolizumab (anti-PD-1) Relatlimab (anti-LAG-3) 2011 2014 2022

pH-sensitive Antibodies Have Potential to Selectively Bind Their Targets in the Low-pH Tumor Microenvironment Exploits the tumor microenvironment using pH-selective properties Intended to alleviate undesirable properties: Dose-limiting toxicities due to on-target/off-tumor binding Higher and more frequent dosing due to poor pharmacokinetics (Target-mediated Drug Disposition, or TMDD) Bolsters specific activities Goal is to unlock previously undruggable immune targets TMAb Platform Sensei’s technology identifies pH-sensitive antibodies designed to bind only at the tumor The tumor microenvironment of pH ~6 is lower than physiological pH of 7.4

Innovative Pipeline of IO Drugs with Broad Commercial Potential *Sensei has entered into a clinical supply agreement with Regeneron supporting the planned evaluation of SNS-101 in combination with Regeneron’s anti-PD-1 therapy Libtayo® (cemiplimab) in a Phase 1/2 clinical trial in solid tumors. *Sensei has entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute. The goal of this collaborative effort is to further elucidate the role of VISTA in immune checkpoint resistance and expand the potential of SNS-101 as a combination therapy beyond anti-PD-1.

James L. Gulley, M.D., Ph.D., F.A.C.P. Co-Director, Center for Immuno-Oncology Clinical Director, National Cancer Institute, NIH Immuno-Oncology Landscape

Cancer Immunity Cyclical Evolution (E8) Expand 3 Engage 2 Expedition 4 Excursion 5 Establish ID 6 Enable 7 Emit antigen 1 Modified from Chen and Mellman, Immunity 2013

Importance of PD-1/PD-L1 blockade NIH. News Headlines: https://ccr.cancer.gov/news/article/investigators-lead-first-human-trials-of-new-immunotherapy-drug (accessed August 2017)

Urothelial: avelumab Apolo AB et al. J Clin Oncol 2017 Urothelial: pembrolizumab Plimack ER P et al. Lancet Oncol 2017 HNSCC: pembrolizumab Seiwert TY et al. Lancet Oncol 2016 NSCLC (squamous only): nivolumab Rizvi NA et al. Lancet Oncol 2015 Urothelial: durvalumab Massard C et al. JCO 2016 Urothelial: atezolizumab Powles T et al. Nature 2014 MSI hi CRC: nivolumab Overman MJ et al. Lancet Oncol 2017 NSCLC: avelumab Gulley JL et al. Lancet Oncol 2017 Rapid, deep, durable responses Across a wide range of tumors Seen in a subset of patients PD-1/PD-L1 inhibition

Co-localization of inflammatory response and PDL1 expression: TILs are being blocked at tumor site (Enable) Taube et al., Sci Trans Med 2012 IFN-γ upregulates PDL1 expression in vitro

What happens when there is little / no immune recognition Strategies to enhance immune recognition include Generating new cells to recognize tumor ACT, vaccine, non-T-cell approaches etc. Expanding effector cells / bringing them to TIME Bi-specific Ab, cytokines etc. Addressing other negative aspects of the TIME TGF-beta, other checkpoints, IL10, etc. Making use of unique properties of TME to engineer specificity pH, proteases, low O2

Expand 3 Engage 2 Expedition 4 Excursion 5 Establish ID 6 Enable 7 Emit antigen 1 Universal Strategy for Immunologically Cold Tumors?

Examples of some combination approaches at NCI QuEST (vaccine, IL-15, bintrafusp alfa) ESMO and AACR HPV Triple (vaccine, IL-12, bintrafusp alfa) ASCO BEST (HDACi, IL-12, bintrafusp alfa)

NCI’s Center for Immuno-Oncology Formed in 2022 from parts of 3 groups Serves as a nidus for future immuno-Oncology growth at the CCR Has about 100 personnel Has CRADAs with 22 companies (pharma/biotech) Cooperative Research and Development Agreement Allows for novel/novel combinations from different companies Only mechanism to provide resources for co-development of agents Preclinical/translational and Clinical Programs in Therapeutic Cancer Vaccines Immune Checkpoint inhibitors Immunocytokines Bispecific Antibodies Cell Therapies (TCR-T, CAR-T, CAR-NK, others) Combination IO approaches

CRADA with Sensei Executed Feb 2, 2023 Ongoing preclinical studies exploring combination approaches Led by Jeff Schlom Clinical trial NCI to act as clinical trial site for SNS-101 Scientific review (branch 6/28 then institute) à IRB

SNS-101 Phase 1/2 Study * Safety Monitoring Committee (SMC) to determine initiation of combination arm based on emerging clinical data ** Currently screening patients in Cohort 2 (1.0 mg/kg) RP2D = Recommended Phase 2 Dose MTD = Maximum Tolerated Dose Phase 1 Dose Escalation - Monotherapy: SNS-101 alone Phase 1 Dose Escalation – Combination: SNS-101 + Libtayo 0.3 mg/kg RP2D Combo Cohort 1 RP2D Mono Cohort X Combo Cohort X Phase 2 Expansion: SNS-101 +/- Libtayo Indication 1 Indication 2 Indication X Phase 1 Study Design Dose escalation using Bayesian Optimal Interval (BOIN) design; plan to initiate combo dosing prior to monotherapy RP2D* Patient Population Study Objectives Dosing Advanced solid tumors Primary endpoint: safety, tolerability & RP2D Secondary endpoint: PK profile, immunogenicity & anti-tumor activity SNS-101 +/- Libtayo (350 mg) dosed as an IV infusion once every 3 weeks SNS-101 starting dose = 0.3 mg/kg; Dose escalation/de-escalation will proceed following the BOIN design until the MTD/RP2D is determined Anticipated Phase 2 Expansion Design Single-arm, Simon two-stage minimax design incorporating an interim futility analysis Patient Population Study Objectives Dosing Advanced solid tumors Tumor types to be determined based on data from Phase 1 study and emerging results from preclinical studies Primary endpoint: Anti-tumor activity Secondary endpoint: Anti-tumor activity, safety, tolerability, PK profile & immunogenicity SNS-101 +/- Libtayo (350 mg) dosed as an IV infusion once every 3 weeks Dose will be determined from the Phase 1 study 1.0 mg/kg** ü

New VISTAs for our partnership Potential for novel / novel combination approaches in the clinic

VISTA is a Potent T cell Checkpoint Extensively Expressed on Myeloid Cells1 1. Lines et al. Cancer research vol. 74,7 (2014) VISTA is a B7 family member that suppresses T cell function Immunosuppressive function believed to be mediated by PSGL-1 receptor T-cell proliferation & activation Extensive VISTA expression on off-tumor myeloid cells demands a conditionally active antibody approach VISTA has inherent pH sensitivity: its extracellular domain is uniquely rich in histidines2 2. Johnston et al., Nature 2019

SNS-101: Selectively Targeting VISTA with a pH-sensitive Antibody pH 6.0 pH 7.4 0.218 132 (~No binding) Additional SNS-101 features IgG1 format Active Fc Monovalent Affinity (KD) [nM] SNS-101 strongly inhibits the VISTA:PSGL-1 interaction and all other potential binding partners at pH 6.0 in vitro IC50 = 7nm 2.59 Å Resolution SNS-101 heavy chain SNS-101 light chain Human VISTA (shown in green and red) Human VISTA epitope for SNS-101 Selectivity for Active VISTApH6 over VISTApH7.4 VISTA:SNS-101 co-crystal structure demonstrates epitope of SNS-101 encompasses VISTA's PSGL-1 epitope SNS-101 is a differentiated, pH-sensitive antibody SNS-101 blocks the key receptor regulating VISTA’s immunosuppressive activity

SNS-101 Has Displayed a Favorable Single-dose PK Profile in Preclinical Studies - No Significant TMDD in Human VISTA KI Mice or Non-human Primates Pharmacokinetics of Single Dose 5 mg/kg SNS-101 in VISTA Knock-in Mice Demonstrated a long mean residence time in the blood, indicating a lack of significant target-mediated drug disposition (TMDD) and clearance in non-malignant tissues SNS-101 displayed linear elimination kinetics unlike a pH-independent anti-VISTA mAb, which demonstrated TMDD and rapid clearance Pharmacokinetics of Single Dose SNS-101 in Cyno monkeys Clinical mAb #1 10 mg/kg

SNS-101 Drove Single-agent Activity and Deepened Anti-tumor Responses to PD-1 in Human VISTA KI Mice ** ** MC38-7r (Anti-mPD-1 insensitive MC38 clone) *** ** ** * P<0.05; ** P<0.01; *** P<0.001 MC38

SNS-101 “Responder Hypothesis” Hypothesis Potential Clinical Direction Combination therapy with SNS-101 and approved anti-PD-(L)1 drugs can overcome adaptive resistance induced by CPI treatment Patients with hot tumors refractory to CPIs SNS-101 can unleash CPI response in immunologically active yet refractory tumors Patients with inflamed but cold tumors Tumor types with high VISTA and PSGL-1 expression & proximity have VISTA-PSGL-1 checkpoint engaged CPI-naïve patients Preclinical and Clinical/Translational Data to Inform Patient and Indication Selection CPI= checkpoint inhibitor

Pharmacokinetics Is PK profile linear? Safety/Toxicology What are key toxicity issues related to SNS-101? Pharmacodynamics Does target engagement with protonated VISTA in the TME modulate directly and/or indirectly cellular activity? Patient Selection/Stratification What population is likely to experience positive benefit from SNS-101 treatment? Does variability in target population affect efficacy and safety? Phase 1/2 Clinical Trial Biomarker Plan

Anticipated SNS-101 Immuno-oncology Biomarkers Blood Serum PK/Safety PK & ADA Immunoassays SNS-101 exposure in blood Anti-SNS-101 antibody detection Blood Serum PBMCs Biomarker Immunoassays Flow cytometry Cytokine analysis Immunophenotyping Whole blood FFPE tissue (pre/on-treatment) Biomarker DNA sequencing RNA sequencing HLA typing TCR / BCR repertoire analysis Gene expression Mutation identification / TMB MSI status Neoantigen prediction FFPE tissue (pre-treatment) Whole blood Cell-free plasma Biomarker DNA sequencing ctDNA tracking Variant tracking of clinically relevant mutations MRD detection FFPE tissue (pre/on-treatment) Biomarker Multiplex IF Cellular phenotyping (52-plex) Spatial analysis of immune cell infiltration and interactions

Expected SNS-101 Program Milestones May 2023: First patient dosed In or before Q1 2024: Dose first patient in combination with Libtayo® 2024: Topline Phase 1 monotherapy data 2024: Initial Phase 1 combination data check