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):
(Exact Name of Registrant as Specified in its Charter)
|(State or Other Jurisdiction
|(Address of Principal Executive Offices)||(Zip Code)|
Registrant’s telephone number, including area code:
(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 Securities Exchange Act of 1934:
Title of each class
Name of each exchange
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 April 20, 2022, Dr. Robert Pierce, Chief R&D Officer of Sensei Biotherapeutics, Inc. (the “Company”) will present a presentation regarding SNS-101 at the World Vaccine Congress 2022, including new preclinical data from a mouse model evaluating the pharmacokinetic profile of SNS-101 and new preclinical data from mouse models evaluating both activity and the pharmacokinetic profile of SNS-101. A copy of the presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information in this Item 7.01 of this Current Report on Form 8-K (including Exhibit 99.1) is being furnished and shall not be deemed “filed” for 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 it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
|104||The cover page from Sensei Biotherapeutics, Inc.’s Form 8-K filed on April 20, 2022, formatted in Inline XBRL.|
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.
Sensei Biotherapeutics, Inc.
Date: April 20, 2022
President and Chief Executive Officer
Robert Pierce, MD World Vaccine Congress 2022 Washington, DC SNS-101, A Unique Tumor-selective Anti-VISTA Monoclonal Antibody with a Novel Mechanism of Action
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 managements beliefs and assumptions and on information currently available to management. These forward-looking statements include, without limitation, statements regarding our industry, business strategy, plans, the preclinical and clinical development of our product candidates, and other financial and operating information. When used in this presentation, the words 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, our reliance on third parties over which we may not always have full control, and other risk and uncertainties that are described in our Annual Report on Form 10-K filed with the SEC on March 15, 2022 and our other Periodic Reports filed with the SEC. Forward-looking statements represent our managements 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 Companys 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.
The Therapeutic Problem: PD-1/PD-L1 Non-Response Anti-PD-1 or PD-L1 More Likely to Respond Less Likely to Respond Treatment T-cells T-cells Inside Tumor T-cells Absent Outside Tumor Green = T-cells Purple = tumor Adapted from Van der Woulde-LL, et al, Trends in Cancer, 2017
Two Platforms to Unleash Anti-Cancer T-cell Activity TMAb (Tumor ImmunoPhage
Platform Microenvironment Activated Biologics) Platform Powerfully self-adjuvanted nanoparticle vaccine can drive
Next-generation tumor activated B cell and T cell responses mAbs Multi-antigen vaccine enables
Binding only in the low-pH tumor personalized approach from microenvironment off-the-shelf components
Target checkpoints and/or other Targets APCs immune pathways Enhanced through addition of
Enable improved PK/PD and immunostimulatory toxicity profiles nanobodies & cytokines 4
VISTA: A Promising but Difficult Target on Myeloid Cells VISTA is a Negative Regulator of T cell Function
VISTA (aka B7-H5; PD-1H) is B7 family ligand wi homology to PD-L1 VISTA suppresses T cell activation1 Expressed on myeloid cells including macropha and neutrophils; NK cells and T-regs2 Inhibition of VISTA may convert myeloid cells t proinflammatory/immune activating state Excellent therapeutic combinability with CTLA-4 PD-1/PD-L1 ICIs, especially in cold tumors3 Identity of critical VISTA binding partner/receptor remains subject of debate. 1 Wang et al, JEM, 2011 2 Lines et al. Cancer research vol. 74,7 (2014) 3 Gao et al. Nature medicine vol. 23,5 (2017)
VISTA Negatively Regulates CD4 and CD8 T Cell Responses VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell
responses Li Wang,1 Rotem Rubinstein,4,5 Janet L. Lines,1 Anna Wasiuk,1 Cory Ahonen,1 Yanxia Guo,1 Li-Fan Lu,1 David Godek,1 Yan Wang,1 Roy A. Fava,3 Andras Fiser,4,5 Steve Almo,5 and Randolph J. Noelle1,2
Wang_L, et al, JEM, 2011
Anti-VISTA mAb Treatment Leads to Tumor Growth Inhibition in Multiple Syngeneic Mouse Tumor Models
WT Mice Bearing MB49 Murine Bladder Carcinom a VISTA Expression on Myeloid Cells in Tumor-Bearing Mice Control-Ig ) 2 (10 mg/kg) (mm Isotype Spleen p-value = 0.001 control size Ascites Tumor 13F3 Anti-VI STA Antibody (10 mg/kg) Mesenteric lymph node Days WT Mice Bearing MCA105 An anti-murine VISTA antibody (13F3) was Murine Sarcoma administered to WT mice bearing tumors ) 2 Control-Ig Myeloid cells from these mice were assessed (mm (10 mg/kg) and found to have high levels of VISTA siz e p-value = 0.001 expression Tumor 13F3 Anti-VISTA Antibody (10 mg/kg) Noelle et. al., US 2013/0177557 Days
PD-1/VISTA Double Knock-out Mice Have Increased
Antigen-specific T cell Responses Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murineT-cell responses Jun Liua,b, Ying Yuana,1,a, Wenna Chena, Juan Putrac, Arief A. Suriawinatac, Austin D. Schenkd, Halli E. Millera, Indira
Guleriae, Richard J. Barthd, Yina H. Huangc, and Li Wanga,2
Liu J. et al. PNAS 2015
Combination of VISTA Inhibition and PD-1 Blockade Yields Synergistic Anti-tumor Responses Mice
Bearing CT26 Tumors Combination) 2 Control-Ig (n=8) (mm Anti-VISTA mAb (n=8) Survival size Anti-PD-L1 Anti-PD-L1 mAb (n=8) Anti-VISTA Tumor Combo (n=8) Percent Control-Ig Time (Days) Time (Days) Liu J. et al. PNAS 2015 Immune-checkpoint
proteins VISTA and PD-1 nonredundatly regulate murine T-cell resposes
Yun Liua,b, Ying Yuana,1, Wenna Chena, Juan Putrac, Arief A. Suriawinatac, Austin D. Schenkd, Halli E. Millera, Indira Gulerae, Richard J. Barthd, Yina H. Huangc, and Li Wanga,2
Anti-VISTA mAb Binding on Myeloid Cells in Blood Results in Significant Target-mediated Drug Disposition (TMDD) Mouse Pharmacokinetics of Anti-VISTA Antibodies (BMS) at 5 mg/kg Antibodies binding VISTA+ cells Week 1 Week 2 (e.g . monocytes) at physiological pH are eliminated from circulation No target through targeted-media ted drug disposition (TMDD) WT mice A n antibody binding at pH 6 will accumulate in the TME resulting in pH-sensitive mAb (binds only at low pH) an improved PK and safety profile pH-non-sensitive mAb (binds at physiologic pH) Johnston et al, Nature, 2019
VISTA Binding to PSGL-1 is pH-dependent Due to a Unique Histidine-rich Extracellular Binding Domain Antibodies that block protonated VISTA VISTAs extracellular histidines interrupt PSGL-1 binding1 domain is uniquely rich in histidines¹ Histidines are protonated at low pH enabling VISTA to the active (acidic pH) and inactive (neutral pH) PSGL-1 binding in terface 1. Johnston et al., Nature 2019
Strongest Interaction between Candidate VISTA Binding Partners is VISTA/PSGL-1 at Low pH 3 VSIG3 pH 6.0 pH 7.4 VSIG8 PSGL-1 Syndecan-2 OD450 2 LRIG1 Mean 1 0 5 . 5 1 2 4 8 125. 2 0 0625 . 0 . 0 0 VISTA (Î¼g/ml) VISTA binds specifically to PSGL-1 and Syndecan-2 in a pH-dependent manner VSIG-3, VSIG-8 and LRIG-1 interactions are very weak (pH 7.4) The VSIG-3 interaction (pH 7.4) is 1/7 the affinity of PSGL-1 (pH 6.0)
Active Protonated VISTA Binds the T cell Checkpoint PSGL-1 in the Tumor Microenvironment Active VISTA Protonated Inactive VISTA Unprotonated Adapted from Yuan-L, Trends Immunol, 2021 Mar;42(3):209-227
pH-dependent mAb Binding to VISTA May Mitigate On-Target/Off-tumor Reactivity Low pH- pH Non-selective Binder selective Binder Blocks VISTA/PSGL-1 Blocks checkpoint VISTA/PSGL-1 Active Fc ï¨ myeloid checkpoint activation IgG1 Fc ï¨ myeloid TMDD ï¨ low tumor Tumor activation drug exposure No significant Binds VISTA on VISTA binding myeloid cells in No significant blood ï¨ TMDD TMDD Potential for Bood No significant myeloid activation myeloid activation AND CRS Decreased risk of CRS Adapted from Yuan-L, Trends Immunol, 2021 Mar;42(3):209-227 14
Critical Design Features for SNS-101 1. Block the critical checkpoint (pH-dependent binding of VISTA to PSGL-1 on T cells) 2. Selectively bind active/protonated VISTA at low pH to avoid: target mediated drug disposition (TMDD) on-target/off-tumor side effects 3. Utilize an Fc-competent IgG (e.g. IgG1) backbone to engage and activate FcÆR on tumor-infiltrating myeloid cells
SNS-101 Inhibits VISTA/PSGL-1 Interaction CTRL-lgG SNS-101 CTRL-lgG SNS101 SITC 2021: Poster titled: Antagonistic pH-selective VISTA antibody SNS-101 potentiates anti-PD-1/PD-L1-induced anti-tumor immunity PSGL-1: VISTA interaction on Primary T-cells at pH 6.0
SNS-101 Has >600-Fold Selectivity for VISTApH6 >600-fold selectivity for VISTA at pH 6.0 Subnanomolar binding at low pH physiological No significant pH binding (7.4) observed at pH 6.0 pH 7.4 132 Monovalent Affinity (KD) [nmol] 0.218 (~No binding) pH-dependent pH-independent SNS-101 benchmark benchmark pH-independent pH-dependent benchmark SNS-101 benchmark pH7.4 pH 6.0 k = 4.59E+06 M-1s-1 a -1 Kd = 1.00E-03 s KD = 2.18E-10 M [Vista] 7.5 nmol 0.2 nmol k = 7.11E+05 M-1s-1 k = 1.45E+06 M-1S-1 k = 4.162E+05 M-1S-1 a a -1 a K = 1.78E-04 s-1 K = 2.25E-03 S K = 9.27E-05 S-1 d d d K = 2.5E-10 M KD = 1.55E-09 M K = 2.23E-10 M D D [Vista] 15 nmol 0.2 nmol [Vista] 15 nmol 0.2 nmol [Vista] 7.5 nmol 0.2 nmol [Vista] 15 nmol 0.2 nmol [Vista] 15 nmol 0.47 nmol
No Significant Binding of SNS-101 to Monocytes, Neutrophils, NK Cells and T-cells in Whole blood at Physiological pH CYNO HUMAN Monocytes Neutrophils NK cells T-cells CRTL PF JNJ SNS101 CRTL PF JNJ SNS101
SNS-101 Displays Favorable PK Profile No significant TMDD in human VISTA KI mice Pharmacokinetics of Single Dose 5 mg/kg SNS-101 in VISTA Knock-in Mice Week 1 Week 2 Week 3 Week 4 Ø Tumor bearing mice have a favorable PK profile Ø Non-tumor bearing mice demonstrate no TMDD VISTA KI mice No Target WT mice Tumor (MB49) in VISTA KI mice SNS-101 (ìg/ml)
MC38 Syngeneic Tumor Model in huVISTA Knock-in Mice Confirms Combinatorial Activity of SNS-101 SNS-101* in Combination with Anti-mouse PD-1 Tumor Growth Inhibition Survival *SNS-101 was grafted on to a mouse IgG2a framework to decrease anti-drug antibody production Anti-PD-1 + SNS-101 (5/10) Anti-PD-1 (1/10) Isotype Control 0/10 Control Anti-PD-1 Anti-PD-1 + SNS-101 Percent Survival Days
Manufacturing of SNS-101 is ongoing No developability issues to date Cell line has demonstrated great productivity/quality (~ 9 grams/liter and low % aggregates) IND-enabling studies have been initiated Single-dose mouse and non-human primate PK Optimized preclinical efficacy models in huVISTA-KI mice GLP multi-dose PK and toxicology studies contracted In vitro and In vivo CRS risk assessment models Translational Medicine studies are underway to support FIH clinical trial in 2023 Generate SNS-101 responder hypothesis ï¨ rationalize early development plan/focus on high probability of success indications Preclinical Development Summary
Preliminary PSGL-1/VISTA Proximity Assay on HNSCC Tumor Samples Low Proximity High Proximity H&N (HN483a) Core C6,R7 H&N (HN483a) Core C5,R4
Beyond VISTA: Tumor Microenvironment Activated Biologics (TMAbs) The tumor microenvironment of pH ~6 is lower than physiological pH of 7.4 Senseis technology identifies antibodies that selectively bind in the distinct biochemical milieu of the tumor, for example, sub-physiologic pH Antibodies that bind at physiological pH may encounter a sink Prevents effective binding at the tumor and may lead to toxicity TMAb antibodies bypass tissue compartments other than the low-pH tumor microenvironment Goal is to unlock previously undruggable immune targets through potential for improved safety and clinical activity profile
Sensei Biotherapeutics Collaborators TMAb Fred Hutchinson Cancer Research Center Edward van der Horst Kimberly Smythe Thomas Thisted Cecilia Yeung Yuliya Kleschenko Brandon Seaton Zuzana Biesova Kanam Malhotra Adimab Arnab Mukherjee Anokhi Cifuentes Nadthakarn Boland Nels Nielson Translational Medicine Jean Campbell Lauren Abel Rachel La Selva Acknowledgements