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 4, 2021
SQZ BIOTECHNOLOGIES COMPANY
(Exact name of registrant as specified in its charter)
Delaware |
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001-39662 |
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46-2431115 |
(State or other jurisdiction of incorporation or organization) |
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(Commission File Number) |
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(I.R.S. Employer Identification No.) |
200 Arsenal Yards Blvd, Suite 210
Watertown, MA 02472
(Address of principal executive offices) (Zip Code)
(617) 758-8672
(Registrant’s telephone number, include area code)
N/A
(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:
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Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
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Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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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 |
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Trading |
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Name of each exchange on which registered |
Common Stock, |
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SQZ |
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The New York Stock 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 June 4, 2021, SQZ Biotechnologies Company (the “Company”) issued a press release titled “SQZ Biotechnologies Initial First-In-Human Data Demonstrates Investigational Cell Therapy is Safe and Can Stimulate Immune Responses in Certain Patients with Advanced or Metastatic HPV16+ Tumors.” A copy of the press release is attached hereto as Exhibit 99.1.
The Company is also furnishing a corporate presentation, attached as Exhibit 99.2 to this Current Report on Form 8-K, which the Company intends to use from time to time in meetings with investors and others beginning on June 4, 2021. The corporate presentation will also be available in the investor relations section of the Company’s website at http://sqzbiotech.com.
The information in this Item 7.01 and Exhibits 99.1 and 99.2 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities and Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section, nor shall they be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, except as expressly set forth by specific reference in such filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
Exhibit |
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Description |
99.1 |
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Press release issued by SQZ Biotechnologies Company on June 4, 2021. |
99.2 |
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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.
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SQZ BIOTECHNOLOGIES COMPANY |
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Date: June 4, 2021 |
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By: |
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/s/ Lawrence Knopf |
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Lawrence Knopf |
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General Counsel |
Exhibit 99.1
Empowering Cells to Change Lives
SQZ Biotechnologies Initial First-In-Human Data Demonstrates Investigational Cell Therapy is Safe and Can Stimulate Immune Responses
in Certain Patients with Advanced or Metastatic HPV16+ Tumors
Doses of Autologous Cell Therapy Manufactured in Under 24 Hours
and Available to Patients in Approximately One Week
Clinical Trial Findings Presented at the
American Society of Clinical Oncology Annual Meeting
WATERTOWN, Mass., June 4, 2021 – SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, today presented initial results from its ongoing Phase 1 clinical trial of SQZ-PBMC-HPV demonstrating that the investigational cell therapy is safe and well-tolerated and can stimulate immune responses in certain patients with advanced or metastatic Human Papillomavirus positive (HPV16+) tumors. The trial also showed that the company’s clinical stage manufacturing process of its autologous cell therapy is fast and reliable. The monotherapy stage trial data of the company’s first Antigen Presenting Cell (APC) platform candidate was presented at the 2021 American Society of Clinical Oncology (ASCO) annual meeting; poster presentation 2536.
“Our vision is to make cell therapies that are safe and available with rapid turnaround times, allowing access to patients who need them,” said Oliver Rosen, M.D., chief medical officer at SQZ Biotechnologies. “The company’s first-in-human data of a cell-based therapeutic vaccine are encouraging and an important first step towards validation of our directed immunity approach. Within this small trial of patients with very advanced disease, four patients who had progressed after multiple prior therapies achieved stable disease. These early outcomes, combined with encouraging safety data and fast clinical-scale manufacturing times, support our plans to initiate the trial’s safety combination phase with immune checkpoint inhibitors.”
Safety & Tolerability
A primary outcome measure in the monotherapy dose escalation phase of the trial is safety and tolerability. Findings from the trial show that SQZ-PBMC-HPV was safe and well-tolerated at all tested dose levels with patients receiving 2 to 10 doses. No dose-limiting toxicities were observed.
“Overall, SQZ-PBMC-HPV has been safe and well tolerated by patients, even advanced patients as we have seen in this study,” said study author Antonio Jimeno, M.D., Ph.D., Professor of Medicine, Oncology and Otolaryngology, University of Colorado School of Medicine, and Co-Leader, Development Therapeutics Program, University of Colorado Cancer Center. “I look forward to completing the single agent portion of the trial and advancing into the combinations of SQZ-PBMC-HPV with immunotherapies.”
There were no grade 3 or higher treatment related serious adverse events (SAEs). In one patient, a grade 2 cytokine release syndrome and immune-related reaction was observed. A related grade 3 adverse event (AE, anemia) was observed in another patient.
Manufacturability
Manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. All patient batches were produced under current good manufacturing practice regulations, met specifications, and yielded multiple cryopreserved doses in less than 24 hours.
The findings show that doses of SQZ-PBMC-HPV were released and available for administration approximately one week from the time a patient’s cells were drawn. Antigen presentation was confirmed in all patient batches independent of individual patient medical history or prognostic score.
Patient Characteristics & Immune Response Biomarkers
The clinical trial enrolled patients with HPV16+ cancers progressing after unlimited prior lines of therapy. The 12 enrolled patients had very advanced disease:
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Median number of prior cancer treatments was four with one patient having received seven prior treatments |
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Eleven patients previously treated with an immune checkpoint inhibitor (ICI) |
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Six of the 12 patients had a Royal Marsden Hospital (RMH) score of 2. (RMH scores range from 0-to-3, with scores of 2 and higher predicting poor prognosis and short life expectancy) |
Despite the treatment refractory status of the enrolled patients, 4 out of 6 patients with RMH scores less than 2, reflecting less advanced disease, achieved stable disease as best overall response. Two of these patients showed an increase in CD8 tumor infiltrating lymphocytes (TILs), an important biomarker in immune-oncology therapy development.
The study authors highlighted two patients – Patients 2 and 7 detailed below – which suggested that less advanced patients with lower tumor burden, such as patient two, might have a higher likelihood of clinical benefit.
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Patient 2: Enrolled 3-and-half years after diagnosis and had a best overall response of progressive disease with ICI therapy. The patient had an RMH score of 1 and low tumor burden. She achieved stable disease while on the SQZ-PBMC-HPV-101 trial and remained on study for over 10 months. Image analysis of the central tumor 28 days after the first dose showed a 2-fold increase in CD8 TILs on treatment compared to baseline |
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Patient 7: Enrolled 1 year after diagnosis and had a partial response with chemotherapy in combination with ICI therapy but then progressed. He achieved stable disease after treatment on the SQZ-PBMC-HPV-101 trial and remained on study for three months. Image analysis of the central tumor showed a 6-fold increase in CD8 TILs on treatment compared to baseline |
The company is now actively enrolling patients in the last monotherapy highest-dose cohort of the Phase 1 trial. These results will inform the dosage approach for the combination therapy phase of the clinical trial with immune checkpoint inhibitors.
Poster Presentation Details
Title: Initial Results of a first-in-human, dose escalation study of a cell-based vaccine in HLA-A* 02+ patients with recurrent, locally advanced or metastatic HPV16+ solid tumors
First Author: Antonio Jimeno, M.D., Ph.D., University of Colorado Cancer Center
Abstract Number: 2536
Poster Session: Developmental Therapeutics -- Immunotherapy
Date and Time: A copy of the poster is available on-demand via the ASCO virtual meeting website.
SQZ-PBMC-HPV-101 Trial Design
SQZ-PBMC-HPV is being evaluated in a Phase 1 clinical trial for the treatment of HPV16+ advanced or metastatic solid tumors. Patients must be positive for the human leukocyte antigen serotype HLA-A*02. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immuno-oncology agents. The study’s primary outcome measures in the monotherapy and combination phases of the trial include safety and tolerability. Antitumor activity is a secondary outcome measure in both the monotherapy and combination stages of the trial, and manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. The monotherapy phase of the study includes escalating dose cohorts with a DLT window of 28 days and the definition of a recommended phase 2 dose. The planned safety combination phase of the study will include SQZ-PBMC-HPV and checkpoint inhibitors that have previously received regulatory approval. DLT will be measured over 42 days in the safety combination phase.
About Human Papillomavirus Positive Cancers
Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer HPV+ tumors account for 4.5% of all cancers worldwide, resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.
About SQZ Biotechnologies
SQZ Biotechnologies is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies to benefit patients with cancer, autoimmune and infectious diseases. The company’s proprietary Cell Squeeze® technology offers the unique ability to deliver multiple biological materials into many patient cell types to engineer what we believe can be a broad range of potential therapeutics. Our goal is to create well-tolerated cell therapies that can provide therapeutic benefit for patients and improve the patient experience over existing cell therapy approaches. With accelerated production timelines under 24 hours and the opportunity to eliminate preconditioning and lengthy hospital stays, our approach could change the way people think about cell therapies. The company’s first therapeutic applications seek to generate target-specific immune responses, both in activation for the treatment of solid tumors and in immune tolerance for the treatment of unwanted immune reactions and autoimmune diseases. For more information, please visit www.sqzbiotech.com.
Forward Looking Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements relating to events and presentations, our product candidates, preclinical and clinical activities, development plans, clinical safety and efficacy, regulatory compliance, and therapeutic impact. These forward-looking statements are based on management's current expectations. Actual results could differ from those projected in any forward-looking statements due to several risk factors. Such factors include, among others, risks and uncertainties related to our limited operating history; our significant losses incurred since inception and expectation to incur significant additional losses for the foreseeable future; the development of our initial product candidates, upon which our business is highly dependent; the impact of the COVID-19 pandemic on our operations and clinical activities; our need for additional funding and our cash runway; the lengthy, expensive, and uncertain process of clinical drug development, including uncertain outcomes of clinical trials and potential delays in regulatory approval; our ability to maintain our relationships with our third party vendors; and protection of our proprietary technology, intellectual property portfolio and the confidentiality of our trade secrets. These and other important factors discussed under the caption "Risk Factors" in our Annual Report on Form 10-K and other filings with the U.S. Securities and Exchange Commission could cause actual results to differ materially from those indicated by the forward-looking statements. Any forward-looking statements represent management's estimates as of this date and SQZ undertakes no duty to update these forward-looking statements, whether as a result of new information, the occurrence of current events, or otherwise, unless required by law.
Certain information contained in this press release relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this press release, we have not independently verified, and we
make no representation as to the adequacy, fairness, accuracy, or completeness of any information obtained from third-party sources.
SQZ Biotechnologies IR Contact:
investors@sqzbiotech.com
SQZ Biotechnologies Media Contact:
John Lacey
Corporate Communications
john.lacey@sqzbiotech.com
781-392-5514
June 2021 Exhibit 99.2
2 This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including statements relating to our development of our product candidates, the promise and potential impact of our preclinical or clinical trial data, the timing of and plans to continue or initiate preclinical studies and clinical trials of our product candidates, the timing and results of any preclinical studies, clinical trials or readouts and the sufficiency of cash to fund operations. These forward-looking statements are based on management's current expectations. The words ”may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “estimate,” “believe,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important 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, including, but not limited to, the following: the impact of the COVID-19 pandemic on our operations, including our preclinical studies and clinical trials, and the continuity of our business; we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding; our cash runway; our limited operating history and the prospects for our future viability; the lengthy, expensive, and uncertain process of clinical drug development, including potential delays in regulatory approval; the continued relationship with our collaboration partners in our development of products, including in our SQZ™ APC oncology pipeline; the approach we are taking to discover and develop product candidates and whether it will lead to marketable products; the expense, time-consuming nature and uncertainty of clinical trials; enrollment and retention of patients; potential side effects of our product candidates; our ability to maintain our relationships with our suppliers; protection of our proprietary technology and the confidentiality of our trade secrets; potential lawsuits for, or claims of, infringement of third-party intellectual property or challenges to the ownership of our intellectual property; our ability to retain key personnel and to manage our growth; the potential volatility of our common stock; costs and resources of operating as a public company; unfavorable or no analyst research or reports; and securities class action litigation against us. These and other important factors discussed in our filings with the US Securities and Exchange Commission could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any such forward-looking statements represent management's estimates as of the date of this presentation. New risk factors and uncertainties may emerge from time to time, and it is not possible to predict all risk factors and uncertainties. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this presentation. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and we make 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. Neither we nor our affiliates, advisors or representatives makes any representation as to the accuracy or completeness of the data included in this presentation or undertake to update such data after the date of this presentation. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. Forward Looking Statements and Legal Disclaimers
3 Demonstrated Safety & Manufacturing: Could Open Broader Cell Therapy Universe Cell Squeeze® Technology Universe of Possible Cell Therapies Electroporation Viral transduction Efficient process Flexible across cell types and cargos Fast and reliable manufacturing Broadly applicable across disease areas Hematology Oncology Solid Tumors Autoimmune Infectious Disease Regenerative medicine Demonstrate cell therapy potential Limited disease applicability Limited cell type and cargo compatibility Complicated manufacturing Current Methods for Creating Cell Therapies
4 Unique Technology Enables Differentiated Capabilities Broad Capabilities Applicable to diverse cell types Robust across material classes Preservation of cell function Rapid Manufacturing (>10B cells/min)
5 Speed and Reliability of SQZ™ Autologous Cell Therapy Potentially Rivals Allogeneic TALENT AND CULTURE 1 Allogene ASCO 2020 2 Median 5 days from enrollment to lymphodepletion and 5-7 days for lymphodepletion regimen. ALLO-501 ALPHA trial 3 Kymriah (tisagenlecleucel) [package insert], Yescarta (axicabtagene ciloleucel) [package insert], Breyanzi (lisocabtagene maraleucel) [package insert]
6 Prototype Expected in 2021 Point-of-Care Vision: Potential to Transform Cell Therapy Through Onsite Manufacturing TALENT AND CULTURE Reduced transportation and logistics costs Potential for same-day treatment No clean room Integrated single system operated by hospital staff On-site production
7 Directing Immune System to Drive Antigen Specific Immunity Oncology Autoimmune Diseases Infectious Diseases and beyond Aiming to redirect, reinforce and reengage immune system through antigen-specific cell therapies
ONCOLOGY 8 Upcoming Milestones Across Pipeline PLATFORM INDICATION Other Solid Tumors KRAS mut Solid Tumors H&N, Cervical, Anal H&N, Cervical, Anal PRE-CLINICAL PHASE 1 Monotherapy biomarker data (ASCO) Combination data HBV IND submission Monotherapy data KRAS IND submission IND-enabling studies UPCOMING MILESTONES NEXT 18 MONTHS AUTO-IMMUNITY Other Solid Tumors CELL SOURCE/ CARGO PBMC + peptide RBC + Peptide + Adjuvant RBC + Peptide INFECTIOUS DISEASE PBMC + mRNA IND submission Solid Tumors PBMC + mRNA
9 SQZ™ Approach Unlocking the Full Potential of Cell Therapies Oncology Autoimmune Diseases Infectious Diseases and beyond Using directed immunity to bring cell therapies to disease areas with significant unmet need
10 Potential to Address Broad Range of Cancers Estimated 39,000 cases/yr in US Primarily HNSCC, Cervical, Anal Platforms Designed for Rapid Expansion into Additional Indications Initial Trials in HPV+ Tumors Could Unlock Additional Cancers Worldwide >630,000 HPV+ diagnoses annually HPV+ Tumors Other Tumors Pancreatic cancer, CRC, NSCLC, heme malignancies & melanoma, for example, have known antigenic drivers In vitro human CD8 activation
11 SQZ™ cell-based therapeutic vaccine approaches aim to drive robust patient CD8 T cell activity Development and manufacturing synergies potentially enable rapid clinical translation Engineering Antigen Presentation for Powerful CD8 Activation CD8 T Cell Infiltration as a Prognostic Indicator in Solid Tumors Focus on engineering antigen presentation SQZ APCs SQZ eAPCs SQZ AACs PC Tumeh et. al. Nature. 2014 Responders Progressors Strong Correlation of CD8 TILs with Clinical Response
12 SQZ™ Approach Unlocking the Full Potential of Cell Therapies Oncology Using directed immunity to bring cell therapies to disease areas with significant unmet need Autoimmune Diseases Infectious Diseases and beyond
13 Powerful CD8 Activation with Robust MHC-I Antigen Presentation Squeezed Antigen MHC-I = CD8 T Cell Activation SQZTM APC Process Dramatically improved potential for efficacy vs Cross-Presentation Other vaccines, including the only approved cancer vaccine (Dendreon) use Cross-Presentation SQZTM technology bypasses need for cross-presentation - more efficiently activating CD8 T cells in pre-clinical studies
14 Flexible APC Candidate Trial Design | Monotherapy & Combination with ICIs Potential for earlier lines of therapy Earlier lines of therapy Later lines of therapy 0.5M cells per kg 2.5M cells per kg 5M cells per kg (DP) Cohort 1 Cohort 2 Monotherapy Enrollment Complete Open for Enrollment Cohort 3a *Additional cohorts defined in latest protocol Combination Therapy Expansion Cohorts Enhanced APCs Upcoming IND Broader patient population Enhanced co-stimulation Trial Across HPV+ tumors: H&N, Cervical, Anal, Penile, Vulvar/Vaginal Current Trial Progress Potential to enroll up to 200 patients in Phase 1 trial Several dosing and boosting schedules being explored 2.5M cells per kg (DP) Cohort 3 Trial ID: NCT04084951
15 SQZ™ APCs Demonstrated Safety and Reliable Manufacturing End-to-End Process Time Viability Manufacturing: Robust, consistent production in <24hrs All manufactured patient APCs induced IFN-γ secretion by T cells No subject met pre-specified DLT criteria No related Grade ≥3 SAEs reported: Grade 2 (related) – CRS (1 pt) Unrelated SAEs - Grade 3 (7 pts), Grade 4 (1 pt) and Grade 5 (1 pt) No dose reduction No treatment-related deaths Safety 100% IFN-γ secretion
16 Encouraging Increase in Immune Activity in Certain Patients 65-year-old woman – cervical cancer 3.5 years after diagnosis following treatment with (1) cisplatin/paclitaxel/ bevacizumab [BOR=CR] and (2) Pembrolizumab [BOR=PD] Low tumor burden, ECOG=0, RMH=1 On treatment for 10+ months, BOR=SD 2-fold increase in CD8 TIL vs. baseline CD8 cells/mm2 in CN BOR Survival FU* RMH Patient 67-year-old male – H&N cancer 1 year after diagnosis following treatment with carbo/5FU/pembro (BOR=PR) High tumor burden, ECOG=1, RMH=0 On treatment for 3 months, BOR=SD 6-fold increase in CD8 TIL vs. baseline Case Study: Patient 2 (Cohort 1 - 0.5e6/kg q3w) Case Study: Patient 7 Cohort 2 (2.5e6/kg q3w) *Survival Follow Up
17 Next Step: Combinations - Potential Synergies with Other I/O Compounds SQZ APCs aim to elicit tumor-specific CD8 T cells Other I/O compounds could synergistically enhance an antigen-specific response Presented at SITC 2020 in SQZ Poster and Roche Oral Presentation SQZTM APCs drive tumor-specific T cell activation I/O drugs enhance activity downstream Antigen-Specific Responses could be Amplified with Combination
18 SQZ™ Approach Unlocking the Full Potential of Cell Therapies Oncology Using directed immunity to bring cell therapies to disease areas with significant unmet need Autoimmune Diseases Infectious Diseases and beyond
Enhancing with Combination-like Functionality Key Features/Benefits: Multiple mRNA as cargo Further amplify MHC-I for more powerful CD8 activation Addition of co-stimulatory factors and cytokines: membrane-bound IL-2, IL-12 and CD86 Potential for combination functionality in single cell therapy Could reduce toxicity normally seen with traditional combinations HLA agnostic – potentially expands addressable patient population by about two-thirds IND targeted by end of the year 19
eAPC IND Planned for Q4 2021 CD86 1 2 3 Signals CD8 T Cell SQZ eAPC IL-2 IL-12 TCR MHC-I Potential to Enhance Responses and Expand Addressable Patient Population Potential to eliminate HLA restrictions and expand addressable patient population 20 TM
21 SQZ™ Approach Unlocking the Full Potential of Cell Therapies Oncology Using directed immunity to bring cell therapies to disease areas with significant unmet need Autoimmune Diseases Infectious Diseases and beyond
Creating Antigen Carriers from RBCs to Direct Immune Response Antigen Carriers (ACs) generated by squeezing RBCs deliver antigen to guide a specific immune response ACs are cleared by the same process as aged RBCs in vivo Professional APCs in lymphoid organs are primarily responsible for RBC clearance Act as “Trojan horses” to deliver antigen to endogenous professional antigen presenting cells 22
23 SQZ™ AACs Demonstrated Robust Activation in Preclinical Studies Antigen + Activating Adjuvant T cell activation Activation Lymphoid Organ SQZ™ AACs Data in HPV Tumor Model As presented at SITC 2020
24 SQZ-AAC-HPV Phase 1 Clinical Trial Across HPV+ Tumor Types Potential for earlier lines of therapy Earlier lines of therapy Later lines of therapy 50 M AACs/kg Dose determined by Cohort 1 observations Additional Cohorts Cohort 1 Cohort 2 Monotherapy Multiple I/O Combo Cohorts Combination Therapy Expansion Cohorts Safety-adjusted dose escalation allowing for data driven escalation No need for escalation in combo cohorts, starting with the recommended phase 2 dose Trial Across HPV+ tumors: H&N, Cervical, Anal, Penile, Vulvar/Vaginal Trial ID: NCT04892043
25 SQZ™ Approach Unlocking the Full Potential of Cell Therapies Oncology Autoimmune Diseases Using directed immunity to bring cell therapies to disease areas with significant unmet need Infectious Diseases and beyond
Directing Tolerogenic Immune Response SQZ™ Tolerizing Antigen Carriers (SQZ TACs) Leveraging antigen carriers from RBCs loaded with antigen only (no adjuvant) tolerize the immune response to that antigen Antigen Antigen + Activating Adjuvant SQZ Cargo T cell activation Activation Tolerization SQZ AACs (Activating Antigen Carrier) SQZ TACs (Tolerizing Antigen Carrier) 26 Engulfment by APCs Lymphoid Organ
27 Prevented Onset of T1D in Multiple Models and Showed Decreased Insulitis SQZ TACs Demonstrate Disease Altering Benefit in T1D Model Antigen-Specific Treg Increase in Pancreas
28 Unlocking the Full Potential of Cell Therapies Oncology Autoimmune Diseases Infectious Diseases and beyond Using directed immunity to bring cell therapies to disease areas with significant unmet need
29 Demonstrated Safety & Manufacturing: Could Open Broader Cell Therapy Universe Cell Squeeze® Technology Versatile technology could enable rapid portfolio growth Demonstrated safety and manufacturing with lead program in clinic Validating Roche collaboration for SQZ™ APCs in oncology Multiple cell therapy platforms in the clinic Multiple milestones expected in next 18 months across pipeline Many potential future opportunities Electroporation Viral transduction Current Methods for Creating Cell Therapies 29 Universe of Possible Cell Therapies Hematology Oncology Solid Tumors Autoimmune Infectious Disease Regenerative medicine
E*CA:2I