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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): January 11, 2021

 

 

 

RUBIUS THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-38586   46-2688109
(State or other jurisdiction
of Incorporation)  
  (Commission
File Number)
  (IRS Employer
Identification Number)  

 

399 Binney Street, Suite 300
Cambridge, MA
  02139
(Address of registrant’s principal executive office)  (Zip code)

 

(617) 679-9600

(Registrant’s telephone number, including 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:

 

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 203.425)

¨ 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 Trading symbol(s) Name of each exchange on which registered
Common Stock, par value $0.001 per share RUBY The Nasdaq Global Select Market

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.

 

Emerging growth company x

 

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 8.01. Other Events.

 

On January 11, 2021, Rubius Therapeutics, Inc. (the “Company”) provided an operational update and outlined its 2021 objectives, which the Company will be presenting at the 39th Annual J.P. Morgan Healthcare Conference during the week of January 11, 2021 (the “J.P. Morgan Conference”). A copy of the press release is filed as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein.

 

A copy of the Company’s presentation to be shared with investors and others from time to time beginning at the J.P. Morgan Conference (the “Investor Presentation”) is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated by reference herein. The information contained in the Investor Presentation should be considered in the context of the Company's filings with the Securities and Exchange Commission and other public announcements the Company may make by press release or otherwise from time to time. Information concerning risk factors affecting the Company's business can be found in its periodic filings with the Securities and Exchange Commission at www.sec.gov. The Investor Presentation is current as of January 11, 2021, and the Company disclaims any obligation to update the Investor Presentation after such date.

  

Item 9.01. Financial Statements and Exhibits.

 

(d) Exhibits.

 

Exhibit
No.
  Description
     
99.1   Press Release issued by Rubius Therapeutics, Inc. on January 11, 2021.
99.2   Investor Presentation of Rubius Therapeutics, Inc., dated January 11, 2021.
104   Cover Page Interactive Data File (embedded within the Inline XBRL document).

  

2

 

 

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.

  

Date: January 11, 2021 RUBIUS THERAPEUTICS, INC.  
   
  By:  /s/ Pablo J. Cagnoni  
    Pablo J. Cagnoni
    Chief Executive Officer

 

3

 

 

 

Exhibit 99.1

 

 

Rubius Therapeutics Provides Operational Update and Outlines 2021 Objectives

at the 39th Annual J.P. Morgan Healthcare Conference

 

Initial Clinical Data Show RTX-240 Stimulates Innate and Adaptive Immunity
(NK Cells and T Cells) Supporting Proof of Mechanism –
Additional Results to be Presented in Early 2021

 

IND Cleared and Patient Screening Underway for Phase 1 Clinical Trial of RTX-321 in Advanced Human Papillomavirus-Positive Cancers

Increased Productivity and Extended Product Shelf Life at Fully Owned Manufacturing Facility

 

CAMBRIDGE, Mass., January 11, 2021 (GLOBE NEWSWIRE) -- Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics™, today provided an operational update and announced its 2021 objectives. Pablo J. Cagnoni, M.D., chief executive officer, will present these updates and review 2020 achievements on Wednesday, January 13, 2021, at 8:20 a.m. EST at the virtual 39th Annual J.P. Morgan Healthcare Conference.

 

“Rubius Therapeutics made significant progress in advancing our oncology pipeline and in-house manufacturing capabilities in 2020,” said Pablo J. Cagnoni, M.D., president and chief executive officer. “To date, in the initial data from the Phase 1 clinical trial of RTX-240 in advanced solid tumors, we have observed activation and expansion of both target cell populations, NK and T cells, indicating the ability of RTX-240 to stimulate both innate and adaptive immune responses. We plan to present additional clinical results in early 2021, and we plan to submit for presentation at a scientific conference.”

 

By showing that RTX-240 is activating and expanding NK and T cells, Rubius Therapeutics believes that the full data set from the Phase 1 clinical trial will unlock the potential of the RED PLATFORM® across the entire pipeline of Red Cell Therapeutics for the treatment of cancer.

 

 

 

 

Clinical Program Updates

 

RTX-240 Phase 1/2 Clinical Trial for the Treatment of Advanced Solid Tumors and Relapsed/Refactory Acute Myeloid Leukemia (AML)

 

RTX-240 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to broadly stimulate the immune system by activating and expanding both NK and memory T cells to generate a potent anti-tumor response.

 

·To date, Rubius has completed dosing of 5 cohorts (n=14) in the Phase 1/2 RTX-240 solid tumor clinical trial. Trial enrollment continues in additional cohorts.
·Key takeaways from initial data to date show:
oNo treatment-related Grade 3 or Grade 4 adverse events and no dose limiting toxicities observed (n=14)
oAll patients showed activation of NK or T cells or both cell types (n=14)
oIn the majority of patients (n=8), all of the following were observed across dose levels:
§Activation of NK cells, activation of T cells, expansion of NK cells and expansion of T cells
·As more patients are enrolled and data mature, the Company expects to disclose additional clinical results, including
oadditional safety and tolerability data;
obiomarkers associated with the activation and expansion of NK and T cells in peripheral blood
oimmune cell trafficking into tumors assessed by optional tumor biopsies from participating patients; and
opotential responses as measured by objective response rate
·Enrollment continues in the Phase 1 clinical trial of RTX-240 in relapsed/refractory AML

 

RTX-321 Artificial Antigen-Presenting Cell (aAPC) Development Program for Human Papillomavirus (HPV) 16-Positive Cancers

 

RTX-321 is an allogeneic, off-the-shelf aAPC therapy product candidate that is engineered to induce a tumor-specific immune response by expanding antigen-specific T cells. RTX-321 expresses hundreds of thousands of copies of an HPV peptide antigen bound to major histocompatibility complex class I proteins, the costimulatory molecule 4-1BBL and the cytokine IL-12 on the cell surface to mimic human T cell-APC interactions.

 

·The Investigational New Drug (IND) application has been cleared and patients are being screened in the Phase 1 clinical trial of RTX-321 in advanced HPV 16+ cancers, including cervical cancer, head and neck cancer and anal cancer

 

Manufacturing Update and Recent Achievements

 

Recognizing the importance of controlling manufacturing to produce consistent and reproducible product at greater scale, Rubius acquired, renovated and operationalized a manufacturing facility in Smithfield, RI. The site has achieved the following milestones:

 

·Provided consistent cGMP supply for the two Phase 1 arms in the ongoing RTX-240 clinical trial in advanced solid tumors and relapsed/refractory AML
oIncreased productivity in manufacturing of cGMP supply of RTX-240 in 50L bioreactors

 

 

 

 

oIncreased liquid in-vial shelf life from 28 to 52 days for RTX-240
oContinuously met red blood cell identity (CD233+, mean corpuscular hemoglobin, purity, enucleation cell population) and target product profile criteria (protein expression, cell viability) for clinical supply lots
·Completed engineering runs and now producing cGMP supply for the Phase 1 clinical trial of RTX-321 for advanced HPV 16-positive cancers
oIntroduced frozen drug substance for the first time as part of the IND application for RTX-321, resulting in a truly off-the-shelf cellular therapy with a potential shelf life of up to several years
oFollowing liquid reformulation, RTX-321 drug product has an in-vial shelf life of 52 days
·Significant potential to expand manufacturing capabilities based on future supply needs and for potential commercial production

 

Preclinical Data 2020 Summary

 

The Company presented preclinical oncology data for RTX-240 and RTX-321 at the following conferences:

 

oSociety for Immunotherapy of Cancer (SITC) Annual Meeting;
oFederation of Clinical Immunology Societies (FOCIS) Virtual Annual Meeting;
oAmerican Association for Cancer Research (AACR) Tumor Immunology Conference; and
oAmerican Society of Gene & Cell Therapy 23rd Annual Meeting

 

Anticipated 2021 Catalysts and Operational Objectives

 

oPresent additional clinical data for the Phase 1 RTX-240 solid tumor trial in early 2021;
oContinue to enroll patients with AML in the second Phase 1 arm of the RTX-240 clinical trial;
oDose the first patient in the RTX-321 clinical trial in HPV-positive tumors;
oContinue to produce cGMP material for the RTX-240 and RTX-321 clinical trials; and
oPresent an integrated clinical program for RTX-240, including plans for expansion cohorts, and oncology pipeline

 

 

 

 

Listen to the Webcast

 

A live audio webcast of Dr. Cagnoni’s presentation will be available on January 13, 2021 at 8:20 a.m. EST within the Investors & Media section of the Rubius Therapeutics website. An archived replay will be accessible for 90 days following the event.

 

About Rubius Therapeutics

 

Rubius Therapeutics is a clinical-stage biopharmaceutical company developing a new class of medicines called Red Cell Therapeutics™. The Company’s proprietary RED PLATFORM® was designed to genetically engineer and culture Red Cell Therapeutics™ that are selective, potent and off-the-shelf allogeneic cellular therapies for the potential treatment of several diseases across multiple therapeutic areas. Rubius’ initial focus is to advance RCT™ product candidates for the treatment of cancer and autoimmune diseases by leveraging two distinct therapeutic modalities — potent cell-cell interaction and tolerance induction. Rubius Therapeutics was recently named among the Top Places to Work in Massachusetts by the Boston Globe, and its manufacturing site was recently named 2020 Top 5 Best Places to Work in Rhode Island among medium-sized companies by Providence Business News. For more information, visit www.rubiustx.com, follow us on Twitter or LinkedIn or like us on Facebook.

 

Forward-Looking Statements

 

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding our expectations regarding the therapeutic potential of our pipeline of Red Cell Therapeutics, including RTX-240 for the treatment of patients with relapsed/refractory or locally advanced solid tumors and RTX-321 for the treatment of HPV 16-positive cancers, our expectations regarding the timing, enrollment, additional data from and success of the future cohorts and phases of the clinical trial of RTX-240, our expectations regarding the biological effects of RTX-240 on innate and adaptive immunity, including activation and increased numbers of NK cells and T cells in the clinical trial of RTX-240, and our expectations regarding the full data set from the Phase 1 clinical trial and its ability to unlock the potential of the RED PLATFORM across our entire pipeline of Red Cell Therapeutics for the treatment of cancer, timelines related to the Phase 1 clinical trial of RTX-321, our expectations regarding our ability to expand manufacturing capabilities, our expectations regarding the potential shelf life of our frozen drug substance for RTX-321, our expectations regarding our cash runway and our strategy, business plans and focus. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the development of our Red Cell Therapeutic product candidates and their therapeutic potential and other risks identified in our SEC filings, including our Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, and subsequent filings with the SEC and risks and uncertainties related to the severity and duration of the impact of COVID-19 on our business and operations. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent our views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements.

 

 

 

 

Contacts:

 

Investors

Elhan Webb, CFA, Vice President of Investor Relations

elhan.webb@rubiustx.com

 

Media

Marissa Hanify, Director, Corporate Communications

Marissa.hanify@rubiustx.com

 

Dan Budwick, 1AB

+1 (973) 271-6085

dan@1abmedia.com

 

 

 

 

Exhibit 99.2

 

JANUARY 2021 REALIZING THE POWER OF REDsv™ A NEW ERA IN CELLULAR MEDICINE 1

 

 

Forward - Looking Statements This presentation may contain forward - looking statements . Forward - looking statements are neither historical facts nor assurances of future performance . Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our development plans, our clinical results and other future conditions . All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial or business performance, conditions, plans, prospects, trends or strategies and other financial and business matters ; our current and prospective product candidates, planned clinical trials and preclinical activities, including timing related to such trials and expected results, research and development costs, current and prospective collaborations ; the estimated size of the market for our product candidates, the timing and success of our development and commercialization of our anticipated product candidates ; and the availability of alternative therapies for our target market . New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties . Except as required by applicable law, we do not plan to publicly update or revise any forward - looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise . 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 . Accordingly, readers are cautioned not to place undue reliance on these forward - looking statements . No representations or warranties (expressed or implied) are made about the accuracy of any such forward - looking statements . 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 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 . Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source . Rubius recommends that investors independently evaluate specific investments and strategies . For further information regarding these risks, uncertainties and other factors, you should read the “Risk Factors” section of our Quarterly Reports on Form 10 - Q filed for the period ended September 30 , 2020 , and Annual Report on Form 10 - K filed for the period ended December 31 , 2019 , and subsequent filings with the Securities and Exchange Commission . This presentation may contain tradenames, trademarks or servicemarks of other companies . Rubius does not intend the use or display of other parties’ tradenames, trademarks or servicemarks to imply a relationship with, or endorsement or sponsorship of, these other parties . 2

 

 

Completed dosing of 5 cohorts (n=14) in Phase 1/2 RTX - 240 solid tumor clinical trial; generating clinical data DELIVERING ON CRITICAL MILESTONES AND BUILDING THE RIGHT CULTURE Dosing patients in Phase 1 arm of RTX - 240 clinical trial in relapsed/refractory acute myeloid leukemia (AML) Screening patients in Phase 1 trial of RTX - 321 for HPV 16+ cancers; frozen drug substance with potential shelf life of up to several years Fully owned manufacturing enables execution of clinical trials; conducting cGMP runs for RTX - 240 and RTX - 321 clinical trials Presented preclinical oncology data supporting lead oncology programs at SITC, FOCIS, AACR & ASGCT Strong Execution of Key Priorities 3

 

 

Present additional clinical data for RTX - 240 solid tumor trial in early 2021, and submit to a scientific conference Anticipated Upcoming Catalysts and Operational Objectives 4 AN INTEGRATED DEVELOPMENT COMPANY Continue to enroll patients in RTX - 240 AML clinical trial Dose first patient in RTX - 321 clinical trial in HPV 16+ cancers Continue to produce cGMP material for RTX - 240 and RTX - 321 trials from Rubius site Cash runway into 2022 Unlocking the potential of the RED PLATFORM in cancer and autoimmune disease Present an integrated clinical program for RTX - 240, including plans for expansion cohorts, and oncology pipeline

 

 

The Promise of the RED PLATFORM ® EXPANSION & DIFFERENTIATION GENETIC ENGINEERING WITH LENTIVIRUS 100 - 1000’s OF DOSES EARLY PROGENITOR CELLS ENUCLEATION & MATURATION RED CELL THERAPEUTIC SINGLE HEALTHY O - DONOR 5 FEATURES • Consistent research and manufacturing process • Only modification is lentivirus to create new product • Universal, scalable, reproducible BENEFITS • Leverages common CMC, toxicology data packages • Shorter timeline to lead candidate • Efficient cost structure

 

 

Red Cell Therapeutics™: The Future of Cellular Therapy 6 Modular platform that mimics immune biology Cellular presentation of potent immune agonists & cytokines POTENTIALLY TRANSFORMATIVE ALLOGENEIC CELLULAR THERAPIES POTENT ADVANTAGEOUS TOLERABILITY SCALABLE Biodistribution confined to vasculature Broadens therapeutic window Off - the - shelf cellular therapy from Rubius manufacturing site

 

 

Fully Owned Manufacturing and Integrated Technical Development & Operations 7 Significant potential to expand manufacturing capabilities based on future needs Providing cGMP clinical supply for RTX - 240 trial and RTX - 321 trials Small - scale production, process development, cGMP manufacturing, analytical development & quality operations Highly experienced cell therapy technical operations team with scalable process

 

 

Scaled platform from 1L to 10L bioreactors Scaled platform to 50L bioreactors 28 - day liquid in - vial shelf life for RTX - 240 52 - day liquid in - vial shelf life for RTX - 240 Produced consistent drug supply for RTX - 240 trials in 50L bioreactors Increased productivity in 50L bioreactor for RTX - 240 Introduced frozen drug substance for RTX - 321 RTX - 240 Case Study Robust Manufacturing Capabilities 8 2016 - 2017 RUBIUS TECHNICAL DEVELOPMENT AND MANUFACTURING JOURNEY Product Profile (Protein Expression, Cell Viability) Red Blood Cell Identity (CD233+, Mean Corpuscular Hemoglobin, Purity, Enucleation Cell Population) 2018 2020 2021

 

 

BROAD IMMUNE SYSTEM STIMULATION Stimulate adaptive and innate immunity • Potential broad therapeutic window of agonists expressed on cell surface • Biodistribution may reduce toxicities of agonists Realize the power of immune agonists CANCER AUTOIMMUNE DISEASES ANTIGEN - SPECIFIC IMMUNE STIMULATION Drive tumor - specific responses • Drive tumor - specific responses and broad immune stimulation • Engineered red blood cells presenting all three signals* to optimally activate T cells Unlock the potential of antigen - specific immunotherapy TARGETING THE APC Induce immune tolerance • Autoantigen delivery and presentation of inhibitory molecules • Aim to create tolerogenic APCs that promote regulatory CD4+ cells Induce immune tolerance in high - potential indications RED PLATFORM ® Enables Multiple Modalities 9 Three signals: 4 - 1BBL, IL - 12, tumor - antigen peptide bound to MHC I

 

 

Clinical - Stage Company Building a Broad Wholly Owned Pipeline PRODUCT CATEGORY PROGRAM PRECLINICAL IND ENABLING PHASE 1 CANCER RTX - 240 RTX - 240 RTX - 321 aAPC (HPV 16+) RTX - 224 RTX - aAPC AUTOIMMUNE DISEASES RTX - T1D R/R Solid Tumors Type 1 Diabetes R/R Solid Tumors R/R Acute Myeloid Leukemia R/R HPV - 16+ Solid Tumors Cancer 10

 

 

RTX - 240: BROAD IMMUNE SYSTEM STIMULATION 11

 

 

RTX - 240: Enrolling Phase 1/2 Clinical Trial in Advanced Solid Tumors & Phase 1 Arm in Relapsed/Refractory AML 12 BROAD IMMUNE SYSTEM STIMULATION POTENTIAL BENEFITS: • Activate existing agonist pathways leading to enhanced potency • Improve anti - tumor activity • Overcome resistance to immunotherapy • Reduce toxicity given biodistribution confined to vasculature 4 - 1BBL NATURAL KILLER (NK) CELL 4 - 1BBL IL - 15TP T CELL STIMULATE ADAPTIVE AND INNATE IMMUNE CELL AGONIST PATHWAYS RTX* - 240 | (4 - 1BBL + IL - 15TP) IL - 15TP * Rubius Therapeutics Terminology: RTX – Red Cell Therapeutic product candidate; mRBC – mouse surrogate model; RCT – experimental construct

 

 

Proposed Mechanism of RTX - 240 PERIPHERAL BLOOD SPLEEN NK cell RTX RBC T cell RTX RBC T cell Red pulp White pulp NK cell T cell NK cell Tumor cell Potential for enhanced efficacy and safety by confining RTX - 240 to the vasculature 13 4 Activation Trafficking Tumor killing Expansion 1 2 3 1 2 3 4

 

 

Exhausted anti - tumor T cell Active anti - tumor T cell Spleen Blood vessel Tumor Spleen Blood vessel Tumor Wu, TD, et al. Grogan JL. Peripheral T Cell Expansion Predicts Tumour Infiltration and Clinical Response. Nature 2020 Beltra JC, et al. Wherry J. Developmental Relationships of Four Exhausted CD8+ T cell Subsets Reveals Underlying Transcriptional and E pigenetic Landscape Control Mechanisms. Immunity 2020 PD - 1 INHIBITION ACTS ON ANTI - TUMOR T CELLS EXISTING OUTSIDE OF T HE TUMOR MICROENVIRONMENT (TME) 14 Tumor - Specific T Cells Exist in the Spleen and Peripheral Blood Checkpoint inhibition Checkpoint inhibition ( a PD - 1) drives tumor - specific T cells arising from the spleen and vasculature to the TME

 

 

T AND NK CELL EXPANSION IN BLOOD (In Vivo with healthy mice) 0 2×10 5 4×10 5 0 5×10 5 1×10 6 1.5×10 6 2×10 6 Number of CD8 RTX - 240 Preclinical Data Demonstrated Mechanism of Action In Vivo 15 CD8+ T Cells NK Cells 0 20 40 60 80 0 5 10 15 20 %CD8 of CD45+ %NK of CD45+ Model details: Normal mice; 4 Doses, 1x10 9 cells at days 0, 3, 7, 10; Sacrifice day 14 ~2x CD8+ T cells ~2x NK cells ~3x ~4x Number of NK Cells CT26 model details: 1x10 9 cells at days:1,5,8; PD evaluated in the tumors on Day 11 B16F10 model details: 1x10 9 cells at days:1,4,8; PD evaluated in the tumors on Day 10 CTRL mRBC - 240 1x10 9 CTRL mRBC - 240 T AND NK CELL TRAFFICKING TO TUMORS (CT26 and B16F10 tumor models)

 

 

mRBC - 240 Resulted in No Liver Toxicity and Significantly Inhibited Tumor Growth as Monotherapy Compared to Anti - 4 - 1BB mAb In Vivo m R C T - C T R L m R C T - 2 1 2 1 E 9 P D 1 m A b 1 5 0 u g m R C T - 2 1 2 1 E 9 + P D 1 m A b 1 5 0 u g 4 - 1 B B m A b 2 0 0 u g 4 - 1 B B m A b 5 0 u g 0 50 100 150 200 250 4 Doses, 1x10 9 cells day 0, 3, 7, 10; Sacrifice day 18 ALT/SGPT (U/L) Dugast , et. al., American Association for Cancer Research ; Poster #3272, 2019 16 0 50 100 150 200 mRBC - 240 reduced tumor burden and was equivalent to anti - 4 - 1BB mAb in vivo B16F10 LUNG METASTASES MODEL Metastases per lung 3 Doses, 1x10 9 cells day 1, 5, 8, Sacrifice day 14 mRBC - 240 showed no liver toxicity in vivo SERUM ALT

 

 

17 RTX - 240 CLINICAL DEVELOPMENT PROGRAM & KEY TAKEAWAYS FROM INITIAL DATA

 

 

RTX - 240 Solid Tumor Clinical Trial Objectives 18 • Determine safety and tolerability, define recommended Phase 2 dose (RP2D) and interval of RTX - 240 • Assess pharmacodynamic (PD) activity of RTX - 240 measured by changes in T and NK cell number and function relative to baseline: – Activation of NK and T cells (e.g., HLA - DR expression, NKp30) – Expansion with increased absolute numbers of target cells – Tumor - trafficking via immunofluorescence* • Measure anti - tumor activity by objective response rate (ORR) • Assess pharmacokinetics (PK) of RTX - 240 18 PHASE 1 OBJECTIVES *Assays performed on a limited set of optional biopsies from participating patients PHASE 1 OBJECTIVES

 

 

RTX - 240 Solid Tumor Clinical Development Plan RTX - 240 Phase 2: Tumor - Specific Expansion Cohort #2 ENROLLING: Phase 1 Dose Escalation 5 Dose Cohorts Completed to Date (n=14) Phase 2: Tumor - Specific Expansion Cohort #1 19 • R/R or locally advanced, unresectable solid tumor for which no standard therapy exists, or for which the patient is ineligible or has declined standard therapy • Median of 3.5 prior lines of therapy (range, 1 - 10) • 10 of 14 patients had prior PD - 1/PD - L1 inhibitor therapy DEVELOPMENT PLAN 19 RELAPSED/ REFRACTORY (R/R) OR LOCALLY ADVANCED SOLID TUMORS ELIGIBILITY CRITERIA 1e8 (n=2) Q4W 1e9 (n=3) Q6W 3e9 (n=3) Q4W 1e10 (n=3) Q4W Further explore dose & interval 1e10 (n=3) Q4W* *Exploratory alternate route of administration

 

 

In the majority of patients (n=8), all of the following were observed across dose levels: ▪ Activation of NK cells ▪ Activation of T cells ▪ Expansion of NK cells ▪ Expansion of T cells Key Takeaways from Initial Data – RTX - 240 Stimulates Adaptive and Innate Immunity, Supporting Proof of Mechanism 20 No treatment - related Grade 3 - 4 adverse events and no dose - limiting toxicities observed to date (n=14) Additional clinical data to be presented in early 2021, and submitted to a scientific conference All patients showed activation of NK or T cells or both cell types (n=14)

 

 

• Determine safety and tolerability, MTD, RP2D and dosing interval of RTX - 240 • Assess PD effects of RTX - 240 as measured by changes in NK and T cell number and function relative to baseline in peripheral blood and paired bone marrow biopsies • Measure anti - tumor activity by ORR • Assess PK of RTX - 240 1e8 Q4W 1e9 Q4W 5e9 Q4W 1e10 Q4W Further explore dose and interval RTX - 240 AML Clinical Development Plan ENROLLING: Phase 1 Dose Escalation Phase 2 Expansion 21 RELAPSED/ REFRACTORY ACUTE MYELOID LEUKEMIA • R/R cytologically confirmed AML • Patients with prior stem cell transplant or transplant ineligible are included ELIGIBILITY CRITERIA KEY PHASE 1 OBJECTIVES: RTX - 240 DEVELOPMENT PLAN

 

 

RTX - 321: ANTIGEN - SPECIFIC IMMUNE STIMULATION 22

 

 

ANTIGEN PRESENTATION Rubius’ First Engineered aAPC will Target HPV+ Tumors – IND Cleared and Screening Patients for Phase 1 Clinical Trial SELECTIVE TUMOR KILLING BY EXPANDING TUMOR - SPECIFIC T CELLS BROAD IMMUNE SYSTEM STIMULATION LEADS TO EPITOPE SPREADING • Replicate immune system function to activate and expand antigen - specific T cells for a potent anti - tumor effect • Induce antigen - specific response and epitope spreading for a broad and effective anti - tumor response RTX - 321 (aAPC) | HPV 16+ Tumors Signal 2 4 - 1BBL T Cell Signal 1 HPV - 16 Antigen Signal 3 IL - 12 23 POTENTIAL BENEFITS:

 

 

0 10 20 30 40 0 2000 4000 6000 OT-1 (5E5) naïve group mRBC-OVA-4-1BBL-IL-12 previously cured (n=7) 7/7 cures 0 10 20 30 0 2000 4000 6000 OT-1 (5E5) naïve group mRBC-OVA-4-1BBL-IL-12 previously cured (n=7) 1E5 EL4 3/7 delayed 3/7 cures Re - challenge with EL4, the “parental” line of EG7.OVA. EL4 expresses other tumor antigens, but not OVA, the antigen that was presented by the aAPC Tumor volume mm 3 2E6 EG7.OVA re - challenge Days post EG7.OVA re - challenge Re - challenge with original tumor Tumor volume mm 3 Days post EL4 challenge OT - 1 (5E5) naïve group Re - challenge of Cured Mice Demonstrates Memory and Epitope Spreading Nixon, et. al., American Society of Gene & Cell Therapy ; Poster #32, 2020 24 EG7.OVA RE - CHALLENGE EL4 CHALLENGE

 

 

RTX - 321 Clinical Development Plan in Advanced HPV+ Tumors SCREENING : Phase 1 Dose Escalation Phase 2 Expansions in Specific Indications 25 PERSISTENT, RECURRENT, OR METASTATIC, UNRESECTABLE, HPV 16 - POSITIVE CANCERS • Cervical cancer, head and neck squamous cell cancer (HNSCC), or squamous cell cancer of the anal canal that is not amenable to curative therapy • HLA - A*02:01 - positive patients • Documentation of HPV 16+ tumor for patients with cervical cancer and HNSCC • Patients will have received standard platinum - or mitomycin C - based chemo and, where clinically appropriate, bevacizumab and/or PD - 1/PD - L1 therapy ELIGIBILITY CRITERIA RTX - 321 DEVELOPMENT PLAN 1e9 Q3W 5e9 Q3W 1e10 Q3W Further explore dose and interval • Determine the safety and tolerability of monotherapy RTX - 321 and RP2D PRIMARY MEASURES • Assess PD changes in immune cell populations in peripheral blood and tumor biopsies • Determine anti - tumor activity of RTX - 321 as measured by ORR, duration of response, progression free survival and overall survival SECONDARY MEASURES

 

 

EXPECTED CATALYSTS 26

 

 

Present additional clinical data for RTX - 240 solid tumor trial in early 2021, and submit to a scientific conference Anticipated Upcoming Catalysts and Operational Objectives 27 AN INTEGRATED DEVELOPMENT COMPANY Continue to enroll patients in RTX - 240 AML clinical trial Dose first patient in RTX - 321 clinical trial in HPV 16+ cancers Continue to produce cGMP material for RTX - 240 and RTX - 321 trials from Rubius site Cash runway into 2022 Unlocking the potential of the RED PLATFORM in cancer and autoimmune disease Present an integrated clinical program for RTX - 240, including plans for expansion cohorts, and oncology pipeline

 

 

REALIZING THE POWER OF RED™ A NEW ERA IN CELLULAR MEDICINE 28