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): January 8, 2020
RUBIUS THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
(State or other jurisdiction
399 Binney Street, Suite 300
|(Address of registrant’s principal executive office)||(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 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 |
|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 þ
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 8, 2020, Rubius Therapeutics, Inc. (the “Company”) issued a press release announcing the appointment of Laurence Turka, M.D., as the Company’s first chief scientific officer, effective January 21, 2020.
As co-founder and chief scientific officer of Rheos Medicines, Dr. Turka built its portfolio of novel therapies targeting the metabolism of immune cells, made key leadership hires and was instrumental in securing a strategic collaboration between Rheos and Roche. Prior to Rheos, he was an entrepreneur-in-residence at Third Rock Ventures, where he played a leading role in the creation of Rheos and provided immunology expertise in evaluating multiple company-building opportunities. Before joining venture capital, Dr. Turka spent 30 years working in academia, most recently serving as the Harold and Ellen Danser Professor of Surgery and professor of medicine at Harvard Medical School and Massachusetts General Hospital. Among the notable discoveries of Dr. Turka's laboratory were novel approaches to transplantation tolerance, the role of Toll-like receptors in T cells and pathways required for the maintenance of regulatory T cell function. Dr. Turka was also an early leader in the field of T cell costimulation and contributed to the development of abatacept and belatacept for the treatment of rheumatoid arthritis and renal transplantation. He is a former president of the American Society of Transplantation, chair of the NIAID Board of Scientific Counselors and editor in chief of The Journal of Clinical Investigation. He is currently the deputy director of the Immune Tolerance Network, serves on the scientific steering committee of the Parker Institute for Cancer Immunotherapy and is the Harold and Ellen Danser Professor of Surgery (part-time) at Harvard Medical School. Dr. Turka received his M.D. from the Yale University School of Medicine, trained in internal medicine at Yale-New Haven Hospital and in nephrology at the Brigham and Women's Hospital/Harvard Medical School. He was elected to membership in the American Society for Clinical Investigation in 1995, and the Association of American Physicians in 2003.
A copy of the press release issued in connection with the announcement is attached hereto as Exhibit 99.1.
On January 13, 2020, the Company updated its investor presentation (the “Investor Presentation”), which the Company expects to use in connection with general corporate presentations and will be made available on the Company’s website or distributed by the Company in hardcopy or electronic form.
A copy of the Company’s updated Investor Presentation is filed as Exhibit 99.2 to this Current Report on Form 8-K. The Investor Presentation is current as of January 13, 2020, and the Company disclaims any obligation to update the Investor Presentation after such date.
Item 9.01. Financial Statements and Exhibits.
|99.1||Press Release issued by Rubius Therapeutics, Inc. on January 8, 2020.|
|99.2||Investor Presentation of Rubius Therapeutics, Inc., dated January 13, 2020.|
|99.1||Press Release issued by Rubius Therapeutics, Inc. on January 8, 2020.|
|99.2||Investor Presentation of Rubius Therapeutics, Inc., dated January 13, 2020.|
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 13, 2020||
RUBIUS THERAPEUTICS, INC.
|By:||/s/ Pablo J. Cagnoni|
|Pablo J. Cagnoni|
|Chief Executive Officer|
Rubius Therapeutics Appoints Internationally
Recognized Autoimmunity and
Translational Immunology Leader Laurence Turka, M.D., as Chief Scientific Officer
CAMBRIDGE, Mass., Jan. 8, 2020 (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, today announced the appointment of Laurence Turka, M.D., as its first chief scientific officer, effective January 21, 2020. Dr. Turka, a distinguished physician-scientist in autoimmunity and translational immunology, joins Rubius from Rheos Medicines, where he was a co-founder and served as chief scientific officer.
“Larry brings to Rubius exceptional insights and an extraordinary record of scientific achievement in immune-mediated diseases,” said Pablo J. Cagnoni, M.D., chief executive officer of Rubius Therapeutics. “Larry joins at a pivotal time as we continue to explore the broad potential of the RED PLATFORM® for the treatment of rare diseases, cancer and autoimmune diseases and as our lead oncology program, RTX-240, is expected to enter the clinic this year. His expertise will be invaluable towards translating our discovery research into important breakthroughs for patients.”
As co-founder and chief scientific officer of Rheos Medicines, Dr. Turka built its portfolio of novel therapies targeting the metabolism of immune cells, made key leadership hires and was instrumental in securing a strategic collaboration between Rheos and Roche. Prior to Rheos, he was an entrepreneur-in-residence at Third Rock Ventures, where he played a leading role in the creation of Rheos and provided immunology expertise in evaluating multiple company-building opportunities. Before joining venture capital, Dr. Turka spent 30 years working in academia, most recently serving as the Harold and Ellen Danser Professor of Surgery and professor of medicine at Harvard Medical School and Massachusetts General Hospital. Among the notable discoveries of Dr. Turka’s laboratory were novel approaches to transplantation tolerance, the role of Toll-like receptors in T cells and pathways required for the maintenance of regulatory T cell function. Dr. Turka was also an early leader in the field of T cell costimulation and contributed to the development of abatacept and belatacept for the treatment of rheumatoid arthritis and renal transplantation. He is a former president of the American Society of Transplantation, chair of the NIAID Board of Scientific Counselors and editor in chief of The Journal of Clinical Investigation. He is currently the deputy director of the Immune Tolerance Network, serves on the scientific steering committee of the Parker Institute for Cancer Immunotherapy and is the Harold and Ellen Danser Professor of Surgery (part-time) at Harvard Medical School. Dr. Turka received his M.D. from the Yale University School of Medicine, trained in internal medicine at Yale-New Haven Hospital and in nephrology at the Brigham and Women’s Hospital/Harvard Medical School. He was elected to membership in the American Society for Clinical Investigation in 1995, and the Association of American Physicians in 2003.
“Rubius’ approach of harnessing the unique properties of red blood cells with the creative potential of genetic engineering using the RED PLATFORM has the potential to deliver on the promise of cellular therapy, and I could not be more excited to join such an innovative company,” said Larry Turka, M.D., chief scientific officer at Rubius Therapeutics. “With broad therapeutic applications across rare diseases, cancer and autoimmune diseases, we have the opportunity to impact the lives of many patients in need.”
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 rare diseases, cancer and autoimmune diseases by leveraging three distinct therapeutic modalities — cellular shielding, potent cell-cell interaction and tolerance induction. For more information, visit www.rubiustx.com, or follow us on Twitter and LinkedIn.
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 the planned timing, recruitment, enrollment and results for our preclinical and clinical activities, including the Phase 1b clinical trial for RTX-134 for the treatment of PKU, our ability to further develop our RCT product candidates, our manufacturing process, our expectations regarding the therapeutic potential of our RCTs, our expectations regarding new and continuing members of our leadership team 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 RCT 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, 2019, and subsequent filings with the SEC. 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.
Vice President, Corporate Communications and Investor Relations
+1 (617) 949-5296
+1 (973) 271-6085
Pablo J. Cagnoni , M.D., Chief Executive Officer JANUARY 2020 REALIZING THE POWER OF RED ™ : A NEW ERA IN CELLULAR MEDICINE
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 Report on Form 10 - Q filed for the period ended September 30 , 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
2019 Achievements: Setting the Stage for Success 3 STRENGTHENED ORGANIZATION & DELIVERED MILESTONES Accelerated Rubius manufacturing site buildout and GMP operations Manufactured clinical - grade RTX - 134 at contract manufacturing organization Filed IND and received clearance for first - ever RCT – RTX - 134 Filed first oncology IND for RTX - 240 Completed GMP engineering runs for RTX - 240 at Rubius manufacturing site Grew patent estate to 10 issued U.S. patents Presented preclinical oncology data at AACR, AACR - NCI - EORTC & SITC Strengthened leadership team with Chief Medical Officer, Chief Scientific Officer, Head of BD, Chief Legal Officer and Chief Quality Officer
Advances and Limitations of Current Cell Therapies 4 Significant opportunities in oncology and beyond for more potent and less toxic cellular medicines • Limited to certain hematologic cancers • Severe side effects • Unpredictable pharmacokinetics and biodistribution • Costly manufacturing • No approved allogeneic therapies CURES IN CERTAIN CANCERS ADVANCES LIMITATIONS REMAIN
Harnessing the Unique Properties of Red Blood Cells 5 • Have a circulation time of ~120 days • Lack a nucleus • Have a predictable biodistribution in the vasculature • > 100 - year history of administering blood to patients WHY RED BLOOD CELLS? O NEGATIVE RBCs CAN BE GIVEN TO ~ 95% OF PEOPLE
Red Cell Therapeutics™ 6 POTENTIALLY TRANSFORMATIVE CELLULAR THERAPIES OFF - THE - SHELF BROAD THERAPEUTIC APPLICATIONS PREDICTABLE BIODISTRIBUTION DEFINED LIFE IN CIRCULATION AND CONVENIENT DOSING ADVANTAGEOUS TOLERABILITY SCALABLE MANUFACTURING RARE DISEASE CANCER AUTOIMMUNE
The Promise of Red Cell Therapeutics™: Highly Potent, Allogeneic and Off - the - Shelf 7 Red Cell Therapeutic (RCT) dose expected to be <1% of normal red cell volume GENETIC E NGINEERING SINGLE HEALTHY O - DONOR EXPANSION & DIFFERENTIATION RED CELL THERAPEUTIC ENUCLEATION & MATURATION RED PLATFORM ® 100 - 1000’s OF DOSES EARLY PROGENITOR CELLS
RED PLATFORM ® Enables Multiple Modalities 8 RARE ENZYME DEFICIENCIES ENZYME REPLACEMENT CELLULAR SHIELDING ENZYMES WITHIN THE RCT CANCER IMMUNE STIMULATION POTENT CELL - CELL INTERACTION AUTOIMMUNE DISEASES IMMUNE MODULATION ANTIGEN - SPECIFIC IMMUNOMODULATORS T CELL NK CELL ANTIGEN - SPECIFIC IMMUNOSTIMULANTS T CELL NON - SPECIFIC IMMUNOMODULATORS NON - SPECIFIC IMMUNOSTIMULANTS TOLERANCE INDUCTION
Building a Broad and Diverse Pipeline 9 PRODUCT CATEGORY PATIENT POPULATION PROGRAM PRECLINICAL IND ENABLING PHASE 1 RARE DISEASES 50,000+ RTX - 134 FPI* & Initial Clinical Data Expected 100,000+ RTX - Uricase 2,000 - 4,000 RTX - CBS 20,000+ RTX - OxOx CANCER 100,000+ RTX - 240 IND on File with FDA 10,000+ RTX - 240 10,000+ RTX - 321 aAPC (HPV+) IND Filing Expected by Year - End 100,000+ RTX - 224 AUTOIMMUNE DISEASES Antigen - Specific RTX - T1D Non - Specific RTX - PV R/R aPD1 Solid Tumors Refractory Gout Type 1 Diabetes Pemphigus Vulgaris R/R aPD1 Solid Tumors R/R AML Post HSCT R/R HPV+ Solid Tumors Phenylketonuria Homocystinuria Hyperoxaluria *FPI: First Patient In
Manufacturing Update 11 • Expected to provide supply for RTX - 240 and RTX - 321 trials • CMO producing RTX - 134 for current Phase 1b clinical trial • Rubius manufacturing site operational • Delivered nine months ahead of schedule • Potential to expand manufacturing capabilities based on future needs
• RTX - 134 shields immunogenic PAL enzyme from the immune system • PAL metabolizes and converts Phe to TCA • Target indication: patients with serum Phe levels ≥ 600 μ mol/L • Infrequent, low volume IV administration • Seek Orphan Drug Designation • Deficiency of the enzyme needed to break down dietary phenylalanine (Phe) • Symptoms: Intellectual disability, delayed development, impaired cognitive function, irreversible brain damage RTX - 134 PHENYLKETONURIA (PKU) PAL ENZYME 15,000 U.S. AND 50,000+ PATIENTS WORLDWIDE Phenylalanine Trans - Cinnamic Acid (TCA) RTX - 134 for the Potential Treatment of Phenylketonuria 13
Trans - Cinnamic Acid (TCA) Phenylalanine ( Phe ) RTX - 134: Simple Three - Step Mechanism of Action 14 Phe Naturally Enters RTX - 134 as it Circulates 1 TCA Exits RTX - 134 and is Processed by the Body 3 PAL Enzyme Breaks Down Phe into TCA inside RTX - 134 2
SINGLE ASCENDING DOSE OF RTX - 134 N=UP TO 12 PATIENTS RTX - 134 Phase 1b Clinical Trial Design 15 Cohort 1 Cohort 2 Cohort 3 Cohort 4 n=2 n=2 n=2 n=2 Optional Cohort 5 Optional Cohort 6 Study design provides flexibility to enroll additional patients to certain cohorts or add additional cohorts PRIMARY OBJECTIVES: • Evaluate the safety and tolerability of RTX - 134 • Correlate dose with percent reduction in serum Phe levels relative to baseline • Determine a preliminary dose to achieve serum Phe levels < 360 µmol/L and < 600 µmol/L SECONDARY OBJECTIVES: • To evaluate pharmacodynamics of RTX - 134, including measurement of TCA Additional optional cohorts at lower, intermediate or higher dose levels may be explored
Initial Clinical Results 16 INITIAL CLINICAL DATA EXPECTED TO INCLUDE: PHASE 1B SINGLE DOSE ADMINISTRATION CLINICAL STUDY • Preliminary safety • Longevity of cells in circulation • Production of TCA as biomarker of MOA
Challenges of Agonist Monoclonal Antibodies and Recombinant Cytokines 18 1 Barthowiak , et. al., Clinical Cancer Research ; 24(5) March 1, 2018 AGONIST ANTIBODIES AND RECOMBINANT CYTOKINES • Artificially engineered • Limited combinability due to toxicity • Systemic administration floods the liver and may lead to hepatotoxicity 1 • Narrow therapeutic window
Rubius Therapeutics’ Differentiated Oncology Approaches BROAD IMMUNE SYSTEM STIMULATION 19 • Stimulate adaptive and innate immunity through immune cell agonists – Presentation of synergistic co - stimulatory ligands and cytokines – Vascular compartmentalization may reduce toxicities – Potential broad therapeutic window ANTIGEN - SPECIFIC IMMUNE STIMULATION • Drive unique, in vivo antigen - specific immune responses – Co - stimulatory ligand induces significant quantity of CD8+T cells – Cytokine potently stimulates desired quality of killer T cells Natural ligand presentation drives potent cell - cell interactions in preclinical models
A Potentially Transformative Approach to Oncology: IND Under Review with FDA & FPI Expected in 2H’20 20 BROAD IMMUNE SYSTEM STIMULATION POTENTIAL BENEFITS: • Improved anti - tumor activity • Overcome resistance to immunotherapy • Reduced toxicity given vascular compartmentalization 4 - 1BBL NK CELL 4 - 1BBL IL - 15TP T CELL STIMULATE ADAPTIVE AND INNATE IMMUNE CELL AGONISTS RTX - 240 | (4 - 1BBL + IL - 15TP)
U t o m i l + X - l i n k i n g A b R T X - 2 1 2 R T X - C T R L 0 25 50 75 100 125 N F k B p a t h w a y a c t i v a t i o n ( f o l d i n c r e a s e o v e r n o t r e a t m e n t ) Realizing the Promise of the 4 - 1BB Pathway: RTX - 240 Stimulated Potent Activation of Immune System 21 NF k B ACTIVATION BY RTX - 240 IN T CELLS RTX - 240 is ~10 - Fold Superior to 4 - 1BB Agonist Antibody in Preclinical Models 100 nM 10 nM 1 nM 0.1 nM 0.01 nM 310 K 155 K 78 K 39 K 19 K 400 K 200 K 100 K 50 K 25 K 4 - 1BB agonist Ab RTX - 240 RCT CTRL RTX/RCT cell # or Ab concentration Dugast , et. al., American Association for Cancer Research ; Poster #3272, 2019
mRCT - 240 Inhibits Tumor Growth as Monotherapy or in Combination with Anti - PD - 1 mAb 22 m R C T - C T R L I V P D 1 m A b I V m R C T - 2 4 0 + P D 1 m A b I V 0 50 100 150 200 250 M e t a s t a s e s p e r L u n g p = 0.0025 mRCT - 240 + anti - PD - 1 mAb reduced tumor burden vs. anti - PD - 1 mAb alone mRCT - 240 reduced tumor burden and was equivalent to 4 - 1BB mAb m R C T - C T R L I V m R C T - I L 1 5 T P I V m R C T - 4 - 1 B B L I V m R C T - 2 4 0 I V 4 - 1 B B m A b I V 0 50 100 150 200 M e t a s t a s e s p e r L u n g p=0.0096 p<0.0001 p<0.0001 p=0.02 p<0.0001 ns B16F10 LUNG METASTASES MODEL B16F10 LUNG METASTASES MODEL m = murine
Lack of Liver Toxicity in Preclinical Models Suggests Better Therapeutic Window than 4 - 1BB mAbs 23 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 m A b 5 0 u g 0 1 10 7 2 10 7 3 10 7 4 10 7 # F 4 / 8 0 Liver Macrophages 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 5 10 4 1 10 5 1 10 6 2 10 6 3 10 6 4 10 6 5 10 6 # C D 8 + / E o m e s + / K L R G 1 + Liver CD8+/ Eomes+ /KLRG1+ 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 5 10 6 1 10 7 1.5 10 7 # C D 8 + T C e l l s Liver Infiltrating T Cells 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 A L T / S G P T ( U / L ) Serum ALT Normal Range Dugast , et. al., American Association for Cancer Research ; Poster #3272, 2019
ANTIGEN - SPECIFIC IMMUNE STIMULATION RCTs as Artificial Antigen Presenting Cells ( aAPC ) 24 Selective tumor killing by expanding tumor - specific T cells POTENTIAL BENEFITS Designed to replicate immune system function to activate and expand antigen - specific T cells for a potent anti - tumor effect mRBC - aAPC | gp100 T CELL Signal 2: 4 - 1BBL Antigen - Specific TCR MHC I Signal 1: gp100 Signal 3: IL - 12 Zhang, et. al., Society for Immunotherapy of Cancer ; Poster #P233, 2019
mRBC - aAPC (gp100) Promotes Antigen - Specific T - Cell Expansion 25 CIRCULATION SPLEEN m R B C - C T R L 1 1 0 9 2 . 5 1 0 8 6 1 0 7 0 1 10 5 2 10 5 3 10 5 4 10 5 Pmel Number C D 9 0 . 1 + C D 8 + n u m b e r ** mRBC-gp100-4-1BBL-IL-12 Pmel Number Pmel Number Antigen - specific T cell expansion occurs in circulation and secondary lymphoid organs Zhang, et. al., Society for Immunotherapy of Cancer ; Poster #P233, 2019 1 × 1 0 9 m R B C - C T R L 1 × 1 0 9 m R B C - g p 1 0 0 - 4 - B B L - I L - 1 2 2 . 5 × 1 0 8 m R B C - g p 1 0 0 - 4 - B B L - I L - 1 2 6 × 1 0 7 m R B C - g p 1 0 0 - 4 - B B L - I L - 1 2 0 1×10 4 2×10 4 3×10 4 4×10 4 5×10 4 C D 9 0 . 1 + C D 8 + n u m b e r i n 5 0 m l b l o o d Day 4 Day 7 Day 11
mRBC - aAPC (gp100) Nearly Eliminates Lung Metastases in Melanoma Model 26 Lung Metastases Count mRBC - CTRL m R B C - C T R L 1 × 1 0 9 2 . 5 × 1 0 8 6 × 1 0 7 0 50 100 150 200 250 Lung Metastasis Count L u n g M e t a s t a s i s C o u n t ** ** ** mRBC-gp100-4-1BBL-IL-12 mRBC - aAPC (gp100) Zhang, et. al., Society for Immunotherapy of Cancer ; Poster #P233, 2019
Artificial Antigen Presenting Cells to Target HPV 16+ Cancers 27 ANTIGEN - SPECIFIC IMMUNE STIMULATION Replicating immune system function to activate and expand antigen - specific T cells for a potent anti - tumor effect RTX - 321 | HPV 16+ Tumors T CELL Signal 2: 4 - 1BBL Antigen - Specific TCR MHC I Signal 1: HPV Signal 3: IL - 12 POTENTIAL BENEFITS: SELECTIVE TUMOR KILLING BY EXPANDING ANTIGEN - SPECIFIC T CELLS
RTX - 321 (HPV+) Demonstrates In Vitro Activity 28 0 1×10 6 2×10 6 3×10 6 4×10 6 0 2 4 6 8 10 RTX Cell Number H P V T C R A c t i v a t i o n ( F o l d c h a n g e i n L u m i n e s e n c e ) RTX-null RTX-321 (HPV+) RTX-aAPC (CMV) • HPV - driven cancers are a global health burden and a foremost cause of infection - related cancers 1 • In the U.S., 51% of cervical cancers and 85% of head and neck cancers are HPV 16 - positive 2 HPV - DRIVEN CANCERS DOSE - DEPENDENT HPV TCR ACTIVATION 3 1. Serrano B, et al. Best Pract Res Clin Obstet Gynaecol . 2018;47:14 - 26. 2. Goodman, M., et al. J Natl Cancer Inst . 2015; Jun; 107(6): djv086. 3. Zhang, et al., American Association for Cancer Research , Poster #3260, 2019
29 INTELLECTUAL PROPERTY
Potential to Realize Broad Depth of Value of Red Cell Therapeutics 30 BROAD AND DEEP INTELLECTUAL PROPERTY COVERING: RAPIDLY EXPANDING PATENT PORTFOLIO Pioneering processes for engineering and culturing RCT product candidates Issued U.S. patents cover RTX - 134, RTX - 240, RTX - 224 and RTX - 321 Cover composition of matter, method of treating and method of making Patent Families 32 Applications Pending Worldwide >165 Issued U.S. Patents 10
31 2020 MILESTONES
Anticipated 2020 Milestones: A Year of Execution 32 AN INTEGRATED DEVELOPMENT COMPANY RTX - 321 IND filing by year - end STRONG FINANCIAL POSITION • $324.7 million in cash, cash equivalents and investments as of September 30, 2019 GMP material for RTX - 240 and RTX - 321 trials from Rubius site RTX - 134 FPI and initial clinical results RTX - 240 IND clearance • Cash runway into mid - 2021
REALIZING THE POWER OF RED ™ : A NEW ERA IN CELLULAR MEDICINE