REALIZING THE POWER OF RED: A NEW ERA IN CELLULAR MEDICINE

Transcription

1 REALIZING THE POWER OF RED: A NEW ERA IN CELLULAR MEDICINE PABLO J. CAGNONI, M.D., CHIEF EXECUTIVE OFFICER JANUARY

2 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, 2018, 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

3 Advances and Limitations of Current Cell Therapies ADVANCES CURES IN CERTAIN CANCERS Limited therapeutic applications Severe side effects LIMITATIONS REMAIN Unpredictable pharmacokinetics and biodistribution Costly manufacturing No approved allogeneic therapies Significant opportunity in oncology and beyond for more potent and less toxic cellular medicines 3

4 Harnessing the Unique Properties of Red Blood Cells O NEGATIVE BLOOD CAN BE GIVEN TO 95% OF PEOPLE RED BLOOD CELLS ü Have a circulation time of ~120 days ü Lack a nucleus ü Have a predictable biodistribution in the vasculature 4

5 Red Cell Therapeutics POTENTIALLY TRANSFORMATIVE CELLULAR THERAPIES CANCER RARE DISEASE AUTOIMMUNE READY- TO-USE BROAD THERAPEUTIC APPLICATIONS PREDICTABLE BIODISTRIBUTION DEFINED LIFE IN CIRCULATION AND CONVENIENT DOSING ADVANTAGEOUS TOLERABILITY SCALABLE MANUFACTURING 5

6 The Promise of Red Cell Therapeutics : Highly Potent, Allogeneic and Off-the-Shelf RED PLATFORM EARLY PROGENITOR CELLS EXPANSION & DIFFERENTIATION RED CELL THERAPEUTIC SINGLE HEALTHY O- DONOR GENETIC ENGINEERING ENUCLEATION & MATURATION s OF DOSES Red Cell Therapeutic (RCT) dose <1% of normal red cells 42 days of storage stability data and counting 6

7 RED PLATFORM Enables Multiple Modalities RARE ENZYME DEFICIENCIES CANCER AUTOIMMUNE DISEASES ENZYME REPLACEMENT IMMUNE MODULATION ANTIGEN PRESENTATION T CELL ENZYMES WITHIN THE RCT NK CELL CANCER CELL T CELL CELLULAR SHIELDING POTENT CELL-CELL INTERACTION ANTIGEN(S) ON RCT SURFACE TOLERANCE INDUCTION 7

8 Building a Broad and Diverse Pipeline PRODUCT CATEGORY PATIENT POPULATION CANDIDATE DISCOVERY LEAD OPTIMIZATION IND ENABLING IND Submission 50,000+ RTX-134 Phenylketonuria IND Filing Expected 1Q 19 RARE DISEASES 100,000+ RTX-Uricase 2,000-4,000 RTX-CBS Refractory gout Homocystinuria 20,000+ RTX-OxOx Hyperoxaluria 100,000+ RTX-240 (formerly RTX-212) R/R apd1 Solid Tumors IND Filing Expected by Early 20 10,000+ RTX-240 R/R AML Post-HSCT CANCER 100,000+ RTX-224 R/R apd1 Solid Tumors Introducing RTX-224 Antigen Dependent RTX-aAPC (HPV) HPV+ Solid Tumors Antigen Dependent Tumor Targeting Heme tumors AUTOIMMUNE DISEASES 60,000+ RTX-PV 100,000+ RTX-T1D Pemphigus Vulgaris Type 1 Diabetes Four to five INDs in rare diseases, cancer and autoimmune diseases planned across 2019 and

9 Strong Execution of 2018 Key Priorities TRANSFORMED FROM A PRIVATELY-HELD COMPANY TO A PUBLIC, FULLY INTEGRATED R&D ORGANIZATION ON THE CUSP OF OUR FIRST CLINICAL TRIAL Completed manufacturing facility purchase and initiated renovations Scaled manufacturing from 50L to 200L bioreactors Transferred manufacturing process to CMO for RTX-134 Generated robust preclinical oncology data to advance additional candidates Executed three successful financings runway into

10 RARE ENZYME DEFICIENCIES 10

11 RTX-134 Filing on Track for 1Q for Phenylketonuria PHENYLKETONURIA (PKU) Deficiency of an enzyme needed to break down dietary phenylalanine Symptoms: Intellectual disability, delayed development, impaired cognitive function, irreversible brain damage Phenylalanine BREAKS DOWN INTO Transcinnamic acid RTX-134 RTX-134 shields immunogenic PAL enzyme from the immune system PAL metabolizes and converts phenylalanine to ammonia and TCA Target indication: patients with serum Phe levels 600 μmol/l Infrequent, low volume IV administration Seek Orphan Drug Designation 15,000 U.S. AND 50,000+ PATIENTS WORLDWIDE PAL ENZYME 11

12 Initial Clinical Data Expected from Part 1 in 2H 19 FDA ALIGNMENT ON PHASE 1b/2a CLINICAL TRIAL DESIGN adult PKU patients Dosing to begin at therapeutically active dose Determine preliminary safety, efficacious dose and dose schedule Established efficacy endpoint reduction in phenylalanine HIGH-LEVEL CLINICAL TRIAL OBJECTIVES PART 1: Single-dose administration Preliminary safety Longevity of cells in circulation Production of trans-cinnamic acid as biomarker of MOA Preliminary dose and schedule PART 2: Multi-dose administration Safety Efficacy magnitude of reduction in phenylalanine Dose and schedule optimization 12

13 CANCER 13

14 Overcoming the Limitations of Immunotherapy RCT PRODUCT CANDIDATES FOR CANCER AGONIST ANTIBODIES AND RECOMBINANT CYTOKINES Natural ligand conformation for potent cell-cell interaction and strong immune synapse formation Co-stimulatory molecules synergistic with each other and with other immunotherapies in preclinical models Confined to the vasculature Artificially engineered Limited combinability due to toxicity Systemic administration that floods the liver and may lead to hepatotoxicity 1 Narrow therapeutic window Potential broad therapeutic window 1 Barthowiak, et. al., Clinical Cancer Research; 24(5) March 1,

15 A Potentially Transformative Approach to Treating Cancer IND Filing Planned by Early 2020 RTX-240 (formerly RTX-212) (4-1BBL + IL-15TP) COMBINATIONS 4-1BBL IL-15TP 4-BBL IL-15TP POTENT STIMULATION OF ADAPTIVE + INNATE IMMUNE SYSTEMS T-CELL NK CELL POTENTIAL BENEFITS: Improved anti-tumor activity Overcomes resistance to immunotherapy 15

16 Realizing the Promise of the 4-1BB Pathway: RTX-240 Stimulated Potent Activation of Immune System NFkB ACTIVATION BY RTX-240 IN T CELLS NFkB pathway activation (fold increase over no treatment) 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 RTX/RCT cell # or Ab concentration 4-1BB agonist Ab Utomil + X-linking Ab RTX-240 RTX-212 RCT CTRL RTX-CTRL RTX-240 is ~15-Fold Superior to 4-1BB Agonist Antibody 16

17 Murine RCT-240 Reduced Tumor Burden as Monotherapy or in Combination with Anti-PD-1 mab ACTIVITY OF mrct-240 DEMONSTRATED IN B16F10 LUNG METASTASES MOUSE MODEL ACTIVITY OF mrct ANTI-PD1 DEMONSTRATED IN B16F10 LUNG METASTASES MOUSE MODEL p< p< p= Metastases per Lung p< p=0.02 ns Metastases per Lung p = mrct-ctrl IV mrct-il15tp IV mrct-4-1bbl IV mrct-240 IV a4-1bb mab IV 0 mrct-ctrl IV apd1 mab IV mrct apd1 mab IV mrct-240 reduced tumor burden and was equivalent to 4-1BB mab mrct anti-pd-1 mab reduced tumor burden vs. anti-pd-1 mab alone 17

18 Lack of Liver Toxicity Suggests Better Therapeutic Window than 4-1BB mabs in Preclinical Models Serum ALT Liver Macrophages ALT/SGPT (U/L) # F4/ Normal Range # CD8+/Eomes+/KLRG mrct-ctrl mrct-ctrl 0 mrct-ctrl mrct-ctrl mrct-240 1E9 apd1 mab 150ug mrct-240 1E9 + apd1 mab 150ug mrct-240 1E9 Liver CD8+/ Eomes+ /KLRG1+ apd1 mab 150ug mrct-212 1E9 apd1 mab 150ug mrct-212 1E9 + apd1 mab 150ug mrct-240 1E9 + apd1 mab 150ug a4-1bb mab 200ug mrct-212 1E9 apd1 mab 150ug mrct-212 1E9 + apd1 mab 150ug a4-1bb mab 200ug a4-1bb mab 200ug a4-1bb mab 200ug a4-1bb mab 50ug a4-1bb mab 50ug a4-1bb mab 50ug a4-1bb mab 50ug # CD8+ T Cells mrct-ctrl mrct-ctrl mrct-ctrl mrct-ctrl mrct-240 1E9 apd1 mab 150ug mrct-240 1E9 + apd1 mab 150ug a4-1bb mab 200ug mrct-212 1E9 apd1 mab 150ug mrct-212 1E9 + apd1 mab 150ug mrct-212 1E9 apd1 mab 150ug mrct-212 1E9 + apd1 mab 150ug a4-1bb mab 200ug a4-1bb mab 50ug a4-1bb mab mab 50ug Liver Infiltrating T Cells mrct-240 1E9 apd1 mab 150ug mrct-240 1E9 + apd1 mab 150ug a4-1bb mab 200ug a4-1bb mab 200ug a4-1bb mab 50ug a4-1bb mab 50ug 18

19 Introducing RTX-224: 4-1BBL Co-Expressed with IL-12 RTX-224 (4-1BBL + IL-12) COMBINATIONS 4-1BBL IL-12 4-BBL IL-12 POTENT STIMULATION OF ADAPTIVE + INNATE IMMUNE SYSTEMS T-CELL NK CELL Drives T Cell and NK cell expansion and activation in preclinical models Synergistic with each other and with other immunotherapies 19

20 RTX-224 Drives Dramatic Tumor Regressions in Preclinical Model MC38 COLORECTAL CANCER MODEL 1500 CTRL mrbc CTRL mrbc + a-pd1 mrct-224 Tumor Growth (mm 3 ) mrct a-pd1 mrct anti-pd-1 mab drove deep regressions in 9 of 11 mice Time (Days) 20

21 RTX-224 Demonstrates Improved Safety Over Recombinant IL-12 in Preclinical Models BF16F10 LUNG METASTASES MOUSE MODEL IFNg Liver enzymes: ALT IFNg (pg/ml) ALT (U/L) mrbc CTRL IL12 mrbc 4-1BBL mrbc mrct-224 ril-12 0 mrbc CTRL IL-12 mrbc 4-1BBL mrbc mrct-224 ril-12 21

22 AUTOIMMUNE DISEASES 22

23 Creating Potent & Specific Therapies to Potentially Cure Autoimmune Disease AUTOIMMUNE DISEASE INITIAL PORTFOLIO OPPORTUNITIES High unmet need Potentially curative Clear path to proof of concept Portfolio expansion potential Pemphigus Vulgaris Type I Diabetes Bullous Pemphigoid Autoimmune Hepatitis Type 2 Membranous Glomerulonephritis Celiac Disease Myasthenia Gravis Neuromyelitis Optica First RCT clinical candidate designed to induce tolerance expected to be selected in

24 MANUFACTURING 24

25 Rapidly Scaling Manufacturing in Smithfield, RI L L L L L Dedicated suites secured at CMO to conduct clinical trials Rubius manufacturing site expected to be operational in 1000L bioreactors by end of

26 INTELLECTUAL PROPERTY 26

27 Potential to Realize Broad Depth of Value of Red Cell Therapeutics BROAD AND DEEP INTELLECTUAL PROPERTY COVERING: Pioneering processes for engineering and culturing RCT product candidates More than 200 RCT pharmaceutical compositions Therapeutic uses in major and rare diseases RAPIDLY EXPANDING PATENT PORTFOLIO 25 >100 1 Patent families Applications pending in all major geographies (e.g. U.S., E.U., JP, BRIC) Issued U.S. Patent for PKU 27

28 2019 MILESTONES 28

29 A New Era in Cellular Medicine CLINICAL-STAGE ON THE IMMEDIATE HORIZON Plan to file first IND for RTX-134 in phenylketonuria during 1Q 19 Initial clinical data expected in 2H 19 Growing oncology pipeline First IND filing planned for RTX-240 by early 2020 Preclinical data in cancer to be presented throughout INDs planned during 2019 and 2020 STRONG FINANCIAL POSITION $408.9 million in cash and investments as of September 30, 2018 Cash runway further extended into 2021 Up to $75 million in debt financing as of December 21,

30 Phenylketonuria is Only the Tip of the Iceberg for the RED PLATFORM PKU Other Rare Enzyme Deficiencies Cancer Autoimmune Diseases 30

31 REALIZING THE POWER OF RED: A NEW ERA IN CELLULAR MEDICINE 31