UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): August 10, 2022
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Item 7.01 Regulation FD Disclosure.
2seventy bio, Inc. intends to provide investors with updated information regarding its ongoing KarMMa-3 Phase 3 Study of ABECMA in adults with relapsed and refractory multiple myeloma who have had two to four prior lines of therapy and are refractory to the last regimen. A copy of the presentation is being furnished as Exhibit 99.1 to this Current Report on Form 8-K. 2seventy bio, Inc. undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
The information in this Current Report on Form 8-K pursuant to Item 7.01 is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section. It may only be incorporated by reference in another filing under the Exchange Act or the Securities Act of 1933, as amended, if such subsequent filing specifically references the information furnished pursuant to Item 7.01 of this Current Report.
Item 9.01 Financial Statements and Exhibits
(d) Exhibits
| Exhibit No. | Description | |||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document and incorporated as Exhibit 101) | |||||||
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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.
| Dated: August 10, 2022 | 2seventy bio, Inc. | ||||||||||
| By: | /s/ Chip Baird | ||||||||||
| Chip Baird | |||||||||||
| Chief Financial Officer | |||||||||||
| (Principal Financial and Accounting Officer) | |||||||||||
Join the Patient Mission Company Presentation August 2022
Cautionary note regarding forward-looking statements 2 These slides and the accompanying oral presentation may contain “forward-looking statements”. These statements include, but are not limited to: statements about our plans, strategies, timelines and expectations with respect to the development, manufacture or sale of our product candidates, including the design, initiation, enrollment and completion of pre-clinical and clinical studies; timelines for the results of ongoing and planned clinical trials for our product candidates and for ABECMA (ide-cel) in additional indications; the timing or likelihood of regulatory filings and acceptances and approvals thereof; expectations as to the market size for ABECMA and any other approved product we may successfully develop; the progress and results of our commercialization of ABECMA, including our goal of increasing manufacturing capacity and improving the manufacturing process and the number of patients that are expected to be treated with ABECMA in the commercial setting and potential late line global revenue for ABECMA; anticipated revenues resulting from sales of ABECMA; statements about the efficacy and perceived therapeutic benefits of our product candidates and the potential indications and market opportunities therefor; statements about the strategic plans for 2seventy bio and potential corporate development opportunities, including manufacturing expectations and benefits received from collaborations; statements about our ability to operate as a stand-alone company and execute our strategic priorities; and expectations regarding our use of capital, expenses and other future financial results, including our net cash spend, cash runway and U.S. net revenue for ABECMA in 2022. Any forward-looking statements in this presentation 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 presentation, including, without limitation, the risk that the market opportunities for our approved product or any future approved product are smaller than we believe they are; the risk that BMS, upon whom we rely for the successful development and commercialization of ABECMA does not devote sufficient resources thereto, is unsuccessful in its efforts, or chooses to terminate its agreements with us; the risk that we and/or BMS will be unable to increase manufacturing and supply capacity for ABECMA; the risk that our BLAs and INDs will not be accepted for filing by the FDA on the timeline that we expect, or at all; the risk that our plans with respect to the preclinical and clinical development and regulatory approval of our product candidates may not be successfully achieved on the planned timeline, or at all; the risk that ABECMA will not be as commercially successful as we may anticipate; and the risk that we are unable to manage our operating expenses or cash use for operations. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in the information statement contained in our Registration Statement on Form 10, as supplemented and/or modified by our most recent Quarterly Report on Form 10-Q and any other filings that we have made or will make with the Securities and Exchange Commission in the future. All information in this press release is as of the date of the release, and 2seventy bio undertakes no duty to update this information unless required by law. This presentation has been prepared by 2seventy bio, Inc., a Delaware corporation, (together with its subsidiaries, the “Company”) for the exclusive use of the party to whom the Company delivers this presentation. This presentation does not constitute an offer to sell or the solicitation of an offer to buy any securities of the Company. The information contained herein is for informational purpose, and may not be relied upon in connection with the purchase or sale of any security. Neither the Company nor any of its affiliates or representatives makes any representation or warranty, expressed or implied, as to the accuracy or completeness of this presentation or any of the information contained herein, or any other written or oral communication transmitted or made available to the you or your affiliates or representatives. The Company and its affiliates and representatives expressly disclaim to the fullest extent permitted by law any and all liability based, in whole or in part, on the presentation or any information contained herein or any other written or oral communication transmitted or made available to you or your affiliates or representatives, including, without limitation, with respect to errors therein or omissions therefrom. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of any securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.
3 It’s about time™ Time Geeks The most committed and passionate geeks driving next gen oncology cell therapeutics
Key “launch” ingredients and plans 4 12 years in the making ABECMA® Deliver to patients and scale to demand NextGen Potential Proof-of-Concept Test, learn & iterate in the clinic Disrupt Relentless innovation – science, medicine & manufacturing Product Engine Double Down Science, translation, capabilities People Culture Experience
Horizons focused on long term learning and disruption 5 Horizon 0: Launch Company Horizon 1: ABECMA® Horizon 2: Clinical Pipeline Horizon X: Disrupt Spin & Double Down Launch & Scale Liquid Tumors: B-NHL & AML Deep Deep Auto (Very Angry T cell) Focus Team & Burn 3rd Line & Beyond Solid Tumors: MUC16, MAGE-A4 & Beyond In-Vivo Editing (Novo) Rapid Innovation Cycle Integration Iteration
2022 Goals – Transformative build & deliver year 6 Cash Runway into 2025 Deliver ABECMA® Amp Up Product Engine Tune Burn + Capabilities Anticipated $250-$300M U.S. revenue in 2022 B-NHL & AML; advance in solid tumors Anticipated $245-265M net cash spend; goal to complete drug product facility build B-NHL: B-cell non-Hodgkin lymphoma AML: acute myeloid leukemia
Cash Runway into 2025 Carries Through Multiple Inflections 7 Increasing mfg. capabilities Earlier line studies 3L data & BLA Earlier line studies Mfg. process improvements Earlier line studies $1-2B late line global revenue**sLVV Horizon X: Deep Geek Horizon 2: Pipeline Horizon 1: ABECMA® Horizon 0: Foundation Skunkworks. Point of greatest long-term conviction. Near-term growth drivers and future approved products.* Commercial backstop. Source of funding. Enabling execution across the horizons. Layered Innovation NextGen AML / MM New Tumor Targets Emerging and undisclosed. Disruptive next-gen… B-NHL FPI AML FPI AML POC MAGE-A4 IND B-NHL POC MUC16 POC MAGE-A4 POC Pivotal AML study Pivotal B-NHL study Early AML data MUC16 IND Early B-NHL data ~450 FTEs DP build underway DP facility online DP facility delivering supply for multiple Phase 1 studies Potential Patients Treated*** High hundreds >1,000 Thousands across indications Financial $170M private placement $245-265M net cash spend ABECMA contributing cash back to business Path to financial sustainability BOTTOM LINE 20232022 Next 3-5 Years Multiple partnerships in place to attack cancer *subject to FDA approval **based on management projections ***across 2seventy portfolio B-NHL: B-cell non-Hodgkin lymphoma; AML: acute myeloid leukemia; POC: Proof-of-Concept; IND: Investigational New Drug Application; DP: Drug Product Novel Architectures Potential IND Potential IND Potential IND
ABECMA® expected to be $1-2B late line global market opportunity 8 2021 Launch • Approved on March 26, 2021 • Significant demand to date from patients and physicians • Unaudited US product net revenue of approximately $150M* 2023 and Beyond • Potential to reach patients in earlier line MM • Growing profitability • Continued capacity expansion • Next-gen development underway Ongoing commercial learnings from ABECMA can benefit the 2seventy pipeline and provide financial backstop from a value and funding perspective 2022 Outlook • Anticipated $250-300M US product net revenue; tracking to upper end of range • Increasing capacity across supply chain; U.S. business will fully utilize capacity as it becomes available • Growing body of clinical data from earlier line studies • Topline data from KarMMa-3 in 2-4L MM *US ABECMA profit and loss shared 50/50 between 2seventy and BMS as part of the collaboration agreement; unaudited, based on information currently available and subject to change
ABECMA real world experience reinforces paradigm-changing efficacy 9 • ASCO 2022 physician poster on real world experience at 11 sites: safety and efficacy in the real world is consistent with KarMMa study • 77% of patients in real world study would not have met the eligibility criteria for KarMMa • Very low rate of manufacturing failure (2.5%) in the real world Hansen et al, Abstract 8042 ASCO 2022 *7 treated patients had manufacturing failures on first attempt, but a 2nd attempt was successful.
KarMMa-3 pivotal study achieves primary endpoint of mPFS Prespecified interim analysis delivers results ahead of original 2023 guidance 10 • The study met its primary endpoint of demonstrating a statistically significant improvement in progression- free survival. • Treatment with ABECMA also showed an improvement in the key secondary endpoint of overall response rate compared to standard regimens. • Follow-up for overall survival, a key secondary endpoint, remains ongoing. • Safety results were consistent with the well- established and predictable profile demonstrated in the pivotal KarMMa trial. • The companies expect to present additional data from this study at a medical meeting in the future and discuss these findings with health authorities. Bristol Myers Squibb and 2seventy bio Announce Topline Results from KarMMa-3 Trial Showing Abecma (idecabtagene vicleucel) Significantly Improves Progression-Free Survival Versus Standard Regimens in Relapsed and Refractory Multiple Myeloma Abecma is the first BCMA-directed CAR T cell therapy to demonstrate superiority versus standard regimens in relapsed and refractory multiple myeloma (PRINCETON, N.J., & CAMBRIDGE, Mass., AUGUST 10, 2022) -- Bristol Myers Squibb (NYSE: BMY) and 2seventy bio, Inc. (Nasdaq: TSVT) today announced positive topline results from KarMMa-3, a Phase 3, global, randomized, multicenter, open-label study evaluating Abecma (idecabtagene vicleucel)
KarMMa-3 Study Design: Primary Endpoint: PFS; Key Secondary Endpoints: ORR, OS 11 The inclusion criteria of this study is triple class exposed and refractory to their last line of therapy. Limited literature exists in that population with these included, approved standard of care regimens in KarMMa-3. However, based on data in triple class refractory, outcomes are poor with low response rates and median PFS that range in the low single digits (months).1 2 Arm A: (N~254) Ide-cel Arm B: (N~127) SOC regimens (Dvd, DPd, IRd, Epd, Kd) 1Gandhi et al. Leukemia 2019; 33:2266–2275. 2Bal et al. Leukemia. 2022 Mar;36(3):877-880
Multiple approved autologous CAR T products establish a powerful platform on which to build. We have yet to scratch the surface with ways to embellish engineered T cells to truly capture the potential of cell therapy. 2seventy bio has the toolbox to do this better than anyone. Autologous CAR T cells work, but their full potential has not yet been realized Our mission is to develop sophisticated and tumor-tailored autologous CAR/TCR T cell products to realize the potential of personalized, cell-based oncology therapeutics. Accelerate innovation through cycles of TSVT’s ASK/ANSWER engine DREAM • Identify fundamental problems • Look beyond the horizon • Explore new biology DEVISE • Define clear hypotheses • Invent compelling solutions • Bridge gaps through partnerships DELIVER • Define prospective data inflections • Forge clear development path • Invest in manufacturing 2.0 2seventy’s R&D philosophy - accelerating innovation 12
R&D engine built to rapidly design, test, learn, & iterate 13 1 2 3 4 5 VECTOROLOGY Maximize payload, innovative design, optimize component co-expression 4 DESIGN LVV mRNA MODALITY Take T cells to the next level, explore alternative chassis 5 ab T CELLS gd T CELLS MANUFACTURING Commoditize LVV, invest in T cell process optimization, scalability, & quality 6 VECTOR CELL PRODUCT TARGETING Validated & novel targets, world class binders, innovative architectures SIGNALING Amplify, diversify, prolong, induce, and/or regulate signal transduction ENHANCEMENT Combat exhaustion, leverage tumor microenvironment, multimodal attacks 1 TCR CCR DARICCAR 2 ENHANCED CO-STIM REGULATED 3 TME INNATE EXHAUSTION
INDICATION [DRUG] TARGET TECHNOLOGY DISCOVERY STAGE R&D IND-ENABLING PRECLINICAL STUDIES CLINICAL STUDIES APPROVED PRODUCTS Multiple Myeloma [ABECMA] BCMA CAR T cell Multiple Myeloma [ABECMA] BCMA CAR T cell AML-Pediatric [DARIC33] CD33 Drug-Regulated CAR T cell (DARIC) B-NHL [bbT369] Dual B cell targets Dual-Targeted CAR T cell Signal Enhanced Gene Edited AML-Adult [DARIC33 Next-Gen] CD33 + Undisclosed Drug-Regulated CAR T cell Dual- Targeted Potency Enhanced Ovarian Cancer MUC16 CAR T cell Pharmacologic Enhancements Solid Tumors MAGE-A4 TCR T cell Potency Enhanced Solid Tumors Multiple CAR / TCR T cell Potency Enhanced Multiple Myeloma Multiple Multi-Targeted CAR T cell Potency Enhanced Additional Indications Undisclosed Multiple Phase 1 Open Phase 1 OpenTSVT Owned SCRI Collaboration Multiple; Including Collab. with Novo Nordisk SCRI Collaboration REGN Collaboration BMS Partnership TSVT Owned Multiple BMS Partnership; Earlier-line Studies Label Expansion REGN / MEDG Collaboration Innovative cell therapy candidates across broad indications 14 2023 IND Submission Product engine generating ~1+ INDs per year
Patients enrolled 1H 2022 • bbT369 outperformed model CD19 CAR in challenging low antigen expressing tumors in vivo • Data supports potential to overcome resistance and elongate durability of response • Phase I trial permits both CD19 CAR relapsed and naïve patients • Trial intended to be enriched for patients with high risk factors as a proving ground to demonstrate improved patient outcomes How to get there: • Devise a sophisticated and disruptive cell therapy: a dual-targeting, potency- enhanced candidate that could solve failure modes of CD19 CAR-Ts • Novel combination of antigens to address antigen escape. • Synergistic antigen receptor signaling domains to augment T cell activation. • Gene edit to enhance potency and reduce T cell exhaustion. DEVISE bbT369 eliminates challenging tumors -20 -10 10 20 30 0 500 1,000 1,500 2,000 2,500 T u m o r V o lu m e ( m m 3 ) CAR T VS. C D 19 C A R bb T 36 9 Low-Antigen Tumor Model Execution bbT369: Designed with purpose. Study underway. 15
CRC-403 study in B-NHL open and enrolling 16 day -5 -2 day 0 day 0-30 day 30 CRC-403: A Phase 1/2 Study of bbT369 in Relapsed and/or Refractory B-Cell Non-Hodgkin Lymphoma (B-NHL) Key Questions / Features QUESTIONS • Is the safety and tolerability of bbT369 in line with prior CAR Ts? • Does bbT369 show anti-B cell activity in R/R B-NHL patients? • Does bbT369 show deep and durable responses? • Does the dual-targeting CAR architecture limit antigen escape? • Do CBLB edited T cells expand and persist? FEATURES • First in human application of 4 2seventy bio innovations: • Dual targeted T cell • Split-costimulation signaling architecture • MegaTAL gene editing tech • CBLB edited T cell • All 4 are believed to have application across our research pipeline, including enhanced liquid tumor settings and solid tumors STUDY DESIGN • Target enrollment: n=50 • 4 study sites • Relapsed/Refractory B-cell NHL after autologous SCT or ≥ 2 prior lines of therapy • B-cell NHL according to WHO 2017 classification • Prior CD19 CAR-T therapy is permitted
How to get there: • Drug regulated CAR Ts overcome the underlying aplasia risk of targeting myeloid cells • Enhance CAR T cell persistence by reducing exhaustive effect of continuous antigen stimulation • Targeting the C2 domain of CD33 designed to deliver target abundance across genotypes limiting antigen escape DEVISE SC-DARIC33: Engineered to kickstart CAR T cell therapy in AML 17 A drug-controlled CAR T cell to enable sequential AML targeting & myeloid recovery Aggressively targeting AML requires pharmacologically-controlled CAR architecture that works under clinically feasible drug dosing
Phase I study (PLAT-08) open and enrolling 18 Study Design: A Study Of SC-DARIC33 In Pediatric And Young Adults With Relapsed Or Refractory CD33+ AML Key Questions / Features QUESTONS • Do SC-DARIC33 T cells engraft & show activity vs CD33+ve cells? • Is SC-DARIC33 safe and does it drive a clinical response? • Can SC-DARIC33 deactivation enable myeloid recovery? FEATURES • First in human application of 2seventy bio’s regulatable CAR T cell technology (DARIC) • First application of a licensed INHIBRX VHH binder in CAR T format targeting a conserved domain of CD33 • Myeloid disease learnings • Provides platform for NextGen multiplex CAR T cells • Establishes CD33 targeting supporting other applications • Potential DARIC technology extension to solid tumor targets STUDY DESIGN • Single-center, academic study • Target enrollment: N=18 • Age ≤ 28 years • Relapsed or refractory CD33+ AML • Prior allogeneic stem cell transplant permitted • Stem cell donor source identified day -5-2 day 0 day 2 day 21 day 42
2seventy’s attack on solid tumors designed to address the key barriers to success 19 ONCOLYTIC VIRUSES COMBINATION STRATEGIES ORTHOGONAL MOAs FLIP RECEPTORS SIGNAL 3 DRIVERS GENE EDITING Can we achieve sensitive & multiplex targeting across the full range of target classes? Can we convert suppressive signals to supportive ones, and re-engage innate immunity? Can we disrupt the physical & biological barriers to T cell infiltration and inflammation?
We have engineered a potent MAGE-A4 TCR with a flip receptor to neutralize TGFb and potentiate T cell activity + Enhanced Potency MAGEA4-CTBR12: Solid tumors 20 What if T cells can deliver heme cancer- like outcomes for patients? Can we substantially enhance the potency of a TCR T cell using a TME signal conversion technology? Lead integrated candidate selected, demonstrates signal conversion & potent tumor control • Limited ability to access deep responses • Some profoundly immunosuppressive pathways are difficult to target systemically Problem 0 5 10 15 20 0 500 1000 1500 2000 2500 3e6 Study Days M e d ia n T u m o r V o lu m e ( m m 3 ) Vehicle B. UTD BW2826 BW9161 DP 3 x 106 T cells MAGEA4 TCR + Flip Receptor Tumor regression achieved with MAGEA4 TCR + TGFb flip receptor in a melanoma xenograft model
Our MUC16/ovarian cancer program aims to exploit CAR T + pharmaceutical combination strategies to unlock solid tumors 21 How to get there: • A bold product concept combining an engineered T cell and a potent pharmacologic agent: • CAR targeting a highly prevalent membrane-retained fragment of MUC16 (uses REGN binder) • A titratable pharmacologic agent to counteract the tumor microenvironment while mitigating off-tumor activity Strive to create a product that: • Targets MUC16-positive solid tumors (expressed in ~80% of ovarian cancers) • Unleashes the potential of T cells in solid tumors by synergizing with transformative pharmaceutical agents • Addresses the challenges of the tumor microenvironment (TME), target heterogeneity and on target / off tumor activity Progress on execution: • Encouraging pre-clinical data: T cells expressing MUC16-targeted CAR Ts clear tumors in a tumor rechallenge model • Program being co-researched as part of TSVT-REGN strategic collaboration: leverage experience of REGN’s investigational MUC16 targeting therapies in ovarian cancer to develop best-in-class cell therapy • Potential 2023 IND DREAM DEVISE DELIVER MUC16 expression data in OvCa: – Chauhan et. al., Modern Pathology, 2006; Cervical – Wang et. al., 2020, Exp Ther Med
Solution Our MUC16 CAR T provides in vivo tumor clearance and can prevent re-growth in a stringent tumor rechallenge model MUC16 CAR shows robust single agent activity in tumor rechallenge model OVCAR3 Ovarian Cancer Xenograft ModelSolution MUC16 CAR exhibits MUC16 ectodomain (“nub”) specificity – does not bind shed CA125 1 10 100 1000 10000 0 5000 10000 15000 20000 BB4015.Muc16 nub Muc16 nub concentration (ng/mL) IF N y ( p g /m L ) 10 100 1000 10000 100000 0 5000 10000 15000 20000 BB4015.CA125 CA125 concentration (U/mL) IF N y ( p g /m L ) CAR vs “nub” [surface retained] CAR vs CA125 [shed] Vehicle UTD OVCAR3.FP Control MUC16 CAR Ovarian Cancer [DEVISE]: Pre-clinical data demonstrate deep responses 22
Key challenges ❑ Hostile/immunosuppressive tumor microenvironment (TME) ❑ Target expression heterogeneity and antigen negative relapse ❑ T cell expansion, persistence & penetration ❑ Healthy tissue liabilities Potential Solutions ✓ Immune checkpoint neutralization, e.g., PD1 ✓ Oncolytic virus-induction of an inflamed TME ✓ Costimulatory enhancement of CAR activity in combo with CD28 bispecifics ✓ Titratable enhancement tools engaging orthogonal targets A MUC16 CAR T cell therapy must overcome several challenges to be successful in ovarian cancer 23 Image adapted from Molecular Therapy (2020): 28, 2320 using BioRender.com. Suppressive cells & cytokines Toxic metabolites Physical barriers Inhibitory ligands Impaired antigen presentation Oxygen deprivation Nutrient deprivation
Our MUC16 program realizes the scientific power of collaboration with Regeneron 24 Tumor targeted co-stimulation Robust toolbox with the potential to unlock deep responses in Ovarian Cancer SCIENCE TRANSLATIONAL MEDICINE Jan 2020 PD-1 inhibitor demonstrating promising results in solid tumors Mouse models, huAbs & pre-clinical data SCIENCE TRANSLATIONAL MEDICINE Jun 2019 Plus novel CPIs in development Multiple CD28 bispecifics in pre-clinical and clinical developmentFully human antibodies MOL. CANCER THERAPEUTICS. Nov 2019 Humanized mouse models MUC16 Know-how Novel Co-stimulatory Bi-specific Combinations Checkpoint Inhibitor Combinations
INDICATION [DRUG] TARGET TECHNOLOGY DISCOVERY STAGE R&D IND-ENABLING PRECLIN. STUDIES CLINICAL STUDIES APPROVED PRODUCTS Multiple Myeloma [ABECMA] BCMA CAR T cell Multiple Myeloma [ABECMA] BCMA CAR T cell AML-Pediatric [DARIC33] CD33 Drug-Regulated CAR T cell (DARIC) B-NHL [bbT369] Dual B cell targets Dual-Targeted CAR T cell Signal Enhanced Gene Edited AML-Adult [DARIC33 Next-Gen] CD33 + Undisclosed Drug-Regulated CAR T cell Dual- Targeted Potency Enhanced Ovarian Cancer MUC16 CAR T cell Pharmacologic Enhancements Solid Tumors MAGE-A4 TCR T cell Potency Enhanced Solid Tumors Multiple CAR / TCR T cell Potency Enhanced Multiple Myeloma Multiple Multi-Targeted CAR T cell Potency Enhanced Additional Indications Undisclosed Multiple Phase 1 Open Phase 1 OpenTSVT Owned SCRI Collaboration Multiple; Including Collab. with Novo Nordisk SCRI Collaboration REGN Collaboration BMS Partnership TSVT Owned Multiple BMS Partnership; Earlier-line Studies Label Expansion REGN / MEDG Collaboration Innovative cell therapy candidates across broad indications 25 2023 IND Submission Product engine generating ~1+ INDs per year
Horizons focused on long term learning and disruption 26 Horizon 0: Launch Company Horizon 1: ABECMA® Horizon 2: Clinical Pipeline Horizon X: Disrupt Spin & Double Down Launch & Scale Liquid Tumors: B-NHL & AML Deep Deep Auto (Very Angry T cell) Focus Team & Burn 3rd Line & Beyond Solid Tumors: MUC16, MAGE-A4 & Beyond In-Vivo Editing (Novo) Rapid Innovation Cycle Integration Iteration
What are the biological barriers to achieving deep and durable responses? 27 27 TARGET CLASS Need to improve sensitivity Need to multiplex across target classes TCRs >> CARsLow or reduced target abundance Target loss & heterogeneous expression Poor T cell engraftment and persistence Immunosuppressive microenvironment Cancer immune cycle breakdown
2seventy’s novel receptor architecture: a new platform for tumor targeting 28 We have overhauled antigen receptor design and significantly advanced our targeting capabilities… • TCRs have 2- to 3-log higher sensitivity to antigen density • New architecture achieves TCR-like sensitivity to surface expressed antigens • May deepen responses in hematological tumors • May improve functional T cell responses in solid tumors • New architecture enables facile targeting of both target classes • For solid tumor targets in particular • Targets are limiting • They are heterogeneous in expression level and heterogeneous in expression pattern • Constructs are compact, readily engineered and vectorized • New receptor architecture is compatible with 2seventy bio’s binder and platform technologies An orthogonal approach to improved T cell signaling and tumor target engagement Enables simultaneous targeting of BOTH cell surface AND intracellular targets Compact, readily engineered, and vectorized facilitating rapid adoption
HemeA TARGET(S) Endogenous gene promoter trap knock-in of F8 transgene TECH • TSVT megaTAL gene edit • TSVT in vivo grade mRNA production / purification platform • AAV for transgene delivery • Genevant LNPs for hepatocyte delivery INDICATION Hemophilia A STATUS Pre-clinical PARTNER Novo Nordisk, Genevant F8-GE: Novo Nordisk Partnered Program to Leverage Gene Editing Capabilities Directly in vivo for Durable Hemophilia A Gene Therapy 29 • Direct in-vivo application of megaTAL technology using TSVT developed in vivo grade mRNA production/purification process • Recent expansion of collaboration with Novo Nordisk including $5M upfront + research costs, $35M of available near-term milestones + downstream sales royalties/milestones. • Validates megaTAL platform and provides support for further expansion into ex-vivo and in vivo applications within the oncology portfolio
2seventy’s manufacturing network: Poised to deliver 30 VELOCITY Enable pipeline speed & decision making to proof-of-concept INNOVATION Multiply our reach, capacity & ability to innovate CAPABILITY Manufacturing partnerships defined by identical goals Secure best-in-class academic partnerships for exploratory programs • Outlets for high-risk programs for clinical validation while preserving flexibility & 2seventy resources • Access to external innovation and programs, network Establish an in-house clinical drug product manufacturing facility in Cambridge, MA • Aimed to ensure ownership of the process, analytics, execution, value creation • Enables deep integration of CMC with research and correlative sciences plus, flexibility to iterate Leverage industry partnerships • Risk-reward partnership with Resilience- new model for access to CDMO capabilities, aligning incentives & promoting agility
Leadership Our seasoned team is ready 31 Board of Directors Philip Gregory, D. Phil. Chief Scientific Officer Chip Baird Chief Financial Officer Nick Leschly Chief Kairos Officer* Dan Lynch Board Chair Jenn Snyder Head of Corporate Affairs Nicola Heffron Chief Operating Officer +450 Awesome 270ers Kathleen Munster SVP, Quality & Operations Ramy Ibrahim, M.D. BIT.BIO Marcela Maus, M.D., Ph.D. Massachusetts General Hospital (MGH) Cancer Center Sarah Glickman Criteo Nick Leschly Chief Kairos Officer Teresa Jurgensen, J.D. General Counsel Denice Torres, J.D. From Johnson & Johnson Michael Jensen, M.D.** Seattle Children’s Kathy Wilkinson Head of People & Culture *Kairos: is an Ancient Greek word meaning the right, critical, or opportune moment; **Board Observer Steve Bernstein, M.D. Chief Medical Officer Susan Abu-Absi, Ph.D. Head of Manufacturing
32 It’s about time™ Time Geeks The most committed and passionate geeks driving next gen oncology cell therapeutics
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