Time is LifeMorgan Stanley 19th Annual Global Healthcare ConferenceSeptember 9, 2021

TM

These slides and the accompanying oral presentation contain forward-looking statements and information. The use of

words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,”

“intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify forward-looking

statements. For example, all statements we make regarding the initiation, timing, progress and results of our

preclinical and clinical studies and our research and development programs, our financial guidance, our ability to

advance product candidates into, and successfully complete, clinical studies, the timing or likelihood of regulatory

filings and approvals, and our financial projections are forward looking. All forward-looking statements are based on

estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain.

All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially

from those that we expected. These statements are also subject to a number of material risks and uncertainties that

are described in our most recent quarterly report on Form 10-Q, as well as our subsequent filings with the Securities

and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. We

undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new

information, future events or otherwise, except as required by law.

forward-looking statements

Time is Life The Why The How

CARE DEEPLY

BE HUMAN

2seventy bio – Time to Launch

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Most experienced team in cell therapy. Done it. Want to do it again and again

Tuned to 100% oncology cell therapy focus – do it smarter and faster

Most advanced and sophisticated scientific toolkit and engine in cell therapy

Capabilities, partners & funding in place to deliver – know what it takes

Delivering on next-gen oncology cell therapy products TODAY

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12 years in the making…2seventy retooled to go ‘back to the future’

- About people & culture mindset

- About learning: be smarter

- About iterating: be faster

- About design: fit for purpose

- Long term: engine behind the products that matters

- Split: A double down to be 1000% focused on future, rewire from top to bottom - all in.

Fit for purpose product engineering

Integrated manufacturing

Ask/Answer/Learn

Speed

Iterate

PEOPLE

Leadership

Our Seasoned Team is Ready

Board of Directors

Philip Gregory, D. Phil.Chief Scientific Officer

Chip BairdChief Financial Officer

Nick LeschlyChief Kairos Officer*

Dan LynchBoard Chair

Duane BaggerlyHead of People & Culture

Susan Abu-Absi, Ph.D.Head of Manufacturing

Jenn SnyderHead of Corporate Affairs

Nicola HeffronChief Operating Officer

Cintia Piccina, PharmDHead of Commercial

+450 Awesome 270ers

Kathleen MunsterSVP, Quality & Operations

Ramy Ibrahim, M.D.BIT.BIO

Marcela Maus, M.D., Ph.D.Massachusetts General Hospital

(MGH) Cancer Center

Denice Torres, J.D.form. Johnson & Johnson

Bill Sellers, M.D.Broad Institute of MIT and Harvard

Nick LeschlyChief Kairos Officer

Teresa Jurgensen, J.D.General Counsel

Kevin Chin, MDHead of Clinical Development

*Kairos: is an Ancient Greek word meaning the right, critical, or opportune moment

• Abecma® ramping

• DARIC33 – 2H21 IND

• bbT369 – 2H21 IND

• Multiple solid tumor and next-gen MM programs

• Abecma® earlier lines

• bbT369 POC data

• DARIC33 POC data

• Solid tumors IND

• Internal DP

• Pivotal data/regulatory submissions for late-stage heme

• POC for solid tumors

• Next-gen MM POC

• IND engine cranking

2seventy: THE leading immuno-

oncology cell therapy company

2seventy bio - privileged starting position and bold trajectory

AT LAUNCH / [YEAR END 2021] +1-2 YEARS +3-5 YEARS …AND BEYOND

2seventy Pipeline – Innovative cell therapy candidates across broad indicationsINDICATION [DRUG] TARGET TECHNOLOGY DREAM DEVISE DELIVER

Multiple Myeloma [ABECMA]

BCMA CAR T cell

Multiple Myeloma [bb21217]

BCMACAR T cellPI3K Enhanced Manufacturing

AML-Pediatric [DARIC33]

CD33 Drug-Regulated CAR T cell (DARIC)

B-NHL[bbT369]

Dual B cell targets

Dual-Targeted CAR T cellSignal Enhanced Gene Edited

AML-Adult[DARIC33 Next-Gen]

CD33 + Undisclosed

Drug-Regulated CAR T cell Dual-Targeted Potency Enhanced

Solid Tumors MAGE-A4TCR T cellPotency Enhanced

Solid Tumors MultipleCAR / TCR T cellPotency Enhanced

Multiple Myeloma MultipleMulti-Targeted CAR T cellPotency Enhanced

Multiple Indications Multiple Multiple

IND 2H 2021

IND 2H 2021TSVT owned

SCRI Collaboration

Multiple

SCRI Collaboration

REGN / MEDG Partnership

BMS Partnership

TSVT

TSVT & UNC

BMS Partnership Data at ASH’21

2seventy’s R&D philosophy - accelerating innovation

Accelerate innovation through cycles

of TSVT’s ASK/ANSWER engine

Identify fundamental problemsLook beyond the horizon

Explore new biology

DREAM

Define clear hypothesesInvent compelling solutions

Bridge gaps through partnership

DEVISE

Prospective data inflectionsDefined development path

Invest in manufacturing v2.0

DELIVER

What opportunities have the greatest potential impact?

What solutions can we conceive to unlock that potential?

What development strategy robustly tests the hypothesis?

What if we pivoted toward the emerging T cell therapy field?

Can we weave an academic/ industry CAR-T partnership?

A revolutionary drug is developed and approved

Solution

• Outside of company’s core business & expertise• CD19 only target with positive clinical data• Will other targets or indications be responsive?

Problem (circa 2013)

64/M del17p R/R CLL patient dosed with 1.4 x 107 total CAR+ T cells

Early clinical data from UPenn highlight a new opportunity

Abecma®: Our first dream, devise, deliver iteration is realized in multiple myeloma

The FIRST CAR T cell therapy for Multiple Myeloma

Strong and fast uptake, illustrating high unmet need and confidence in the unprecedented efficacy of ABECMA

Building on the Abecma Foundation

Launch Strong out of the Gate

Over 65 sites activated in the US, first patient apheresed the week after launch through BMS collaboration

Demand stronger than anticipated. Partnership efforts at all stages of supply chain to expand capacity

Strong access and reimbursement position, very few patients face payer delays

US ABECMA Revenue of $24M* in 2Q

*US ABECMA profit and loss shared 50/50 between bluebird and BMS as part of the collaboration agreement

Expanding eligible patient population

Expand capacity to match demand

Independently progress our novel MM next-gens

Future

Tech Integration

Recoding R&D engine built to rapidly build, test, learn, & improve

TCR CCR DARIC

ENHANCED REGULATED

TME INNATE EXHAUSTION

gd T CELLSCO-STIM

CELL PRODUCTMANUFACTURING

CAR VECTOROLOGYTARGETING

MODALITYSIGNALING

ENHANCEMENT

DESIGN LVV

VECTOR

ab T CELLS

mRNA1

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Validated & novel targets,

world class binders, innovative architectures

Amplify, diversify, prolong,

induce, and/or regulate signal transduction

Combat exhaustion, leverage

tumor microenvironment, multimodal attacks

Maximize payload, innovative design, optimize component co-expression

Take T cells to the next level, explore alternative chassis

Commoditize LVV, invest in T cell process optimization, scalability, & quality

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How to get there:

• Devise a sophisticated and disruptive cell therapy: a dual-targeting, potency-enhanced candidate that solves 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.

Strive to create a product that:

• Meets the significant need in bNHL

• Addresses shortcomings of existing therapies by increasing response rate and durability of response to a larger fraction of patients.

Progress on execution:

• Encouraging pre-clinical data: bbT369 clears single and low antigen tumors, and achieves deep, durable responses

• Clinical development plan poised to quickly determine if bbT369 can provide better outcomes for patients

• IND anticipated in 2H21

DREAM DEVISE DELIVER

bbT369 is purpose-built to enhance depth and durability of response in B-NHL

Anticipated IND Filing 2H21

bbT369 pre-clinical data demonstrates potential to

deliver against challenging tumors

• bbT369 outperforms 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 will include both CD19 CAR relapsed and naïve patients

• Trial will be enriched for patients with high risk factors as a proving ground to quickly demonstrate improved patient outcomes

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CAR T

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bbT3

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Low-Antigen Tumor Model

bbT369: Pre-clinical data outperforms model CD19 CAR supporting planned Phase I

Execution

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

Strive to create a product that:

• Addresses the average life expectancy of 3 months post relapse

• Addresses underlying barriers preventing transformative outcomes

Progress on execution:

• Maximize speed to clinical study via collaboration with world-class translational center

• Test hypothesis in pediatric setting to reduce confounding variables

• IND 2H 2021

DREAM DEVISE DELIVER

DARIC33: Engineered to kick start CAR T cell therapy in AML

DARIC33 in AML: Sensitive, drug-regulated tumor control achieved

Aggressively targeting AML requires pharmacologically-controlled CAR architecture that works under clinically feasible drug dosing

Can we devise a drug-controlled CAR T cell to enable sequential AML targeting &

myeloid recovery?

2seventy’s attack on solid tumors addresses the key barriers to success

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?

ONCOLYTIC VIRUSES

COMBINATIONSTRATEGIES

ORTHOGONAL MOAs

We have engineered a potent MAGE-A4 TCR with a flip receptor to neutralize TGFb and

potentiate T cell activity

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Enhanced Potency

MAGEA4-CTBR12: Solid Tumors

What if we are only a step away from T cells that 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

• Checkpoint blockade validates T cell MoA• Substantial opportunity for improved outcomes• Additional pathway interrogation in re-targeted T

cells may access deep responses• Some profoundly immunosuppressive pathways

are difficult to target systemically

Problem

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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

Dreaming, Devising, and Delivering on the future of cell therapy

DREAM DEVISE DELIVER

MANUFACTURING

VECTOROLOGY

TARGETING

MODALITY

SIGNALING

ENHANCEMENT

Unexplored target classesExtensive binder multiplexing

Integrated signals 1, 2, & 3Multiplex gene editing

Layered regulation & inducibility

Synergized combinationsOrthogonal MoA

Next-level ex vivo auto/alloOpportunistic asset plays

Expanded payload capacityMultiplex transduction

Commoditized LVVRapid, scalable in-house DP mfg

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2seventy’s manufacturing network: poised to deliver

Deliver an In-house clinical DP manufacturing facility• Under construction in our labs, Cambridge, Ma

• Ensures ownership of the process, analytics, execution, value creation

• Enables ‘deep’ integration of CMC with research and correlative sciences plus, flexibility to iterate

Deliver “best-in-class” Academic partnerships for ‘exploratory’ programs• Outlets for high-risk programs for clinical validation

while preserving flexibility & bbb resources

• Access to external innovation and programs, network

Deliver on game-changing industry partnerships • Risk-reward partnership with

Resilience- new model for access to CDMO++ capabilities, aligning incentives & promoting agility

VELOCITYEnable pipeline speed & decisions making to POC

INNOVATIONMultiply our reach, capacity & ability to innovate

CAPABILITYManufacturing partnerships defined by identical goals

2seventy bio: a clear and differentiated strategy, well-funded to deliver

• Deliver ABECMA commercially and expand product opportunity

• Relentless innovation focus on product engine – ask/answer/learn & iterate

• ABECMA launch exceeding plan• Innovative cell therapy candidates

across broad indications• 2 INDs 2021

• New leadership team in place• BOD retooling for oncology focus

• $75M private stock offering (WholeCo)• Resilience collaboration brings $110M

upfront and $25M+ savings/year• Anticipating approximately 24 months

of runway at launch

✓ Strategy + Vision

✓ Products that Matter

✓ Leadership + Team

✓ Funding + Financial

Anticipate ~$975M Wholeco cash balance at time of split; 2seventy poised to launch with approximately 24 months of runway