Time is Life - investor.bluebirdbio.com
Transcript of Time is Life - investor.bluebirdbio.com
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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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