Time is Life Morgan Stanley 19th Annual Global Healthcare Conference September 9, 2021 - bluebird bio, Inc.
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TM Time is Life Morgan Stanley 19th Annual Global Healthcare Conference September 9, 2021
forward-looking statements 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.
CARE DEEPLY
Time is
Life The Why The How
BE HUMAN
2seventy bio – Time to Launch 1 Most experienced team in cell therapy. Done it. Want to do it again and again 2 Tuned to 100% oncology cell therapy focus – do it smarter and faster 3 Most advanced and sophisticated scientific toolkit and engine in cell therapy 4 Capabilities, partners & funding in place to deliver – know what it takes 5 Delivering on next-gen oncology cell therapy products TODAY 4
12 years in the making…2seventy retooled to go ‘back to the future’
Speed
- About people & culture mindset
- About learning: be smarter Fit for purpose
- About iterating: be faster product engineering
- About design: fit for purpose Integrated manufacturing
- Long term: engine behind the Ask/Answer/Learn
products that matters
- Split: A double down to be 1000%
focused on future, rewire from Iterate
top to bottom - all in.
PEOPLE
Our Seasoned Team is Ready
Leadership Board of Directors
Nick Leschly Chip Baird Nicola Heffron Philip Gregory, D. Phil. Dan Lynch Denice Torres, J.D.
Chief Kairos Officer* Chief Financial Officer Chief Operating Officer Chief Scientific Officer Board Chair form. Johnson & Johnson
Duane Baggerly Kevin Chin, MD Susan Abu-Absi, Ph.D. Cintia Piccina, PharmD Ramy Ibrahim, M.D. Bill Sellers, M.D.
Head of People & Culture Head of Clinical Development Head of Manufacturing Head of Commercial BIT.BIO Broad Institute of MIT and Harvard
Jenn Snyder Teresa Jurgensen, J.D. Kathleen Munster Marcela Maus, M.D., Ph.D. Nick Leschly
Head of Corporate Affairs General Counsel SVP, Quality & Operations Massachusetts General Hospital Chief Kairos Officer
(MGH) Cancer Center
+450 Awesome 270ers
*Kairos: is an Ancient Greek word meaning the right, critical, or opportune moment
2seventy bio - privileged starting position and bold trajectory
2seventy: THE
leading immuno-
oncology cell
therapy company
• Pivotal data/regulatory
submissions for late-
stage heme
• Abecma® earlier • POC for solid tumors
lines • Next-gen MM POC
• Abecma® ramping • bbT369 POC data • IND engine cranking
• DARIC33 – 2H21 IND • DARIC33 POC data
• bbT369 – 2H21 IND • Solid tumors IND
• Multiple solid tumor • Internal DP
and next-gen MM
programs
AT LAUNCH / [YEAR …AND BEYOND
+1-2 YEARS +3-5 YEARS
END 2021]
2seventy Pipeline – Innovative cell therapy candidates across broad indications
INDICATION [DRUG] TARGET TECHNOLOGY DREAM DEVISE DELIVER
Multiple Myeloma BMS Partnership
BCMA CAR T cell
[ABECMA]
Multiple Myeloma CAR T cell
BCMA
PI3K Enhanced Manufacturing
BMS Partnership Data at ASH’21
[bb21217]
AML-Pediatric
CD33 Drug-Regulated CAR T cell (DARIC) SCRI Collaboration IND 2H 2021
[DARIC33]
B-NHL Dual B cell Dual-Targeted CAR T cell
targets Signal Enhanced Gene Edited
TSVT owned IND 2H 2021
[bbT369]
AML-Adult CD33 + Drug-Regulated CAR T cell Dual-
SCRI Collaboration
[DARIC33 Next-Gen] Undisclosed Targeted Potency Enhanced
TCR T cell
Solid Tumors MAGE-A4
Potency Enhanced
REGN / MEDG Partnership
CAR / TCR T cell
Solid Tumors Multiple
Potency Enhanced
TSVT & UNC
Multi-Targeted CAR T cell
Multiple Myeloma Multiple
Potency Enhanced
TSVT
Multiple Indications Multiple Multiple Multiple
2seventy’s R&D philosophy - accelerating innovation
DREAM
Identify fundamental problems
What opportunities have the
Look beyond the horizon greatest potential impact?
Explore new biology
DEVISE
Define clear hypotheses
What solutions can we conceive to
Invent compelling solutions unlock that potential?
Bridge gaps through partnership
Accelerate innovation through DELIVER
cycles Prospective data inflections
What development strategy
of TSVT’s ASK/ANSWER engine Defined development path robustly tests the hypothesis?
Invest in manufacturing v2.0
Abecma®: Our first dream, devise, deliver iteration is realized in multiple myeloma
What if we pivoted toward the Can we weave an academic/ A revolutionary drug is
emerging T cell therapy field? industry CAR-T partnership? developed and approved
Problem (circa 2013) Solution
• Outside of company’s core business & expertise
• CD19 only target with positive clinical data
• Will other targets or indications be responsive?
Early clinical data from UPenn highlight a new opportunity
64/M del17p R/R CLL patient dosed with 1.4 x 107 total CAR+ T cells
The FIRST CAR T cell therapy for Multiple MyelomaBuilding on the Abecma Foundation
Launch Strong out of the Gate
Strong and fast uptake, illustrating high unmet need and
confidence in the unprecedented efficacy of ABECMA Future
Expanding eligible patient population
Over 65 sites activated in the US, first patient apheresed
the week after launch through BMS collaboration
Expand capacity to match demand
Demand stronger than anticipated. Partnership efforts at
all stages of supply chain to expand capacity Independently progress our novel
MM next-gens
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 agreementRecoding R&D engine built to rapidly build, test, learn, & improve
4
1 TARGETING CAR TCR CCR DARIC
4 VECTOROLOGY DESIGN LVV mRNA
Validated & novel targets, Maximize payload,
world class binders, innovative design, optimize
5
innovative architectures component co-expression
2
Platform Iteration
Tech Integration
2 SIGNALING ENHANCED CO-STIM REGULATED 5 MODALITY ab T CELLS gd T CELLS
Amplify, diversify, prolong, 1 3 Take T cells to the next
induce, and/or regulate level, explore alternative
signal transduction chassis
3 ENHANCEMENT TME INNATE EXHAUSTION
6 MANUFACTURING VECTOR CELL PRODUCT
Combat exhaustion, leverage Commoditize LVV, invest in T
tumor microenvironment, cell process optimization,
multimodal attacks scalability, & qualitybbT369 is purpose-built to enhance depth and durability of response in B-NHL
DREAM DEVISE DELIVER
Strive to create a How to get there: Progress on execution:
product that: • Devise a sophisticated and • Encouraging pre-clinical data:
• Meets the significant need in disruptive cell therapy: a dual- bbT369 clears single and low
bNHL targeting, potency-enhanced antigen tumors, and achieves
candidate that solves failure deep, durable responses
• Addresses shortcomings of modes of CD19 CAR-Ts
existing therapies by increasing • Clinical development plan
response rate and durability of • Novel combination of antigens poised to quickly determine if
to address antigen escape. bbT369 can provide better
response to a larger fraction of
patients. • Synergistic antigen receptor outcomes for patients
signaling domains to augment
• IND anticipated in 2H21
T cell activation.
• Gene edit to enhance potency
and reduce T cell exhaustion.bbT369: Pre-clinical data outperforms model CD19 CAR supporting planned Phase I
bbT369 pre-clinical data demonstrates potential to
deliver against challenging tumors
• bbT369 outperforms model CD19 CAR in
Execution
challenging low antigen expressing tumors in
vivo
• Data supports potential to overcome
CD19CAR
resistance and elongate durability of response
2,500
Tumor Volume (mm3)
Low-Antigen
• Phase I trial will include both CD19 CAR
2,000
Tumor Model
1,500 relapsed and naïve patients
VS. 1,000 • Trial will be enriched for patients with high
500
risk factors as a proving ground to quickly
demonstrate improved patient outcomes
0
bbT369
-20 -10 CAR T 10 20 30
Anticipated IND Filing 2H21DARIC33: Engineered to kick start CAR T cell therapy in AML
DREAM DEVISE DELIVER
Strive to create a How to get there: Progress on execution:
product that: • Drug regulated CAR Ts • Maximize speed to clinical study
• Addresses the average life overcome the underlying via collaboration with world-
expectancy of 3 months post aplasia risk of targeting myeloid class translational center
relapse cells
• Test hypothesis in pediatric
• Addresses underlying barriers • Enhance CAR T cell persistence setting to reduce confounding
preventing transformative by reducing exhaustive effect of variables
outcomes continuous antigen stimulation
• IND 2H 2021DARIC33 in AML: Sensitive, drug-regulated tumor control achieved
Can we devise 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 dosing2seventy’s attack on solid tumors addresses the key barriers to success
Can we achieve sensitive & Can we convert suppressive signals Can we disrupt the physical &
multiplex targeting across the full to supportive ones, and re-engage biological barriers to T cell
range of target classes? innate immunity? infiltration and inflammation?
ONCOLYTIC ORTHOGONAL COMBINATION
VIRUSES MOAs STRATEGIESMAGEA4-CTBR12: Solid Tumors
What if we are only a step away from T Can we substantially enhance the Lead integrated candidate selected,
cells that deliver heme cancer-like potency of a TCR T cell using a TME demonstrates signal conversion &
outcomes for patients? signal conversion technology? potent tumor control
We have engineered a potent MAGE-A4 TCR Tumor regression achieved with MAGEA4
with a flip receptor to neutralize TGFb and TCR + TGFb flip receptor in a melanoma
potentiate T cell activity xenograft model
3e6
+
Median Tumor Volume (mm3)
2500 Vehicle
B. UTD
2000
BW2826
1500 BW9161
MAGEA4 TCR +
Flip Receptor
1000
Problem
500
• Checkpoint blockade validates T cell MoA
• Substantial opportunity for improved outcomes 0
• Additional pathway interrogation in re-targeted T 0 5 10 15 20
cells may access deep responses Study Days
• Some profoundly immunosuppressive pathways DP
Enhanced Potency 3 x 106 T cells
are difficult to target systemicallyDreaming, Devising, and Delivering on the future of cell therapy
1
Unexplored target classes
TARGETING Extensive binder multiplexing
2 Integrated signals 1, 2, & 3
SIGNALING Multiplex gene editing
Layered regulation & inducibility
3
Synergized combinations
ENHANCEMENT Orthogonal MoA
DREAM DEVISE DELIVER
4
Expanded payload capacity
VECTOROLOGY Multiplex transduction
5
Next-level ex vivo auto/allo
MODALITY Opportunistic asset plays
6
Commoditized LVV
MANUFACTURING Rapid, scalable in-house DP mfg2seventy’s manufacturing network: poised to deliver
VELOCITY INNOVATION CAPABILITY
Enable pipeline speed & decisions making to POC Multiply our reach, capacity & ability to innovate Manufacturing partnerships defined by identical goals
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 on game-
changing industry
partnerships
• Risk-reward partnership with
Deliver “best-in-class” Academic Resilience- new model for
partnerships for ‘exploratory’ programs access to CDMO++
capabilities, aligning
• Outlets for high-risk programs for clinical validation
incentives & promoting agility
while preserving flexibility & bbb resources
• Access to external innovation and programs,
network2seventy bio: a clear and differentiated strategy, well-funded to deliver
• Deliver ABECMA commercially and
expand product opportunity
✓ Strategy + Vision • Relentless innovation focus on product
engine – ask/answer/learn & iterate
• ABECMA launch exceeding plan Anticipate ~$975M
• Innovative cell therapy candidates
✓ Products that Matter across broad indications Wholeco cash
• 2 INDs 2021 balance at time of
split; 2seventy poised
✓ Leadership + • New leadership team in place to launch with
Team • BOD retooling for oncology focus
approximately 24
months of runway
• $75M private stock offering (WholeCo)
• Resilience collaboration brings $110M
✓ Funding + Financial upfront and $25M+ savings/year
• Anticipating approximately 24 months
of runway at launchYou can also read
