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Dear bluebird bio, Inc. Stockholder In January 2021, we announced a transformative milestone for bluebird bio, Inc.-our intent to separate our oncology portfolio and programs from our severe genetic disease portfolio and

Key Takeaway: Dear bluebird bio, Inc. Stockholder In January 2021, we announced a transformative milestone for bluebird bio, Inc.-our intent to separate our oncology portfolio and programs from our severe genetic disease portfolio and programs, thereby creating two independent, publicly trade

Full Press Release Details

Dear bluebird bio, Inc. Stockholder
In January 2021, we announced a transformative milestone for bluebird bio, Inc.-our intent to separate our oncology portfolio and programs from our severe genetic disease portfolio and programs, thereby creating two independent, publicly traded companies. The strategic objectives of the separation are to unlock value, enhance operational performance and strategic flexibility and tailor the capital structures to best serve these distinct businesses.
We believe the best way to realize the full potential of this separation is for bluebird bio, Inc. and 2seventy bio, Inc. to operate independently, with distinct management teams and boards of directors dedicated to their unique business strategies. Through this separation, we have the potential to create two focused, durable businesses that are well-positioned with the resources, talent and foundation to be industry leaders in their respective fields.
Going forward, bluebird bio, Inc. intends to focus primarily on its programs in severe genetic disease, including betibeglogene autotemcel (beti-cel formerly LentiGlobin gene therapy for -thalassemia), LentiGlobin gene therapy for sickle cell disease, and elivaldogene autotemcel (eli-cel formerly Lenti-D gene therapy for cerebral adrenoleukodystrophy). 2seventy bio, Inc. plans to focus primarily on the discovery and development of novel engineered cell therapies for cancer, including chimeric antigen receptor (CAR) and T cell receptor (TCR) T cell therapies. 2seventy bio, Inc. expects to commercialize idecabtagene vicleucel (ide-cel being commercialized as Abecma) in the United States and develop bb21217 through its collaboration arrangement with Bristol-Myers Squibb.
Upon completion of the separation, 2seventy bio, Inc. will be spun out of bluebird bio, Inc. and established as an independent, publicly traded company. The separation is anticipated to be generally tax-free to bluebird bio, Inc. stockholders. Under the terms of the distribution, each bluebird bio, Inc. stockholder will receive one share of 2seventy bio, Inc. common stock for every three shares of bluebird bio, Inc. common stock held of record on October 19, 2021, the record date for the distribution. You do not need to take any action to receive the common stock of 2seventy bio, Inc. to which you are entitled as a bluebird bio, Inc. stockholder as of the record date.
Please read the attached information statement, which is being shared with all bluebird bio, Inc. stockholders as of the record date for the distribution. It describes the separation in detail and contains important information about bluebird bio, Inc. and 2seventy bio, Inc.
We thank you for your continued support of bluebird bio, Inc.
Sincerely,
Daniel S. Lynch
Chairman of the Board
bluebird bio, Inc.
Dear Future 2seventy bio, Inc. Stockholder
On behalf of the entire future 2seventy bio, Inc. team, I am pleased to welcome you as a future stockholder of our new company.
2seventy bio, Inc. will be a cell and gene therapy company focused on the research, development, and commercialization of transformative treatments for cancer. Its programs will be based on chimeric antigen receptor (CAR) technology and T cell receptor technology. At launch, 2seventy bio, Inc.'s programs will include idecabtagene vicleucel ide-cel, or Abecma, and bb21217, CAR-T cell product candidates for the treatment of multiple myeloma, which are partnered under a collaboration arrangement with Bristol-Myers Squibb. We believe our team's expertise in T cell engineering technology and lentiviral vector gene delivery approaches, experience in research, development, and manufacturing of cell therapies and a suite of technologies will enable us to develop a pipeline of highly innovative, targeted cellular therapies for patients with cancer.
Our common stock has been approved for listing on the Nasdaq Global Select Market under the symbol "TSVT" in connection with the distribution of our company's common stock by bluebird bio, Inc.
I invite you to learn more about 2seventy bio, Inc. by reviewing the enclosed information statement. We look forward to our future as an independent company, and to your support as a 2seventy bio, Inc. stockholder as we begin this new and exciting chapter.
Sincerely,
Nick Leschly
Chief Executive Officer
2seventy bio, Inc.
INFORMATION STATEMENT
This information statement is being furnished to you as a holder of common stock of bluebird bio, Inc. ("bluebird bio") in connection with the distribution of shares of common stock of 2seventy bio, Inc., or 2seventy bio. 2seventy bio, which is currently a wholly owned subsidiary of bluebird bio, will hold, directly or indirectly, assets and liabilities related to bluebird bio's oncology portfolio and programs. To implement the distribution, bluebird bio will distribute all of the outstanding shares of 2seventy bio common stock on a pro rata basis to holders of bluebird bio common stock in a manner that is intended to be generally tax-free to bluebird bio stockholders for U.S. federal income tax purposes.
You will receive one share of 2seventy bio common stock for every three shares of bluebird bio common stock held of record by you as of the close of business on October 19, 2021, the record date for the distribution. Holders of bluebird bio common stock will receive cash in lieu of any fractional shares of 2seventy bio common stock that those holders would have received after application of the above ratio. As discussed under "The Separation and Distribution-Trading Between the Record Date and Distribution Date," if you sell your shares of bluebird bio common stock in the "regular way" market after the record date and before the distribution, you also will be selling your right to receive shares of 2seventy bio common stock in connection with the distribution. 2seventy bio expects that shares of its common stock will be distributed by bluebird bio to you on November 4, 2021. The date of distribution of 2seventy bio common stock is referred to in this information statement as the "distribution date."
No vote of bluebird bio stockholders is required for the distribution. Therefore, you are not being asked for a proxy, and you are requested not to send bluebird bio a proxy, in connection with the distribution. You do not need to pay any consideration, exchange or surrender your existing shares of bluebird bio common stock or take any other action to receive your shares of 2seventy bio common stock.
There is no current trading market for 2seventy bio common stock. 2seventy bio expects that a limited market, commonly known as a "when issued" trading market, will develop on or shortly before the record date for the distribution, and that "regular way" trading of 2seventy bio common stock will begin on the first trading day following the completion of the distribution. 2seventy bio's common stock on the Nasdaq Global Select Market under the symbol "TSVT".
We are an "emerging growth company" as that term is used in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act. As an emerging growth company, we will be subject to reduced public company reporting requirements.
In reviewing this information statement, you should carefully consider the matters described under the caption "Risk Factors" beginning on page 22.
Neither the U.S. Securities and Exchange Commission nor any state securities commission has approved or disapproved these securities or determined if this information statement is truthful or complete. Any representation to the contrary is a criminal offense.
This information statement does not constitute an offer to sell or the solicitation of an offer to buy any securities.
This information statement is first being mailed to bluebird bio stockholders on or about October 20, 2021.
The date of this information statement is October 18, 2021.
PRESENTATION OF INFORMATION 5
QUESTIONS AND ANSWERS ABOUT THE SEPARATION AND DISTRIBUTION 7
INFORMATION STATEMENT SUMMARY 16
SUMMARY HISTORICAL AND UNAUDITED PRO FORMA COMBINED FINANCIAL INFORMATION 24
RISK FACTORS 26
CAUTIONARY STATEMENT CONCERNING FORWARD-LOOKING STATEMENTS 77
DIVIDEND POLICY 79
CAPITALIZATION 80
UNAUDITED PRO FORMA COMBINED FINANCIAL STATEMENTS 81
MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS 88
BUSINESS 109
MANAGEMENT 146
EXECUTIVE COMPENSATION 153
CERTAIN RELATIONSHIPS AND RELATED PERSON TRANSACTIONS 168
SECURITY OWNERSHIP BY CERTAIN BENEFICIAL OWNERS AND MANAGEMENT 173
THE SEPARATION AND DISTRIBUTION 175
MATERIAL U.S. FEDERAL INCOME TAX CONSEQUENCES 180
DESCRIPTION OF 2SEVENTY BIO'S CAPITAL STOCK 184
WHERE YOU CAN FIND MORE INFORMATION 188
INDEX TO COMBINED FINANCIAL STATEMENTS F- 1
PRESENTATION OF INFORMATION
Except as otherwise indicated or unless the context otherwise requires, the information included in this information statement about 2seventy bio assumes the completion of all of the transactions referred to in this information statement in connection with the separation and distribution.
Unless the context otherwise requires, references in this information statement to the following terms shall have the following respective meanings
"bluebird bio" refers to bluebird bio, Inc., a Delaware corporation, and its consolidated subsidiaries
"distribution" refers to the distribution by bluebird bio to bluebird bio stockholders of record as of the record date of all of the outstanding shares of 2seventy bio, as further described in this information statement
"separation" refers to the separation of bluebird bio's oncology portfolio and programs from bluebird bio's severe genetic disease portfolio and programs, and the creation, as a result of the distribution, of an independent, publicly traded company, 2seventy bio, that holds the oncology portfolio and programs, as further described in this information statement and
"2seventy bio," "we," "us," "our," "our company" and "the company" refer to 2seventy bio, Inc., a Delaware corporation, together with its subsidiaries, as the context requires, in each case as they will exist, assuming the completion of all the transactions referred to in this information statement in connection with the separation and the distribution.
This information statement describes the portfolio and programs to be transferred to 2seventy bio by bluebird bio in the separation as if the transferred portfolio and programs were 2seventy bio's portfolio and programs for all historical periods described. References in this information statement to 2seventy bio's historical assets, liabilities, products, businesses or activities of 2seventy bio's portfolio and programs are generally intended to refer to the historical assets, liabilities, products, businesses or activities of the transferred portfolio and programs as they were conducted as part of bluebird bio prior to the separation.
You should not assume that the information contained in this information statement is accurate as of any date other than the date set forth on the cover. Changes to the information contained in this information statement may occur after that date, and we undertake no obligation to update the information, except in the normal course of our public disclosure obligations or as required by applicable law.
Websites described in this information statement and the content therein or connected thereto shall not be deemed incorporated into this information statement.
Trademarks, Trade Names and Service Marks
2seventy bio owns and has rights to use the trademarks, service marks and trade names that it uses in conjunction with the operation of its business, including 2seventy bio, 2seventybio, and 2seventy. In addition, 2seventy bio's trademarks are undergoing examination and registration in the United States and other jurisdictions. 2seventy bio's trademark rights may be limited to select markets. Each trademark, trade name or service mark of any other company appearing in this information statement is, to 2seventy bio's knowledge, owned by such other company.
Industry and Other Data
This information statement contains estimates, projections and other information concerning our industry, our business, and the markets for certain diseases, including data regarding the estimated size of those markets, and the incidence and prevalence of certain medical conditions. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. Unless otherwise expressly stated, we obtained this industry, business, market and other data from reports, research surveys, studies and similar data prepared by market research firms and other third parties, industry, medical and general publications, government data and similar sources.
QUESTIONS AND ANSWERS ABOUT THE SEPARATION AND DISTRIBUTION
What is 2seventy bio and why is bluebird bio separating 2seventy bio's portfolio and programs and distributing 2seventy bio's common stock 2seventy bio, which is currently a wholly owned subsidiary of bluebird bio, was formed to hold bluebird bio's oncology portfolio and programs. The separation of 2seventy bio from bluebird bio and the distribution of 2seventy bio common stock are intended to provide you with equity investments in two separate, independent public companies, each of which is able to focus on its respective business strategies. bluebird bio and 2seventy bio believe the separation will enable each business to pursue focused growth and investment strategies in its respective therapeutic areas of expertise resulting in the enhanced long-term performance of each business, as discussed in "The Separation and Distribution-Overview" and "The Separation and Distribution-Reasons for the Separation."
Why am I receiving this document bluebird bio is delivering this information statement to you because you are a holder of record of shares of bluebird bio common stock. If you remain a holder of shares of bluebird bio common stock as of the close of business on October 19, 2021, you will be entitled to receive one share of 2seventy bio common stock for every three shares of bluebird bio common stock that you held of record at the close of business on such date. This information statement will help you understand how the separation will affect your investment in bluebird bio and your investment in 2seventy bio after the distribution.
How will the separation of 2seventy bio from bluebird bio work To accomplish the separation, bluebird bio will distribute all of the outstanding shares of 2seventy bio common stock to bluebird bio stockholders on a pro rata basis.
Why is the separation of 2seventy bio structured as a distribution bluebird bio believes that a generally tax-free distribution for U.S. federal income tax purposes of shares of 2seventy bio common stock to the bluebird bio stockholders is an efficient way to separate its oncology portfolio and programs in a manner that will create long-term value for bluebird bio, 2seventy bio and their respective stockholders. For more information, see "The Separation and Distribution-Conditions to the Distribution."
What is the record date for the distribution The record date for the distribution will be October 19, 2021.
When will the distribution occur It is expected that all of the shares of 2seventy bio common stock will be distributed by bluebird bio on November 4, 2021, to holders of record of bluebird bio common stock as of the close of business on October 19, 2021. We refer to the date on which shares of 2seventy bio common stock are distributed as the "distribution date."
What do stockholders need to do to participate in the distribution Nothing. Stockholders of bluebird bio as of the record date will not be required to take any action to receive 2seventy bio common stock, but are urged to read this entire information statement carefully. No stockholder approval of the distribution is required or sought. Therefore, you are not being asked for a proxy to vote on the separation, and you are requested not to send us a proxy. You will neither be required to pay anything for the shares of 2seventy bio common stock nor be required to surrender any shares of bluebird bio common stock to participate in the distribution. Please do not send in your bluebird bio stock certificates.
The distribution will not affect the number of outstanding shares of bluebird bio common stock or any rights of bluebird bio stockholders, although it will affect the market value of each outstanding share of bluebird bio common stock. See "Questions and Answers about the Separation and Distribution-Will the distribution affect the market price of my bluebird bio common stock " for more information.
How will bluebird bio distribute shares of 2seventy bio common stock Registered stockholders If you are a registered stockholder (meaning you hold physical bluebird bio stock certificates or you own your shares of bluebird bio common stock directly through an account with bluebird bio's transfer agent, American Stock Transfer Trust, LLC), the distribution agent, American Stock Transfer Trust Company, LLC, will credit the number of whole shares of 2seventy bio common stock you receive in the distribution to your book-entry account on or shortly after the distribution date, and the distribution agent will mail you a check for any cash in lieu of fractional shares you are entitled to receive.
"Street name" or beneficial stockholders If you own your shares of bluebird bio common stock beneficially through a bank, bluebird bio or other nominee, your bank, broker or other nominee will credit your account with the number of whole shares of 2seventy bio common stock you receive in the distribution on or shortly after the distribution date. Please contact your bank, broker or other nominee for further information about your account.
We will not issue any physical stock certificates to any stockholders receiving shares in the distribution, even if requested. See "The Separation and Distribution-When and How You Will Receive the Distribution" for more information.
How many shares of 2seventy bio common stock will I receive in the distribution bluebird bio will distribute to you one share of 2seventy bio common stock for every three shares of bluebird bio common stock you hold of record as of the close of business on October 19, 2021, the record date. Based on approximately 69,862,379 shares of bluebird bio common stock outstanding as of September 27, 2021, a total of approximately 23,287,457 shares of 2seventy bio common stock will be distributed. For more information, see "The Separation and Distribution-The Number of Shares of 2seventy bio Common Stock You Will Receive."
Will 2seventy bio issue fractional shares in the distribution 2seventy bio will not distribute fractional shares of its common stock in the distribution. Instead, all fractional shares that bluebird bio registered stockholders would otherwise have been entitled to receive will be aggregated into whole shares and sold in the open market by the distribution agent. We expect the distribution agent, acting on behalf of bluebird bio, to take about two weeks after the distribution date to fully distribute the aggregate net cash proceeds of these sales on a pro rata basis (based on the fractional share such holder would otherwise be entitled to receive) to those stockholders who would otherwise have been entitled to receive fractional shares. Recipients of cash in lieu of fractional shares will not be entitled to any interest on the amounts of payment made in lieu of fractional shares. For more information, see "The Separation and Distribution-The Number of Shares of 2seventy bio Common Stock You Will Receive."
What are the conditions to the distribution The distribution is subject to the satisfaction (or waiver by bluebird bio in its sole discretion) of a number of conditions to be set forth in the separation agreement, including, among others, that bluebird bio will have received a private letter ruling from the Internal Revenue Service, or the IRS, and an opinion from Goodwin Procter LLP, both satisfactory to bluebird bio's board of directors and both continuing to be valid, together confirming that the distribution, together with certain related transactions, generally is tax-free for U.S. federal income tax purposes under Sections 355 and 368(a)(1)(D) of the Internal Revenue Code of 1986, as amended, or the Code.
bluebird bio and 2seventy bio cannot assure you that any or all of these conditions will be met, and bluebird bio may waive any of these conditions to the distribution. In addition, bluebird bio can determine, at any time, not to proceed with the distribution. For more information, see "The Separation and Distribution-Conditions to the Distribution."
What is the expected date of completion of the distribution The completion and timing of the distribution are dependent upon a number of conditions. It is expected that the shares of 2seventy bio common stock will be distributed by bluebird bio on November 4, 2021 to the holders of record of shares of bluebird bio common stock as of the close of business on the record date. However, no assurance can be provided as to the timing of the distribution or that all conditions to the distribution will be met.
Can bluebird bio decide to cancel the distribution of 2seventy bio common stock even if all the conditions have been met Yes, until the distribution has occurred, bluebird bio has the right to terminate the distribution, even if all of the conditions are satisfied. See "The Separation and Distribution-Conditions to the Distribution" for more information.
What if I want to sell my bluebird bio common stock or my 2seventy bio common stock You should consult with your advisors, such as your broker, bank or tax advisor.
What is "regular way" and "ex-distribution" trading of bluebird bio stock Beginning on or shortly before the record date and continuing up to and including the distribution date, it is expected that there will be two markets in shares of bluebird bio common stock a "regular way" market and an "ex-distribution" market. Shares of bluebird bio common stock that trade in the "regular way" market will trade with an entitlement to shares of 2seventy bio common stock distributed pursuant to the distribution. Shares that trade in the "ex-distribution" market will trade without an entitlement to shares of 2seventy bio common stock distributed pursuant to the distribution.
If you hold shares of bluebird bio common stock on the record date and you decide to sell any shares of bluebird bio common stock before the distribution date, you should make sure your broker, bank or other nominee understands whether you want to sell your shares of bluebird bio common stock with or without your entitlement to receive 2seventy bio common stock pursuant to the distribution. See "The Separation and Distribution-Trading Between the Record Date and Distribution Date" for more information.
Where will I be able to trade shares of 2seventy bio common stock Currently, there is no public market for 2seventy bio common stock. 2seventy bio's common stock is approved for listing on the Nasdaq Global Select Market under the symbol "TSVT".
2seventy bio anticipates that trading in shares of its common stock will begin on a "when issued" basis on or shortly before the record date for the distribution and will continue up to and including the distribution date. "When issued" trading in the context of a separation refers to a sale or purchase made conditionally on or before the distribution date because the securities of the separated entity have not yet been distributed. "When issued" trades generally settle within two weeks after the distribution date. On the first trading day following the distribution date, any "when issued" trading of our common stock will end and "regular way" trading will begin. "Regular way" trading refers to trading after the security has been distributed and typically involves a trade that settles on the second full trading day following the date of the trade. See "The Separation and Distribution-Trading Between the Record Date and Distribution Date" for more information. We cannot predict the trading prices for our common stock before, on or after the distribution date.
What will happen to the listing of shares of bluebird bio common stock Shares of bluebird bio common stock will continue to trade on the Nasdaq Global Select Market after the distribution.
Will the number of shares of bluebird bio common stock that I own change as a result of the distribution No. The number of shares of bluebird bio common stock that you own will not change as a result of the distribution.
Will the distribution affect the market price of my bluebird bio common stock Yes. As a result of the distribution, bluebird bio expects the trading price of shares of bluebird bio common stock immediately following the distribution to be lower than the "regular way" trading price of such shares immediately prior to the distribution because the trading price will no longer reflect the value of the oncology portfolio and programs. Furthermore, as the market assesses bluebird bio following the separation, the trading price of shares of bluebird bio common stock may fluctuate. There can be no assurance that, following the distribution, the combined trading prices of bluebird bio common stock and 2seventy bio common stock will equal or exceed what the trading price of bluebird bio common stock would have been in the absence of the separation, and it is possible the post-distribution combined equity value of bluebird bio and 2seventy bio will be less than bluebird bio's equity value prior to the distribution.
What are the material U.S. federal income tax consequences of the distribution It is a condition to the distribution that bluebird bio receive a private letter ruling from the IRS and an opinion from Goodwin Procter LLP, both satisfactory to bluebird bio's board of directors and both continuing to be valid, together confirming that the distribution, together with certain related transactions, subject to certain caveats, generally is tax-free for U.S. federal income tax purposes under Sections 355 and 368(a)(1)(D) of the Code. Assuming that the distribution, together with certain related transactions, so qualifies, for U.S. federal income tax purposes, no gain or loss will be recognized by you and no amount will be included in your income upon receipt of shares of 2seventy bio common stock pursuant to the distribution. You will, however, recognize gain or loss for U.S. federal income tax purposes with respect to cash received in lieu of a fractional share of 2seventy bio common stock.
You should consult your own tax advisor as to the particular consequences of the distribution to you, including the applicability and effect of any U.S. federal, state and local tax laws, as well as non-U.S. tax laws. For more information regarding the material U.S. federal income tax consequences of the distribution and for information regarding the types of investors subject to special rules to whom the above summary may not apply, see "Material U.S. Federal Income Tax Consequences."
How will I determine my tax basis in the shares of 2seventy bio common stock I receive in the distribution For U.S. federal income tax purposes, generally, your aggregate basis in the common stock that you hold in bluebird bio and the new 2seventy bio common stock received in the distribution (including any fractional share interest in 2seventy bio common stock for which cash is received) will equal the aggregate basis in the shares of bluebird bio common stock held by you immediately before the distribution, allocated between your shares of bluebird bio common stock and 2seventy bio common stock (including any fractional share interest in 2seventy bio common stock for which cash is received) you receive in the distribution in proportion to the relative fair market value of each on the distribution date.
You should consult your own tax advisor as to the particular consequences of the distribution to you, including the application of the tax basis allocation rules and the application of state, local and non-U.S. tax laws. For more information regarding the material U.S. federal income tax consequences of the distribution and for information regarding the types of investors subject to special rules to whom the above summary may not apply, see "Material U.S. Federal Income Tax Consequences."
What will 2seventy bio's relationship be with bluebird bio following the distribution To effect a decisive and efficient separation into two thriving companies, 2seventy bio intends to enter into a separation agreement and certain other agreements with bluebird bio, including a tax matters agreement, an employee matters agreement, an intellectual property license agreement, a transition services agreement under which we will temporarily receive certain services from bluebird bio and a second transition services agreement under which we will temporarily provide certain services to bluebird bio. These agreements will provide for the separation between bluebird bio and 2seventy bio of the assets, employees, liabilities and obligations (including investments, property and employee benefits) of bluebird bio attributable to periods prior to, at and after the distribution and will govern the relationship between bluebird bio and 2seventy bio subsequent to the completion of the distribution. For additional information regarding the separation agreement and other transaction agreements, see "Risk Factors-Risks Related to the Separation" and "Certain Relationships and Related Person Transactions-Agreements with bluebird bio."
Who will manage 2seventy bio after the distribution 2seventy bio will benefit from having in place a management team with a substantial background in the biotechnology business. 2seventy bio's management team possesses deep knowledge of and experience in its industry. 2seventy bio's management team is expected to include Nick Leschly, bluebird bio's president and chief executive officer who is expected to be 2seventy bio's president and chief executive officer after the distribution, William D. Baird, bluebird bio's chief financial officer who is expected to be 2seventy bio's chief financial officer after the distribution, and Philip Gregory who is expected to be 2seventy bio's chief scientific officer after the distribution. For more information regarding bluebird bio's expected management team and leadership structure, see "Management."
Are there risks associated with owning 2seventy bio common stock Yes. Ownership of 2seventy bio common stock is subject to both general and specific risks related to 2seventy bio's business, the industry in which it operates, its ongoing relationships with bluebird bio and its status as a separate, publicly traded company. Ownership of 2seventy bio common stock is also subject to risks related to the separation. These risks are described in the "Risk Factors" section of this information statement beginning on page 22. You are encouraged to read that section carefully.
Does 2seventy bio plan to pay dividends 2seventy bio does not expect to pay a regular cash dividend following the distribution. The payment of any dividends in the future, and the timing and amount thereof, is within the discretion of 2seventy bio's board of directors. See "Dividend Policy."
Who will be the distribution agent, transfer agent and registrar for the 2seventy bio common stock The distribution agent, transfer agent and registrar for 2seventy bio common stock will be American Stock Transfer Trust Company, LLC. For registered holders with questions relating to the transfer or mechanics of the stock distribution, you should contact
Address 6201 15th Avenue, Brooklyn, NY 11219, Attn Reorganization Department Tel (877) 248-6417 (toll-free) or (718) 921-8317 E-mail info astfinancial.com
How can I contact bluebird bio or 2seventy bio with any questions Before the distribution, if you have any questions relating to bluebird bio or 2seventy bio's business performance, you should contact
bluebird bio, Inc. Investor Relations Department 60 Binney Street Cambridge, MA 02142 Tel 617-245-2107 E-mail investor bluebirdbio.com
After the distribution, 2seventy bio stockholders who have any questions relating to 2seventy bio's business performance should contact 2seventy bio at
2seventy bio, Inc. Investor Relations Department 60 Binney Street Cambridge, MA 02142 Tel 617-914-8736 E-mail elizabeth.pingpank 2seventybio.com
INFORMATION STATEMENT SUMMARY
The following is a summary of material information discussed in this information statement. This summary may not contain all the details concerning the separation or other information that may be important to you. To better understand the separation and 2seventy bio's business and financial position, you should carefully review this entire information statement, including the risks discussed under "Risk Factors."
Except as otherwise indicated or unless the context otherwise requires, the information included in this information statement assumes the completion of all of the transactions referred to in this information statement in connection with the separation. Some of the statements in this summary constitute forward-looking statements. See "Cautionary Statement Concerning Forward-Looking Statements."
2seventy bio is a cell and gene therapy company focused on the research, development, and commercialization of transformative treatments for cancer. We are led by an accomplished team with significant expertise and experience in this field, from discovery through clinical development to regulatory approval of Abecma (idecabtagene vicleucel, or ide-cel), the first FDA-approved chimeric antigen receptor technology (CAR T) cell therapy for multiple myeloma. Our approach combines our expertise in T cell engineering technology and lentiviral vector gene delivery approaches, experience in research, development, and manufacturing of cell therapies and a suite of technologies that can be selectively deployed to develop highly innovative, targeted cellular therapies for patients with cancer. We are advancing multiple preclinical and clinical programs in oncology and, together with our partner Bristol-Myers Squibb (BMS), delivering Abecma to multiple myeloma patients in the United States following approval by the FDA of Abecma in March 2021 for the treatment of adults with multiple myeloma who have received at least four prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody.
In recent years, growing understanding of cancer cell metabolism and genomics, as well as of the body's immune response to tumor cells, has led to the development of new classes of therapies against cancer targets and pathways that have dramatically reshaped the treatment landscape. The advent of immunotherapy, particularly engineered cell therapies, has offered the potential of moving past the treatment paradigm of maintenance of cancer as a "chronic" disease. However, there remain few curative therapies and, in some settings such as solid tumors, current approaches do not offer significant depth or durability of outcome for most cancer types and patients. Monotherapies have historically been of limited efficacy in cancer, and drugs are typically combined to deliver an outsized effect relative to the action of any of the individual components. One potential advantage of combination therapies is the ability to address the heterogeneity of single target expression and or mechanisms for relapse and resistance specific to a particular mechanism or target.
While medicines such as Abecma have highlighted the power of first-generation CAR T cell therapy by achieving previously unobtainable levels of efficacy in the late line setting, we believe that to be broadly successful in the treatment of cancer, a combination therapy approach is necessary, and that our multiplex approach to next-generation autologous cellular therapy, which allows multiple encoded mechanisms of action to be delivered within a single drug product, represents an attractive solution. Based on our experience in the research and development of Abecma, we believe we can develop next-generation, engineered cell therapies to bring new options to patients suffering from a broad range of different tumor types.
In designing our next-generation product candidates, we aim to address the limitations of first-generation T cell therapies by augmenting them with additional technologies. Our approach is to create multiplex engineered cell therapies by combining (1) CAR and T cell receptor technology, which programs T cells to recognize and kill cancer cells based on the cell surface expression or presentation of intracellular protein targets, respectively (2) dual-targeting CAR architecture for multi-target tumor cell recognition (3) our core lentiviral gene transfer technology which delivers these genetic cargos (and more) to program a patient's own T cells to the kill the cancer cells (4) our megaTAL-based gene editing technology which allows us to perform site specific gene addition or deletion from the genome to improve the properties of the T cell and (5) genetically encoded technologies for
engineering T cells to enhance the cytotoxic activity and reprogram the tumor microenvironment for more effective anti-tumor responses.
Our strategy is to apply our broad range of technologies to design multiplex product candidates that address the key treatment challenges in cancer. Unlike other oncology-focused companies in our space, we believe our breadth of technology enables us to develop tailored products focused on the specific areas of cancer biology we have identified. We selectively combine the relevant features and components from our range of tools and technologies to address the defined attributes of a cellular therapy necessary for anti-tumor effect.
To execute on our strategy, we plan to
Commercialize Abecma and develop bb21217 through our collaboration with BMS, the learnings from which allow us to leverage our clinical experience and product revenue stream to further invest in our next-generation proprietary programs.
Leverage our leadership position in autologous CAR T therapies to advance into the clinic our next-generation programs in B cell non-Hodgkin's lymphoma, acute myeloid leukemia, and multiple myeloma.
Apply our multiplex approach to the discovery and design of transformative cell and gene therapy products for the treatment of solid tumors.
Seek to extend our approach to other cell types beyond T cells and to include allogeneic approaches, as we gain additional experience in our autologous T cell programs.
Build upon our existing internal lentiviral vector manufacturing know-how and experience through selective investments in manufacturing collaborations and expanding our internal capabilities over time, with the objectives of enabling rapid iteration on clinical learnings into research and development, increasing the efficiency of manufacturing processes, and improving the overall patient and healthcare professional experience.
Our oncology programs use a lentiviral vector to deliver the genetic cargo necessary to program a patient's own T cells to recognize specific proteins or protein fragments on the surface of cancer cells to kill the cancer cells. Our current programs are based on CAR technology to program T cells to recognize cancer cells based on expression of specific cell surface antigens, and T cell receptor technology to program T cells to recognize cancer cells based on protein fragments derived from either intracellular or extracellular proteins displayed on the tumor cell surface. The genetically engineered T cells are designed to supplement a patient's immune system and may be further engineered to overcome immune evasion mechanisms employed by cancer cells. Our approach is to create multiplex engineered cell therapies by combining our foundational lentiviral vector and CAR T cell receptor (TCR) technology with next-generation tools to address the challenges in existing cancer treatments.
Dual-Targeting Polyclonal responses are a hallmark of adaptive immunity, but most T cell therapies have been devised with antigen receptors specific to a single target antigen. There are now many documented cases of cancer deploying its intrinsic genetic plasticity to escape mono-targeted T cell therapies (both with cellular and more classical modalities, such as small molecules and antibodies). In such cases, our solution is to utilize a dual-targeting antigen receptor, including a multi-chain, dual-targeting architecture that is able to respond when either target antigen is present on a cancer cell, as well as an architecture that leverages the unique properties of humanized single-domain camelid-derived antibodies.
DARIC. We have developed a pharmacologically-regulated split antigen receptor architecture, which we refer to as DARIC, that comprises separate antigen targeting and signal transduction componentry. DARIC receptors become poised for anti-tumor function only when the two components are brought together as heterodimers, a process that is strictly dependent on the bridging function of the drug rapamycin. This technology enables pharmacological, on-demand' control of engineered T cell responses. Controlling the
on' and off' states of engineered T cells also creates opportunities to pursue cancers and cancer targets with disease characteristics and expression profiles that are incompatible with constitutively responsive antigen receptors.
Reversal of immunosuppression. Patients who present in the clinic with advanced metastatic disease are host to tumors that have evolved to evade endogenous immunity via a variety of mechanisms. Tumor infiltrating T cells lose potency over time due to repetitive antigen stimulation and exhaustion in a tumor microenvironment that suppresses T cell function. Checkpoint engagement, hypoxia, poor nutrient conditions, and exposure to immunosuppressive cell types and cytokines all significantly blunt T cell potency and thwart attempts to regress tumors in clinically meaningful ways. We have developed a suite of synthetic biology innovations that antagonize and rewire immunosuppressive signaling and response pathways. We have focused significant attention on transforming growth factor beta (TGF ), a profoundly immunosuppressive cytokine found at high levels in many solid tumors. Our chimeric TGF flip receptor (CTBR) technology converts this suppressive signal into a supportive interleukin receptor signal that enhances T cell function. Suppressive to enhancing signal conversion operates in a localized, engineered T cell intrinsic manner, enhancing potency within the microenvironment of the tumor where the highest concentrations of activated TGF ligand are present. We have also developed several approaches to modulate T cell metabolism to allow for enhanced function and potency in the metabolically challenging tumor microenvironment.
Co-stimulation. Parallel track costimulatory domains, also known as chimeric costimulatory receptors, offer a unique set of functional attributes that culminate in enhanced anti-tumor activity. This technology pairs enhanced targeting breadth with a qualitatively distinct and more potent functional response, simultaneously countering two potential mechanisms of resistance.
Gene editing. megaTALs are highly specific, compact nucleases that efficiently catalyze the formation and mutagenic resolution of double-stranded breaks at pre-specified genetic target sequences. Using our megaTAL gene editing platform, we have demonstrated that disrupting genes that intersect with T cell signaling and response pathways can promote more potent immune responses. In addition, we have developed a full suite of on-target editing assays, functional bioassays, and off-target discovery and verification analytics to deeply characterize gene editing events and their functional consequences in target cells enabling the potential application of this technology in the clinical setting.
mRNA capabilities. We have also developed messenger RNA (mRNA) capabilities that enable transient gene expression, both in cells cultured ex vivo and for organ-specific in vivo delivery. We manufacture mRNA starting from a proprietary plasmid template outfitted with an encoded poly-A tract, an approach that results in highly homogenous mRNA species following in vitro transcription. Our purification process includes double-stranded RNA (dsRNA) depletion steps to minimize immunogenicity and optimize cell viability. A robust suite of analytical assays is in place to ensure that consistently pure and potent material is generated. We have developed clinical-scale electroporation processes for ex vivo mRNA delivery and are actively using these processes to improve T cell potency via our megaTAL gene editing platform. This technology can potentially be further leveraged to transiently express other factors that may be advantageous to ex vivo manufactured T cells.
Cellular chassis. Beyond genetic modifications we are also developing approaches aimed at selecting for or enriching distinct cell types for tumor targeting that may be broadly applicable to both autologous and allogeneic settings. For instance, our bb21217 program utilizes a PI3K-inhibiting small molecule to enrich for memory-like T cells with the goal of extending the durability of action of our CAR T cells for multiple myeloma. In addition, we have developed approaches for the selection, transduction and expansion of gamma delta T cells. We believe gamma delta T cells may be useful in the allogeneic setting due to the absence of alloreactivity or graft-versus-host disease while demonstrating potent anti-tumor activity.
Further, we continue to invest in our core foundational technologies and build upon our leadership position in autologous engineered cell therapy products based on CAR and TCR approaches
Next-generation lentiviral vector design. With decades of experience in this technology, we have extensively refined the componentry and methodology behind lentiviral vector design and manufacturing. Our transfer plasmid design elements include several innovations that have created advanced gene expression tuning capabilities and the delivery of large and complex genetic payloads via transgene stacking. We have developed proprietary codon optimization algorithms, promoter variants, and regulatory elements that together enable constitutive and or responsive expression profiles across a range of transgene expression levels. These mature capabilities enable highly efficient transfer of sophisticated genetic modules, such as the multiplex product concepts represented by our next-generation programs.
Target selection and validation. Cancer targets with profiles that make them appropriate for cell therapy development have diverse structural features, biochemical properties, and sub-cellular distribution characteristics. To support novel target identification, we have developed significant in-house expertise and external collaborations in the areas of data mining, functional genomics, and primary tissue analysis. We have also built a full suite of target validation assays to perform confirmatory studies assessing tumor and normal tissue expression properties. In addition, we have developed significant internal expertise specific to the de-risking of potential off-target liabilities of TCR engineered T cells. We have focused the bulk of our efforts on select hematological and solid tumor indications. This approach allows us to deeply interrogate the target landscape in cancers where T cell therapies may have the highest potential for technical success.
Receptor engineering. We have access to state-of-the-art binder capabilities through our collaboration arrangements that cover the full range of potential cancer targets. For intracellular targets of interest, our partners develop TCRs and fully humanized peptide-in-groove' (PiG) scFv reagents. For surface proteins, we have multiple providers of immunization-sourced, fully humanized scFv and single-domain reagents.
Manufacturing process innovations. Our analytical development, clinical bioassays, correlative research, and data sciences teams have unique access to clinical trial data using CAR T therapies. We are continuously interrogating these data sets to isolate key manufacturing variables and correlates of clinical signals that enable hypothesis testing. These activities derive insights that inform process research directions for optimizing T cell manufacturing through reagents, processes, and culture timing, and for the discovery of underlying biological relationships between clinical and correlative data.
Summary of Risk Factors
An investment in 2seventy bio's common stock is subject to a number of risks, including risks related to our business, risks related to the separation and risks related to our common stock. The following list of risk factors is not exhaustive. Please read the information in the section captioned "Risk Factors" for a more thorough description of these and other risks.
Risks Related to Our Business
Because we have a limited operating history, valuing our business and predicting our prospects is challenging.
Our business has incurred significant losses and we anticipate that we will continue to incur significant losses for the foreseeable future.
We will need to raise additional funding to advance our product candidates, which may not be available on acceptable terms, or at all.
Research and development of biopharmaceutical products is inherently risky. We may encounter substantial delays in our clinical studies, or we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities.
If we encounter difficulties in enrolling subjects in our clinical studies, we could be delayed or prevented from proceeding with clinical trials of our product candidates.
If the market opportunities for our approved product, Abecma, or any future products are smaller than we believe they are, and if we are not able to successfully identify patients and achieve significant market share, our revenues may be adversely affected and our business may suffer.
We cannot predict when or if we will obtain marketing approval to commercialize our product candidates, and the marketing approval of our product and any future products may ultimately be for more narrow indications than we expect.
Delays in the commencement and completion of clinical trials could increase costs and delay or prevent regulatory approval and commercialization of our product candidates.
If our product candidates are ultimately not approved for any reason, our business, prospects, results of operations and financial condition would be adversely affected.
Patients receiving T cell-based immunotherapies, such as Abecma or bb21217 in ongoing clinical trials, may experience serious adverse events, including neurotoxicity and cytokine release syndrome.
Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage public perception of our product and any future product candidates.
We may not be successful in our efforts to identify or discover additional product candidates.
We are dependent on BMS for the successful commercialization of Abecma and successful development of bb21217.
Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of our product candidates in other jurisdictions.
We rely on third parties to conduct some or all aspects of our lentiviral vector production, drug product manufacturing, and testing, and these third parties may not perform satisfactorily.
We may not be successful in obtaining or maintaining necessary rights to gene therapy product components and processes for our development pipeline through acquisitions and in-licenses.
We have limited experience as a commercial company and the marketing and sale any future approved drugs may be unsuccessful or less successful than anticipated.
We are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws and health information privacy and security laws.
Last updated: Oct 19, 2021