What changed in this filing

/stocks — the workspaceLOADING

Item 7. Management’s Discussion and Analysis

2022-03-08 compared with 2021-03-03 · 90 added, 131 removed, 198 unchanged (53% of the section changed)

5 unchanged sentences

our actual results could differ materially from the results described in, or implied by, the forward-looking statements contained in the following discussion and analysis.

Magenta Therapeutics is a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplants to more patients with blood cancers, genetic diseases and autoimmune diseases.

Magenta’s drug development pipeline includes multiple product candidates designed to improve stem cell transplants.

Our lead clinical program is designed to more efficiently and reliably mobilize and collect sufficient functional stem cells for use in stem cell transplantation, a process known as mobilization.

We are also developing product candidates that are designed to deplete targeted cells in the bone marrow to make space for the bone marrow to receive newly transplanted stem cells, a process known as conditioning.

Our mobilization program is intended to enable rapid, reliable, predictable and safe mobilization and collection of high numbers of functional stem cells for transplant.

Magenta’s targeted conditioning programs are intended to enhance the efficacy of and/or reduce the dosing levels, intensity or, in some cases, even the need for chemotoxic agents.

Stem cell transplant is an established and, for certain patients, can be a curative medical procedure that can reset a patient’s blood and immune system after the patient has received treatment for certain blood cancers, genetic diseases or autoimmune diseases.

Stem cell transplants involve a three-step process:

(i) stem cells are mobilized out of the patient’s or donor’s bone marrow and collected from the blood (or, in rare cases, surgically extracted from their bone marrow);

(ii) the patient’s bone marrow is cleared of any remaining stem cells in order to make space to receive new transplanted stem cells;

and (iii) the stem cells are transplanted into the patient via infusion where they fasten to, or engraft in, the bone marrow and grow into the blood cells and platelets that form the basis of a reset and rebuilt blood and immune system.

All transplants are categorized as either autologous or allogeneic depending on the source of the new stem cells for the transplant.

In an autologous transplant, the patient’s own stem cells are used.

In an allogeneic transplant, patients receive cells from a stem cell donor.

Stem cell transplant, whether autologous or allogeneic, has broad applicability across disease settings, including blood cancers, gene therapies for genetic diseases and autoimmune diseases.

It is the current standard of care for certain blood cancers such as acute myeloid leukemia, or AML, myelodysplastic syndromes, or MDS, multiple myeloma and non-Hodgkin’s

Hematopoietic stem cell, or HSC, -based gene therapies also rely on the same steps of the stem cell transplant process with an additional step where collected stem cells are gene-corrected or modified to address the underlying disease prior to transplant.

Such gene therapy approaches that leverage the stem cell transplant procedure are being investigated by numerous companies in a variety of diseases, including sickle cell disease, beta-thalassemia and lysosomal storage disorders.

Autoimmune diseases such as multiple sclerosis and systemic sclerosis may also benefit from resetting the immune system through stem cell transplant.

Currently, the number of days required to mobilize and collect a patient’s or donor’s stem cells is a minimum of five days in blood cancer patients and healthy donors and as many as 30 days or more in patients with sickle cell disease.

When planning for a patient’s transplant, transplanting physicians cannot reliably predict

at the outset how long it will take for patients to mobilize the number of cells required.

Many patients require multiple collections, including approximately 40% of blood cancer patients and 75% of sickle cell disease patients.

In addition, each day scheduled for attempted mobilization and collection can cause an accumulation of both the direct costs associated with the repeated use of mobilization agents and other healthcare resources, including personnel time, and the indirect costs associated with the need to block time in the limited number of chairs in transplant centers that are used to collect stem cells.

Similarly, HSC-based

gene therapies could benefit from more efficient collection of stem cells which could potentially reduce gene therapy manufacturing timelines and costs.

Additionally, there are no approved mobilization options for patients with sickle cell disease and autoimmune diseases, and the off-label

use of currently available medicines is associated with significant safety risks including vaso-occlusive events in sickle cell disease patients.

Magenta is developing MGTA-145

for stem cell mobilization in a broad range of diseases, for both autologous and allogeneic transplants.

is Magenta’s biologic stem cell mobilization product candidate designed to address these time and cost inefficiencies while enabling the rapid, reliable, predictable and safe collection of functional blood stem cells for transplant in a single day.

In 2020, we completed a Phase 1 clinical trial in healthy volunteers to evaluate the ability of MGTA-145,

in combination with plerixafor, to mobilize stem cells.

Based on the results of the study, we have advanced the program into three ongoing and planned Phase 2 clinical trials, including an autologous transplant trial in multiple myeloma patients;

an allogeneic transplant trial with healthy donor cells collected for transplant in patients with acute myeloid leukemia, myelodysplastic syndromes or acute lymphocytic leukemia, or ALL;

and lastly, a planned trial in partnership with bluebird bio, Inc.

to mobilize and collect the stem cells of sickle cell disease patients.

In addition to the opportunity to address the challenges in mobilization and collection of stem cells, Magenta also seeks to improve patient conditioning prior to transplant.

Conditioning is the process by which patients are treated with chemotherapy prior to transplant to ensure that the bone marrow has sufficient space to receive newly transplanted stem cells.

Currently, only approximately 50% of eligible patients receive a stem cell transplant, in part because of the risks and toxicities of the chemotherapeutic agents available today.

Magenta’s lead conditioning program, MGTA-117,

is designed to selectively deplete stem cells and reduce the need for high-dose or high-intensity chemotherapeutic agents in oncology applications and potentially eliminate the use of busulfan in gene therapy applications.

Our additional research-stage conditioning programs target stem and/or immune cells and are being designed to eliminate toxic chemotherapy conditioning regimens across multiple disease settings.

Our C100 program focuses on addressing opportunities in immune reset for autoimmune diseases.

Our C300 program is being designed to provide for lymphodepletion prior to cell therapies such as chimeric antigen receptor T cells, or CAR-T.

Our G100 program is being designed to provide prophylaxis of graft-versus-host disease, a common post-transplant complication following allogeneic stem cell transplant.

Magenta is also evaluating two programs with potential in cell therapy.

Each is a small molecule used to manufacture a high number of functional stem cells, from either a donor or gene-modified stem cells from a patient.

is a cell therapy designed to generate higher cell doses that are well matched to the patient, which has been shown to improve the speed and success of engraftment in stem cell transplant and improve disease outcomes.

In June 2020, we announced that we discontinued enrollment in our Phase 2 trial of MGTA-456

in inherited metabolic diseases.

Enrollment in an investigator-initiated trial in patients with blood cancers has been completed, and we plan to use these data, when available, to inform a decision regarding future program development in blood cancers.

Our second cell therapy program, E478, is a small molecule aryl hydrocarbon receptor, or AHR, antagonist which

uses the same mechanism used to manufacture MGTA-456

to expand gene-modified HSCs for stem cell-based gene therapy and genome editing.

Magenta Therapeutics, Inc.

is a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplants to more patients with blood cancers, genetic diseases and autoimmune diseases.

Magenta’s drug development pipeline includes multiple clinical and preclinical product candidates designed to improve stem cell transplants.

We are developing product candidates that are designed to deplete targeted cells in the bone marrow to make space for the bone marrow to receive newly transplanted stem cells, a process known as conditioning.

Our targeted conditioning programs are intended to enhance the efficacy of and/or reduce the dosing levels, intensity or, in some cases, even the need for chemotoxic agents.

Our first targeted conditioning program, MGTA-117,

has entered clinical development in a Phase 1/2 trial, and our second program, a CD45-antibody drug conjugate, or CD45-ADC,

is advancing in preclinical development.

In addition to our conditioning programs, we are also developing a product candidate, MGTA-145,

to improve the process by which stem cells are stimulated out of the bone marrow and into the bloodstream so they are available for collection for future reinfusion, known as mobilization, which is required for all transplants and gene therapy applications.

is a Phase 2 clinical stage program intended to enable rapid, reliable, predictable and safe mobilization and collection of high numbers of functional stem cells for transplant.

In addition to our product candidates, Magenta’s research efforts are evaluating several early-stage targets that include a program for targeted lymphodepletion prior to therapies such as chimeric antigen receptor T-cells

We also have a cell therapy program, E478, which is a small molecule aryl hydrocarbon receptor, or AHR, antagonist designed to increase the numbers of gene-modified HSCs for stem cell-based gene therapy and genome editing.

In December 2021, we notified Novartis International Pharmaceutical Ltd., or Novartis, of our termination of the Novartis license related to our cell therapy program, MGTA-456,

which becomes effective 90 days from the date of notification.

Magenta intends to become a fully integrated discovery, development, and commercial company in the field of stem cell transplant.

We are developing our product candidates to be used individually or, in some cases, in combination with each other.

We are developing our product candidates to be used individually or, in some cases, in combination with each other or together with other therapies.

As a result, our portfolio could be tailored to the patient’s disease, such that a patient may receive more than one Magenta therapy as part of his or her individual stem cell transplant.

1 unchanged sentence

global pandemic, which could delay or halt the development of our product candidates.

See “—Recent Developments” and “Item 1A.

See “Item 1A.

Risk Factors” for further discussion of the current and expected impact on our business and product candidates.

Since our inception in 2015, we have focused substantially all of our efforts and financial resources on organizing and staffing our company, business planning, raising capital, acquiring and developing our technology, identifying potential product candidates, and undertaking preclinical studies, and in the case of MGTA-145

and MGTA-145.

clinical trials.

We do not have any products approved for sale and have not generated any revenue from product sales.

In June 2018, we completed an initial public offering of our common stock.

In May 2019, we issued and sold 4,887,500 shares of our common stock, including the underwriters’ exercise in full of their option to purchase additional shares of common stock, in a follow-on

public offering at a public offering price of $13.25 per share, resulting in net proceeds of $60.3 million after underwriting discounts and commissions and other offering expenses.

In June 2020, we issued and sold 8,625,000 shares of our common stock, including the underwriters’ exercise in full of their option to purchase additional shares of common stock, in a follow-on

public offering at a public offering price of $8.00 per share, resulting in net proceeds of $64.6 million after underwriting discounts and commissions and other offering expenses.

Since our inception, we have incurred significant operating losses.

Our ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our product candidates.

Our net loss was $74.9 million and $76.8 million for the years ended December 31, 2020 and 2019, respectively.

Net losses were $71.1 million and $74.9 million for the years ended December 31, 2021 and 2020, respectively.

As of December 31, 2021, we had an accumulated deficit of $325.6 million.

1 unchanged sentence

We expect our expenses and capital requirements will increase in connection with our ongoing activities, particularly as we:

initiate, enroll and conduct new Phase 2 clinical trials for MGTA-145;

initiate and conduct preclinical studies and clinical trials of our product candidates, including MGTA-117;

initiate, enroll and conduct a Phase 1/2 clinical trial for MGTA-117

and Phase 2 clinical trials for MGTA-145

initiate and conduct preclinical studies and clinical trials of our other product candidates;

develop any other future product candidates we may choose to pursue;

16 unchanged sentences

As of December 31, 2021, we had cash, cash equivalents and marketable securities of $176.9 million.

Based on our updated operating plan, we believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the first quarter of 2023.

See “—Liquidity and Capital Resources.”

Impact of the COVID-19

On March 11, 2020, the World Health Organization declared COVID-19

a global pandemic, and on March 13, 2020, the U.S.

declared a national emergency with respect to COVID-19.

federal government subsequently issued initial 15-day

social distancing guidelines which were in effect through April 30, 2020 as a measure to reduce the escalation of the spread of COVID-19

More than 40 states and certain U.S.

territories, including the Commonwealth of Massachusetts where our operations are located, followed suit and instituted quarantines, restrictions on travel, “stay at home” rules, restrictions on types of businesses that may continue to operate and restrictions on the types of construction projects that may continue.

Based on our operating plan, we believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the fourth quarter of 2023.

Management’s Discussion and Analysis of Financial Condition and Results of Operations – Liquidity and Capital Resources.”

Impact of the Ongoing COVID-19

In March 2020, COVID-19

was declared a pandemic by the World Health Organization.

as a result, more than 40 states and certain U.S.

territories, including the Commonwealth of Massachusetts where our operations are located, instituted quarantines, restrictions on travel, “stay at home” rules, restrictions on types of businesses that may continue to operate and restrictions on the types of construction projects that may continue.

As a result, the COVID-19

3 unchanged sentences

in the Cambridge community.

We have established a work-from-home policy for all employees, other than those who are performing or supporting business-critical research and development operations, such as certain members of our laboratory and facilities staff.

For those employees, we have implemented stringent safety measures designed to comply with applicable federal, state and local guidelines instituted in response to the COVID-19

We have established a work-from-home policy for all employees, as well as safety measures for those using our offices and laboratory facilities that are designed to comply with applicable federal, state and local guidelines instituted in response to the COVID-19

We will continue to assess those measures as COVID-19-related

guidelines evolve.

We have also maintained efficient communication with our partners and clinical sites as the COVID-19

2 unchanged sentences

The future impact of the COVID-19

pandemic on our industry, the healthcare system and our current and future operations and financial condition will, however, depend on future developments, which are highly uncertain and cannot be predicted with confidence, including the scope, severity and duration of the pandemic, the actions taken to contain the pandemic or mitigate its impact, as well as the effect of any relaxation of current restrictions within the Cambridge community or regions in which our partners and clinical sites are located, and the direct and indirect economic effects of the pandemic and containment measures, among others.

vaccines, as well as the effect of any relaxation of current restrictions within the Cambridge community or regions in which our partners and clinical sites are located, and the direct and indirect economic effects of the pandemic and containment measures, among others.

See “Item 1A.

7 unchanged sentences

expenses incurred in connection with the preclinical and clinical development of our product candidates, including under agreements with contract research organizations, or CROs;

the cost of consultants and contract manufacturing organizations, or CMOs, that manufacture drug products for use in our preclinical studies and clinical trials;

the cost of consultants and third-party contract development and manufacturing organizations, or CDMOs, that manufacture drug products for use in our preclinical studies and clinical trials;

facilities, depreciation and other expenses, which include direct and allocated expenses for rent and maintenance of facilities, insurance and supplies;

4 unchanged sentences

Our direct research and development expenses are tracked on a program-by-program

basis and consist primarily of external costs, such as fees paid to consultants, central laboratories, contractors, CMOs and CROs in connection with our preclinical and clinical development activities.

basis and consist primarily of external costs, such as fees paid to consultants, central laboratories, contractors, CDMOs and CROs

in connection with our preclinical and clinical development activities.

We do not allocate employee costs, costs associated with our platform technology or facility expenses, including depreciation or other indirect costs, to specific product development programs because these costs are deployed across multiple product development programs and, as such, are not separately classified.

54 unchanged sentences

CROs in connection with preclinical and clinical trials;

CMOs in connection with the production of preclinical and clinical trial materials;

CDMOs in connection with the production of preclinical and clinical trial materials;

investigative sites in connection with clinical trials.

34 unchanged sentences

Total research and development expenses

Expenses related to our conditioning program decreased primarily due to lower process development and manufacturing costs.

In 2019, we incurred higher manufacturing costs to support our IND-enabling

studies and future clinical trials.

The decrease in expenses related to our mobilization program was primarily due to a

decrease in clinical trial costs for our MGTA-145

Phase 1 clinical trials which were completed in the first quarter of 2020.

Expenses related to our cell therapy program decreased primarily due to the completion of the investigator-initiated Phase 2 clinical trial of MGTA-456 in

patients with blood cancers in the second quarter of 2020 and the discontinuance of the Phase 2 trial in inherited metabolic diseases in June 2020.

The increase in personnel related costs was primarily due to the hiring of more senior level employees in our research and development function.

The decrease in consultant costs was primarily due to a decrease in stock-based compensation.

Consultant costs for the year ended December 31, 2020 and 2019 included stock-based compensation expense of $0.5 million and $1.6 million, respectively.

Expenses related to our conditioning program decreased primarily due to a decrease in manufacturing costs as we completed our process development activities to support the submission of our investigational new drug application and future clinical trials, partially offset by an increase in clinical trial costs related to our Phase 1/2 dose escalation trial which was initiated in December 2021.

The increase in expenses related to our mobilization program was primarily due to an increase in process development activities to support future manufacturing.

Expenses related to our cell therapy program decreased primarily due to the discontinuance of enrollment in our MGTA-456

Phase 2 trial in inherited metabolic diseases in June 2020.

The increase in personnel related costs was due primarily to an increase in headcount in our research and development function and an increase in stock-based compensation.

Personnel related costs for the years ended December 31, 2021 and 2020 included stock-based compensation expense of $3.7 million and $3.1 million, respectively.

The increase in facility related and other was primarily due to higher operating costs related to our Cambridge, Massachusetts facility.

General and Administrative Expenses

5 unchanged sentences

Total general and administrative expenses

The increase in personnel related costs was due primarily to an increase in headcount to support our business including an increase in stock-based compensation.

Personnel related costs for the year ended December 31, 2020 and 2019 included stock-based compensation expense of $6.3 million and $5.4 million, respectively.

The increase in professional and consultant costs was primarily due to an increase in patent related legal costs.

The increase in facility related and other was primarily due to an increase in director and officer insurance and recruiting costs.

The decrease in personnel related costs was due primarily to a decrease in headcount in our general and administrative function.

The decrease in professional and consultant costs was primarily due to lower patent and recruitment costs.

The increase in facility related and other was primarily due to higher operating costs related to our Cambridge, Massachusetts facility and higher director and officers’ insurance costs.

Interest and Other Income, Net

The decrease in interest and other income, net was primarily due to a decrease in interest income of $2.5 million resulting from lower interest rates on invested balances.

Interest income and other income, net for the year ended December 31, 2021 consisted primarily of sublease income of $3.5 million and interest income $0.1 million.

Interest income and other income, net for the year ended December 31, 2020 consisted primarily of sublease income of $2.9 million and interest income of $1.0 million.

The increase in sublease income of $0.6 million was due to higher sublessor operating expenses.

The decrease in interest income was due to lower interest rates and lower invested balances.

Liquidity and Capital Resources

1 unchanged sentence

We have not yet commercialized any of our product candidates and we do not expect to generate revenue from sales of any product candidates for several years, if at all.

In June 2018, we completed the IPO of our common stock.

In May 2019, we issued and sold 4,887,500 shares of our common stock, including the underwriters’ exercise in full of their option to purchase additional shares of common stock, in a follow-on

public offering at a public offering price of $13.25 per share, resulting in net proceeds of $60.3 million after deducting underwriting discounts and commissions and other offering expenses.

In June 2018, we completed the initial public offering, or IPO, of our common stock resulting in net proceeds of $89.9 million after deducting underwriting discounts and commissions and other offering expenses.

In May 2019, we completed a follow-on

public offering resulting in net proceeds of $60.3 million after deducting underwriting discounts and commissions and other offering expenses.

In June 2020, we issued and sold 8,625,000 shares of our common stock, including the underwriters’ exercise in full of their option to purchase additional shares of common stock, in a follow-on

public offering at a public offering price of $8.00 per share, resulting in net proceeds of $64.6 million after deducting underwriting discounts and commission and other offering expenses.

In May 2021, we issued and sold 9,599,998 shares of our common stock in a private placement at a purchase price of $9.00 per share, resulting in net proceeds of $86.1 million, after deducting offering expenses.

On August 8, 2019, we filed a shelf registration statement on Form S-3,

14 unchanged sentences

charges of $13.1 million.

Net cash used by changes in our operating assets and liabilities for the year ended December 31, 2020 consisted of a decrease of $2.7 million in accounts payable and accrued expenses and other current liabilities, partially offset by a decrease of $1.4 million in prepaid expenses and other current assets.

During the year ended December 31, 2019, operating activities used $57.1 million of cash, primarily resulting from our net loss of $76.8 million, partially offset by non-cash

charges of $10.8 million and cash provided by changes in our operating assets and liabilities of $8.8 million.

Net cash provided by changes in our operating assets and liabilities for the year ended December 31, 2019 consisted primarily of a $5.0 million increase in deferred rent and a $5.2 million increase in accounts payable and accrued expenses and other current liabilities, partially offset by an increase of $1.4 million in prepaid expenses and other current assets.

Net cash used by changes in our operating assets and liabilities for the year ended December 31, 2021 consisted of an increase of $1.1 million in prepaid expenses and other current assets and a decrease of $0.6 million in accounts payable and accrued expenses and other current liabilities.

During the year ended December 31, 2020, operating activities used $64.0 million of cash, primarily resulting from our net loss of $74.9 million and net cash used by changes in our operating assets and liabilities of $1.2 million, partially offset by non-cash

charges of $12.1 million.

Net cash used by changes in our operating assets and liabilities for the year ended December 31, 2020 consisted of a decrease of $2.7 million in accounts

payable and accrued expenses and other current liabilities, partially offset by a decrease of $1.4 million in prepaid expenses and other current assets.

Changes in accounts payable, accrued expenses and other current liabilities and prepaid expenses in both periods were generally due to the timing of vendor invoicing and payments.

Investing Activities

During the year ended December 31, 2020, net cash used by investing activities was primarily attributable to net purchases of marketable securities of $10.2 million.

During the year ended December 31, 2019, net cash provided by investing activities was primarily attributable to net maturities of marketable securities of $4.6 million, partially offset by purchases of property and equipment of $3.1 million, consisting primarily of lab equipment and leasehold improvements.

During the year ended December 31, 2021, net cash provided by investing activities was $43.4 million, primarily attributable to net maturities of marketable securities of $44.7 million.

During the year ended December 31, 2020, net cash used by investing activities was $10.6 million, primarily attributable to net purchases of marketable securities of $10.2 million.

Financing Activities

During the year ended December 31, 2021, net cash provided by financing activities was $89.6 million, consisting of proceeds from the May 2021 private placement, net of offering costs, of $86.1 million and proceeds from the exercise of stock options of $3.4 million.

During the year ended December 31, 2020, net cash provided by financing activities was $67.7 million, consisting of proceeds from our follow-on

public offering, net of underwriting discounts and commissions and offering costs, of $64.6 million and proceeds from the exercise of stock options of $3.1 million.

During the year ended December 31, 2019, net cash provided by financing activities was $62.3 million, consisting of proceeds from our follow-on

public offering, net of underwriting discounts, commissions and offering costs, of $60.3 million and proceeds from the exercise of stock options of $2.0 million.

Funding Requirements

1 unchanged sentence

In addition, we expect to incur additional costs associated with operating as a public company.

The timing and amount of our operating expenditures will depend largely on:

the initiation, progress, timing, costs and results of current and future preclinical studies and clinical trials for our product candidates, including the continuing impact of the COVID-19

pandemic on our operations;

the clinical development plans we establish for these product candidates;

the number and characteristics of product candidates that we develop or may in-license;

the terms of any collaboration agreements we may choose to conclude;

the outcome, timing and cost of meeting and maintaining compliance with regulatory requirements established by the Food and Drug Administration, the European Medical Agency and other comparable foreign regulatory authorities;

the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights;

the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us;

the effect of existing or new competing technological and market developments;

the cost and timing of completion of commercial-scale outsourced manufacturing activities;

the cost of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own.

As of December 31, 2021, we had cash, cash equivalents and marketable securities of $176.9 million.

We believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the first quarter of 2023.

We believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the fourth quarter of 2023.

We have based these estimates on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect.

1 unchanged sentence

Our future funding requirements will depend on and could increase significantly as a result of many factors, including those listed above.

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our operations through a combination of equity offerings, including sales under our ATM Program, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements.

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our operations through a combination of equity offerings, including sales under our ATM Program, debt financings, collaborations, strategic alliances, marketing and distribution arrangements, or licensing arrangements.

We do not currently have any committed external source of funds.

1 unchanged sentence

Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making acquisitions or capital expenditures or declaring dividends.

If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us.

If we are unable to raise additional funds through equity or debt financings or other arrangements when needed, we may be required to delay, limit, reduce or terminate

our research, product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Although we continue to pursue these plans, there is no assurance that we will be successful in obtaining sufficient funding on terms acceptable to us to fund continuing operations, if at all.

Sheet Arrangements

We did not have during the periods presented, and we do not currently have, any off-balance

sheet arrangements, as defined in the rules and regulations of the SEC.

If we raise additional funds through collaborations, strategic alliances, marketing and distribution arrangements, or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us.

If we are unable to raise additional funds through equity or debt financings or other arrangements when needed, we may be required to delay, limit, reduce or terminate our research, product development or future commercialization efforts, or

grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Although we continue to pursue these plans, there is no assurance that we will be successful in obtaining sufficient funding on terms acceptable to us to fund our continuing operations, if at all.

Contractual Obligations and Commitments

Our cash flows are dependent on a number of factors in addition to our operational expenditures, including our contractual and other obligations.

As a result, our liquidity and capital resources in future periods should be analyzed in conjunction with such factors.

Lease Obligations

We have a sublease for up to approximately 69,000 square feet of office and laboratory space in Cambridge, Massachusetts, which expires in February 2028.

We are obligated to make remaining rent payments of $45.1 million through February 2028, of which $6.4 million are due in 2022.

Research and Development and Manufacturing Agreements

We enter into contracts in the normal course of business with CROs, CDMOs and other third parties for clinical trials, preclinical research studies and testing and manufacturing services.

These contracts do not contain any minimum purchase commitments and are cancelable by us upon prior written notice.

Payments due upon cancellation consist only of payments for services provided or expenses incurred, including noncancelable obligations of our service providers, up to the date of cancellation and in some cases, wind-down costs.

The exact amount of such obligations is dependent on the timing of termination and the terms of the related agreement and are not known.

License and Collaboration Agreements

In March 2018, we entered into a collaboration agreement with Heidelberg Pharma Research GmbH, or HDPR, whereby the parties agreed to combine our stem cell platform with proprietary antibodies across up to four exclusive targets with HDPR’s proprietary Antibody Targeted Amanitin Conjugates platform.

Upon the exercise of certain license rights, we may be obligated to pay HDPR development, regulatory and commercial milestone payments of up to $83.5 million per target as well as royalties on net sales of products licensed under the agreement.

We have a license agreement with the President and Fellows of Harvard College, entered into in November 2016, for an exclusive, worldwide, royalty-bearing license for certain technologies related to conditioning and mobilization.

We are obligated to pay milestone payments of up to $7.4 million for the first two licensed products upon the achievement of certain development and regulatory milestones and to pay royalties on a product-by-product

and country-by-country

basis on net sales of products licensed under the agreement.

To date, we have paid $0.3 million related to the achievement of certain of these milestones.

As of December 31, 2021, we were unable to estimate the timing or likelihood of achieving the remaining milestones or generating future product sales.

Recently Issued and Adopted Accounting Pronouncements

1 unchanged sentence

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 7. Management’s Discussion and Analysis