| --- | --- | --- | --- | --- | |----------------------------------------------------------|-------|-------|-------|-------| | | | | | | | | | | | | | | | | | | | | | | | | | Cure blood cancers through cell and genome engineering | | | | | | November 2022 | | | | | | Confidential | | | | | Disclaimer This presentation (the "Presentation") contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 about Vor Biopharma Inc. ("Vor," "Vor Bio" or the "Company") ...

(Mark One) UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 OR For the transition period from __________________ to __________________ Commission File Number: 001-39979 VOR BIOPHARMA INC. (Exact Name of Registrant as Specified in its Charter) (State or other jurisdiction of incorporation or organization) 100 Cambridgepark Drive, Suite 101 Cambridge, Massachusetts 02140 (Address of princip ...

| --- | --- | |---------------------------------------------|-------| | | | | | | | Cure blood cancers through cell and genome | | | engineering | | | September 2022 | | 1 Confidential Disclaimer This presentation (the "Presentation") contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 about Vor Biopharma Inc. ("Vor," "Vor Bio" or the "Company"). The words "aim," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potenti ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from __________________ to __________________ Commission File Number: 001-39979 VOR BIOPHARMA INC. (Exact Name of Registrant as Specified in its Charter) (State or ot ...

[PART I. FINANCIAL INFORMATION](index=6&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) [Financial Statements (Unaudited)](index=6&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) The company presents its unaudited condensed consolidated financial statements for Q1 2022 and Q1 2021 [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets decreased to $234.3 million while total liabilities increased to $39.8 million as of Q1 2022 Condensed Consolidated Balance Sheet Highlights (in thousands) | Balance Sheet Item | March 31, 2022 | December 31, 2021 | | :--- | :--- | :--- | | Cash and cash equivalents | $90,042 | $119,801 | | Marketable securities | $91,575 | $87,668 | | **Total Assets** | **$234,269** | **$242,590** | | Total current liabilities | $18,145 | $10,153 | | **Total Liabilities** | **$39,822** | **$26,327** | | **Total Stockholders' Equity** | **$194,447** | **$216,263** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The company's net loss increased to $22.7 million in Q1 2022, driven by higher R&D and G&A expenses Statement of Operations Highlights (in thousands, except per share data) | Operating Item | Three Months Ended March 31, 2022 | Three Months Ended March 31, 2021 | | :--- | :--- | :--- | | Research and development | $15,280 | $8,941 | | General and administrative | $7,520 | $4,789 | | **Total operating expenses** | **$22,800** | **$13,730** | | **Loss from operations** | **$(22,800)** | **$(13,730)** | | **Net loss** | **$(22,737)** | **$(13,723)** | | Net loss per share, basic and diluted | $(0.61) | $(0.67) | [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operations increased to $22.9 million in Q1 2022, reflecting a higher net loss Cash Flow Highlights (in thousands) | Cash Flow Activity | Three Months Ended March 31, 2022 | Three Months Ended March 31, 2021 | | :--- | :--- | :--- | | Net cash used in operating activities | $(22,904) | $(17,649) | | Net cash used in investing activities | $(7,055) | $(1,171) | | Net cash provided by financing activities | $200 | $232,848 | | **Net (decrease) increase in cash** | **$(29,759)** | **$214,028** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) Notes detail key accounting policies, cash sufficiency, stock compensation, and significant new lease agreements - The company is a clinical-stage cell and genome engineering company focused on treating hematological malignancies and anticipates incurring significant operating losses for the next several years[26](index=26&type=chunk)[28](index=28&type=chunk) - Management believes existing **cash, cash equivalents, and marketable securities of $181.6 million** are sufficient to fund operations for at least one year[28](index=28&type=chunk)[65](index=65&type=chunk) - The company entered into two lease amendments for its Cambridge facility, involving **$8.4 million and $21.9 million** in total fixed rent payments[49](index=49&type=chunk)[50](index=50&type=chunk)[51](index=51&type=chunk) Stock-Based Compensation Expense (in thousands) | Expense Category | Three Months Ended March 31, 2022 | Three Months Ended March 31, 2021 | | :--- | :--- | :--- | | Research and development | $796 | $449 | | General and administrative | $950 | $442 | | **Total** | **$1,746** | **$891** | [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=16&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company discusses its clinical programs, financial results, and capital resources, including its funding runway - The company is a clinical-stage cell and genome engineering company focused on treating blood cancers by engineering hematopoietic stem cells (HSCs)[59](index=59&type=chunk) - The lead product candidate, VOR33, is in a Phase 1/2a trial, with **initial clinical data anticipated in H2 2022**[60](index=60&type=chunk) - The company plans to submit an IND for its VCAR33 ALLO program in the **first half of 2023**[61](index=61&type=chunk) - As of March 31, 2022, the company had **$181.6 million in cash, cash equivalents, and marketable securities**, expected to fund operations into Q4 2023[65](index=65&type=chunk) - In March 2022, the company filed a **$350.0 million universal shelf registration** and a **$125.0 million at-the-market (ATM) facility**[86](index=86&type=chunk) [Results of Operations](index=19&type=section&id=Results%20of%20Operations) Operating expenses increased to $22.8 million in Q1 2022, driven by higher personnel and external R&D costs Comparison of Operating Results (in thousands) | Item | Three Months Ended March 31, 2022 | Three Months Ended March 31, 2021 | Change | | :--- | :--- | :--- | :--- | | Research and development | $15,280 | $8,941 | $6,339 | | General and administrative | $7,520 | $4,789 | $2,731 | | **Total operating expenses** | **$22,800** | **$13,730** | **$9,070** | | **Net loss** | **$(22,737)** | **$(13,723)** | **$(9,014)** | - The **$6.4 million increase in R&D expenses** was primarily due to a $2.5 million rise in external costs, a $2.7 million increase in personnel costs, and a $0.6 million increase in facilities expenses[82](index=82&type=chunk) - The **$2.7 million increase in G&A expenses** was driven by a $1.7 million rise in personnel costs, a $0.5 million increase in professional fees, and a $0.5 million increase in facilities expenses[83](index=83&type=chunk) [Liquidity and Capital Resources](index=20&type=section&id=Liquidity%20and%20Capital%20Resources) The company has funded operations primarily through equity sales and established new financing facilities in March 2022 - The company has funded operations with **$344.0 million in net proceeds** from equity and debt financings as of March 31, 2022[85](index=85&type=chunk) - **Net cash used in operating activities increased by $5.3 million** year-over-year, primarily due to higher operating expenses related to advancing VOR33 and increased personnel costs[96](index=96&type=chunk) - **Net cash used in investing activities was $7.1 million** in Q1 2022, consisting of $5.1 million for marketable securities and $2.0 million for property and equipment[97](index=97&type=chunk) - **Net cash provided by financing activities was only $0.2 million** in Q1 2022 from stock option exercises, compared to $232.8 million in Q1 2021 which included IPO proceeds[98](index=98&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=23&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is interest rate sensitivity, which is considered immaterial - Primary market risk exposure is to interest rate changes affecting cash equivalents and marketable securities, but the **impact is considered immaterial** due to their short-term maturities[102](index=102&type=chunk) - The company has **no outstanding debt** as of March 31, 2022, and therefore no related interest rate risk[103](index=103&type=chunk) - Foreign currency exchange risk and inflation are **not considered to have a material effect** on the company's financial statements[104](index=104&type=chunk)[105](index=105&type=chunk) [Controls and Procedures](index=23&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of the end of the quarter - Based on an evaluation as of March 31, 2022, the CEO and CFO concluded that the company's **disclosure controls and procedures were effective** at the reasonable assurance level[107](index=107&type=chunk) - There were **no material changes in internal control** over financial reporting during the quarter ended March 31, 2022[108](index=108&type=chunk) [PART II. OTHER INFORMATION](index=24&type=section&id=PART%20II.%20OTHER%20INFORMATION) [Legal Proceedings](index=24&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings - As of the report date, the company is **not a party to any material legal proceedings**[110](index=110&type=chunk) [Risk Factors](index=24&type=section&id=Item%201A.%20Risk%20Factors) The company faces numerous risks related to its financial position, clinical development, and intellectual property - The company has a history of **significant net losses ($22.7M for Q1 2022)** and expects to incur losses for the foreseeable future[112](index=112&type=chunk) - The company is **substantially dependent on the success** of its two most advanced product candidates, VOR33 and VCAR33 ALLO[135](index=135&type=chunk) - Engineered hematopoietic stem cells (eHSCs) are a **novel, unproven technology** that is not yet clinically validated[131](index=131&type=chunk) - The company is **highly dependent on intellectual property licensed** from third parties like Columbia University and the National Cancer Institute (NCI)[255](index=255&type=chunk)[256](index=256&type=chunk) - The **COVID-19 pandemic has caused delays** in the VOR33 Phase 1/2a clinical trial and could continue to disrupt operations[342](index=342&type=chunk) [Risks Related to Financial Position and Capital Needs](index=24&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Need%20for%20Additional%20Capital) The company has a history of net losses and will require substantial additional funding to continue operations - The company has incurred significant net losses since inception, with an **accumulated deficit of $152.9 million** as of March 31, 2022[112](index=112&type=chunk) - **Substantial additional funding is required**, as existing cash of $181.6 million is expected to fund operations only into Q4 2023[115](index=115&type=chunk)[116](index=116&type=chunk) - The company's **limited operating history** and lack of commercial products make it difficult to evaluate its future viability[124](index=124&type=chunk) [Risks Related to Discovery, Development, Manufacturing and Commercialization](index=28&type=section&id=Risks%20Related%20to%20Discovery%2C%20Development%2C%20Manufacturing%20and%20Commercialization) The company's novel technology, reliance on lead candidates, and complex manufacturing present significant risks - **eHSCs are a novel technology not yet clinically validated**, and the company's approach is unproven and faces numerous development challenges[131](index=131&type=chunk) - Product candidates could cause **serious adverse events**, such as off-target gene alterations, which could delay or prevent regulatory approval[141](index=141&type=chunk)[143](index=143&type=chunk) - Developing VOR33 for use with an approved therapy like Mylotarg presents complexities, and prospects could be harmed if **Mylotarg is withdrawn from the market**[157](index=157&type=chunk) - **Manufacturing of eHSCs and CAR-T therapies is complex**, susceptible to product loss, and difficult to scale[192](index=192&type=chunk)[193](index=193&type=chunk) [Risks Related to Regulatory Review](index=42&type=section&id=Risks%20Related%20to%20Regulatory%20Review) The company faces an uncertain regulatory landscape for its novel genome engineering technology - Clinical trials may **fail to demonstrate safety and efficacy**, and positive preclinical results are not predictive of clinical success[210](index=210&type=chunk)[212](index=212&type=chunk) - The **regulatory landscape for genome engineering technology is novel and uncertain**, which could lengthen the review process and increase costs[219](index=219&type=chunk)[220](index=220&type=chunk)[222](index=222&type=chunk) - Regulators may not consider the proposed **clinical trial endpoints to be clinically meaningful** for a novel therapy like VOR33[225](index=225&type=chunk) - **Difficulties in enrolling patients** in clinical trials for rare diseases could increase development costs and delay or prevent regulatory approvals[229](index=229&type=chunk) [Risks Related to Third-Party Relationships](index=48&type=section&id=Risks%20Related%20to%20Our%20Relationships%20with%20Third%20Parties) The business model relies heavily on third-party CROs and manufacturers, including single-source suppliers - The company **relies on third parties like CROs** to conduct clinical trials, reducing control over the process[236](index=236&type=chunk)[238](index=238&type=chunk) - The company **relies on third-party manufacturers**, including single-source suppliers, increasing the risk of supply shortages and cost issues[241](index=241&type=chunk)[242](index=242&type=chunk) - **Future collaborations are important** for development and commercialization but pose risks such as loss of control and potential disputes[246](index=246&type=chunk)[247](index=247&type=chunk) [Risks Related to Intellectual Property](index=51&type=section&id=Risks%20Related%20to%20Our%20Intellectual%20Property) The company depends on licensed IP and faces a complex landscape for technologies like CRISPR-Cas9 - The company is **highly dependent on exclusive licenses** from Columbia University and the National Cancer Institute; termination would severely harm the business[255](index=255&type=chunk)[256](index=256&type=chunk)[257](index=257&type=chunk) - The company will need to **acquire licenses for key technologies like CRISPR-Cas9**, for which the IP landscape is complex and unsettled[283](index=283&type=chunk)[284](index=284&type=chunk) - **Third parties may claim infringement**, which could lead to costly litigation and block commercialization[288](index=288&type=chunk)[289](index=289&type=chunk) - Some in-licensed IP was discovered via government funding and may be subject to federal regulations, including **"march-in" rights**[294](index=294&type=chunk) [Risks Related to Regulatory and Legal Compliance](index=60&type=section&id=Risks%20Related%20to%20Regulatory%20and%20Other%20Legal%20Compliance%20Matters) The company faces extensive compliance risks from healthcare laws, reform efforts, and international regulations - Even if approved, products will be subject to **continual and extensive regulation**, including potential marketing restrictions and post-marketing study requirements[311](index=311&type=chunk) - Relationships with healthcare providers are subject to complex **anti-kickback, fraud and abuse laws** with severe penalties for violations[322](index=322&type=chunk)[323](index=323&type=chunk) - **Healthcare reform efforts** could increase costs, affect pricing, and reduce demand for the company's products[327](index=327&type=chunk)[328](index=328&type=chunk)[329](index=329&type=chunk) - International operations are subject to laws like the **Foreign Corrupt Practices Act (FCPA)** and stringent data privacy laws[334](index=334&type=chunk)[338](index=338&type=chunk) [Risks Related to COVID-19, Operations, and IT](index=66&type=section&id=Risks%20Related%20to%20COVID-19%2C%20Employee%20Matters%2C%20Managing%20Growth%20and%20Information%20Technology) The COVID-19 pandemic, talent retention, growth management, and IT security pose operational challenges - The **COVID-19 pandemic has caused delays** in clinical trial enrollment for VOR33 and may continue to adversely affect operations[340](index=340&type=chunk)[342](index=342&type=chunk) - The company is **highly dependent on its key executives** and faces intense competition for qualified personnel[344](index=344&type=chunk)[345](index=345&type=chunk) - The company expects to **expand its operations**, which may strain resources and lead to operational mistakes if not managed effectively[347](index=347&type=chunk)[348](index=348&type=chunk) - Internal and third-party computer systems are **vulnerable to security breaches**, which could disrupt development and compromise sensitive data[350](index=350&type=chunk) [Risks Related to Common Stock Ownership](index=69&type=section&id=Risks%20Related%20to%20the%20Ownership%20of%20Our%20Common%20Stock) Common stock ownership risks include price volatility, insider control, and reduced disclosure requirements - The **market price of the common stock is likely to be volatile**, and an active trading market may not be sustained[353](index=353&type=chunk)[354](index=354&type=chunk) - **Insiders hold a substantial amount of common stock**, giving them significant influence and potentially preventing a change of control[360](index=360&type=chunk) - The company's status as an **"emerging growth company"** allows it to rely on reduced disclosure requirements[364](index=364&type=chunk)[366](index=366&type=chunk) - The company **does not expect to pay dividends** for the foreseeable future, so stockholders must rely on capital appreciation[371](index=371&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=73&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company details the use of its $186.3 million in net proceeds from its February 2021 IPO - The company closed its IPO on February 9, 2021, receiving **net proceeds of approximately $186.3 million**[379](index=379&type=chunk)[380](index=380&type=chunk) - As of March 31, 2022, **$4.0 million of the IPO net proceeds have been used** to fund development programs and for general corporate purposes[381](index=381&type=chunk) - In January 2022, the company **repurchased 7,660 shares of unvested common stock** from a former employee[384](index=384&type=chunk) [Exhibits](index=75&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the report, including an ATM agreement and required officer certifications - Lists exhibits filed with the report, including an **Open Market Sale Agreement with Jefferies LLC**, CEO/CFO certifications, and XBRL data files[386](index=386&type=chunk)

| --- | --- | --- | --- | --- | |----------------------------------------------------------|-------|-------|-------|-------| | | | | | | | | | | | | | | | | | | | | | | | | | Cure blood cancers through cell and genome engineering | | | | | | March 2022 | | | | | | Confidential | | | | | Disclaimer This presentation (the "Presentation") contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 about Vor Biopharma Inc. ("Vor," "Vor Bio" or the "Company") th ...

[PART I](index=6&type=section&id=PART%20I) This section details the company's business operations, strategic initiatives, associated risks, and general corporate information [Business](index=6&type=section&id=Item%201.%20Business) Vor Biopharma is a clinical-stage cell and genome engineering company focused on treating blood cancers, developing eHSCs and CAR-T therapies [Overview and Strategy](index=6&type=section&id=Overview%20and%20Strategy) Vor Bio is a clinical-stage company engineering hematopoietic stem cells for blood cancers, focusing on AML - Vor Bio is a clinical-stage company engineering hematopoietic stem cells (HSCs) to enable the use of targeted therapies post-transplant for blood cancers, with an initial focus on Acute Myeloid Leukemia (AML)[14](index=14&type=chunk)[15](index=15&type=chunk) - The company's core strategy includes demonstrating the safety and efficacy of its lead product VOR33, advancing its in-house CAR-T therapies (VCAR33), developing 'Treatment Systems' that combine eHSCs and CAR-Ts, and establishing in-house cGMP manufacturing[37](index=37&type=chunk)[41](index=41&type=chunk) - The proprietary platform aims to overcome the on-target toxicity of traditional cancer therapies by genetically modifying healthy donor HSCs to remove cell surface targets, thereby protecting them from targeted treatments[17](index=17&type=chunk)[42](index=42&type=chunk) [Pipeline and Programs](index=13&type=section&id=Pipeline%20and%20Programs) The company's pipeline includes lead candidate VOR33 in Phase 1/2a for AML, and VCAR33 CAR-T programs Product Pipeline and Anticipated Milestones | Program | Modality | Indication | Stage | Anticipated Milestones | | :--- | :--- | :--- | :--- | :--- | | **VOR33 + Mylotarg** | eHSC + ADC | AML, MDS, MPN | Phase 1/2 | 2H 2022: Initial clinical data | | **VCAR33ALLO** | CAR-T (Allogeneic) | AML Post-transplant | Preclinical | 1H 2023 IND submission | | **VCAR33AUTO** | CAR-T (Autologous) | Bridge-to-transplant AML | Phase 1/2 (NMDP-sponsored) | 2022: Initial monotherapy clinical proof-of-concept data | | **VOR33 + VCAR33 Treatment System** | eHSC + CAR-T | AML | Preclinical | IND filing following initial VOR33 and VCARALLO data | | **VOR33-CLL1 + VCAR33-CLL1 Treatment System** | Multiplex-edited eHSC + Multi-specific CAR-T | AML | Discovery/Validation | - | - The lead product, VOR33, is an eHSC where the CD33 surface target is removed. It is being evaluated in the VBP101 Phase 1/2a clinical trial for AML patients at high risk of relapse, with initial data expected in the second half of 2022[51](index=51&type=chunk)[74](index=74&type=chunk) - The VCAR33 program consists of two CAR-T therapies targeting CD33: VCAR33AUTO (autologous cells, in an ongoing NMDP-sponsored trial) and VCAR33ALLO (allogeneic cells, IND submission planned for 1H 2023)[86](index=86&type=chunk)[89](index=89&type=chunk) - The company is developing a 'Treatment System' combining VOR33 with VCAR33ALLO, using the same healthy donor cell source for both products to potentially improve persistence and reduce toxicity[97](index=97&type=chunk)[98](index=98&type=chunk) - Discovery efforts are underway for additional targets (CD123, EMR2, CD5) and multiplex engineering to address tumor heterogeneity and escape mechanisms, with the VOR33-CLL1 + VCAR33-CLL1 Treatment System as the first multiplex program[101](index=101&type=chunk)[104](index=104&type=chunk)[111](index=111&type=chunk) [Manufacturing, Commercialization, and Competition](index=28&type=section&id=Manufacturing,%20Commercialization,%20and%20Competition) The company is establishing in-house manufacturing, targeting AML transplant markets, and navigating competition - The company is building an in-house cGMP clinical manufacturing facility in Cambridge, MA, expected to be operational in 2022 to support its eHSC and CAR-T pipeline[135](index=135&type=chunk)[49](index=49&type=chunk) - The commercial strategy targets the approximately **12,000 annual allogeneic HSCTs** performed globally for AML, focusing on the concentrated network of specialized transplant centers[115](index=115&type=chunk)[116](index=116&type=chunk) - Key competitors include companies developing gene-engineered HSCs (Tmunity Therapeutics), CD33-directed therapies (Johnson & Johnson, Amgen, 2seventy bio), and various CAR-T therapies for AML[137](index=137&type=chunk)[138](index=138&type=chunk)[139](index=139&type=chunk) [Intellectual Property and Licensing](index=33&type=section&id=Intellectual%20Property%20and%20Licensing) The company holds exclusive licenses from Columbia University and NIH for its core eHSC and CAR-T intellectual property - The company holds an exclusive worldwide license from Columbia University for patents related to engineering lineage-specific cell surface antigens like CD33 in HSCs, which is central to the VOR33 program[122](index=122&type=chunk)[147](index=147&type=chunk) - An exclusive worldwide license was obtained from the National Institutes of Health (NIH) for intellectual property related to CAR therapies targeting CD33, which underpins the VCAR33 program[126](index=126&type=chunk)[155](index=155&type=chunk) - As of February 28, 2022, the company's owned patent portfolio includes approximately **88 pending U.S. and foreign patent applications**, **22 pending U.S. provisional applications**, and **one granted U.S. patent**. The licensed portfolio includes **seven granted patents** and approximately **46 pending applications**[146](index=146&type=chunk) [Government Regulation](index=36&type=section&id=Government%20Regulation) The company's cell product candidates are regulated as biologics by the FDA, requiring BLA approval and subject to healthcare laws - The company's cell product candidates are regulated as biologics by the FDA and will require the submission and approval of a Biologics License Application (BLA) for marketing authorization[163](index=163&type=chunk) - VOR33 has received Fast Track designation and Orphan Drug Designation (ODD) from the FDA for the treatment of AML, which may facilitate development and provide market exclusivity upon approval[73](index=73&type=chunk)[186](index=186&type=chunk) - The company is subject to extensive U.S. healthcare laws, including the federal Anti-Kickback Statute, False Claims Act, and HIPAA, which regulate business practices, marketing, and data privacy[208](index=208&type=chunk)[209](index=209&type=chunk)[211](index=211&type=chunk) - The regulatory landscape for genome engineering and gene therapy is novel and evolving, which creates uncertainty regarding the time, cost, and requirements for obtaining regulatory approval[369](index=369&type=chunk)[370](index=370&type=chunk) [Risk Factors](index=52&type=section&id=Item%201A.%20Risk%20Factors) The company faces substantial risks including net losses, unproven technology, clinical trial safety, manufacturing, and regulatory uncertainties - The company has a history of significant net losses (**$68.9 million in 2021**) and expects to incur losses for the foreseeable future, requiring substantial additional funding to advance its programs[250](index=250&type=chunk)[254](index=254&type=chunk) - Engineered hematopoietic stem cells (eHSCs) are a novel, unproven technology, and the company's success is highly dependent on its two most advanced candidates, VOR33 and VCAR33[273](index=273&type=chunk)[277](index=277&type=chunk) - There is a significant risk of serious adverse events or undesirable side effects from the company's product candidates, the genome engineering process (e.g., off-target effects), or the associated HSCT and CAR-T procedures (e.g., cytokine release syndrome)[282](index=282&type=chunk)[284](index=284&type=chunk)[288](index=288&type=chunk) - The company relies on third parties for manufacturing materials and conducting clinical trials, and is highly dependent on intellectual property licensed from Columbia University and the NIH, the termination of which would harm the business[397](index=397&type=chunk)[411](index=411&type=chunk) - The regulatory landscape for genome engineering technology is novel and uncertain, which could lead to unpredictable timelines, costs, and challenges in obtaining approval for product candidates[369](index=369&type=chunk) - The COVID-19 pandemic has caused and may continue to cause disruptions, including delays in clinical trial site activation and patient enrollment for the VOR33 Phase 1/2a trial[503](index=503&type=chunk)[505](index=505&type=chunk) [Unresolved Staff Comments](index=111&type=section&id=Item%201B.%20Unresolved%20Staff%20Comments) The company reports that it has no unresolved staff comments from the SEC - Not applicable; the company has no unresolved comments from the SEC staff[547](index=547&type=chunk) [Properties](index=111&type=section&id=Item%202.%20Properties) The company's principal executive office, laboratory, and manufacturing space is located in Cambridge, Massachusetts - The company leases approximately **73,235 square feet** of office, lab, and manufacturing space in Cambridge, Massachusetts, under a lease that expires in August 2030[548](index=548&type=chunk) [Legal Proceedings](index=111&type=section&id=Item%203.%20Legal%20Proceedings) The company is not currently subject to any material legal proceedings - The company is not currently a party to any material legal proceedings[549](index=549&type=chunk) [Mine Safety Disclosures](index=111&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This section is not applicable to the company - Not applicable[550](index=550&type=chunk) [PART II](index=112&type=section&id=PART%20II) This section covers the company's stock market information, financial performance analysis, and internal controls [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=112&type=section&id=Item%205.%20Market%20for%20Registrant's%20Common%20Equity,%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common stock trades on Nasdaq since February 2021, with no dividends paid and IPO proceeds unutilized - The company's common stock trades on the Nasdaq Global Select Market under the symbol 'VOR', commencing on February 5, 2021[553](index=553&type=chunk) - The company has never declared or paid cash dividends and does not anticipate doing so in the foreseeable future, intending to retain earnings for business development[555](index=555&type=chunk) - The company received net proceeds of **$186.3 million** from its February 2021 IPO. As of December 31, 2021, none of these proceeds had been used[557](index=557&type=chunk)[558](index=558&type=chunk) [Selected Financial Data](index=112&type=section&id=Item%206.%20%5BReserved%5D) This section is reserved and contains no information - This item is noted as '[Reserved]' and provides no data[559](index=559&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=113&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company reported a **$68.9 million** net loss in 2021 due to increased R&D and G&A expenses, with cash to fund operations into Q4 2023 Results of Operations (2021 vs. 2020) | (in thousands) | 2021 | 2020 | Change | | :--- | :--- | :--- | :--- | | Research and development | $47,529 | $31,618 | $15,911 | | General and administrative | $21,489 | $11,748 | $9,741 | | **Total operating expenses** | **$69,018** | **$43,366** | **$25,652** | | Loss from operations | $(69,018) | $(43,366) | $(25,652) | | **Net loss** | **$(68,899)** | **$(43,337)** | **$(25,562)** | - Research and development expenses increased by **$15.9 million** in 2021, driven by higher personnel costs from increased headcount (**$10.5 million**), increased facilities and other expenses (**$2.2 million**), and higher external costs for clinical programs and preclinical studies (**$3.2 million**)[585](index=585&type=chunk) - General and administrative expenses rose by **$9.8 million** in 2021, primarily due to increased personnel costs (**$4.6 million**), higher professional fees for legal and insurance services (**$4.3 million**), and increased facility costs (**$0.9 million**)[586](index=586&type=chunk) - As of December 31, 2021, the company had **$207.5 million** in cash, cash equivalents, and investments. This balance is expected to fund operating expenses and capital requirements into the fourth quarter of 2023[569](index=569&type=chunk)[592](index=592&type=chunk) Cash Flow Summary (2021 vs. 2020) | (in thousands) | 2021 | 2020 | | :--- | :--- | :--- | | Net cash used in operating activities | $(69,144) | $(36,292) | | Net cash used in investing activities | $(91,651) | $(4,161) | | Net cash provided by financing activities | $232,911 | $82,526 | [Quantitative and Qualitative Disclosures About Market Risk](index=124&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Vor Biopharma is not required to provide the information for this item - The company is a smaller reporting company and is not required to provide this information[625](index=625&type=chunk) [Financial Statements and Supplementary Data](index=125&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) This section refers to the full financial statements and supplementary data appended to the Form 10-K - This item directs to the full financial statements which are appended to the report, starting on page F-1[626](index=626&type=chunk) [Changes in and Disagreements With Accountants on Accounting and Financial Disclosure](index=125&type=section&id=Item%209.%20Changes%20in%20and%20Disagreements%20With%20Accountants%20on%20Accounting%20and%20Financial%20Disclosure) The company reports no changes in or disagreements with its accountants on accounting and financial disclosure - None reported[627](index=627&type=chunk) [Controls and Procedures](index=125&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2021 - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2021[628](index=628&type=chunk) - Management's assessment concluded that internal control over financial reporting was effective as of December 31, 2021[629](index=629&type=chunk) - No attestation report from the independent auditor on internal control is included, as permitted for emerging growth companies[630](index=630&type=chunk) [Other Information](index=125&type=section&id=Item%209B.%20Other%20Information) The company reports no other information - None[631](index=631&type=chunk) [PART III](index=126&type=section&id=PART%20III) This section provides details on the company's governance, executive compensation, ownership structure, and related party transactions [Directors, Executive Officers and Corporate Governance](index=126&type=section&id=Item%2010.%20Directors,%20Executive%20Officers%20and%20Corporate%20Governance) This section provides biographical information for executive officers and non-employee directors, detailing board and committee composition - The company's key executive officers are Robert Ang (President & CEO), Tirtha Chakraborty (Chief Scientific Officer), Nathan Jorgensen (Chief Financial Officer), and Christopher Slapak (Chief Medical Officer)[635](index=635&type=chunk) - The Board of Directors is chaired by Matthew Patterson and includes members with extensive experience in biotechnology, finance, and medicine[635](index=635&type=chunk)[642](index=642&type=chunk) - The Audit Committee is chaired by Daniella Beckman, who is qualified as an audit committee financial expert[650](index=650&type=chunk) [Executive Compensation](index=129&type=section&id=Item%2011.%20Executive%20Compensation) This section details executive compensation for 2021, including salary, bonuses, equity awards, and severance plans 2021 Summary Compensation Table | Name and Principal Position | Year | Salary ($) | Option Awards ($) | Non-Equity Incentive Plan Compensation ($) | All Other Compensation ($) | Total ($) | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | **Robert Ang, M.B.B.S.** | 2021 | 507,760 | 919,080 | 218,705 | 17,992 | 1,663,537 | | President and CEO | 2020 | 424,173 | 1,619,356 | 211,200 | 500,015 | 2,754,744 | | **Tirtha Chakraborty, Ph.D.** | 2021 | 384,022 | — | 138,701 | 17,915 | 540,638 | | Chief Scientific Officer | 2020 | 298,439 | 718,008 | 111,784 | 2,059 | 1,177,890 | | **Christopher Slapak, M.D.** | 2021 | 428,012 | — | 150,593 | 12,043 | 590,648 | | Chief Medical Officer | 2020 | 176,846 | 627,356 | 136,800 | 283,344 | 1,224,346 | - In 2021, target annual performance bonuses were **50% of base salary** for the CEO and **40%** for the other named executive officers[662](index=662&type=chunk) - The company has an Executive Severance and Change in Control Benefits Plan that provides for salary continuation, COBRA payments, and potential bonus payments and equity acceleration upon qualifying terminations, with enhanced benefits if the termination occurs within one year of a change in control[673](index=673&type=chunk)[674](index=674&type=chunk) [Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters](index=140&type=section&id=Item%2012.%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholder%20Matters) Significant beneficial ownership of common stock is concentrated among key institutional investors and management as of March 1, 2022 Beneficial Ownership as of March 1, 2022 | Name of Beneficial Owner | Percentage of Shares Beneficially Owned | | :--- | :--- | | **Greater than 5% stockholders** | | | Entities affiliated with RA Capital Healthcare Fund, L.P. | 29.7% | | Entities affiliated with 5AM Ventures VI, L.P. | 17.0% | | PureTech Health LLC | 8.6% | | Entities affiliated with FMR, LLC | 8.5% | | **Management** | | | All current executive officers and directors as a group (10 persons) | 20.7% | [Certain Relationships and Related Transactions, and Director Independence](index=142&type=section&id=Item%2013.%20Certain%20Relationships%20and%20Related%20Transactions,%20and%20Director%20Independence) This section details related party transactions, including Series B financing and IPO participation, and confirms director independence - In 2020 and 2021, the company sold Series B preferred stock to related parties, including entities affiliated with RA Capital (**$40.0 million**), 5AM Ventures (**$20.0 million**), and FMR, LLC (**$19.4 million**)[737](index=737&type=chunk)[738](index=738&type=chunk) - Several **5% stockholders**, including funds affiliated with RA Capital, 5AM Ventures, and FMR, LLC, purchased an aggregate of **$89.5 million** of common stock in the company's IPO[742](index=742&type=chunk) - In October 2020, the company forgave a **$497,920** promissory note, including principal and accrued interest, that was issued to CEO Robert Ang in 2019[743](index=743&type=chunk) - The Board of Directors has determined that all directors are independent under Nasdaq Listing Rules, with the exception of CEO Robert Ang[753](index=753&type=chunk) [Principal Accountant Fees and Services](index=145&type=section&id=Item%2014.%20Principal%20Accountant%20Fees%20and%20Services) This section outlines the fees billed by Ernst & Young LLP for audit and tax services in 2021 and 2020 Accountant Fees (2021 vs. 2020) | (in thousands) | 2021 | 2020 | | :--- | :--- | :--- | | Audit Fees | $815,623 | $870,000 | | Tax Fees | $62,500 | $0 | | **Total** | **$878,123** | **$870,000** | [PART IV](index=147&type=section&id=PART%20IV) This section lists all exhibits filed with the annual report and confirms no 10-K summary is provided [Exhibits, Financial Statement Schedules](index=147&type=section&id=Item%2015.%20Exhibits,%20Financial%20Statement%20Schedules) This section lists all exhibits filed with the Form 10-K, including corporate documents and material contracts - This item lists all exhibits filed as part of the Annual Report, including corporate governance documents, material contracts, and required certifications[761](index=761&type=chunk)[763](index=763&type=chunk)[765](index=765&type=chunk) [Form 10-K Summary](index=149&type=section&id=Item%2016.%20Form%2010-K%20Summary) The company indicates that there is no Form 10-K summary - None[767](index=767&type=chunk) [Financial Statements](index=151&type=section&id=Financial%20Statements) This section presents the company's audited consolidated financial statements and detailed explanatory notes [Consolidated Financial Statements](index=153&type=section&id=Consolidated%20Financial%20Statements) The 2021 consolidated financial statements report a **$68.9 million** net loss, **$242.6 million** total assets, and **$216.3 million** equity Consolidated Balance Sheet Highlights (as of Dec 31) | (in thousands) | 2021 | 2020 | | :--- | :--- | :--- | | Cash and cash equivalents | $119,801 | $48,539 | | Investments | $87,668 | $0 | | **Total assets** | **$242,590** | **$75,908** | | Total liabilities | $26,327 | $27,637 | | Total stockholders' equity (deficit) | $216,263 | $(59,065) | Consolidated Statement of Operations Highlights (Year Ended Dec 31) | (in thousands, except per share data) | 2021 | 2020 | | :--- | :--- | :--- | | Total operating expenses | $69,018 | $43,366 | | **Net loss** | **$(68,899)** | **$(43,337)** | | Net loss per share, basic and diluted | $(2.10) | $(230.57) | [Notes to Consolidated Financial Statements](index=157&type=section&id=Notes%20to%20Consolidated%20Financial%20Statements) The notes detail the February 2021 IPO proceeds, license agreements, NOL carryforwards, and expanded facility lease obligations - The company completed its IPO on February 9, 2021, receiving net proceeds of **$186.3 million**. Upon the IPO, all outstanding redeemable convertible preferred stock converted into common stock[791](index=791&type=chunk)[792](index=792&type=chunk) - As of December 31, 2021, the company had **$119.3 million** in federal and **$109.2 million** in state net operating loss (NOL) carryforwards. A full valuation allowance has been recorded against the net deferred tax assets[876](index=876&type=chunk)[877](index=877&type=chunk) - The company is obligated to make potential future payments under its license agreements, including up to **$6.3 million** in regulatory and commercial milestones to Columbia University and up to **$14.0 million** in clinical, regulatory, and sales milestones to the NIH[869](index=869&type=chunk)[871](index=871&type=chunk) - In June 2021, the company amended its Cambridge, MA lease, expanding its space by over **40,000 square feet** and increasing its total future lease payment obligations[861](index=861&type=chunk)[862](index=862&type=chunk)[863](index=863&type=chunk)

Vor Biopharma's Platform and Vision - Vor Biopharma is focused on curing blood cancers through cell and genome engineering[11] - The company's paradigm involves engineering hematopoietic stem cells (eHSCs) to remove target expression on healthy cells, making cancer killing more specific[7] - Vor's platform combines genome engineering with hematopoietic stem cells and CAR-T-cell therapies to create treatment-resistant transplants[10] VOR33 and VCAR33 Programs - VOR33 aims to provide treatment-resistant HSC transplants[19] - VCAR33 is an allogeneic CAR-T therapy with potential advantages for healthy donor cell source and addressing tumor heterogeneity[24] - The VCAR33 construct is being studied in a Phase 1/2 clinical trial sponsored by the National Marrow Donor Program (NMDP)[26] Clinical Development and Milestones - Vor anticipates initial clinical data for VOR33 in the first half of 2022[25,73] - The company plans to file an IND for the VOR33 + VCAR33 treatment system in the second half of 2022, following initial VOR33 and NMDP clinical data[25,73] - A Phase 1/2a clinical trial (VBP101) is underway, evaluating VOR33 + Mylotarg in transplant-eligible AML patients at high risk of relapse[48,49] Market and Financial Position - Approximately 20,000 AML cases are diagnosed annually[13] - For patients who relapse post-transplant, 2-year survival is less than 20%[17] - Vor Biopharma secured $203 million in gross proceeds from its IPO in February 2021, providing a cash runway into mid-2023[73]

Vor Biopharma's Platform and Vision - Vor Biopharma is focused on curing blood cancers through cell and genome engineering[11] - The company's paradigm involves engineering hematopoietic stem cells (eHSCs) to remove target expression on healthy cells, making cancer killing more specific[7] - Vor's platform combines genome engineering with hematopoietic stem cells and CAR-T-cell therapies to create treatment-resistant transplants[10] VOR33 and VCAR33 Programs - VOR33 aims to provide treatment-resistant HSC transplants[19] - VCAR33 is an allogeneic CAR-T therapy with potential advantages for healthy donor cell source and addressing tumor heterogeneity[24] - The VCAR33 construct is being studied in a Phase 1/2 clinical trial sponsored by the National Marrow Donor Program (NMDP)[26] Clinical Development and Milestones - Vor anticipates initial clinical data for VOR33 in the first half of 2022[25,73] - The company plans to file an IND for the VOR33 + VCAR33 treatment system in the second half of 2022, following initial VOR33 and NMDP clinical data[25,73] - A Phase 1/2a clinical trial (VBP101) is underway, evaluating VOR33 + Mylotarg in transplant-eligible AML patients at high risk of relapse[48,49] Market and Financial Position - Approximately 20,000 AML cases are diagnosed annually[13] - For patients who relapse post-transplant, 2-year survival is less than 20%[17] - Vor Biopharma secured $203 million in gross proceeds from its IPO in February 2021, providing a cash runway into mid-2023[73]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from __________________ to __________________ Commission File Number: 001-39979 VOR BIOPHARMA INC. (Exact Name of Registrant as Specified in its Charter) | Delaw ...